my immune glossary

8/13/2019 My Immune Glossary

1/24

Sara Paradise

updated from Ahmed

IMMUNOLOGY BLOCK I GLOSSARY

Innate Immune system

PRR Pattern recognition receptors. Receptors that are present on innate

immune cells (neutrophils, macrophages, and dendritic cells) andrecognize specific molecular structures (PAMPs) on the outside of the

antigen cell wall. Example includes !Rs.

!o""#"i$e re%eptors &!LR's(

Receptors expressed on outside of " cells which promote wea# "cell acti$ation %& recognizing molecular patterns on th&mus'

independentantigens.

Acti$ated %& adaptor protein M&, which fre*uentl& results in

+-" acti$ation. ithout M&, !R cannot %ecome acti$ated.his method is does not re*uire /01 ligand from cell, and

produces much wea#er signal (i.e. dont get strong germinal center

formation of " cell memor&) $s. acti$ation with /01 ligand from cell.

My)** Adaptor protein located on inside of !R of innate cells to induce+-" acti$ation of 2!'3 gene. ithout M&, there is no

acti$ation of !Rs and organism will not %e a%le to deal with

infections and dies.

PAMP Pathogen'associated molecular patterns. Molecular patterns 4 mannose'

rich oligosaccharides, peptidogl&cans, and lipol&saccharides coating

%acterial cell walls and unmeth&lated /p5 +A 4 allowing the innateimmune s&stem to recognize them as 6non'self.7

Ad+u,ant -illed %acteria or %acterial extracts added to immunizations to allow

dendritic cells to recognize purified antigens such as proteins, since thesepurified specimens lac# the PAMPs that allow PRRs to recognize them.

Allow dendritic cells to %ecome acti$ated to full antigen'presenting status

in the a%sence of infection.

Comp"ement system 81 proteins produced %& li$er which are in high concentration in %lood9

come together during 6complement acti$ation7 to #ill and clear pathogensfrom extracellular fluid. 8 pathwa&s include Ag:A% complex,


2/24

;;;Ag:lectin complex;;;, and pathogen surface coating. Pro$ides

doc#ing site for leu#oc&tes on pathogens and is chemoattractant for

neutrophils (/


3/24

)efensins Antimicro%ial peptide found on s#in, mucosal tissues9 #ill pathogens $ia

cationic charge. "ind to pathogen and puncture cell mem%ranes, altering

polarization and #illing cell.

Chemo$inessolu%le factors which attract other cells to site

CC /lass of chemo#ines containing dou%le c&steine %ond

CCR6 /hemo#ine receptor which is induced %& endritic cell !R%inding to an Antigen. Attracts l&mphoc&te with integrin to %ind

strongl& to 2/AM on endothelial cell surface

CCL 73 !&mph +ode chemo#ine. /hemo#ine signal which attracts " cellswith mature receptors into EB

CCL 38 !&mph +ode chemo#ine. Along with //!3C, attracts " cells with

mature receptors into secondar& l&mphoid organ (i.e. l&mph node)

C9C /lass of chemo#ines which contains an extra amino acid %etween them.Most important for innate inflammation.

IL#* &C9CL*( Protein released %& macrophages and dendritic cells which attractsneutrophils to infection site $ia chemotaxis

C9CL3: !&mph +ode chemo#ine. Attracts " cell into primar& follicle

Cyto$inessolu%le factors made %& cell

!N; fami"y

!N; Re%eptor + receptors recognize c&to#ines of the umor +ecrosis famil&

(i.e. /01 ligand and +'a). /ells containing these receptors are

trimeri%and induce cell to undergo apoptosis.Examples: +R'2, +R'22, ;as

!N;#


4/24

"loc#ing it with +'F agonists puts the %ra#es on the immune

s&stem o$erall (helps auto'immune).

C)=> "i2and /&to#ine that is part of + famil& and acts as ligand to %ind

/01 and amplif& immune response.

;as Re%eptor 2ntracellular receptor9 %inds as ligand to promote cell death $ia

%aspases inside the target cell.

;as Li2and !igand that can %e expressed %& /0G cells and %& C cells.

as ligand %inding to as receptor cell death. hen cells get

acti$ated, the& express as ligand to #ill themsel$es

(downregulation).

!G;#


5/24

Adhesion Mo"e%u"es

Immuno"o2i%a" Synapse

6@&napse7 %etween 'cell and AP/. 2mportant s&napse for naO$e cell.

2ncludes %inding of /3 on cell to ">.C, ">.3 of AP/. his allows cell to release /01 ligand, which %inds to /01 receptor on AP/ and

increases its acti$ation.

I!IM 2mmunoreceptor &rosine'%ased 2nhi%ition Motifs. ound on /!A'0,

PC, and other inhi%itor& structures. @ame as an 2AM %ut inhi%itor&.

"rings in ;phosphatases; which o%$iousl& do the opposite of #inases.

I!AM 2mmunoreceptor &rosine'%ased Acti$ation Motifs. hese are in$ariant

(i.e. not changea%le) proteins found on the c&tosolic side of the

C)R:EI2a#I2B %omp"eDes9 contain certain amino acid se*uences with 3

t&rosines re*uired for signal transduction. /an %ind t&rosine #inase and%ecome phosphor&lated to acti$ate recruitment of other #inases within the

cell (%oth enz&mes and non'enz&mes, adaptor proteins.

ICAM: Onendothe"ium/ 2ntercellular adhesion molecules that are part of

2mmunoglo%ulin superfamil&. Present on the surface of endothelium and%inds proteins of the integrin famil&.

ICAM#3 and ICAM#7

Adhesion molecules located on endothelium which %ind to integrins onl&mphoc&tes to allow them into @4FEendothe"ium. "inding causes

conformational change in structure of 2/AM, allowing tight %inding to

$ascular surface and e$entual extra$asation.

FCAM#3 Adhesion molecules located on endothelial cells which %ind to B!A'0

integrin on l&mphoc&te to allow them to access periphera" tissuewhereinur& has occurred. =pregulated on cell surface in response to

macrophages releasing +'a c&to#ine (i.e. immune response initiated).

Addressins On endothe"ia" %e""s/ Dligosaccharides located on the outside ofendothelial cells which %ind !'selectin.

Se"e%tins On "ympho%ytes su%h as !#%e""s/ 5l&coproteins that ha$e distal lectin'li#edomains %ind to car% groups (/AMs) on endothelial cells.

L#se"e%tin @electin expressed on naO$e cells which 6selects l&mph node7 %&homing l&mphoc&te to EB. "ind to oligosaccharides (addressins) on

endothelial cells. ownregulated in effector cells in so that cell does

not return to l&mph node %ut instead migrates to peripher&.


6/24

Inte2rins On "ympho%ytes/ Molecules on surface of professional AP/s that %ind to

cell'adhesion molecules (2/AMs) and extracellular matrix in response to

chemo#ine release, pro$iding a strong adhesion to EB or endothelium atsite of inur&.

! %e""s

L;A#3: Part of inside#out si2na"in2 me%hanism. 2ntegrin molecule

expressed on cell that %inds 2/AM'C (adhesion molecule) onsurface of AP/9 responsi%le for initial %inding %etween AP/ and

cell, as at first it %inds with low affinit&, %ut once /R %inds to

M/Npeptide complex on AP/ !A'CN2/AM undergoes

conformational change grows stronger, prolonging cell'to'cellcontact. Also functions in endothelial cell adhesionNtransport.

eficienc& leads to poor wound healing.

FLA#= Another t&pe of integrin which %inds to FCAM#3 on acti$atedendothelium at sites of inflammation. =pregulated on cell

surface once cells ha$e %een presented with antigen (i.e. naO$e

effector cells).B %e""s

B7 inte2rins L;A#3 andCR#: expressed on l&mphoc&te. "inds to 2/AM on

acti$ated endothelium to allow extra$asation. "inds to 2/AM on

AP/ to allow tight cell'to'cell interactions %etween cells andAP/s.

Mono%ytes

MAC#3 2ntegrin on monoc&tes which %inds 2/AMs and B/AMs duringinflammation

Leu$o%yte Adhesion )efi%ien%y &LA)(

eficienc& where integrins or selectins on l&mphoc&te are mutated9

l&mphoc&tes ha$e trou%le entering tissue so there are recurrent %acterialand fungal infections

Adapti,e Immune System

C"ona" se"e%tion /entral principle of adapti$e immunit&9 each l&mphoc&te %ears a specific

receptor with uni*ue specificit&, and %inding of that receptor with a

compati%le antigen will cause l&mphoc&te acti$ation. he differentiatedcells deri$ed from an acti$ated l&mphoc&te will %ear receptors of identical

specificit& to parental l&mphoc&te


7/24

Immuno2"o.u"in Anti%od& proteins which can occur as either transmem%rane proteins or

secreted anti%odies from " cells. /onsist of < main classes: 5MEA,

defined %& their hea$& chain constant region. a$e 6immunoglo%ulindomain7, which is a conser$ed motif of C11'CC1 amino acids folded up

into a compact structure which is sta%ilized %& intrachain disulfide %onds.

@ea,y %hain , , Q, F,

Li2ht %hain -, S

Isotype he different structures of hea,y %hainconstant regions that define the

2g5, 2gM, 2gE, 2gA, and 2g classes. +ai$e " cells can onl& produce the

isotype &I2M( and 5 &I2)( isotypes/ iffer in num%er of interchaindisulfide %onds, length of hinge region, etc. Dnce the& are presented which

antigen, the& can undergo 6class'switching7 to form other t&pes. !ight

chains do not undergo class'switching.

Constant re2ion Part of hea$& and light chains that do not change.

Faria."e re2ion Part of hea$& and light chains that are $aria%le

@yper,aria."e re2ion

8 different parts of $aria%le region (/RC, /R3, and /R8) that areespeciall& $aria%le, and confer antigen specificit&. Present on %oth hea$&

and light chains and correspond to BT and BT genes on ea$& and !ight

chains, respecti$el&.

/R8 is most$aria%le of the 8 h&per$aria%le regions, which corresponds

to the oining regions %etween B, , and T genes.

Mono,a"ent /an %ind onl& C Ag

Bi,a"ent /an %ind 3 Ags

;rame1or$ re2ion a$a Comp"ementarity )eterminin2 Re2ion &C)(

he other part of the $aria%le chain (i.e., the part that is not h&per$aria%le)

4pitope Part of antigen which %inds to anti%od& $ia non'co$alent interactions. or"'cells, A% usuall& recognizes part of Ag that is on outsideH recognizes

shape or %onformationa" epitope/ or 'cells, A% does not necessaril&

onl& recognize outside of Ag.

B#%e"" Re%eptor "/R. Mem%er of 2mmunoglo%ulin supergene famil&.

)imer of heterodimers4 light chain G hea$& chain lin#ed %& intrachainsulfide %onding x3. /ontains constant region (c) 4 / terminus 4, which

defines its isot&pe and regulates the %iological acti$it& of the molecule,

and $aria%le region (a%) at top end 4 + terminus 4 which %inds antigen.


8/24

!i#es to %ind "on20 linear epitopes found on outside of antigen

(conformational epitopes 4 recognize shape).

Papain Enz&me which clea$es A"DBE intrachain disulfide, so produces 3

mono$alent a%fragments

Pepsin Enz&me which clea$es "E!D intrachain disulfide, so produces C%i$alent a%fragment.

!#%e"" Re%eptor /R. Mem%er of 2mmunoglo%ulin supergene famil&. /onsists of a

heterodimerof a and B %hains(or in some cases and 9 primiti$ereceptor) with constant region cand $aria%le region a%,$er& similar to

"/Rs. Also ha$e 8 /Rs in h&per$aria%le region and antigen %inds to

%oth a and " chain. he a and " chains %ind to %oth the peptide andM/.

M@C Restri%tion /Rs recognize antigen as a processed short, linear epitope %ound

to M/ /lass 2 or 22 on the surface of AP/. /R %inds %oth theepitope and M/.

Superanti2ens Ber& dangerous antigens which %ind directl& to the framewor#

constant region of /R $s. h&per$aria%le region, which is much

more common. +o processing of antigens into peptide re*uired.Allows them to acti$ate man&, man& cells to release c&to#ines

all at once. 2ncludes staphy"o%o%%a" enterotoDin A and B/

@aptens @mall molecules such as drug meta%olites, metals, pol&saccharides, andlipids which are recognized %& immune receptors %ut onl& %ecome

immunogenic (i.e. initiate immune response) when %ound to carrier

protein.

Examples include pol&saccharides in $accines, c&closporine in transplant

patients, h/5 in pregnanc&, and penicillin. Must use anti'haptenanti%odies to detect presence of these haptens.

Peni%i""in Penicillin is an anti%iotic that contains %eta'lactams and inhi%it

peptidogl&can s&nthesis of the %acterial cell wall. A penicillinallerg& occurs when &our %od& generates an immune response to

the hapten'carrier conugate, causing reactions such as rashes,

hi$es, itch& e&es, swollen lips, tongue, or face. Dccurs in 3? ofpatients.

Immuno2ens Antigens (haptens) which actuall& cause immune response, %ut onl& when%ound to protein carrier. Example is +P %ound to "o$in @erum

al%umin ("@A).

M@C mo"e%u"es Maor istocompati%ilit& /omplex. /omplex located on " and cells


9/24

which come in two different $arieties M/ /lass 2 and M/ /lass 22."oth ha$e alpha and %eta region, %ut in M/ /lass 2 alpha region isenlarged and %inds peptides, $s. M/ /lass 22 where %oth a and " %ind

peptides.

Lymphocyte Development

RSS Recom%ination signal se*uences. /onser$ed se$enmer and nonamer

se*uences flan#ing the exons (so on the introns) of the B, , and T genesin l&mphoc&tes. "ound %& RA5 proteins and let them #now that exon

splicing se*uence is near%&.

RAG307 6!&mphoid'specific recom%inase genes7. RA5 genes and RA5 proteins

are on"y eDpressed durin2 "ympho%yte development9 the& allow and "

cells to undergo somatic recom%ination %& causing endonucleol&ticclea$age on the


10/24

CCL 73 /hemo#ine signal which attracts " cells with mature receptors into EB

CCL 38 Along with //!3C, attracts " cells with mature receptors into secondar&

l&mphoid organ (i.e. l&mph node)

C9CL3: Attracts " cell into primar& follicle

B cell maturation into effector B cells

Mar2ina" Jone B Ce""s

MU " cells. !ocated ust outside of central arteriole of white pulp of

spleen so first to recei$e antigens. o not de$elop until Lthmonth of life.!imited antigen receptor repertoire9 onl& recognize %acterial

pol&saccharides and few other PAMPs.

B3 %e""s " cells which reside in peritoneal and pleural ca$ities. 62nnate'li#e7 inthat the& form earl& in fetal life (though after S cells) and onl&

recognize limited num%er of Ags.

!hymus#independent A2

Antigens which present to " cells and cause stimulation without elper

s. Antigens must form multiple cross'lin#s to " cell to achie$e strong

enough stimulation, therefore 2gM is usuall& expressed (penta$alent).

Lin$ed re%o2nition he fact that " cells are acti$ated %& cells is due to the fact that cells

and " cells recognize different epitopes of the same Antigen. Ex) " cells

recognize pol&saccharide and cells onl& recognize protein on M/.

B7 ;o""i%u"ar a$a Con,entiona" B %e""s

" cells which are located in l&mphoid follicles. Must recei$e signal C(specific Ag:A% %inding) as well as signal 3 (/R:/01 costimulation) in

order to acti$ate.

C"ona" 4Dpansion /lonal expansion of " cells occurs in germinal centers 4 site of intense "cell proliferation. !ight zone of follicle is where follicular dendritic cells

present to Ag. ar# zone is " cell proliferati$e zone.

;o""i%u"ar )endriti% Ce""s

+on'hematopoeitic fi%ro%last li#e cells which trap antigens and present to

"3 cells.

Affinity Maturation @ur$i$al of the fittest7 for " cells. " cells with receptor that has highest

affinit& for Antigen will %e induced to continue to proliferate.

@e$eral


11/24

rounds of somatic mutation in $aria%le region, antigen selection, and high

affinit& %inding ma& occur to increase affinit& for antigens and cause "

cell proliferation.

Somati% @ypermutation

escri%es the fact that /R coding regions of +A (antigen'%indingregions) mutate at C,111,111,111 times normal rate during " cell clonal

expansion. Re*uires specific enz&me 4 AI)4 to occur. he mutations

are permanent and passed down to progen&.

P"asma Ce""s @ecreted anti%od&. Processed %& alternati$e RNA post#trans%riptiona"pro%essin2/

Isotype S1it%hin2 Mechanism that alters constant region (/) of hea$& chain, switching them

from 2gM and 2g to another t&pe $ia A2 enz&me splicing at gene le$el.

epends on stimulus, help from cells, and c&to#ines. Altering hea$&

chain altering effector acti$it&. =suall& occurs after 3

nd

Ag exposure.2sot&pe switching ma& occur again, though cannot switch to more

downstream 2g5.

IL#= @ecreted %& 3 and promotes switching to 2g5C and 2gE ($ia @AL)

I;N# @ecreted %& C and promotes switching to 2g53a!G;#? @ecreted %& reg and promotes switching to 2gA

AI) en-yme Enz&me which recognizes 6switch regions7 upstream of /onstant ea$&

/hain locus and can splice them to ma#e different rearrangements (except2g, which uses post'transcriptional processing).

@umora" Immune response

A-A Anti%od& immune response. +eutralizes toxins, aggregates

antigens, A//, Promote phagoc&tosis, opsonization, and pre$ents

%inding of other pathogens $ia M//.

I2M constant region of hea$& chain. Mostl& located in circulation.

Expressed on naO$e " cell surface and therefore does not undergosomatic h&permutation. Relati$el& low affinit& for antigen, %ut

often used in agglutination reactions and pre$alent in MU" and

"C:Ag %inding due to pentameric structure (multi$alent %indsmore antigen).

I2) 5 constant region of hea$& chain. Expressed on naO$e " cellsurface.


12/24

I2G constant region of hea$& chain9 can cross placental %arrier. +-cells %ind here and acti$ate $ia A// (Anti%od& dependent

cellular c&totoxicit&).

I2a < constant region of hea$& chain. Expressed on mature " cell

surface and can undergo somatic h&permutation. as multiple$alences. ransported across epithelial cells to mucosa or to

lumen of lactating %reast, sali$ar& glands, and tear glands, where it

can neutralize %acteria and toxins to protect mucosal surfaces.

I24 constant region of hea$& chain. Mast cells %ind here and acti$ate

allerg& response.

! Ce""s


13/24

2f /R recognizes M/'/lass 2 / sends signal for /R to continue

de$elopment and %ecome /G9 if /R recognized M/'/lass 22 /0 sends signal for /R to continue de$elopment and %ecome /0G.

M@C Restri%tion/

AIR4 )efi%ien%y Autoimmune regulator deficienc& which causes causing rare autoimmunepol&endocrine s&ndrome 4 &pe 2 (AP@'C). A2RE is a transcription factor

expressed in th&mic medullar& epithelial cells that a""o1s spe%ia"i-ed%orti%a" epithe"ia" APC's to present protein or protein fra2ments in

thymus that are norma""y on"y eDpressed in the periphery/

eficienc& lac# of protein in corticall& medullar& cells that allows

peptide presentation lac# of central tolerance (no neg. selection)autoimmune pro%lems in peripher&

Go"di"o%$s !heory h&moc&te de$elopment (i.e. positi$e or negati$e selection) depends upon

the strength of the signal the cell recei$es from its microen$ironment.

Mo"e%u"ar !e%hniues

;"o1 Cytometry Ma#e cell suspension, add A%s, add proteins. Appl& laser9 if the A% has

attached to Ag, it will fluoresce and &ou can count num%er of antigens.

Allows &ou to anal&ze the patterns of protein expression on a or " cell

%ased on anti.odyinteractions with the proteinson the cell surface.

Ex) categorizing different stages of cell de$elopment: ta#e from th&mus,

mush it up, ma#e a single'cell suspension, la%el A%s with fluorescentanti%odies that recognize either /0 or /. Dne axis is loo#ing at

whether the cell expressed / protein, further out on the x'axis, cells

express /. Dn the &'axis, cells that express the anti%od& thats

associated with expression of the /0 protein appear.

Mono%"ona" Anti.odies

Produced %& a single clone of " l&mpho&ctes. =suall& produced %&ma#ing h&%rid A%'forming cells from a fusion of non'secreting m&eloma

cells with immune spleen cells. !a% artifact or sign of malignanc&, as

there is outgrowth of single clone of cell (+on'hodg#in l&mphoma).

=sed to ma#e drugs in mice. he pro%lem is that if &ou gi$e human a

mouse A%, human will react. /hange +A to allow mouse A%s to ma#e it

loo# more li#e human A% so no response occurs.

Po"y%"ona" Anti.odies

hese anti%odies recognize multiple epitopes of antigens so the& canacti$ate multiple l&mphoc&te clones of di$erse specificit&. +ormal


14/24

immune response to influenza, as Ag has multiple epitopes and multiple

A%s will %ind.

A22"utination Aggregation or clumping of antigenNanti%od& complexes. =se 2gM in

la%orator& tests %ecause it is penta$alent and can crosslin# multiple Ags.

Final T cell maturation

C)* ! %e""s /luster of differentiation . Receptor't&pe displa&ed on /&totoxic Recognize ,ira"antigen presented %& peptideM@C C"ass Icomplex on

surface of infected cell and %ind to them $ia 2/AM interactions. Dnce

%ound, C!L's%ecome polarized and release granules containing perforin

(puncture cell mem%rane), 2ran-yme(serine protease to chop up +A),and 2ranu"ysinto #ill cell rapidl& $ia apoptosis.

Produce c&to#ines such as I;N'to express M/ /lass 2 on target cell

and to increase macrophage acti$ation. Also express ;as "i2andtoregulate and #ill l&mphoc&tes.

Apoptosis 6Programmed cell death7. /ell destro&s itself from within %& using

nucleases to shred +A into pieces of 311 %ps, clea$ing %etween

nucleosomes. Also can #ill $iral +A in host cell.

C)= ! %e""s cells which contain man& su%classes, categorized %& the

c&to#ine that the& release. Recognize a $ariet& of antigens presented %&

M/ /lass 22 molecules on surface of infected cell.

!@#3 IN;LAMMA!ORY/0 cells7.

Prin%ipa" ;un%tion Acti$ate macrophages (see 6macrophage acti$ation7

under AP/ section) $ia I;N#, which recognizes %acterial antigens onmacrophage surface and stimulate their micro%icidal acti$it& and #illengulfed %acteria. @&nergizes with 2+'a released from macrophages to

allow diapedesis of macrophages into site of inur&.

Also acts as co'stimulator for naO$e " cells allowing them to ma#e more

anti%odies and undergo isot&pe switching.

!@#7 elper cells whose main function is to acti$ate " cells to produce A%s

through isot&pe switching9 initiates allerg& response and attac#s parasitic

worms.


15/24

@ecretes IL#=EIL#3:, which acti$ates " cells to %ecome I24. IL#=

initiates the a""er2y response%& causing isot&pe switching to 2gE

and crosslin#ing of 2gE on "cells to c receptors on mast cells,causing them to degranulate and release histamine, prostaglandin,

and leu#otrienes. IL#3: acti$atesgo%let cells to secrete mu%us.

Also secretes c&to#ine IL, which promotes " cell to displa& I2A

for eosinophil maturation and degranulation. Regulated %&

GA!A#: .

S!A! Acti$ated %& IL#=9 causes promotion of 5AA'8 and isot&pe

switching to 2gE.

!@#36 Effector cells whose main function is to re%ruit neutrophi"sto %"ear

.a%teria from eDtra%e""u"ar spa%es 6clean'up crew7. @ecretesIL#36

and IL#, which allow more C> de$elopment %& upregulating

transcription factor ROR ! and recruit more neutrophils to site of%acterial infection to clean up. e$elopment induced %& !G;#? and IL#.

Ma& ha$e a role in autoimmunediseasessuch as /rohns, 2"@,

Rheumatoid arthritis, and M@.

!re2 Regulates num%er of l&mphoc&tes %& downregulating macrophage and

dendritic cell acti$ation. A$oids autoimmune responses. e$elop in

response to !G;#? which increase production of ;O9. @ecrete!G;#

? and IL#3>to inhi%it C.

;as "i2and !igand that is part of + famil& and is important in inducing apoptosisof "ympho%ytesto terminate immune response once it has %een

completed. /&totoxic cells and helper cells contain as receptor. as

ligand %inding to as receptor apoptosis. Mutation in as gene producesl&mphoproliferati$e disease in which cells cant %e cleared.

)e"ayed Inf"ammatory Response

2f pre$iousl& infected with antigen, acti$ated C will release c&to#inesand a%ti,ate ma%ropha2e, causing inflammator& response. 2t is dela&ed

%ecause it ta#es a few da&s for hC cells to induce macrophage response.

Ex) " test. +aO$e cells would not ha$e this effect %ecause there wouldnot %e enough to recognize " antigen.

hC cells release 2+' to induce expression of $ascular adhesionmolecules, +'F and J to cause local tissue destruction and increased

expression of adhesion molecules, chemo#ines to recruit macrophages to

site of antigen, and 2!'8N5M'/@ to produce monoc&tes %& %one marrow

stem cells.


16/24

Conta%t @ypersensiti,ity

ela&ed h&persensiti$it& response for things li#e poison i,y. Poison i$&is pentadecacatechol, lipid solu%le chemical that penetrates s#in and reacts

with proteins, creating haptenated proteins (altered self) which can %e

ta#en up %& !angerhans cells (s#in macrophages) and %rought to l&mphnodes to present antigen. 2mmune response is therefore not generated on

first exposure, %ut upon multiple exposures C cells are recruited to site.

! %e"" primin2 6Memor& cells7 which ha$e seen antigen %efore. /ause inflammator&

response.

Cyto$ines re"eased .y Professiona" APC's

IL#= /&to#ine secreted %&APC's which induces GA!A#: to ma#e more

!@7cells. Also promotes isot&pe switching of " cells to 2gE and 2g5C.

IL# /&to#ine, along with !G;'?(and sometimes 2!'38), secreted %& APC's

which increases ROR ! to ma#e more !@36.

IL#37 /&to#ine produced %& mature dendriti% %e""s and ma%ropha2es/

2ncreases production of !#.et, which ma#es more !h3/

!G;#? /&to#ine produced %& APC'sin response to pathogen %inding of !R, i.e.

/auses production of ;oDP:, which ma#es more !re2%e""s.

C)'s

C)R: %omp"eD Part of /R @ignaling complex. /onsists of:

@eterodimer of 50

@eterodimer of 0

@omodimer of %hain

Each component is necessar& for the initial transport of an


17/24

C)38E73 Analogous to /0N/ for 'cells, these are co'stimulator& molecules

located on " cells that %ind to M/'peptide complexes to facilitate 2AM

in 2ga and 2g" complexes.

C)7 XXXXXXXXXXXXXXXXXXXXXXXXXY

C)7*EB6 /3 found on '/ells. Most important co'stimulator& signal %etween

them and the dendritic cells (AP/) to a%ti,ate the !#Ce"". "ind to the ">

motif of AP/s.

C):=0C):*# ematopoietic stem cells. RootNprogenitors ha$e this 2 thin#.

C)=>EC)=>L /01 %inds /01!. /01!(ligand) is expressed on activated'cells,/01 found on the "'/ellsNAP/s. 2nteraction is important to promote

2sot&pe @witching and a%ti,ate the B#%e"" ("'cells are AP/s). Also

acti$ate macrophage and dendritic cells and release 2!'C, +'F, and 2+'

V.

C)=ECs$ All src famil& #insases share certain structure including an @3, @8, andinhi%itor& domain in the signal transduction pathwa&. /s# phosphor&lates

the 22M motif, causing inhi%ition9 /0< is a phosphatase that

dephosphor&lates it and uninhi%its the signaling pathwa&.

ILsIL#3 2nterleu#in'C. Pro#inf"ammatory %yto$inesecreted %& macrophages

during innate immune response (though it can %e acti$ated %& cell /01ligand). unction to enhance response and induce acute'phase protein

secretion. /onsidered an endo2enous pyro2en/;IL-1 & IL-1: increase endothelial adhesion to allow leukocytes tomigrate to target site of infx and can re-set the hypothalamic

thermoregulatory center. * is assoc with increased sensitivity to pain

that comes with fever and activated by inflammasome complex.IL-1R: modulates IL- inflammatory and immune rsp by !-" IL-1

IL#7: 2nterleu#in'3 growth factor that is important in acti$ating naO$e cells,apges it promotes clonal expansion and production of more high'affinit&

2!'3 receptors as well as secretion of more 2!'3 $ia autocrine acti$it&.

IL#= Produced %& h3 helper cells. Promotes differentiation into h3 cellswhile inhi%iting hC formation. Promotes isot&pe switching (to 2gE).

IL#: Produced %& (%ronchial) epithelial cells under influence of acti$ated Mast/ells. 2s a c&to#ine that acti$ates eosinophils and promotes their formation

in %one marrow. 2s ;+D; a chemoattractant.


18/24

IL#: @ecreted %& macrophages and dendritic cells during innate immune

response. Promotes !h36 formation(so does 5'J) to enhance

response and induce acute'phase protein secretion. 2nhi%its hC Z h3formation.

IL#6 /&to#ines located in the microen$ironment of the de$eloping and " cellthat are important for maintainin2 de,e"opment9 a""o1 ! %e""s to .e%ome

Memory %e""s/ 2f missing, $er& %ad immunodeficienc& disorder since

&oure not a%le to ma#e memor& cells.

IL#3> An immunoregulator& c&to#ine made %& regcells. Also made %& certain

parasitic worms.

IL#37 Proinflammator& c&to#ine that promotes hC de$elopment from a naO$e

'cell. 2nhi%its h3 de$elopment. 2+'V does this as well. /an %e

acti$ated %& cell /01 ligand.

IL#3 /&to#ine which is also important for memor& cell sur$i$al.

IL#36 2mportant for remo$al of staph and candida. 2n APE/E patients %od& is

producing anti%odies to 2!'C>, resulting in candidiais and ectodermald&stroph&.

i!nal Transduction

I!AM 2mmunoreceptor &rosine'%ased Acti$ation Motifs. hese are in$ariant

(i.e. not changea%le) proteins found on the c&tosolic side of the /R8N2ga'2g" complexes9 contain certain amino acid se*uences with 3 t&rosinesre*uired for signal transduction. /an %ind t&rosine #inase and %ecome

phosphor&lated to acti$ate recruitment of other #inases within the cell

(%oth enz&mes and non'enz&mes, adaptor proteins.

his complex is also found on the cER2 and cgammaR222 immune

receptors of +- cells, macrophages, neutrophils, mast cells, and %asophils.

I2a#I2B Part of "/R signal transduction complex.

SRC @R/s are t&rosine #inase enz&mes which phosphor&late t&rosines afterligand %inds. hese proteins are post'translationall& modified to include a

fatt& acid tail, and therefore are attracted to lipid rafts in cell mem%ranes.

Example: /R lc# @R/ t&rosine #inase

Lipid Rafts eterogeneous regions within the plasma mem%rane which $ar& influidit&, and therefore re2u"ateand promote protein'protein interactions


19/24

as well as cell signaling complex formation. 5P2'lin#ed proteins (proteins

that associate upon %inding of signal ligand) and ac&lated proteins such as

src'famil& #inases are often found in lipid rafts.

Adaptor proteins Proteins which are non'enz&matic, %ut form part of macromolecular "/R

and /R signaling complex

Re%eptor !yrosine Kinases

a$e their own inherent enz&matic acti$it& and can transduce signal toinside of cell on their own.

Examples: Epidermal 5rowth actor (E5) receptor, 2nsulin receptor

Re%eptor#asso%iated !yrosine Kinases

/ell receptors which do not ha$e their own enz&matic acti$it&, so must

recruit other molecules to the site of the receptor to transduce messagesinside the cell $ia 6second'messenger7. /ontains regions which interact

with phosphor&lated t&rosines, prolines on adaptor proteins, and cellmem%rane.

Examples: Antigen receptors, c receptors, c&to#ine receptors

S@7 domain Region of receptor associated - which %inds to phosphor&lated

(acti$ated) t&rosines

S@: domain Region of receptor'associated - which %inds to proline amino acids on

adaptor protein.

S%affo"din2 proteins @tructural proteins which contain multiple t&rosine phosphor&lation sites

and therefore recruit multiple signaling proteins to %ind to it. acilitate

complex formations that facilitate cell signaling. here does scaffoldingoccurYYY

Immuno"o2i%a" synapse

Co#re%eptors 2n addition to /RN"/R %inding to M/'peptide complex, these A!@D%ind M/'peptide complexes, sta%ilizing their association and recruiting

t&rosine #inases to the A2RY

T"R i!nal Transduction


20/24

C)=EC)* /an act as co'stimulator& molecules for /Rs9 %ind M/'antigen

complex after ligand %inding, assisting 2/AMs of /8s to

%ecome phosphor&lated %& !c#

L%$ Q ;yn @R/ famil& t&rosine'#inase which associates specificall& with '

cell /0 (M/ /lass 22) or / (M/ /lass 2) co'receptors,promoting the phosphor&lation of 2AM on /8 complex. 2nitial

phosphor&lation e$ent.

JAP#6> Adaptor protein which is recruited after phosphor&lation of !c#

and &n9 %inds to -eta %hainoff of /R in c&toplasm.

PLC# Acti$ated %& UAP'>1 to clea$e P2P3into two products, A5 Z 2P8

)AG iac&lgl&cerol. P!/' clea$es P2P 3into A5 and 2P89 A5acti$ates ras, which phosphor&lates protein to acti$ate +-"

transcription factor, which %inds to promoter region of 2!'3 geneturning on its transcription.

Ras Part of small 5 protein class in all cells. Kinasethat

phosphor&lates a protein to acti$ate +-" transcription factor,

which %inds to promoter region of 2!'3 gene turning on itstranscription. 2mportant for acti$ating MAP #inase.

IP: 2nositol triphosphate. P!/' clea$es P2P 3into A5 and 2P89 2P8%inds to receptors on the ER, releasing /a3G into c&tosol. /alcium

then %inds to receptors on plasma mem%rane to increase /alcium

entr& into cell and %inds calmodulin to modulate acti$it&.

Ca"%ineurin Phosphatase which, when %ound %& /alcium in response to 2P8,

dephosphor&lates +A, allowing transcription of 2!'3 gene.

N;A! ranscription factor. /alcineurin dephosphor&lates +A,

allowing it to migrate into nucleus where it %inds to promoter

region of 2!'3 to allow transcription to occur.

Cy%"osporin AE;K>

rugs which %loc#s calcineurin acti$it& so it cannotdepshophor&late +A and it is stuc# in the c&toplasm9 ."o%$s

transcription of 2!'3 gene

IL#7 2ene 2nterleu#in 3 gene. l&mphoc&tes ma#e 2!'3 a few hours after

the& are stimulated to help them proliferate and clonall& expand.

ranscription occurs due to the %inding of transcription factors

(N;A!, +-", Ap'C) to promoter region of the gene.


21/24

Production of 2!'3 gene results in production of 2!'3 receptor,

which 2!'3 c&to#ine can %ind to in autocrine'li#e wa& to induce cell proliferation, differentiation, and sur$i$al of cells into

effector cells.

IL#7 !;'s +A, +-", Ap'C. An&thing that %loc#s their production will

downregulate 2!'3 gene transcription.

Si2na" 3 Acti$ation of signal transduction cascade as descri%e in steps

a%o$e9 defined as %inding of /R to AP/ M/Npeptide complex

allows %e"" to .e%ome a%ti,ated/

C)7*0 Si2na" 7 /o'stimulator& molecule that is alwa&s present on surface of nai$e

cells allows %e"" sur,i,a"/

/3 %inds to "> molecule on AP/ and sends signals to induce cell acti$ation. /auses proliferation, differentiation, and sur$i$al

%& pro$iding signal for cell notto undergo negati$e selection andpromoting %etter 2!'3 transcription and translation.

-nown as 6signal 37, with signal C %eing the signal produced %&the /R %inding to the AP/ M/Npeptide complex.

Si2na" : Production of c&to#ines allows differentiation

B6/3C)*>0 B6/7EC)*

Molecule on surface of AP/ that interacts with /3costimulator& molecule on cell. 3 t&pes include ">.C and ">.3

(a#a /1 and /L).

B"R#s

C)38E73 Analogous to /0N/ for 'cells, these are co'receptor

molecules that %ind to M/'peptide complexes to facilitate 2AMin 2ga and 2g" complexes. /R3C is also #nown as /R3.

Lyn @R/ famil& &rosine #inase. Phosphor&lates 2AM of 2gaN2g"

after cross'lin#ing of co'receptor and "/R

C)= &rosine phosphatase which dephosphor&lates an inhi.itory

t&rosine residue, promoting phosphor&lation of 2AM. Dnceacti$ated with antigen, /0< changes from large form into smaller

form, /0


22/24

Si2na" 3 Antigen presentation to /01 on cell surface of " cell

C)=>0 Si2na" 7 /o'stimulator& molecule on surface of " cell that %inds to theth&mus'dependent antigen, internalizes /01'Ag complex,

processes protein into pieces, and re'presents protein on M/'

/lass 22 molecule on cell surface. 2f /0G cell has /R thatrecognizes the epitope, it will express /01 ligand. /01 ligand

%inds to /01 on " cell, which sends signals to induce " cell

proliferation, differentiation, and sur$i$al. Criti%a" se%ond

si2na"in2 step for B %e""sthat is re*uired for isot&pe switching,

germinal center formation, and " cell memor&.

/01 is also on cell surface of AP/ macrophages and dendriticcells, which allows cells to help them acti$ate %& expressing

/01 ligand. Allows AP/s to produce pro'inflammator&

c&to#ines such as +'a, 2!'C3, and 2!'C.

/01 is mem%er of tumer necrosis superfamil& (!N;

superfamil&). !rimeri-eswhen interacts with ligand, facilitatingsignal transduction %& the cell. Acti$ation of + superfamil&

causes acti$ation of +-" , inducing 2!'3 gene transcription.

AKES!A! TA-s (6ust another Kinases7) are found on the c&toplasmic tail

of [half'a'dimer proteins on a cell. hen c&to#ines successfull&

%ind to %oth half'dimers of and " receptors, the assem%led

whole 6dimeri-es7. his %rings t1o AKs ad+a%entto each otherso that the& can ac#'each other on (ie: phosphory"ateeach other).

hus acti$ated, S!A!s (transcription factors) can now in turn %e

phosphor&lated %& the acti$ated TA-s. hese S!A!sdimeri-e

and 2o to the nu%"eus 1here they promote 2ene eDpression/

APC's

)endriti% Ce""

Lan2erhan Ce""s 2mmature dendritic cell that li$es on the s#in

Ma%ropha2es

Ma%ropha2e A%ti,ation

Macrophage acti$ation is tightl& regulated %& hC cells. hC cells re*uire

cell'to'cell contact with macrophages to recognize pathogen, which is in

macrophage phagosome.

Macrophages re*uire two signals for acti$ation: I;N# from !@3 %e""s ,and %inding of /01 ligand onto /01 receptor. Dnce acti$ated,

macrophages undergo a num%er of changes to enhance their micro%icidal


23/24

acti$it&. he& produce /\/!3 and !N;#a, which attracts more

macrophages to site and allows diapedesis through endothelium.

2ncreased expression of ">, /01, M/ class 22 molecules, and +receptors signal latent cells and increase immune response.

Macrophages secrete IL#37, which increases production of C effectorcells and 2ro1th fa%tors IL#: and GM#CS;, which increase macrophage

production in %one marrow. Macrophage acti$ation is strongl& inhi.ited

%& IL#3> and !G;#?(produced %& !re2cells).

2n diseases such as tu%erculosis, ma& produce 2ranu"oma(mass of

macrophages surrounded %& hC cells) due to ina%ilit& of macrophages to

#ill antigen. hC cells continue to get recruited to site, producing largeanatomical lesion.

Others

S3P @phingosine'C'phosphate9 molecule floating around !&mph +ode whichma& %ind to cell, if @CP receptor present. 2f @CP receptor +D present,

the cell will sta& in l&mph node. rug that %loc#s @CP receptor isimmune suppressor drug.

A)CC Anti%od&'dependent /ell /&totoxicit&. +- /ells ha$e cVR andeosinophils ha$e cQR (receptors). Anti%odies (2g5 and 2gE) %ind to

antigen, and now the +- G Eosinophil cells can %ind to these receptors

and cross'lin# for u%er'#illing potentialK A%'dependent, /ell'/&totoxicit&

ALPS: Autoimmune l&mphatic proliferati$e disease. amaged asNas! results in

alps.

AI) Auto'2mmune /&tosine eaminase. /R22/A! enz&me for @omatic

&permutationK

AIR4 Auto'2mmuneRE is expressed in the th&mus. Allows the production of

short strips of peptides from areas that 'cells would not otherwise %e a%le

to sample (ie: insulin).

BM! "one'Marrow ransplant. as %etter outcome than chemo in leu#emia

#ids (.C and ">.3


24/24

P)3 !i#e /!A'0 ^ an inhi%itor& co'stimulator& molecule. "inds to PC'

!igand. 22M motif.

AKES!A! TA-s (6ust another Kinases7) are found on the c&toplasmic tail of [half'

a'dimer proteins on a cell. hen c&to#ines successfull& %ind to %oth half'

dimers of and " receptors, the assem%led whole 6dimeri-es7. his%rings t1o AKs ad+a%entto each other so that the& can ac#'each other

on (ie: phosphory"ateeach other). hus acti$ated, S!A!s (transcription

factors) can now in turn %e phosphor&lated %& the acti$ated TA-s. hese

S!A!sdimeri-e and 2o to the nu%"eus 1here they promote 2ene

eDpression/

KIR mo"e%u"es 2nhi%itor& receptors on +- /ells.

;%RIIB c'Receptor found on " cells that %inds to anti%od& stems, %ut then

;inhi%its; the "'cells acti$ation than#s to its 22M motifs.

;oDP: +aO$e 'cells in the presence of 5'J can express oxP8. @eparate from

that fact, some /0G cells in the th&mus during de$elopment also expressoxP8 (_

my immune glossary

Documents