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    Faculty of Health and Life SciencesSchool of Allied Health Sciences

    Module HandbookModule Handbook

    BIOM 2004BIOM 2004Infammation andInfammation and

    ImmunobiologyImmunobiologyor Biomedical Scienceor Biomedical Science

    BIOM 2904BIOM 2904Studies in Infammation andStudies in Infammation andImmunobiology or BiomedicalImmunobiology or Biomedical

    ScienceScience

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    Name of Student

    Student E-mail address

    2

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    CO!"!S

    #elcome toBIOM2004$2904%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%&%%&&'

    (& Introduction to t)eModule%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%&%%%&&'

    1.1. Modulecharacteristics..3

    1.2. Contact details ofsta5

    2& Module s*eci+cinormation%%%%%%%%%%%%%%%%%%%%%%%%%%%%%&%%%%%%%,2.1. Learningoutcomes.62.2. Hand-indates.72.3. Modulecalendar...2.!. Mar"ings#stem..$2.5. Late su%mission of assignments...13

    '& -eerencingguide%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%&%%%%%%%%(43.1. &uide to 'urnitin and the (irtual Learning)n*ironment..1!'& 2& #H"-" !O S!.-! / O1- I-S! HOM"#O-3%%%%%%&&&%&&&&&&&&&&&&&&(,3.3. 'e+t%oo"s.....163.!. ,e%sites and

    ournals..17

    3

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    4& Student eedback rom *re5iousyears%%%%%%%%%%%%%%%%%%%%&%%%%%%&&(6

    //endi+ 1. 0afet#

    declaration...............................1

    //endi+ 2. Learning material for #ourstart1$

    #"7COM" !O BIOM2004$2904

    ,elcome to the M244!2$4! nammation and mmuno%iolog#module hich ill introduce #ou to our immune s#stem and ho it%attles to re/air our %od# and /rotect it from the attac" of

    threatening e+ternal in*aders8

    'hroughout the module9 together e ill del*e into the orld ofs#stems and molecules9 loo"ing at the mechanisms used tomaintain human defenses and com%at diseases. 'he course ill gi*ea detailed account of the indi*idual com/onents of the immunes#stem and ho the# interact9 and the mechanisms in*ol*ed in theaethiolog# and treatment of disease states in autoimmunit#9h#/ersensiti*it#9 immunode:cienc# and malignanc#. ;our studies ofthese areas ill also e+tend into the :nal #ear of the degree/rogramme as M34433$43 mmuno/atholog# module.

    4

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    7ecture )andouts may be *ro5ided at t)e discretion o t)e7ecturer i so: ;ill be gi5en out at t)e lecture and ;illsu**lement and not re*lace t)e -eading 7ist&

    @racticals for M244! are designed as a seDuence of the folloingla%orator# %ased sessionse "?clusion C)romatogra*)y@

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    =r >uta ?urmona*iciene AModule 7eaderB0enior Lecturer in iomedical 0ciences mmunolog#9Hathorn %uilding9 >oom H 1.1e-mail rfurmona*icieneEdmu.ac.u"

    =r oom H 1.14e-mail uma"hanth.*en"atramangiriaEdmu.ac.u"

    =r Cari"a ,eldon@' Lecturer in iomedical 0ciencese-mail Cari"a.,eldonEdmu.ac.u"

    2& MO817" S

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    1 - 'o descri%e %asic as/ects of immunolog# and inammation atthe molecular and s#stemic le*el.2 - 'o /resent the a%o*e in the form of essa#s and oral

    /resentations.

    ullDtime students are e?*ected to attend t;oullDtime students are e?*ected to attend t;o

    *ractical sessions: tutorial session and all*ractical sessions: tutorial session and alllecture sessionslecture sessions

    Studies students are e?*ected to attend one oStudies students are e?*ected to attend one ot)et)e

    *racticals E*lease contact module leader or*racticals E*lease contact module leader ormoremore

    inormationFinormationF

    IG< and IC students are e?*ected to attendIG< and IC students are e?*ected to attendlecture sessions onlylecture sessions only

    2&2&.SS"SSM"!S .8 H.8DI 8.!"S

    .ssessments or ullDtime students.ssessments or ullDtime students

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    #eek 7ecture !itle StaA 1 ntroduction to the module >?2 nnate mmunit# >?3 da/ti*e mmunit# >?! Humoral mmunit#9 cell acti*ation9 anti%odies >?7 Com/lement in mmunit#

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    Practical 1Practical 1!1"#!1"#

    Practical $Practical $!1"#!1"#

    EssayEssay1"#1"#

    .ssessments o Biomedical Studies Students.ssessments o Biomedical Studies Students

    2)r "?amination2)r "?amination K 60L o Module MarkK 60L o Module MarkCourse;orkCourse;ork K '0L o Module MarkK '0L o Module Mark

    Breakdo;n o Course;orkBreakdo;n o Course;ork

    EssayEssay !1%#!1%#PracticalPractical!1%#!1%#

    .ssessments o IG< and IC Students.ssessments o IG< and IC Students

    2)r "?amination2)r "?amination K 60L o Module MarkK 60L o Module MarkCourse;orkCourse;ork K '0L o Module MarkK '0L o Module Mark

    Breakdo;n o Course;orkBreakdo;n o Course;ork

    EssayEssay !&"#!&"#

    .ssessment rationale.ssessment rationale&eneric >egulations of =e Montfort&eneric >egulations of =e Montfort

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    Section .

    Candidates should attem/t four A!B Duestions out of a total of si+ A6BDuestions from section Aeach orth 12.5 IB. 'hese are shortDuestions.

    Section B

    Candidates should attem/t to A2B Duestions out of a total of fourA!B Duestions from section Aeach orth 25IB. 'hese are longer9essa# t#/e Duestions.

    -"GISIO

    ac"ground material reDuired for ansering the Duestions arecontained in the lecture notes. 0o #ou should %egin to identif#discrete sections ithin the notes and com/ose essa# /lans aroundthem. )ssa# /lans should %e no longer then half a side of ! andcontain a fe /oints A14-15B hich are eas# to remem%er. 'hen%egin to re*ise %# riting essa#s. ;ou cannot e+/ect to score ell inan essa# Duestion if #ou ha*e not tried riting essa#s as /art of#our re*ision. 'he *er# act riting the essa# hel/s #ou to remem%erthe facts and hat should %e mentioned here.

    M.-3 8"SC-I

    )ach com/onent of the ritten courseor" ithin the module ill %egi*en a grade or I mar" as follos

    'hese descri/tors are inter-related ith regard to mar"s of !4 anda%o*e there is an assum/tion that in aarding mar"s in one %andor" ill ha*e met the reDuirements of the previous %andJ ithregard to mar"s of 3$ and %elo there is an assum/tion that inaarding mar"s in one %and or" ill F' ha*e met thereDuirements of the /re*ious higher %and.

    ,hen mar"ing an indi*idual /iece of or" there is an e+/ectationthat it ill clearl# demonstrate most of the criteria ithin each%and

    Mark-ange

    Criteria

    90D(00L

    >es/onds to allof the assessment criteria for thetas".

    =is/la#s e+ce/tional degree of originalit#.

    )+ce/tional anal#tical9 /ro%lem-sol*ing andor

    12

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    creati*e s"ills

    Fo fault can %e found ith the or" other than*er# minor errors9 for e+am/le minor t#/ogra/hicalissues

    0D9L

    >es/onds to allof the assessment criteria for thetas".

    ,or" of outstanding Dualit#9 e*idenced %# an a%ilit#to engage criticall# and anal#ticall# ith sourcematerial.

    Li"el# to e+hi%it inde/endent lines of argument.

    Highl# original andor creati*e res/onses.

    )+tremel# ide range of rele*ant sources usedhere a//ro/riate

    60D69L

    >es/onds to allof the assessment criteria for thetas".

    n e+tremel#9 ell de*elo/ed res/onse shoingclear "noledge and the a%ilit# to inter/ret andora//l# that "noledge.

    n authoritati*e gras/ of the su%ect9 signi:cantoriginalit# and insight9

    0igni:cant e*idence of a%ilit# to sustain anargument9 to thin" anal#ticall#9 criticall# andorcreati*el# and to s#nthesise material.

    )*idence of e+tensi*e stud#9 a//ro/riate to tas".

    ,0D,9L

    >es/onds to mostof the assessment criteria for thetas".

    detailed res/onse demonstrating a thorough gras/of theor#9 understanding of conce/ts9 /rinci/les9methodolog# and content.

    Clear e*idence of insight and critical udgement inselecting9 ordering and anal#sing content.

    =emonstrates a%ilit# to s#nthesise material9 toconstruct res/onses and demonstrate creati*e s"illshich re*eal insight and ma# oer some originalit#.

    =ras on an a//ro/riate range of /ro/erl#referenced sources.

    0D9L

    >es/onds to mostof the assessment criteria for thetas".

    n eecti*e res/onse demonstrating e*idence of aclear gras/ of rele*ant material9 /rinci/les and "e#conce/ts

    n a%ilit# to construct and organise arguments.

    0ome degree of critical anal#sis9 insight andcreati*it#.

    =emonstrating some conce/tual a%ilit#9 criticalanal#sis and a degree of insight.

    ccurate9 clearl# ritten/resented

    13

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    40D49L

    >es/onds to someof the assessment criteria for thetas".

    res/onse demonstrating an understanding of %asic/oints and /rinci/les suKcient to sho that some oflearning outcomesassessment criteria ha*e %eenachie*ed at a %asic le*el.

    0uita%l# organised or" demonstrating a reasona%lele*el of understanding

    Co*ers the %asic su%ect matter and is a//ro/riatel#/resented %ut is rather too deri*ati*e andinsuKcientl# anal#tical.

    =emonstrates limited conce/tual a%ilit#9 le*els ofe*aluation and demonstration of creati*e s"ills.

    =emonstrates adherence to the referencingcon*entions a//ro/riate to the su%ect andor tas".

    '0D'9L

    *erall insuNcientres/onse to theassessment criteria.

    ea" res/onse9 hich9 hile addressingsome elements of the tas"9 contains signi:cant ga/sand inaccuracies.

    ndicates an anser that shos onl# ea"l#de*elo/ed elements of understanding andor others"ills a//ro/riate to the tas".

    Ma# contain ea"nesses in /resentation

    that constitute a signi:cant o%stacle incommunicating meaning to the assessor.

    20D29L

    *erall insuNcientres/onse to theassessment criteria.

    /oor res/onse9 hich falls su%stantiall#short of achie*ing the learning outcomes.

    =emonstrates little "noledge andor others"ills a//ro/riate to the tas"

    Little e*idence of argument andor coherentuse of material

    (0D(9L

    *erall insuNcientres/onse to theassessment criteria.

    *er# /oor res/onse demonstrating ferele*ant facts

    =is/la#s onl# isolated or no "noledgeandor other s"ills a//ro/riate to the tas".

    Little adherence to the tas"

    0D9L

    *erall insuNcientres/onse to theassessment criteria.

    =is/la#s *irtuall# no "noledge andor other s"ills

    a//ro/riate to the tas". ,or" is ina//ro/riate to assessment tas" gi*en

    14

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    @lease :nd %elo some more information a%out these descri/tors.

    O1- 1I8" !O !H" 1IG"-SI! 18"--.81.!" M.-38"SC-I

    'he

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    criteria being a**lied in any *articular assessment and toseek clari+cation rom your tutors i necessary&

    ""8B.C3

    ?eed%ac" on formal assessments ould %e lin"ed to the mar"ingcriteria. 'his feed%ac" can ta"e dierent forms9 including genericoral feed%ac" to a hole class or indi*idual comment sheets. 'heaim of the feed%ac" is to hel/ #ou de*elo/ the "noledge and s"illsneeded for successful com/letion of the module.

    nformal feed%ac" from tutors is used to inform #ou of #our /rogressand ma# ta"e /lace through indi*idual meetings9 classroomdiscussions and other means such as online e+changes. @eerfeed%ac" %eteen students ma# %e encouraged through grou/meetings9 seminars9 class discussions and the use of socialnetor"ing sites on the internet. ;ou should ma"e use of all thesedierent forms of feed%ac" to e*aluate #our learning and identif#further a//ro/riate learning acti*ities.

    2&& 7.!" S1BMISSIO O .SSIM"!S

    'he folloing regulations ill a//l# for all M module assessmentshanded in late

    o !4I ca/ for or" su%mitted unauthorised u/ to 7 actualda#safter original su%mission date.

    o 4I for or" su%mitted unauthorised more than 7 actualda#safter original su%mission date.

    ssessments ma# %e handed in late %# *riorarrangement ith themodule leader. 'o do this #ou must ha*e

    iB a *alid reason for the re/ort to %e handed in late.

    iiB an Extension to Coursework Applicationa*aila%le from the0tudent d*ice Centre. ring this ith #ou hen #ou see themodule leader to reDuest an e+tension9 hich must %e %eforethe deadline date.

    n e+tension date can then %e agreed u/on %eteen the studentand module leader should the circumstances arrant this.

    '& -""-"CI 1I8"

    16

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    '&(& 1I8" !O !1-I!I .8 !H" GI-!1.7

    7".-I "GI-OM"!

    #)at are *lagiarism and collusionn #our second #ear #ou ill "ee/ u/ the good /ractice of citing andreferencing the or" of others. ?ailure to do so and /assing of theor" of others as #our on is "non as /lagiarism. Co/#ing or"from fello students is "non as collusion. 'hese are %oth treatedas academic oences and further details are found in the egulations and @roceduresecting 0tudents9 cha/ter ! cademic ences Nseehtt/mle.dmu.ac.u"regulationsgeneralO.

    'o learn a%out citation and referencing9 the Li%rar# has a num%er ofself-stud# %oo"lets including nformation Citation and @lagiarismhich are a*aila%le on-line and in the li%rar#. N0ee

    htt/.li%rar#.dmu.ac.u"0u//ort0elfstud#inde+./h/P/ageQ$O. 'hese ill ena%le #ou to im/ro*e #our academic s"ills.

    ;our module team ill also ha*e su//ort materials to hel/ #ou9 andalong ith #our /ersonal tutor ill %e a%le to /ro*ide #ou iths/eci:c guidance.

    #)at is !urnitin'urnitin is a e%-%ased /lagiarism detection tool idel# used in

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    Concluding remarks

    ;ou must not co/# te+t9 diagrams9 :gures or e*en strings of ideasfrom anysource S /rinted te+ts9 the orld-ide-e%9 C=->Ms orfrom colleagues.

    ;ou must %e aare of the current regulations regarding /lagiarismoences. @lease read carefull# the

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    or your start: es*ecially i you )a5e ne5er studied

    immunology beore: you can e?*lore t)e learning

    material in .**endi? 2 / t)is ;ill gi5e you . le5el

    background in t)e subPect&

    '& '& !"!BOO3S

    t Honours Le*el #ou are e+/ected to %e or"ing from refereedTournal articles here*er a*aila%le. Current te+t %oo"s9 hoe*er9/ro*ide a foundation on hich to %uild the "noledge #ou reDuire9therefore #ou should use the folloing te+t%oo"s

    !)e main module te?tbook

    =a*id Male9 Tonathan rosto9 =a*id >oth and *an >oitt.Immunolog9 Mos%#9 24129 thedition.

    -ecommended reading%ul R %%as9 ndre H Lichtman and 0hi* @illai. Cellular an!molecular Immunolog" )lse*ier9 241!9 thedition.

    nthon# L =e?ranco and >ichard M Loc"sle#. Immunit9 0inauerssociates ncor/orated9 2415.

    Helen Cha/el9 Mansel Haene#9 0ira Mis%ah and Feil 0noden.

    Essentials of Clinical Immunolog9 ,ile#-lac"ell9 241!9 6th

    edition.

    Tohn @la#fair and &regor# ancroft. Infection an! Immunit9 +fordoderic" Fairn and Matthe Hel%ert. Immunolog for me!icalstu!ents" )lse*ier9 24479 2ndedition.

    'homas T Rindt9 >ichard &olds%# and ar%ara s%orne.

    Immunolog9 @algra*e9 24469 6th

    edition.

    urt)er readingrthur M Les". Intro!uction to Protein Arc#itecture$ t#e %tructuraliolog of Proteins9 +ford

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    '&4& #"BSI!"S .8 QO1-.7S

    1seul Immunology ;ebsitesmmunolog# and Micro%iolog# nline from the

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    appreciate all t#e assistance in Immunolog0 It reall ma!e meenlig#tene! an! ma!e me look forwar! to speciali6e in t#e course0-

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    .

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    s#stemVs eorts to resist and o*ercome colds9 u and food /oisoning9 fore+am/le9 %ut hen e are ell e tend to thin" that our immune s#stemhas la/sed into inacti*it#. n fact9 nothing is further from the truth.

    ,e cannot tal" a%out the immune s#stem ithout tal"ing a%out the

    usuall# microsco/ic organisms that are /ro%a%l# the reason for itse+istence. Here the ord V/athogensV is used as the general term forinfectious organisms or agents that cause disease.

    (&(&2 Inection is diAerent rom disease immunity *re5entsdisease

    t is im/ortant to distinguish %eteen infection Athe entr# of a /athogeninto the %od#B and disease Athe damaging eects of the /athogen on the%od#B. mmunit# /re*ents disease it might also /re*ent infection9 thoughinfection freDuentl# occurs %ut is dealt ith so Duic"l# %# the immunes#stem that e ne*er "no it ha//ened.

    (&(&'Immunity Occurs .s . -esult O Inection

    t is im/ortant to understand that much of our most im/ortant immunit# isgained through e+/osure to infection. ,e "no this %ecause man#infections do not occur more than once in the same /erson. n fact9 as ill%e descri%ed later9 a :rst infection can actuall# ma"e the immune s#stemor" much %etter.

    nfections %# %acteria and *iruses are usuall# dealt ith *er# ell9although some can cause serious and e*en fatal illnesses. A'oda# e ha*e

    the hel/ of medicines such as anti%iotics to deal ith /ersistent or life-threatening %acterial infections.B n general9 the immune s#stem has moretrou%le ith ungi: ;orms and *roto>oa. ?ungi ha*e tough cell allsthat /re*ent attac" %# the immune s#stem hile /arasitic orms and/rotoWoa ha*e e*ol*ed e+tremel# cle*er a#s to side-ste/ the %estattem/ts of the immune s#stem to :ght them.

    (&2 Ho; t)e Immune System Is Organised

    'he immune s#stem is a com/le+ netor" hich is diKcult to classif#sim/l#. ,e can categorise the dierent '-cell t#/es that carr# out *arious

    functions and e can also classif# according to the o*erall functionsthemsel*es9 most of hich in*ol*e dierent t#/es of cell or"ing together.,e ha*e tried to summarise %oth a//roaches %rie# in this section.

    3ey *oints

    immune cells are uniDuel# mo%ile

    cells of the immune s#stem ha*e s/ecial and dierent functions

    the immune s#stem /ro*ides non-s/eci:c and s/eci:c immunit#

    (&2&(Immune Cells are 1niuely Mobile

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    'he immune s#stem is made u/ of cells hich ma"e u/ the immunetissues. Man# of these cells can also ander a%out the %od#. 'he mo%ilit#of its cells is a uniDue and im/ortant /ro/ert# of the immune s#stem itallos #oung cells to mo*e from their site of origin to dierent /arts of the

    %od#9 as and hen the# are most needed.

    'he *ital role that cell mo%ilit# /la#s in immunit# is illustrated in /eo/leho ha*e a genetic defect that aects cell mo*ement through the %od#such /eo/le ala#s ha*e seriousl# damaged immune s#stems.

    (&2&2Cells o t)e Immune System Ha5e S*ecial and 8iAerentunctions

    'he dierent cells of the immune s#stem ha*e man# dierent functions.ndi*idual cells are s/ecialised to do /articular o%s and this is necessar#for the s#stem to deal ith the man# dierent /athogens and the man#dierent a#s the# use to infect and damage us.

    Man# %oo"s on immunolog# attem/t to teach im/ortant conce/ts usingthe analogies of %attles and ar. 'he danger is that the analog# itself ma#mean dierent things to dierent /eo/le9 so e ill tr# to "ee/ theanalogies sim/le to a*oid confusion. ?or e+am/le it is Duite useful to thin"of the cells of the immune s#stem or"ing together as an arm# - most/eo/le are aare that an arm# is made u/ of man# dierent s/ecialists.

    n the immune s#stem the s/ecialist cells ha*e %ecome this a# /artl#

    %ecause the# ere %orn to it and /artl# %ecause the# learn9 or areeducated9 to do certain things. 'he# /rotect us and maintain the internalen*ironment of our %odies.

    n the classi:cation of the cells of the immune s#stem throughout this%oo" Astarred in the glossar#B9 all the cell t#/es and their descendants thatoccur in the %lood are included9 ith one e+ce/tionJ the red %lood cells.

    'he cells of the immune s#stem are therefore /rimaril# the l#m/hoc#tesand /hagoc#tes. 'hese cells can interact ith man# - /erha/s all - othercells in the %od#.

    (&2&'!)e Immune System

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    2 3ee*ing ymeDric) s;eat& !)ese en>ymes

    can kill *at)ogens&

    It is easier or *at)ogens to enter t)e body at its o*eningsT t)enose: ears: eyes and mout): or e?am*le& Because o t)is ;e )a5edeences at all t)e bodys o*enings& Sticky mucus in t)e nose and;a? in t)e ear are good tra*s or *at)ogens& !ears and sali5a)a5e en>ymes to )ill bacteria&

    !)e body also makes good use o riendly bacteria& !)ese li5e int)e gut: 5agina and uret)ra and )el* kee* *at)ogens out&

    2&( onDS*eci+c Immunity

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    'he %od#Vs /h#sical and chemical %arriers /ro*ide innate immunit# theimmunit# ith hich e are %orn. t is also called non-s/eci:c or naturalimmunit#9 for o%*ious reasons9 and it has to im/ortant features. ?irst9 itis eecti*e against a ide range of micro%es9 irres/ecti*e of their t#/e.

    0econd9 its eecti*eness does not change ith e+/erience of infectionAsee %eloB. 'his sets it a/art from ada/ti*e immunit#9 hich is dealt ithin greater detail later.

    2&(&2!)e Skin Is a !oug)

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    /ro%lems. a%ies of all mammals are %orn ithout commensal %acteriaand their gut %ecomes colonised ith them in the earl# da#s of life.

    ' #)at Ha**ens i

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    other cells ha*e s/ecial roles in non-s/eci:c immunit#

    some cells are "illers the# attac" micro%es directl#

    cells also ma"e chemicals hich hel/ the :ght against disease

    '&(&(Infammation is

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    and destro# the %acteria hich multi/l# ra/idl# in the ound9 using the/rocess of /hagoc#tosis Asee %eloB. lthough and it can %e a /ainful andun/leasant reaction9 and its /resence o%*iousl# indicates that somethingundesira%le has occurred9 it is *alua%le %ecause it contains the infection9ho/efull# /re*enting it from s/reading throughout the %od# and causing

    much more serious damage.

    '&(&'

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    '&(&4Ot)er Cells Ha5e S*ecial -oles in onDS*eci+cImmunity

    Feutro/hils ha*e some near relati*es that loo" similar9 %ut hich ha*e

    dierent /rotecti*e o%s. "osino*)ilsare im/ortant in /rotection againstsome /arasitic orms9 and also ha*e a s/ecial role in allergies such as ha#fe*er. MastDcells and baso*)ilsare other relati*es of the neutro/hilshich li*e in tissues close to mucous mem%ranes Asuch as those that linethe lungs and the gutB9 and are im/ortant for dealing ith /arasites thatin*ade through the gut and lungs. Hoe*er9 the# too are in*ol*ed inallergies.

    '&(&Some Cells .re 3illers

    7ym*)ocytes ha*e an im/ortant role in s/eci:c immunit#9 Adescri%ed%elo in Y=esigner =efenceYB %ut the %od# has a *er# im/ortant set ofcells that are close relati*es of l#m/hoc#tes %ut hich /ro*ide im/ortantnon-s/eci:c immunit#. atural killer9 or 39 cells are large cells ith agranular a//earance under the microsco/e Athis has gi*en them the nameof large granular lym*)ocytesB. 'he# can "ill man# dierent t#/es ofcells and the# do other things too. 'he# hel/ in anti-*iral immunit#9 in anti-tumour immunit# and9 sur/risingl#9 in controlling the /roduction of cells inthe %one marro.

    FR cells can "ill cells *er# easil# ithout needing s/ecial acti*ation :rstand so form an im/ortant :rst line of defence against in*ading /athogens.

    'he# are ala#s a*aila%le in the %od# to do this and are an im/ortant /art

    of the non-s/eci:c immune res/onse to infection.

    ecause of their a%ilit# to "ill some tumour cells in8vitro9 research into necancer treatments is loo"ing at %oosting the acti*it# of FR cells ithselected cytokinesAsee interferons %eloB.

    '&(&,Cells .lso Make C)emicals #)ic) Hel* t)e ig)t.gainst 8isease

    lthough some immune cells themsel*es interact Vface- to-faceV ith/athogens9 man# of them manufacture and secrete s/ecial su%stances

    that then loc" onto /athogens9 or hich arm other cells to do the attac".

    'he com*lement systemincludes more than 24 /roteins hich circulatein the %lood. 'hese /roteins are made %# macro/hages and or" togetherin a cascade to deal ith micro%es in *arious a#s. 0ome of thecom/lement /roteins9 for e+am/le9 coat %acteria and ma"e them Vmorea//etisingV to macro/hages. 0e*eral of the com/lement /roteins also or"together to form a sort of Vhole-/unchV9 hich a%s holes in the cell allsand mem%ranes of %acteria and /arasites. 'his s/ells %ad nes for the/athogens as the# %ecome lea"# and soon die as a result.

    'here is also a large collection of so-called acute *)ase *roteins that

    circulate in the %lood and are made9 as their name im/lies9 in the earl#and acute /hase of inammation that accom/anies an infection. 'hese

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    /roteins can coat in*ading /athogens to /re*ent them infecting tissuecells or to ma"e them more li"el# to %e eaten %# /hagoc#tes.

    Intererons are made %# cells infected ith *iruses. 'he# inhi%it thegroth of *iruses in other cells9 so can %e useful in /re*enting the s/read

    of *iruses through the %od#. nterferons %elong to a large famil# of /roteinscalled c#to"ines. nterferons are %eing in*estigated for their /otential tocontrol FR cells.

    4 8esigner 8eence

    !o +g)t some *at)ogens: our bodies use s*ecially designeddeences& !)ese are *ro5ided by t;o diAerent ty*es o ;)ite

    blood cells: called BDcells and !Dcells&

    BDcellsBDcells are actories t)at make c)emical

    ;ea*ons called antibodies& .ntibodies target*at)ogens: *articularly bacteria:by

    U sitting on t)e surace o t)e bacteria andattracting s*ecial *roteins: some o

    ;)ic) *unc) )oles in t)em&

    U coating t)e bacteria: making t)em sticky and easier or t)e*)agocyte to grab&

    Most o t)e antibody actories die soon ater t)e inection )asbeen sto**ed but a e; ;ill li5e on and remember t)e *at)ogen it)ey meet it again&

    !)ese BDmemory cells ;ill t)en s;itly make more antibodies;)ic) ;ill kill t)e in5aders beore t)ey )a5e time to make us ill&!)is immune memory e?*lains t)e success o immunisation&

    !Dcells

    Giruses and some bacteria li5e inside cells ;)ere antibodiescannot get to t)em: but !Dcells can target t)e inected cells& !)eystick on to t)ese inected cells and kill t)em& !Dcells also tell ot)ercells in t)e immune system ;)at to do and ;)en to do it&

    'here are four main t#/es of '-cell Z

    X Hel*er !Dcells - hel/ -cells to ma"e eKcientanti%odies. 'he# also tell other '-cells hat to do.

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    X 3iller !Dcells- "ill %od# cells that ha*e %een infected%# *iruses using direct9 cell-to-cell com%at or %#ordering them to self-destruct.

    X -egulator !Dcells- tell the immune s#stem to inddon hen an infection is o*er.

    X Memory !Dcells- Ali"e memor# -cellsB remem%erthe /athogen so that the %od# can react moreDuic"l# to it the ne+t time.

    4&( .n O5er5ie; o t)e S*eci+c Immune System

    Re# /oints

    non-s/eci:c immunit# cannot co/e alone

    s/eci:c immunit# is s/eci:c for /articular /athogens

    l#m/hoc#tes are the "e# to s/eci:c immunit#

    l#m/hoc#tes recognise s/eci:c antigens and remem%er them

    l#m/hoc#tes ha*e rece/tors to hel/ them recognise antigens

    4&(&(onDS*eci+c Immunity Cannot Co*e .lone

    'he mechanisms of non-s/eci:c immunit# act Duic"l# in res/onse to agreat range of dierent infections. 'he# are9 hoe*er9 not designed todeal s/eci:call# ith one /articular micro%e9 nor are the# made moreeecti*e %# re/eated use. n fact9 im/ortant as the# are9 the# are notenough on their on. ,e also need the other face of the immune s#stem9the s/eci:c immune s#stem hich can recognise /articular /athogens9

    react to them *er# eecti*el# and remem%er them for ne+t time.

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    4&(&2S*eci+c Immunity is S*eci+c or

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    cells from another /erson are trans/lanted to re/lace the marro. 0omechildren ha*e a rare mutation that /re*ents the th#mus from de*elo/ingand the# ha*e to %e isolated in a sterile en*ironment to /rotect them frominfection. 'he# too can no %e hel/ed %# a trans/lant of health# th#mustissue.

    MO-" IO-M.!IO O 7M

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    Aon the surface ofa l#m/hoc#teB%ind to an antigenAon a /athogenB9a signal is sent

    from the rece/torsto the cell nucleus.

    'his instructsthe l#m/hoc#te toturn

    on the genes thatit needs to read to

    /roduce /rotecti*e /roteins. f the l#m/hoc#te is a -cell9 the/rotein /roduced is an anti%od#J if it is a '-cell9 the /rotein is ac#to"ine.

    f course9 com/licated as this ma# sound9 this is *er# muchan o*ersim/li:cation. ther signals are needed to ma"e sure the

    cell is correctl# acti*ated. Hoe*er9 the cru+ of the holereaction is the interaction of the rece/tor on the l#m/hoc#te

    iththe antigen from the /athogen.

    4&(&47ym*)ocytes -ecognise S*eci+c

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    4&(&7ym*)ocytes Ha5e -ece*tors !o Hel* !)em -ecognise.ntigens

    L#m/hoc#tes ha*e /roteins actuall# on their cell surface mem%ranes

    hich are called rece/tors. 'hese rece/tors hel/ l#m/hoc#tes to recognise/athogens %# %inding to antigens on the /athogenVs surface. 'his ise+/lained in detail a%o*e

    4&2 !)e -ole o BDCells

    Re# /oints

    -cells can recognise and react to s/eci:c antigens

    -cells ma"e anti%odies hich com%ine ith antigens s/eci:call#

    dierent t#/es of anti%odies are found in dierent /laces andthe# dodierent things

    antigen acti*ates a -cell and it ma"es a clone

    some acti*ated -cells /roduce anti%od# others %ecomememor# cells

    the %od#Vs genes ha*e a cle*er tric" that allos millions of t#/esofdierent anti%odies to %e made

    4&2&(BDCells Can -ecognise and -eact to S*eci+c .ntigens

    ,hen a -cell meets the antigen to hich it is /rogrammed to react9 it%ecomes acti*ated. 'he cell starts to ma"e anti%odies hich com%inechemicall# ith molecules of the same antigen that stimulated the -cellin the :rst /lace. 'his selecti*e acti*ation of l#m/hoc#tes %# antigen is the%asis of immune s/eci:cit#. *er# im/ortant fact to remem%er at thisstage is that there are millions of dierent antigens and therefore

    e*er#one can ma"e millions of dierent -cells9 %ut one -cell can onl#recognise and react to one antigen.

    4&2&2BDCells Make .ntibodies #)ic) Combine ;it) .ntigensS*eci+cally

    nti%odies ere the :rst molecules of the immune s#stem to %edisco*ered and to ha*e their %iochemical structure anal#sed in detail.

    'he# come in se*eral dierent forms9 %ut the# all ha*e a similar %asicstructure. )*er# anti%od# molecule is ;-sha/ed ith to arms at the end ofa tail. t the end of each arm are s/ecial sites that com%ine ith antigen.

    'he tail end does not %ind antigen9 %ut does %ind to other things that

    determine the function of that /articular anti%od#.

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    nti%odies %ring a%out the ultimate destruction of the micro%e in anum%er of dierent a#s. central function of anti%od# is to /romote/hagoc#tosis. @hagoc#tes ha*e rece/tors on their surface for the tails ofanti%odies. 'he tails stic" out all o*er the micro%e9 /ro*iding hand# targetsto hich /hagoc#tes can attach themsel*es. 0o a /hagoc#te can recognise

    and then engulf a micro%e coated in anti%od# much more easil# than anuncoated /athogen. 'his enhancement of /hagoc#tosis is calledo*sonisation.

    'he tails of anti%odies also%ind ith com/lement /roteins.

    'his %inding e*ent causes therelease of chemicals hichattract more /hagoc#tes to

    the site9 so enhancing theeecti*eness of inammation.t also forms the com/lementVhole-/unchV hich a%s holes inthe /athogen9 lettingthe inside out and the

    outside in.

    ,hen anti%odies %ind to theouter /roteins of a

    *irus9 the# can /re*ent itattaching itself to a

    %od# cell. 'his limits *irus re/lication and so slos the s/read of the*irus through the %od#. nti%od# can also %ind to the agellae of %acteria.

    'his sto/s them simming around and clum/s them together9 ma"ingthem sitting targets for /hagoc#tes.

    4&2&'8iAerent !y*es o .ntibodies .re ound in 8iAerent

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    !y*e o antibody

    7ocation S*ecial unctions

    g& lood and %od# =eal ith %acteria intissues and *irusesan#here in the

    %od# gM lood mostl# [uic" resistance to%acteria in the %lood

    g 0ecreted across mucousmem%ranes

    @rotects against*iruses and othermicro%es in gut9lungs etc.

    g) n mast cells and %aso/hils inthe %od# %ut es/eciall# nearmucous mem%ranes

    >esistance to orminfections andagents of allerg#

    g= Mostl# on -cells ntigen rece/tor on-cells

    4&2&4.ntigen .cti5ates a BDCell and it Makes a Clone

    ,e ill use -cells to e+/lain hat ha//ens hen a l#m/hoc#te isacti*ated %# antigen and hat follos a//lies in general to '-cells as ell.ne -cell ma"es one anti%od#9 and during -cell de*elo/ment A%eforethe# ha*e e*er met an antigenB indi*idual cells %ecome /rogrammed toma"e ust that anti%od#. ,hen it is turned on %# its corres/onding antigen9a -cell /roduces man# co/ies of itself AclonesB and ma"es a lot of its on*er# s/ecial and s/eci:c anti%od#.

    ne of the real %eauties of /roducing clones of identical cells is that it is*er# economic it is a a# of e+/anding ust that %it of the immune s#stemthat is needed. ,hen the %od# is threatened %# a /articular /athogen ithits on uniDue antigens9 it ma"es sense for the %od# to /ut most of itsenerg# into /roducing cells hich react to those s/eci:c antigens.

    4&2&4Some .cti5ated BDCells

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    4&' !)e -ole o !DCells

    Re# /oints

    '-cells ha*e a great range of functions in s/eci:c immunit#

    '-cells react to antigens and /roduce clones

    '-cells form su%-sets hel/er '-cells9 "iller '-cells and regulator '-cells

    '-cells can remem%er too9 ust li"e -cells

    '-cells recognise antigens in a dierent a# to -cells

    4&'&(!DCells Ha5e a reat -ange o unctions in S*eci+cImmunity

    '-cells are li"e -cells in man# a#s9 %ut the# do Duite dierent o%s. -cells9 as e ha*e seen9 ma"e anti%odies that %ind ith antigen. -cells dolittle else in /ro*iding /rotection against infection. '-cells9 on the otherhand9 can secrete im/ortant molecules and the# also interact Vface-to-faceV ith other immune cells. s e sa earlier9 '-cells originate fromstem cells in the %one marro and9 after maturing in the th#mus9 the#

    enter the secondar# l#m/hoid tissues Al#m/h nodes and s/leenB herethe# la# in ait for antigen to %e %rought to them.

    4&'&2!DCells -eact to .ntigens and

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    'hin" a%out a /articular micro%eJ sa# a %acterium9 inducing a res/onse.0/eci:c '-cell and s/eci:c -cell clones %ecome acti*ated %# result of theco-o/eration %eteen the to cell t#/es. 'he -cell interacts ith the '-cell through cell-to-cell contact and this hel/s to turn on the '-cell. 'heacti*ated '-cell then returns the fa*our %# sending %ac" similar messages

    *ia solu%le molecules called c#to"ines hich it releases into thesurroundings.

    '-hel/er cells also acti*ate macro/hages and /romote inammation. 'o dothis the cells ma"e c#to"ines9 %ut dierent ones from those that hel/ -cells. >emem%er ho im/ortant macro/hages are in /rotection9 so here isanother e+am/le of ho s/eci:c cells that /ro*ide s/eci:c immunit# co-o/erate ith cells im/ortant in non-s/eci:c immunit#. Macro/hagesacti*ated %# '-cell c#to"ines are much %etter at /hagoc#tosis anddigesting the micro%es the# ha*e engulfed. n interesting e+am/le is thetu%ercle %acillus that causes tu%erculosis this li*es inside macro/hageshich9 ithout acti*ation %# '-cells9 :nd it im/ossi%le to :ght the

    %acterium eecti*el#.

    !D 3iller Cells

    '-"iller cells AC= '-cellsB can "ill other cells of the %od#. t :rst9 this doesnot sound sensi%le9 %ut the# ha*e a *ital role in /rotection against *irusinfections. ;ou ill understand this hen #ou thin" that *iruses ha*e toli*e inside cells in order to multi/l#. nti%odies are no hel/ %ecause the#cannot get into cells to "ill the *irus. ut '-cells are dierent. 'he '-"illercell recognises if a cell contains a s/eci:c *irus %ecause little %its of tell-tale *iral /rotein are e+/ressed on the surface of the infected cell. 'henthe '-"iller cell reall# goes to or". single '-"iller cell can "ill man#*irus-infected cells.

    '-cells "ill in a fascinating a#. t in*ol*es to mechanisms. n the :rst9 the"iller cell /unches holes in the mem%rane of the target cell9 causing itscontents Aincluding incom/lete *irus /articlesB to lea" out. n the second9the "iller cell acti*ates the mechanism that causes the cell to self-destruct8 t has %een realised onl# Duite recentl# that all cells are /ro%a%l#geneticall# /rogrammed to self-destruct under certain circumstances thisis ust /art of the good maintenance of the %od#. ,hat '-"iller cells do is toacti*ate this /rogrammed cell death. 'he self-destruction /rocess is reall#cle*er %ecause not onl# does it destro# the home of the *irus Athe cell that

    it has infectedB9 the destruction machiner# also destro#s the *irus itself.

    -egulator !DCells

    oth C=! '-cells and C= '-cells also regulate immune res/onses - the#can su//ress other cells. )+actl# hich '-cells do this and ho the# do ithas /uWWled immunologists for man# #ears. t one time9 it as fashiona%leto tal" a%out '-su//ressor cells9 %ut the maorit# *ie no is thatsu//ression is a /ro/ert# of se*eral dierent t#/es of '-cell. Fonetheless itis an im/ortant conce/t that the immune s#stem can su//ress itselfthrough the action of s/eci:c '-cells. ;ou can imagine that9 once theantigen has %een dealt ith9 it is more hel/ful to the %od# to turn o the

    immune res/onse than to allo it to carr# on.

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    >egulation in some cases reects a %alance %eteen the actions ofdierent t#/es of hel/ /ro*ided %# ' hel/er cells - those that or" ith -cells on the one hand and those that acti*ate macro/hages on the other.

    'here are also t#/es of '-cells that regulate each other. ' "iller and hel/ercells interact as ell. 0o9 #ou can see that interactions %eteen dierent

    t#/es of '-cell are central to the normal functioning of the immune s#stem.

    !DCells Can -emember !oo

    ,e tal" a%out '-cells in a general sense as /ro*iding memor# in ust thesame a# as -cells do. 'he# sur*i*e Duietl# for man# #ears in l#m/hnodes ust aiting for the same micro%e to come along again. ,e %elie*ethat a '-hel/er cell9 for e+am/le9 hen it is re-aa"ened %# anotherencounter ith its s/eci:c antigen9 goes on %eing a hel/er cell again - %utit is ust /ossi%le that /articular '-cells can su%tl# change their functions inlater immune res/onses.

    MO-" O !DC"77S .8 BDC"77S

    '-cells recognise antigens in a dierent a# from -cells.

    '-cells are similar to -cells in se*eral res/ects9 %ut the# do notreact to

    antigens in the same a#. '-cells can onl# react to /rotein antigensthat

    ha*e %een %ro"en don into fragments called *e*tides insideinfected

    %od# cells or acti*ated immune cells. od# cells /ush these/e/tides

    out to their cell surface9 /resenting them in such a a# that otherimmune cells can easil# recognise them. 'he# do this %# %inding theVforeignV /e/tides to im/ortant cell-to-cell recognition molecules

    calledMaPor Histocom*atability Com*le?AMHCB molecules. useful

    analog# is to thin" of the MHC molecule as a sort of ag hichcarries

    a message along the lines of YHel/ under attac"8Y

    'he %inding of '-cell rece/tors to the MHC-/e/tide assem%l# can%ring

    a%out the acti*ation of that '-cell. 'his is a com/le+ /rocess fore+am/le9 ith '-"iller cells the C= molecules on their surface

    engageMHC Class molecules ith /e/tide in them on the /resenting cell.Hel/er '-cells9 on the other hand ha*e a C=! molecule on their

    surface

    hich engages an MHC Class molecule on the /resenting cell.Fo9 MHC Class molecules onl# /resent %its of /roteins that ere

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    made inside the /resenting cell. Class molecules onl# /resent %itsof

    /roteins made outside the cell that ere then ta"en u/ %# the

    /rocessing cell. ll cells ha*e Class molecules9 so hen infectedith*irus the# are all a%le to %e identi:ed as :t for destruction %# C=c#toto+ic cells.

    Class molecules are much more limited in the cells that e+/ressthem9

    so onl# some cells ha*e the /resenting a%ilit# to acti*ate thehel/ing or

    am/lif#ing cells of the immune s#stem.

    good idea hen #ou thin" a%out it. ?or their eorts in unra*elling

    this mar*ellous machiner#9 >olf \in"ernagel and @eter =ohert#ere

    aarded the Fo%el @riWe in 1$$6.

    MO-" O .!I"S

    fter #ou ha*e read the sections on -cells and '-cells #ou ma# li"eto

    "no a %it more a%out antigens and ho the l#m/hoc#tes interactith

    them. t ma# hel/ to e+/and a little on hat antigens are.

    ?irst9 the term is functional an#thing that can e*o"e a s/eci:cimmune

    res/onse is usuall# called an antigen. ,e "no that su%stances inall

    classes of chemicals can or" in this a# /roteins9 car%oh#drates9nucleic acids9 li/ids9 organic and inorganic su%stances ha*e this/ro/ert#. 0o it is not ust the /roteins on the outside of a %acteriumthat can function as antigens9 %ut also things inside the cells andsu%stances in our en*ironment.

    ,e "no a lot a%out /rotein antigens9 and it is reactions againstthem that are at the heart of /rotecti*e immunit#.

    'here are im/ortant dierences a%out the a# that '-cells and -cells recognise antigens. 'he C> of % %inds to small areas9called antigenic determinants9 on the surface of the /rotein.ecause the seDuence of a /articular /rotein does not usuall#re/eat itself9 dierent determinants ha*e dierent structures.

    'hus9 -cells of dierent :ne s/eci:cit# can react to dierentdeterminants on the same cell. ne antigen therefore canacti*ate se*eral dierent clones of -cells.

    'he same is %asicall# true of '-cell s/eci:cit#9 %ut hereas -cells

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    recognise determinants on intact /roteins9 '-cells need the/rotein to %e %ro"en don and /resented to them in a *er#/articular a# in order to %e recognised.

    Stimulating Immunity

    great deal of eort is /ut into medical research to tr# to :nd a#s ofstimulating our immune s#stem to or" e*en %etter than it does. urimmune s#stem is %eautifull# designed - most of the time e are unaareof ho ell it or"s - %ut there is a ar going on ith the micro%es and/arasites around us. 0ome of these /athogens are dangerous andinfection can "ill %efore /rotecti*e immunit# can %uild u/.

    Re# /oints

    immunisation mimics infection ithout /roducing disease

    some *accines are tremendousl# successful small/o+ aseradicatedthrough mass immunisation

    *accines must %e safe as ell as /rotecti*e

    some /athogens mutate9 ma"ing immunisation diKcult

    ne *accines are under de*elo/ment

    animal *accines are idel# used and are *er# eecti*e

    &( Immunisation

    Immunisation gi5es t)e immune system ad5ance inormationabout a *at)ogen so t)at it can be ready to do battle i necessary&

    !oday: in t)e 13 ;e are usually immunised against di*)t)eria:;)oo*ing coug): *olio: measles: tetanus: mum*s: rubella and !B&In an unimmunised *erson t)ese illnesses can cause *ermanentdamage and: in some cases: deat)&

    #)en ;e are immunised against an inectious disease likemeasles: our immune system is *us)ed into action& !)e 5accineEt)e substance t)at ;e are immunised ;it)F acti5ates BDcells and!Dcells in t)e same ;ay as a real inection ;ould do& In act: t)e5accine looks like t)e real measles 5irus but it )as been c)angedso t)at it is not dangerous&

    !)e end result is t)at our immune system orms memory cells& I;e are e?*osed to t)e real measles 5irus later: our body ;ill beable to destroy it beore it )arms us&

    &(&( Immunisation Mimics Inection #it)out

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    ne of the most im/ortant tools in the :ght against these /athogens isimmunisation. 'he /rinci/les of immunisation are *er# sim/le. A'he termdiers from V*accinationV in that immunisation is the loo"ed-for result of*accination.B 'he %od# is gi*en an altered form of a /athogen hich tric"s

    the immune s#stem into res/onding to it as if it ere a real infection.mmunit# to the /athogen forms and hen the real /athogen is met laterin life9 the %od# is a%le to mount a massi*e and *er# eecti*e res/onse.

    0ome acDuired immunit# is /ermanent %ut some not. 'o %e eecti*e9 theimmunit# /roduced %# immunisation should %e as good and as long-lasting as that induced %# a real infection. tVs also im/ortant that the*accine does not cause the serious disease of the natural infection andthat it does not ha*e damaging eects on the /erson %eing immunisedand is as safe as it /ossi%l# can %e.

    0ome *accines are tremendousl# successful small/o+ as eradicated

    through mass immunisation. 0mall/o+9 a *iral disease9 as com/letel#eradicated during the late 1$74s as a result of mass immunisation ith ahugel# successful *accine. 'he de*elo/ment of an eecti*e *accine forsmall/o+ %egan to hundred #ears ago. )dard Tenner "ne nothing of*iruses9 %ut he o%ser*ed that mil"maids ho caught co/o+9 a tri*ialinfection in humans9 ne*er got small/o+9 the terri%le disease thatdis:gured man# and "illed a%out 25I of its *ictims. TennerVs e+/erimentas to inect some /us from a co/o+ sca% into a small %o# and then tosho that hen the %o# as later inected ith small/o+ /us9 he did notget small/o+.

    Tenner had con:dentl# /redicted the successful outcome of hise+/eriment. 'hin" hat e li"e a%out the ethics of that e+/eriment Ahichould ne*er %e /ermitted toda#B9 it as a landmar" in the :ght againstdisease hich formed the %asis of *accination ith *accinia *irus and theorld-ide eradication of small/o+. 'he ho/e is that diseases li"e /olioand measles might also %e soon eradicated through mass glo%alimmunisation.

    )radication of a disease de/ends on to *ital factors. 'he :rst9 hich is*er# much under human control9 is the num%er of /eo/le immunised. ;oudonVt usuall# ha*e to immunise a%solutel# e*er#%od#9 %ut a high/ro/ortion must %e /rotected to /re*ent the infection %eing transmitted. fthis is achie*ed9 then the *irus could9 li"e small/o+9 %ecome e+tinct9

    /ro*iding man is the onl# host of the infectious organism. A>emem%er9other animals carr# man# of the same /athogens.B 'he second factor9 notunder human control9 is that the target /athogen must %e *er# sta%le. 'hismeans that it does not mutate and change itself so that /eo/le immunisedremain /ermanentl# /rotected against infection. ,e are all familiar iththe a# the inuenWa *iruses mutate and gi*e rise to e/idemics. 'hes/read of these can %e /redicted accuratel# %# scientists ho e+amine the*irus t#/e in*ol*ed in a ne out%rea". 'his is h# u *accines ith thecurrent strains need to %e gi*en to /eo/le at ris" e*er# #ear.

    &(&2Gaccines Must be Sae as #ell as

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    /athogen outside of the %od# or %# treating it ith chemicals9 it can%ecome attenuatedAea"enedB. t is still a%le to infect and stimulate animmune res/onse9 %ut it is una%le to cause disease. t the %eginning ofthis %oo" the distinction as made %eteen infection and disease - anattenuated *accine should induce immunit# %ut not disease.

    ,e ha*e a *ariet# of successful %acterial *accines against hole %acterialcells or the to+ins the# /roduce. 0ome of the most eecti*e *irus *accinesare made of attenuated li*e *irus %ut dead *irus /articles can also ma"eeecti*e *accines Ai.e. he/atitis9 ra%ies and /olioB. ut the success of*accines made of these dead /articles de/ends on their a%ilit# to /ro*o"ea strong immune res/onse %ecause the /articles are too fee%le to infectcells as the real *irus ould. 'his is an Vonl# sometimes successfulVstrateg# hich /uts the s#stem on alert ithout /ro/erl# mimic"inginfection. 'he search is on for safe *ersions of *iruses that can %e used in*accines

    n the earl# #ears of *accine de*elo/ment9 ine+/erience in *accine/roduction led to serious /ro%lems and some deaths. n the 1$54s forinstance9 at a time of maor /olio e/idemics9 a %atch of "illed /olio *irus/articles as not /ro/erl# inacti*ated. 'oda#9 e understand that such/otential dangers e+ist - one of the reasons h# the research andde*elo/ment of *accines is such a slo /rocess. @u%lic con:dence in*accine safet# is *er# im/ortant9 not least to countriesV healthde/artments9 %ecause *accines are gi*en for the good of %oth theindi*idual %eing immunised and the ider good of a societ# that ants torid itself of dangerous infectious diseases. n the

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    ,e should remem%er that immunisation is Duite idel# used for animalsas ell %ecause the# ha*e their on health /ro%lems9 in addition to man#the# share ith humans. ?eline enteritis and canine distem/er aree+am/les of life threatening diseases that can no %e *accinated against.%*iousl# good health is im/ortant in com/anion and farm animals and

    the *accines used are designed to /rotect animals from serious disease9 tomaintain health# farm animals for food9 and to /re*ent catastro/hic:nancial loss for farmers hose animals ma# suer these diseases. tVsorth noting that *accines for animal diseases are de*elo/ed through thesame research /rocess as are *accines for human diseases.

    , .I8S E.cuired Immune 8e+ciencySyndromeF

    In an immunode+ciency t)e immune system does too little& .I8Sis an immunode+ciency condition caused by t)e HIG 5irus&

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    =0 is not the onl# cause of immunode:cienc#

    ,&(&(.ids Is a Syndrome Caused by HIG

    s#ndrome is a com/le+ condition ith multi/le s#m/toms9 /resentingitself in dierent a#s in dierent /eo/le. =09 to gi*e it its shortenedname9 is a s#ndrome in hich a /ersonVs immune s#stem essentiall#%ecomes ineecti*e - the# %ecome immunode:cient. ,hen the immunes#stem ceases to function as ell as it should e %ecome susce/ti%le toall sorts of infections that ould usuall# %e uncommon or tri*ial.

    *er the #ears since =0 as :rst recognised9 %etter treatment for =0related illnesses has %een increasing life e+/ectanc#.

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    the de*elo/ment of ne medicines remains an urgent /riorit#. utscientists are o/timistic that =0 ill soon %ecome9 if not cura%le9 at leasta managea%le illness.

    )+actl# hen and here H( :rst a//eared is a matter for heated

    argument9 li"e man# other as/ects of =0 %iolog#9 %ut the general *ie isthat it is a fairl# recent arri*al amongst *iruses that infect humans. t/ro%a%l# arose as a *ersion of a *irus that infected a ild animal9 anfrican chim/anWee9 it is no thought. Man# animal s/ecies ha*e theiron *ersions of immunode:cienc# *irus that cause their on s/ecies-s/eci:c *ersion of =0. >esearch into these related animal diseases hasgi*en scientists im/ortant insight into ho H( in:ltrates and then hiac"sthe cells of the immune s#stem.

    ,&(&'!)e Sym*toms o .ids Gary but by t)e !ime SomeoneHas .ids: Ot)er

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    )*er#one is aare of =0 as a %ig /u%lic health /ro%lem and it recei*esintense co*erage %ecause it causes /remature death in otherise health#and #oung /eo/le. 'his has dis/elled man# of the misconce/tions a%out=0 hich e+isted a fe #ears ago and it has also %rought to scientistVsattention some indi*iduals ho seem to %e resistant to H( infection e*en

    though the# are e+/osed re/eatedl# to H(. 0tud# of such /o/ulations isundou%tedl# im/ortant to hel/ us unra*el the genetic inuences in*ol*edin resistance to H(.

    ,&2 HIG Is ot t)e Only Cause o Immunode+ciency

    'here are man# other sources of immunode:ciencies. 0ome children are%orn ithout an immune s#stem hich or"s /ro/erl#. 'hese /eo/le ha*e*rimary de+ciencies9 %ut these are relati*el# uncommon. More freDuentare acDuired Aor secondar#B de:ciencies9 =0 %eing ust one e+am/le.

    0ome medicines can cause immunode:cienc# S for e+am/le those used totreat cancers or /re*ent graft reection ma# ha*e these eects9 %ut thiscan usuall# %e controlled %# getting the dose at ust the right %alance.)*en ithout medicines that might ha*e this eect9 some cancers seem toinduce de:ciencies.

    Mice and rats also ha*e a great range of ell studied immunode:cienciesand ha*e %een *ital in unra*elling the role of dierent l#m/hoid tissuesand cells in s/eci:c immunit#.

    6 Su**ressing Immunity

    6&( .utoimmune 8iseases

    7ike any ot)er body system: t)e immune system can become

    aulty& Sometimes t)e bodys cells and c)emicals ;)ic) normallydeal ;it) *at)ogens: turn against t)e body itsel& !)is can cause a5ariety o illnesses kno;n as autoimmune diseases&

    -)eumatoid .rt)ritis E-.F D In t)is disease t)e body starts toattack its o;n Points ;)ic) become infamed and may be badlydamaged& It can aAect young *eo*le as ;ell as older *eo*le&.lt)oug) many *eo*le ;it) -. can be )el*ed by medicines: somebecome 5ery disabled&

    8iabetes D In t)e ty*e o diabetes young *eo*le get: t)e bodydamages s*ecial cells in its o;n *ancreas& !)ese cells normallymake insulin: a )ormone ;)ic) is needed by t)e body to turn

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    carbo)ydrates into energy&

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    utoimmune disease can in*ol*e a single organ or tissue9 as in diabetes:or se*eral as in r)eumatoid art)ritisAreall# a s#ndromeB hich aectsnot onl# oints %ut also %lood *essels9 s"in9 tendons among other tissues.side from these to the other diseases that are %est "non and mostcommon are th#roid disease Agoitre: t)yroiditisB9 multi*le sclerosis

    hich aects the %rain and s/inal cord9 s#stemic lu/us er#thematosusAVlu/usVB aecting "idne#s9 s"in and %rain and *ernicious anaemiaaecting the intestine. 'here are also autoimmune *ersions of li*erdisease and there are se*eral %lood diseases such as autoimmunehaemol#tic anaemias that are medicall# im/ortant too. Man# cases of%lindness in adults result from an autoimmune reaction against the e#e.

    'hese diseases /resent us ith a real challenge the# are freDuent andcause tremendous morbidity. 'his is a %ig cost to the /erson ith theillness9 their famil# and societ# in general. @atients ma# need to ta"e a*ariet# of medicines to control the illness and its s#m/toms for man##ears and ma# %ecome relati*el# immo%ile and una%le to or"9 for

    e+am/le.

    6&(&'Some Cases o .utoimmunity .re enetic: Some -esultrom Inection

    ,e do not #et reall# understand h# autoimmune diseases arise in the:rst /lace. ,e "no that susce/ti%ilit# ma# %e inherited in some diseases%ut there are o%*iousl# man# factors that need to con*erge for oneindi*idual to %ecome ill. nfection is /ro%a%l# crucial in man#9 %ut there isalmost certainl# not going to %e a *irus that causes9 for e+am/le9rheumatoid arthritis %ut rather a range of related infections that

    /reci/itate in susce/ti%le /eo/le a chain of e*ents that lead to '-cells%ecoming sitched on %# some self antigens. n some diseases9 e donVtreall# "no hat the crucial antigens are.

    6&(&4.utoimmune 8isease is 8iNcult to !reat But !)ere .re"Aecti5e Medicines and -esearc) Into o5el !)era*ies is in

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    6&2 .llergies

    .n allergy is an e?aggerated immune res*onse& In ast)ma:infamed narro;ed air;ays create breat)ing *roblems& !)e

    condition is usually caused by underlying allergy&

    Hay e5er is an allergy to *ollen& #)en someone ;it) )ay e5erbreat)es in *ollen *articles: t)e *ollen reacts ;it) s*ecial ;)itecells: called mastDcells t)at line t)e nasal *assages& Cruciale?*eriments in animals )a5e s)o;n t)at t)ese cells t)en bursto*en& !)ey release c)emicals: including )istamine: ;)ic) *roducean immediate infammation& !)is leads to a streaming nose: runnyeyes and snee>ing&

    #)y do some *eo*le )a5e allergies !)e main reason is t)at: in*eo*le ;it) allergies: t)e mastDcells are coated ;it) a s*ecial sorto antibody ;)ic) reacts ;it) allergens& !)is reaction makes t)emastDcells o*en& Ot)er *eo*le dont make t)ese s*ecialantibodies&

    Re# /oints

    an allerg# is a condition here an immune res/onse to a foreignantigen causes incidental damage to the %od#

    allergies in*ol*e mast-cells and a s/ecial class of anti%od#

    the allergic res/onse has se*eral stages

    food allerg# and intolerance can %e se*ere allergies ha//en hen the immune s#stem does too much

    the incidence of asthma seems to %e increasing

    6&2&(.n .llergy Is a Condition #)ere an Immune -es*onseto a oreign .ntigen Causes Incidental 8amage to t)eBody

    Most /eo/le are familiar ith the idea that e can %e allergic to things in

    our en*ironment such as cat fur9 )ouse dust9 /ollens9 food or chemicals -these are called allergens. 'he ord allerg# is sometimes used *er#loosel# to descri%e all sorts of reactions to en*ironmental su%stances9 %utit has a *er# /recise meaning to immunologists. llergies are conditionshere an immune res/onse to a foreign antigen Athe allergenB causes/ro%lems for the %od#.

    '#/icall#9 the allerg# suerer %ecomes immunologicall# sensitised to catfur9 for e+am/le9 hich acts as a /oerful antigen. ,hen the samematerial is again encountered later on9 a reaction occurs that isun/leasant in its eects and can %e *er# dangerous in some cases.

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    'he reactions ma# in*ol*e an asthmatic attac"9 a s"in rash or *omitingand diarrhoea. )+/osure to allergens often ha//ens through mucosalmem%ranes of the res/irator# tract or gut9 hence the s#m/tomsassociated ith these s#stems.

    6&2&2.llergies In5ol5e MastDCells and a S*ecial Class o.ntibody

    'he critical com/onent of allergies of this sort is a s/ecial t#/e of anti%od#"non as Ig"hich has the uniDue /ro/ert# of sensitising mast-cells. nfact9 the /resence of g) anti%odies against the foreign antigen AtheallergenB is used to actuall# diagnose allerg#. Mast-cells are normall#associated ith mucous mem%ranes9 so allergies *er# often in*ol*e thelungs and gut.

    ,hen mast-cells meet the antigen that %inds to the g) anti%odies on theirsurface9 these cells %urst o/en releasing man# natural com/ounds that

    cause the mucous mem%ranes to sell and %ecome inamed histamine isone of the su%stances9 hence the use of anti-histamines and similarmedicines in allerg#. 'he sensitisation is usuall# initiated %# %reathing oreating the material.

    ,h# do some /eo/le %ecome allergic to /articular su%stances hileothers9 ho li*e in the same en*ironment9 do notP

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    ,ithin a matter of minutes of e+/osure to the allergen9 an allergic /ersoncan e+/erience massi*e constriction of the aira#s hich could suocatethem ithout treatment. AtVs orth noting that man# /eo/le are intolerantto certain foods for reasons other than allerg# e.g. lactose intolerance.B

    6&2&

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    *erson ;it) a trans*lanted organ ;ould attack and destroy t)eintruder organ& #e describe t)is as t)e organ being rePected&

    !o gi5e t)e best c)ance o success: donors and recei5ers oorgans are careully matc)ed using tissue ty*ing tec)niues& But

    t)is is not enoug)& Medicines are needed to dam* do;n t)eimmune system&

    'here are medie*al references to trans/lantation of lim%s %ut it is onl# inthe tentieth centur# that trans/lantation has %ecome a /ractical realit#.gainst ides/read indierence and resistance9 grou/s of doctorsthroughout the orld /erse*ered ith e+/erimental surger# and shoed9in the 1$64s and 1$74s9 ho "idne#s9 lungs9 hearts and li*ers could %etrans/lanted from one indi*idual to another. 0uccess rates ha*e increasedsigni:cantl# since then "idne# trans/lants9 for e+am/le9 are no highl#successful.

    Re# /oints

    the techniDues for trans/lanting organs and tissues are *er#ad*anced %ut e still face immunological /ro%lems

    graft reection can %e /re*ented using tissue t#/ing andimmunosu//ressi*e medicines

    there are not enough organs to su//l# all the /eo/le hodes/eratel# need trans/lants

    +enotrans/lantation Ausing animal organsB might %e an ansertothe organ su//l# /ro%lem

    %one marro grafts and stem cells are a s/ecial case

    6&'&(!)e !ec)niues or !rans*lanting Organs and !issues.re Gery .d5anced But #e Still ace Immunological

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    'rans/lants of cells9 tissues or organs %eteen dierent indi*iduals arerecognised as foreign %# the reci/ientVs immune s#stem and are reected.

    'he antigens on the trans/lanted organ that matter most are themolecules of the MHC- these molecules are on all cells and tissues andtheir real o% is to control '-cell acti*ation in res/onse to foreign antigens.

    'he# ere o%*iousl# not /ut there to frustrate trans/lant surgeons9 %ut thefact is the# do. ecause e all ha*e slightl# dierent MHC molecules9 the'-cells of the host react *er# strongl# to the MHC molecules of the donor.'he ensuing immune res/onse destro#s the graft or trans/lant. s inallerg# and autoimmunit#9 the mechanisms that ha*e e*ol*ed to /rotectus from /athogens are actuall# those that do harm.

    ;ears of careful research in la%orator# animals ha*e gi*en us a greatunderstanding of h# and ho grafts are reected. n the discussion of"idne# or heart grafting it is too eas# to forget that trans/lantation hasactuall# %een going on *er# successfull# ith other tissues. loodtransfusion is a form of trans/lantation. t is com/arati*el# eas# to match

    %lood grou/ antigens to ensure that transfused %lood is not destro#ed %#the reci/ient. ut transfused red %lood cells are not e+/ected to sur*i*einde:nitel#9 and in an# case9 the# cannot %ecause the# ha*e a limited lifes/an. Corneal trans/lantation has %een a routine medical treatment for#ears. 'he cornea is unusual in that l#m/hoc#tes do not normall# ha*eaccess to it9 so reection is not a great /ro%lem.

    6&'&2rat -ePection Can Be

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    6&'&'!)ere .re ot "noug) Organs to Su**ly .ll t)e

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    (er# good tissue t#/e matching is *ital9 and e*en then the graft can9 undersome circumstances9 attac" and damage the reci/ient. 'his is graft-*ersus-host disease and can %e *er# serious. @eo/le ith /articular formsof leu"aemia recei*e trans/lanted %one marro9 ha*ing :rst recei*edaggressi*e chemothera/# to eecti*el# destro# their on fault# marro.

    lthough there are /otentiall# serious ris"s9 the success rate is no *er#high S gi*ing the /atient %ac" a health# immune s#stem.

    =es/ite im/ro*ements in %one marro trans/lants there is a much moree+citing /ros/ect hich might ma"e %one marro trans/lants a thing ofthe /ast. t turns out that normal %lood contains stem cells9 admittedl# intin# num%ers9 and these can no %e /uri:ed9 concentrated and used tore/o/ulate the marro of /atients. etter than adult %lood9 the %lood inthe *eins of um%ilical cords has much larger num%ers of stem cells andthese are no %eing used in a fe /laces ith great success.

    'his is a mar*ellous use of human tissue that otherise is mostl#discarded. ne thing for sure9 there is an enormous su//l# of cords and

    the# gi*e us fe medical and ethical /ro%lems.

    .nimals and -esearc)

    Im*ro5ing our biological understanding and our ability toimmunise against: diagnose and treat illness de*ends on a 5arietyo researc) met)ods including researc) in animals&

    Here are e?am*les ;)ere animals )a5e been necessary inresearc) in t)e immune systemD

    it ;as disco5ered t)at !Dcells and BDcells are im*ortant inimmunity because o researc) in mice and c)ickens

    t)e disco5ery o t)e mec)anisms ;)ic) lead to gratrePection de*ended on researc) in rats and mice& !)e abilityto su**ress t)e immune system in mice and subseuentresearc) in dogs led to eAecti5e antiDrePection medicine;)ic) made organ trans*lantation successul

    antibodies: mainly raised in rabbits and mice: are used to

    diagnose disease&.nimals )el* us +nd out )o; t)e body deends itsel againstinection and )o; autoimmune diseases de5elo*& 8iabetes:multi*le sclerosis and r)eumatoid art)ritis are all e?am*les ;)eret)e study o animals )as suggested ne; ;ays to *re5ent andtreat t)ese diseases in )umans& .nd *otential ne; medicines:;)ic) look *romising on com*uter and in t)e test tube: need tobe studied in animals beore t)ey can be tested and used in*eo*le& O course: t)e use o animals s)ould be a5oided ;)ere5er*ossible&

    ,e tend to thin" of medical ad*ances in terms of tangi%le /rogress - nemedicines9 surgical /rocedures and medical de*ices. ut under/inningthese ad*ances is much more %asic research hich /ro%a%l# doesnVt ma"e

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    gri//ing reading to non-scientists %ut hich can add enormousl# to9sometimes e*en radicall# change9 hat researchers "no a%out ho9 forinstance9 the immune s#stem functions.

    iologicall#9 humans are *er# li"e other animals in so man# im/ortant

    a#s. 'his means that hat e can o%ser*e in animals ill %e useful inunderstanding hat is going on in humans. 'his is es/eciall# true ofimmunit# and resistance to infection. ,e "no from man# #ears of stud#that e9 as humans9 react to infections in *er# similar a#s to mice9 rats9dogs9 horses and so on. t follos that9 %# loo"ing at the %od#Vs immunes#stem in animal studies9 e can deri*e im/ortant %ene:t for humans.

    'here are man# e+am/les of immunological disco*eries in animals thatha*e greatl# hel/ed the understanding9 diagnosis and treatment of humanillness9 and se*eral e+am/les ha*e %een mentioned alread#.

    Much of our fundamental understanding of the cells and mechanisms ofimmunit# comes from research in animals. ?or e+am/le9 the stud# of mice

    that naturall# lac" a th#mus taught us a%out the crucial role this organ/la#s in '-cell de*elo/ment and in /articular ho it destro#s most of thosecells that might cause autoimmune damage. 0imilarl#9 the role of theursa of ?a%ricius9 a l#m/hoid organ in %irds9 in dictating the de*elo/mentof -cells taught us that there are also critical e*ents in their life histor#.

    'his "noledge has %een a//lied in man# a#s including9 for e+am/le9 tothe understanding of the origins and nature of some tumours of l#m/hoidcells.

    'he fundamental disco*er# that l#m/hoc#tes are the actual agents of/rotecti*e immunit# came from e+/eriments in animals herel#m/hoc#tes ere transferred %eteen geneticall# identical indi*idualmice - and ith the l#m/hoc#tes9 it as found9 came the immunit#. 'hisas a crucial disco*er#. t also /a*ed the a# to identif#ing the m#riadand com/le+ migration /atha#s that these cells follo in the normalcourse of their li*es in /ro*iding /rotection against infectious disease. t ishard to o*erestimate the im/ortance of fundamental disco*eries such asthese the# not onl# ha*e sha/ed our understanding of the functioning ofthe immune s#stem %ut the# contri%ute to gi*ing us a rational Athat is9logicalB %asis u/on hich to design medicines to aect immune function.

    'he genetic reasons for the reection of trans/lants ere elucidated :rst inanimals9 and methods to "ee/ trans/lants from %eing reected ere

    de*elo/ed in animals. 'hese same studies also led to a signi:cantad*ance in understanding ho our genes selecti*el# control immuneres/onses in a general a# and this has /ro*ed a%solutel# in*alua%le inresearch on autoimmune disease and allerg#9 to gi*e onl# to e+am/les.

    'hese are e+am/les here animal research has not onl# ena%lede+/eriments and anal#sis that ould %e im/ossi%le in humans9 %ut it hasalso greatl# s/eeded u/ the rate of disco*er# of im/ortant facts.

    Modern methods of genetic modi:cation are used to add s/eci:c genes toor to delete them from indi*idual mice and rats9 for e+am/le. ?rom thesetransgenic animals e learn *er# Duic"l# a%out the im/ortance of/articular genes in immunit#. 'hus9 through /ro*iding im/ortant %asic

    information %oth a%out ho the %od# maintains good health and the

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    nature of disease /rocesses9 a#s are o/ened to de*elo/ ne thera/iesfor otherise intracta%le diseases.utoimmune diseases are a s/ecial challenge %ecause e "no so littlea%out man# of them. )*en so9 the stud# of diseases mainl# in mice andrats9 and also *eterinar# research into immune-related /ro%lems of our

    com/anion animals9 ha*e gi*en us great insights into the origins andmechanisms of the diseases themsel*es.

    ?rom this9 man# scientists ha*e %een a%le to e+amine the /otential of nemedicines or s/ecial treatment a//roaches for their eecti*eness %eforeusing them in humans. Feer a//roaches to treatment of diseases li"erheumatoid arthritis9 multi/le sclerosis and dia%etes hich use natural/roducts of the %od# ha*e come directl# from e+/eriments in la%orator#rodents. n the same a#9 ne insights and /otential ne treatments forasthma and allerg# are %eing de*elo/ed from animal studies.

    nother area that has de/ended on animals is the identi:cation of

    /athogens and other cell t#/es and in the diagnosis of disease. @athogenscannot usuall# %e identi:ed sim/l# %# e+amining %lood sam/les. ut/athogens Aand also some tumours for instanceB e+/ress tell-talesu%stances and these can %e detected %# tests hich use anti%od#.

    'o o%tain VmonoclonalV anti%od# for use in hos/itals and la%oratories9anti%od# :rst needs to %e raised in animals Amainl# miceB %# immunisingthem ith the rele*ant antigen. 'heir anti%od# /roducing Al#m/hoidB cellscan then %e used as the %asis for anti%od# /roduction in *itro. 'he a%ilit#to do this in *itro9 after the initial animal cells ha*e %een o%tained9 is Duiterecent %ecause it de/ends on modern la%orator# techniDues to :rstVimmortaliseV these otherise short-li*ed cells and then clone them toensure that the# are s/eci:c to a single anti%od# onl#J hence9 the termVmonoclonalV anti%odies. V@ol#clonalV anti%odies9 raised in ra%%its fore+am/le9 recognise a %roader range of antigenic structures9 and so areused here the target antigen is un"non or here there are a *ariet# ofantigens that could %e rele*ant.

    &( #)y .re .nimals eeded to 8e5elo*Medicines

    A statement from t#e Animals in 'e!icines Researc# Information Centre

    1A'RIC5 9 Pro+ect %ponsor$

    ll ne medicines that doctors /rescri%e are de*elo/ed ith the hel/ ofinformation from animal studies. 'his is also the case for *accines. tVssim/l# not #et /ossi%le to adeDuatel# in*estigate the range of eects amedicine ma# ha*e using com/uters and in *itro methods alone9 %eforegoing into human testing. ll ne medicines must %e studied in /eo/le%efore the# can %e licensed %ut onl# after doctors and scientists ha*elearned enough a%out a medicine to feel con:dent that the# can do soithout undue ris".

    ,e recognise that man# /eo/le :nd animal research hard to acce/t. 0omema# %elie*e that there is no usti:cation for using animals for an# reason9

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    no matter ho im/ortant9 and regardless of the attention /aid to animalelfare. 0ome others ma# acce/t9 in theor#9 the use of animals formedical /ur/oses %ut :nd it diKcult to understand h# toda#9 gi*en ra/idad*ances in technolog#9 all the research cannot %e done in other a#s.

    n fact9 much of that research is done in other a#s S it stands to reasonthat /harmaceutical com/anies use the most modern technolog# the#can. ut re/lacing all animal research9 if achie*a%le9 is going to %e a longslo /rocess. 'he reason is that medicines can aect and %e aected %#countless interactions %eteen all the cells9 organs and s#stems in the%od# - actions and reactions that9 in man# areas9 e are onl# ust %arel#%eginning to understand. Com/uters ma"e theoretical models %ased onthe information the# are gi*en. # its *er# nature9 cell culture loo"s at %itsof our %iolog# in isolation. 0ome Duestions can onl# %e addressed in thehole li*ing %od# - :rst in animals and then in /eo/le.

    &2 Balancing Human and .nimal 7ie

    f course9 there are dierences %eteen humans and other animals %utthese are small com/ared to the similarities. Most of those /otentialeects of medicines that cannot #et %e in*estigated outside the li*ing%od# can %e /redicted on the %asis of carefull# designed and conductedanimal studies. ,ithout these /reliminar# tests9 stud#ing /otential nemedicines in /eo/le ould /ut those indi*iduals at considera%le ris".

    )*en ith strong feelings a%out our res/onsi%ilities to res/ect and /rotectanimal life9 most of us ould feel it rong to ris" causing harm to /eo/lein order to a*oid harming animals. >ecognising this9 go*ernment

    de/artments of health around the orld demand information from animaltests %efore the# ill allo medicines to %e tested and used in /atients. tthe same time9 go*ernments also recognise that animals used in researchshould %e /rotected from unnecessar# use and ill-treatment. n the

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    ut ust to underline the /oint9 it as onl# /ossi%le to do this on com/uter%ecause researchers alread# "ne the structure the# needed. n mostcases9 com/uters still :ll a more con*entional role of alloing /eo/le toor" more Duic"l# and eKcientl# than ould otherise %e remotel#

    /ossi%le. lso9 remem%er that VdesigningV a molecule is not the same asVtestingV it.

    )Duall#9 cell culture or" has /rogressed enormousl#. d*ances in ourunderstanding of cell %iolog# mean that e can gro a ide range of cellsand "ee/ them ali*e9 ena%ling researchers to stud# the direct eects oftest com/ounds on s/eci:c cells9 hether for the desired %iologicalacti*it# or for safet#. 'his allos some or" that used to ha*e to %e donein animals to %e done in8vitro.

    &4 Hig)D!)roug)*ut Screening

    'here are also acti*it# screens in hich anti%odies are used in a *ariet# ofa#s in state of the art ro%otic s#stems to search collections ofcom/ounds for an# that might ha*e a /articular acti*it#.

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    ma# still cause une+/ected /ro%lems in some /eo/le9 /articularl# hen*er# large num%ers of /eo/le are ta"ing it. ut doctors and scientists ha*eto do the %est the# can to a*oid causing harm to /eo/le.

    'he use of animals in research is not an eas# or a comforta%le su%ect. t

    ould certainl# %e /refera%le if all the necessar# research could %e donein other a#s.mmunolog# is an area hich has %oth contri%uted to and %ene:ted fromad*ances in in8vitrotechnologies %ut animals are still needed.

    Clearl#9 animals should onl# %e used here necessar# and ala#s ithcare. ut illness caused %# underl#ing /ro%lems in the immune s#stem -thin" of asthma9 dia%etes9 rheumatoid arthritis and =0 to name a fe -aect *ast num%ers of /eo/le.

    &, !)e uture

    Much of hat e "no a%out the intricacies of the immune s#stem and ofhat can go rong9 has onl# %een recentl# disco*ered. 'ranslating this%asic "noledge into treatments for /eo/le li*ing ith related medical/ro%lems is a long uncertain /rocess. ut alread# real /rogress is %eingmade. Fe treatments for H( and =0 are ma"ing a dramatic dierence.Man# /eo/le recei*ing the ne medicines for multi/le sclerosis ha*e9 forthe :rst time9 a treatment that ma"es a maor im/act on their Dualit# oflife.

    'here are ne a//roaches to *accination9 such as =F *accinesmentioned in the %oo"9 and Vthera/euticV *accines Ahich should %e a%le

    to harness the /oer of the immune s#stem to hel/ deal ith a conditiononce it is diagnosedB. Fe *accines are thought li"el# to ma"e a hugeim/act on medicine in future.

    Fe a//roaches to the treatment of dia%etes are %eing e+/lored9 someell-ad*anced in the /harmaceutical industr# /i/eline. ncreasedunderstanding of the genetic %asis and underl#ing mechanisms in*ol*ed inother autoimmune conditions such as rheumatoid arthritis9 asthma9 andallerg# gi*e real ho/e for /re*ention9 im/ro*ed treatment and cure in thefuture. )*en no9 ne a#s to treat the inammator# as/ect of theseconditions are in de*elo/ment. 'here are de*elo/ments in trans/lantation9including the /ossi%ilit# that in the future9 animal organs ma# %e a%le to

    used9 sa*ing man# li*es e*er# #ear.

    'he list of /ossi%ilities9 e*en in the ne+t fe decades9 is too long to tr# toco*er here. >esearchers %uild on the "noledge gained from the or" thathas gone %efore them9 adding to it their on e+/erience and originalideas. 'he# use a com%ination of the %est a*aila%le research methods9including the use of animals here necessar#9 to understand ho our%odies function in %oth health and disease and to :nd a#s to /re*ent9treat and cure illness.

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    7OSS.-

    cute @hase @roteins - Made in the earl# stages of inammation.'he# coat in*ading /athogens to /re*ent themin*ading tissue cells and aid attac" %# /hagoc#tes.

    da/ti*e immunit# - nother term for s/eci:c acDuired immunit#.

    llergens - 0u%stances that induce allerg#.

    naemia - Condition in hich the num%er of red %lood cells arereduced.

    nti%odies - @rotein molecules /roduced %# the immune s#stem.)ach anti%od# is s/eci:c for its on antigen.

    ntigen - n antigen is a su%stance hich stimulates animmune res/onse.

    ntigen /resenting 0/ecialised cells of the immune s#stem that /rocesscells A@CB - antigens from /athogens and then stic" them ontheir

    surface. '-cells :nd it easier to recognise foreignantigens that are /resented in this a#.

    ntigenic determinant - 'he /art of a foreign antigen that an anti%od#or a '-cell %inds to.

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    to/ic - 0u%ect to multi/le allergies.

    ttenuated - ,ea"ened. (iruses are attenuated %efore %eing usedin *accines so that the *accine does not causethe disease it is tr#ing to /re*ent.

    -cell rece/tor AC>B - rece/tor on the surface of a -cell that %indsantigen.

    acteria - 0im/le9 single-celled microsco/ic organisms that cancause disease. )+am/le Feisseria meningitidis9 one of thes/ecies of %acteria that can cause meningitis.

    aso/hil ] - t#/e of hite cell.

    Commensal %acteria - acteria usuall# found on or inside the %od#9in the gut for e+am/le. 'hese %acteria do not cause diseaseand hel/ to /re*ent /athogenic %acteria getting a

    foothold.

    Com/lement s#stem - /rotein cascade in the %lood. ,henacti*ated9 the /roteins can /unch holes in %acteria andinfected %od# cells9 "illing them.

    Ciclos/orin - =rug hich dam/s don the immune s#stem.

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    mmune res/onse - ction %# the immune s#stem against material that isforeign to the %od#.

    mmune sur*eillance - 'he immune s#stem maintains a s#stem todetect foreign antigens and react to them *er#Duic"l#.

    mmune s#stem - 'he %od# s#stem that res/onds /rotecti*el# toinfection.

    mmunisation - 0ame as *accination. nducing immunit#arti:ciall# %# gi*ing a /erson an e+tract9 a /uri:ed antigenor a modi:ed form of a /athogen.

    mmunit# - >esistance to infection.

    mmunoglo%ulin - nti%od#. 'here are se*eral su%t#/es g9 g&9 g)9fore+am/le. )ach t#/e has its on function in

    the %od#.

    mmunological memor# - 'he ca/acit# of the immune s#stem to remem%er andrecognise a /athogen ne+t time it gets into

    the %od#.

    mmunosu//ressi*e - 0omething hich dam/s don the immuneres/onse.

    nfection - n*asion of the %od# %# another li*ing organism.nfection does not ala#s lead to disease.

    nnate - n-%orn. nother term a//lied to natural immunit#.

    nterferons - @roteins made %# cells infected ith *iruses. 'he#inhi%it groth of *iruses in other cells.

    Riller Ac#toto+icB '-cell]- ne t#/e of "iller cell9 a l#m/hoc#tes that isacti*ated %# a s/eci:c antigen and hich then attac"s%acteria or infected %od# cells.

    Large granular lso "non as natural "iller AFRB cell. Can "illdierent t#/es l#m/hoc#te ] AFRB - of cells and hel/ in anti-*iral and anti-tumour immunit#.

    L#m/hoc#te ] - hite cell. )ither -cell or '-cell.

    L#m/hoid tissues - 0ee /rimar# and secondar# l#m/hoid tissues.

    Macro/hages ] - Large hite cells hich carr# out /hagoc#tosis.

    Maor Histocom/ati%ilit# n im/ortant antigen recognition s#stem thatregulates Com/le+ AMHCB - immuneres/onses.

    Mast-cell ] - Large cells hich degranulate9 releasing/ac"ets of histamine in res/onse to an allergen.

    Monoc#tes ] - 0ee mononuclear /hagoc#tes.

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    Mononuclear /hagoc#tes ] -

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    @rotecti*e immunit# - 'he resistance e de*elo/ to infection %#%eing e+/osed to it.

    @rotoWoa - 0ingle-celled organisms such as @lasmodiumthat causes malaria.

    @us - 0tic"# #ello discharge that results from a%acterial infection. Consists of dead %acteriaand dead hite cells.

    >eected - ?oreign tissue Ausuall# trans/lanted tissueBattac"ed %# the hosts immune s#stem.

    >heumatoid arthritis - n autoimmune disease9 that is one here the%odies immune s#stem attac"s the%od# itself9 in this case the tissues of theoints.

    0econdar# l#m/hoid L#m/h nodes and s/leen here l#m/hoc#tesma"e immune tissues - res/onses.

    0elf-antigens - ntigens that are /art of the %od#.

    0e/tic - @utrefaction folloing infection.

    0/eci:c immunit# - nl# or"s against /articular in*adingmicro%es9 associated ith ' and -cells.

    0/eci:cit# - 'he a%ilit# of l#m/hoc#tes to res/ond to onl#one /articular t#/e of in*ading micro%e.

    '-cell rece/tor - site on the '-cell hich can %ind to the MHCand %ring a%out acti*ation of that '-cell.

    'h#mus - lo%ulated gland found ust %elo the lar#n+.

    'h#roiditis - nammation of the th#roid gland.

    'issue match - 0election of donor tissue that is as geneticall#similar as /ossi%le to the reci/ient tissue tominimise reection.

    'rans/lantation - 'ransfer of an organ or tissue from one /erson

    to another. rgans commonl# trans/lantedinclude "idne#9 heart9 li*er and lungs.

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    ,orms - @arasitic orms9 hich can de*elo/ strategiesto side ste/ the immune s#stem.

    ^enograft - graft in hich the donor tissue comes from adierent s/ecies of animal from the reci/ient.

    ]Cells of the immune s#stem