immune system (ii)

THE IMMUNE SYSTEM (II)

OVERVIEW

A) DEFENCE AGAINST MICROBIAL INVASION

B) FOUR FEATURES OF THE IMMUNE SYSTEM

C) HUMORAL IMMUNITYD) CELL-MEDIATED IMMUNITYE) DISORDERS OF THE IMMUNE SYSTEMF) TYPES OF IMMUNITYG) BLOOD GROUPS and THE RHESUS

FACTORH) ANTIBIOTICS

DEFENCE MECHANISMS

SPECIFIC ACQUIRED/ ADAPTIVE IMMUNITY

Third Line of Defence1.Humoral Immunity

2.Cell-Mediated Immunity

CELL-MEDIATED IMMUNITY:is directed against any factor that

changes a normal cell into

an abnormal cell.

Fig. 19 T lymphocyte activation by cell surface antigen. Binding requires the

presence of both foreign and normal (self) antigens.

small peptide molecules with various functions

Lymphokines:

each type of T cell produces a different type of lymphokine

T cells attack:-

1) cells infected by microorganisms, most commonly a virus

2) transplanted organs and tissues

3) cancer-causing cells

• T cells do not release antibodies

• the whole cell is involved in the attack

T cells arise from:

precursor cells in the bone marrow

Stem cells of the bone marrow mature in the thymus gland

Immature T cells turn either into a

cytotoxic cell, helper cell or a suppressor cell

Once mature, where do T cells go?

T cells: stay in the blood

migrate to:

1. the tissue fluid2. lymph nodes3. other organs

e.g. spleen

Stem cells develop into thymocytes inside the thymus

at this stage any cells that recognise ‘self’ are destroyed

Why is this important?

So that the body does not attack itself

So that the body does not attack itself

T-cell receptors are : glycoproteins identical on a surface (about 105)

Variable and constant regions in both receptor types

T-cell receptors: recognise antigens only if they are

combined with self antigens

T-cell receptors: recognise antigens only if they are

combined with self antigens

self antigens : are glycoproteins produced

by a group of genes called the major histocompatibility complex (MHC)

These proteins are called MHC proteinsare present on the surfaces of most vertebrate cells

Three types of MHC proteins

B ody cells M acrophagesB cellsT cells

M HC I M HC II

P roteins ofcom plem ent

M HC III

Role of MHC in T cell function

the genes encoding the MHC proteins are highly polymorphic (have many forms), so that very few individuals in a population possess the same set of alleles

MHC proteins on the tissue cells serve as self markers that enable the individual’s immune system to distinguish its cells from foreign cells, an ability called self-versus-nonself recognition

What happens to lymphocytes that bind

self-MHC?

Killed!! Otherwise they attack

the body

Antibodies bind to

an intact antigen

T cell receptors bind to a piece of the antigen

displayed on the surface of an antigen-presenting cell

T cell receptors bind to a piece of the antigen

displayed on the surface of an antigen-presenting cell

Antibodies & T cell receptors bind differently:

Macrophages are antigen-

presenting cells.

Three types of T cells

1. Helper T cell

2. Cytotoxic T cell / Killer cell 3. Suppressor T cell

Types of T cells Function

Helper T cell (TH or TH-CD4) [CD4 is a surface protein]

[CD = cluster of differentiation]

Commander of the immune response.

Help B cells differentiate into antibody-secreting plasma cells by secreting lymphokines.

The HIV virus that causes AIDS preferentially infects and destroys TH cells.

Types of T cells FunctionHelper T cell (TH or TH-CD4)

Commander of the immune response

Help B cells differentiate into antibody-secreting plasma cells by secreting lymphokines.


Helper T cell (TH or TH-CD4)

The HIV virus that causes AIDS preferentially infects and destroys TH cells.

Types of T cells FunctionKiller cell or cytotoxic cell (TC or TC-CD8)

Kill tumour cells, body cells infected with viruses and transplanted tissue.


Killer cell or cytotoxic cell (TC or TC-CD8)

Recruited by helper T cells.

Kill by a pore-forming molecule called perforin and enzymes.

These enzymes enter the cell through the perforin channels and induce the cell to commit suicide. [see next slide]

Cytotoxic T Cells Lyse Infected Cells

Natural killer cell

Perforin Granzyme

Cancercell is killed

NK cells & TC Cells Lyse Infected Cells using perforin & granzymes

Cytotoxic T cellBUT they

recognise infected cells in a different

way…….

Natural killer cells kill cells:

Cytotoxic T cells kill cells:

possessing low levels of MHC class I

molecules

possessing antigenic fragments bound to

MHC class I molecules

Types of T cells

Function

Suppressor T cell

Dampens the activity of T and B cells, scaling back the defence after the infection has been checked.

Summary of the main stages of

the cell-mediated and

humoral immune

responses.

[dendritic cell =

antigen presenting cell]

What happens when T cells are activated by contact with a specific antigenic determinant?

The cytotoxic T cell proliferates

[clonal expansion]

to produce

1.memory T cells

2.active cytotoxic T cells

OVERVIEW





Two disorders of the immune system:

Juvenile diabetes: an autoimmune disease

Juvenile diabetes: an autoimmune disease

AIDS : Helper T cell destruction

AIDS : Helper T cell destruction

Autoimmune diseases are produced as the immune system fails to:

This failure results in TWO things:

This failure results in TWO things:

recognise & tolerate self antigens

1. activation of T cells

1. activation of T cells

2. production of autoantibodies by B cells = inflammation + organ damage

2. production of autoantibodies by B cells = inflammation + organ damage

Are autoimmune diseases common?

• there are over 40 known or suspected autoimmune diseases

• affect 5% - 7% of the population

PSORIASIS

AIDS:Stands for :Acquired Immune Deficiency Syndrome

Caused by: a retrovirus –Human Immunodeficiency Virus (HIV)

AIDS is a Pandemic disease

Pandemic: distributed worldwide and affects many people

Why does the HIV attack helper T cells?

Recognises the CD4

receptors associated with these

cells

The course of an HIV infection

When is a person considered to have AIDS?

When the TH cell level has dropped significantly

Immunosuppression results in an increase in:

opportunistic infectionscancers

AIDS The HIV virus does not kill it cripples the immune

system

Common diseases that the immune system normally could defeat become life-threatening

Can show no effects for several months all the way up to 10 years

The progression of the disease can be slowed down by:

Targeting viral

enzymes

Protease:

to complete viral proteins

Reverse transcriptase:

-catalyzes synthesis of DNA from viral RNA

-lacks proofreading function, which leads to a pool of mutant viruses

Why is it difficult to develop a vaccine?

It is customary to give a cocktail of drugs rather

than one drug at a time to an AIDS patient. Why ?

More chance to keep virus under control. If a viral enzyme has changed shape, at least virus is prevented from reproducing by another drug.

Question: [MAY, 2006]

Use your knowledge of biology to explain the following:

Despite great progress and advances in medical research, no drug able to effectively destroy the HIV virus has as yet been produced.

[5 marks]

OVERVIEW





Two types of acquired immunity:

AcquiredImmunity

Immunity

Activeantigens received

Passiveantibodies received

NaturalNatural activee.g. fighting infection,rejecting transplant

Natural passivefrom mother via milk or placenta

ArtificialArtificial activevaccination (injection of antigens)

Artificial passiveinjection of antibodies

providing immunity artificially

Immunisation / Vaccination :-

Immunisation Immunisation :-

• Whole live microorganism

• Dead microorganism

• Attenuated (harmless) microorganism

• Toxoid (harmless form of toxin)

A preparation containing antigenic material:

What is the source of antibodies that are used in artificial passive immunity?

1. Horse is injected with antigen.

2. Blood is taken from the horse & serum is obtained.

3. Person is injected with the horse serum that contains antibodies.

MAY 2005 Paper2

Why do immunologists use horses, as opposed to other possible choices of animal, during the production of anti-venom? (2)

Since the horse is large, a lot of blood can be removed from it. Thus a large volume of serum can be extracted.

Why are patients being treated for snake bite given a small dose of anti-venom prior to administration of the full dose?

To check for possible allergic reactions.

How long does active immunity last?• It depends on the antigen

• Some disease-causing bacteria multiply into new forms that the body does not recognise, requiring annual vaccinations, like the flu shot

• Booster shot - reminds the immune system of the antigen

How long does active immunity last?

May last for a lifetime

e.g. chicken pox


A patient cannot be vaccinated if he or she had been taking immunosuppressive medication within the previous two months.

[5 marks]

Answer to Question: [MAY, 2003]

Vaccines rely on production of primary immune response. Antigenic molecules are injected.Individual responds by producing a primary immune response.Immunosuppressive drugs prevent responses by immune system.Especially dangerous if live attenuated forms are injected since recipient cannot respond to defend himself.


Use your knowledge of biology to explain the following statement:

lactation is important for passive immunity;

[5 marks]

lactation is important for passive immunity;

[5 marks]

OVERVIEW





• A person’s blood type is determined by antigens found on surface of red blood cells

Blood Groups

• the most important systems include: ABO Rh (rhesus) MNSKellLewisDuffy Kidd

More than 30 Blood Grouping Systems

in syllabus

ABO system ABO blood types = Types A, B, AB and O Rh factor = Rh positive and Rh negative

the immune system: is tolerant of its own RBC antigens

makes antibodies that bind to those that differ

BUT

Antigens [agglutinogens]: are glycoproteins or

glycolipids

ABO systemAntibodies

[agglutinins]:

specific against blood group antigen

A- antigen

b- antibody

ABO System: four types of blood groups

http://bioweb.wku.edu/courses/BIOL115/wyatt/Genetics/Alleles/images/memb_protein_B.gif

http://bioweb.wku.edu/courses/BIOL115/wyatt/Genetics/Alleles/images/memb_protein_AB.gif

http://bioweb.wku.edu/courses/BIOL115/wyatt/Genetics/Alleles/images/memb_protein_O.gif

Antigen (agglutinogen)

on RBC membrane

Agglutinin(antibody)in plasma

Blood group

A b AB a B

AB nil ABnil ab O

45%

40%

11%

4%

UNIVERSAL DONORS

-blood group O persons

-can donate blood to anybody

UNIVERSAL RECIPIENTS

-blood group AB persons

-can receive blood from anybody

Blood Transfusion

In a transfusion, blood MUST In a transfusion, blood MUST be compatible. be compatible. WHY?

Otherwise, an antigen-antibody reaction

occurs.

Donor’s antigens match

Recipient’s antibodies

Agglutination

For blood to agglutinate:

A

a

RecipientDonor

Oa+b

Ab

Ba

ABo

Oa+b - - - -Ab + - + -Ba + + - -

ABo + + + -

Key - no agglutination + agglutination

Donor (no antigen) Recipient NO

Agglutination

a b

RecipientDonor

Oa+b

Ab

Ba

ABo

Oa+b - - - -Ab + - + -Ba + + - -

ABo + + + -


DonorRecipient

Agglutination

A

a b

RecipientDonor

Oa+b

Ab

Ba

ABo

Oa+b - - - -Ab + - + -Ba + + - -

ABo + + + -


DonorRecipient NO

Agglutination

b

A

RecipientDonor

Oa+b

Ab

Ba

ABo

Oa+b - - - -Ab + - + -Ba + + - -

ABo + + + -


DonorRecipient

Agglutination

Aa

RecipientDonor

Oa+b

Ab

Ba

ABo

Oa+b - - - -Ab + - + -Ba + + - -

ABo + + + -


DonorRecipient

(no antibody) NO Agglutination

The Rhesus (Rh) Factor

Rh+

85% of the total population:

15% of the total population:

Rh-

[Rh antigens absent]

[Rh antigens present: agglutinogen D])

Why called ‘Rhesus factor?

The Rhesus factor gets its name from its having first been detected in the blood of the rhesus

monkey

Rh Dangers During Pregnancy

Rh- mother with a

Rh+ foetus

What is the probability of a child to be Rh+?

i) Father is rhesus positive (heterozygous) and mother rhesus negative?

Rhesus negative: Rh- Rh-

Rhesus positive: Rh+ Rh-

Parents: Rh+ Rh- X Rh- Rh-

Gametes: Rh+ Rh- X Rh-

F1 genotype: Rh+ Rh- Rh- Rh-

50%

What is the probability of a child to be Rh+?

ii) Father is rhesus positive (homozygous) and mother rhesus negative?

Rhesus negative: Rh- Rh-

Rhesus positive: Rh+ Rh+

Parents: Rh+ Rh+ X Rh- Rh-

Gametes: Rh+ X Rh-

F1 genotype: Rh+ Rh-

100%


Mother’s blood

Foetus’s blood

Risk

Positive Positive Positive Negative Negative Negative

Negative PositiveFirst child All other children

Can RBC from foetus cross the placenta?

These RBC stimulate antibody

production in mother…….

YESYES

(antibody: anti-D)

After Protection with anti-D: injection is given within 72 h of giving birth

Lymphocytes cannot ‘see’ RBC from foetus

Anti-D (antibody against rhesus antigen)

B cell

PlacentaRBC cells in

foetus


Rh- woman with Rh+ foetus

Cells from Rh+ foetus

enter mother

Woman produces antibodies against Rh+

cells

In the next Rh+

pregnancy, antibodies

attack foetal RBC

How Rh sensitization occurs

A Rhesus Baby is usually:

premature anaemic jaundiced Haemolytic disease of

the newborn

Surfaceantigens

Opposingantibodies Agglutination (clumping) and haemolysis+

Phototherapy to treat jaundice Jaundice occurs when there is a build-up of bilirubin in

the blood. Bilirubin is an orange/red pigment produced by the

breakdown of red blood cells. As bilirubin begins to build up, it deposits on the fatty

tissue under the skin causing the baby's skin and whites of the baby's eyes to appear yellow.

Blood of such a baby needs to be

completely replaced by a transfusion of

healthy blood.

OVERVIEW





Antibiotics:• compounds produced by a microbe

• inhibit the growth of other microbes

Sir Alexander Fleming (1955)

Penicillium

Antibiotics can harm the bodyWeaken the immune system as they suppress the body’s natural defence system Destroy the

beneficial flora in the gut

Antibiotics are effective against:

BUT NOT EFFECTIVE BUT NOT EFFECTIVE AGAINST:AGAINST: VirusesViruses

BacteriaSome fungi BacteriaSome fungi

Use your knowledge of biological processes to comment on the following scenario:

Medical practitioners sometimes prescribe antibiotics when a person is affected by a viral cold.

[MAY, 2003]

Antibiotics deal with secondary infections (opportunistic

infections) - infections that occur because of a weakened immune

system.

Question: [MAY, 2003]Use your knowledge of biological processes to comment on the following scenario:

Medical authorities often recommend that prescription of antibiotics should be carried out sparingly.Bacteria have high reproductive rates and short generation timeAntibiotics effective against normal bacteriaEmergence of mutant forms resistant to antibioticsSelection pressure through antibiotic use favours rapid increase in numbers of resistant formsEmergence of disease forms with no cure

[5 marks]

Antibiotics are not equally effective against all bacteria:

An antibiotic will affect only those bacteria

which have a particular property in common

e.g. penicillin - kills only Gram positive bacteria

WHY?

Inhibits formation of peptidoglycan walls. G+ bacteria have a thick

peptidoglycan wall.

Inhibits formation of peptidoglycan walls. G+ bacteria have a thick

peptidoglycan wall.

Gram positiveGram positive Gram negativeGram negative

BROAD SPECTRUM ANTIBIOTICS:

Affect a wide range of microbes

BROAD SPECTRUM ANTIBIOTICS:

Affect a wide range of microbes

NARROW SPECTRUM ANTIBIOTICS:

Affect a few species

NARROW SPECTRUM ANTIBIOTICS:

Affect a few species

Antibiotics can be:BACTERIOSTATIC

inhibit the growth and multiplication of

microbes

BACTERIOSTATICinhibit the growth and

multiplication of microbes

BACTERICIDAL kill microbes, like penicillin

BACTERICIDAL kill microbes, like penicillin

Question

There are two main types of immune response. These are labelled Type 1 and Type 2 in the diagram below:

i) Name response types 1 and 2. [2]

Type 1: Type 2:

ii) Name the cells X and Y. [2]

X: Y: B cell T cell

Humoral responseCell mediated response

iii) Where in the body are the stem cells shown in the diagram produced? [1]

iv) Plasma cells in the type 1 response secrete antibodies. Name the other type of cell (C) in this system and describe its function. [2]

Cell name:

Bone marrow

Memory cell

Function: Brings about fast production of antibodies in the secondary response.

Helper T cell, cytotoxic T cell and suppressor T cell

iv) Name the three types of differentiated cell (D, E and F) in the type 2 response. [2]

vi) Describe the function of one of the cell types you named in part (v). [1]

• Helper T cell: commander of the immune response

• Cytotoxic T cell: kills cancer cells, body cells infected with viruses and transplanted tissues

• Suppressor T cell: Dampens the activity of T and B cells, scaling back the defence after the infection has been checked

Essay: Compare and contrast humoral and cell mediated immunity.

Introduction:

Definition of immunity

Both humoral and cell mediated immunity defend body once barriers are penetrated

Body:•Part of the 3rd line of defence; specific acquired immunity •What each defends the body against•Brought about by lymphocytes – B and T: where made and where they mature; both are destroyed if they recognise self as nonself

Essay: Compare and contrast humoral and cell mediated immunity.

B and T cells:

look alike;

release different chemicals – B cells = antibodies and T cells = lymphokines;

3 types of T cell but 1 type of B cell

• Both types of lymphocyte have receptors on surface:

thousands of receptors on surface all receptors are alike specific receptors: variable region diversity of receptors they are made before the cell ever encounters an

antigen both receptors are encoded by genes assembled by

the recombination of segments of DNA• Both types of lymphocyte have MHCII markers

• Receptors differ in:

their structure the genes that encode them what they recognise – whole antigens = B cells ,

T cells = antigen fragments bound to MHC

• Both types of immunity involve memory cells: the need of helper T cells to stimulate B cells to

proliferate secondary response

• Both distinguish self from non-self: autoimmune disease

Conclusion:

Although humoral and cell mediated immunity differ in many ways, they share four features: specificity, diversity, ability to distinguish self from non-self and immunological memory which enable an organism to survive attacks by pathogens.

THE END

immune system (ii)

Documents

cell t cell receptors

type of t cell

suppressor t cell

t cells attack

cancercausing cells

cytotoxic t cell killer

helper cell

cytotoxic cell