immune system (ii)

THE IMMUNE SYSTEM (II)

The immune system does not design

antibodies or T-cell receptors expressly to bind invading antigens

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

PASSIVE MECHANISMS

ACTIVE MECHANISMS

First Line of Defence1.Skin

2.Mucous membranes

NON SPECIFIC INNATE IMMUNITY

SPECIFIC ACQUIRED IMMUNITY

Second Line of Defence1.Inflammation2.Complement Proteins3.Natural Killer Cells

Third Line of Defence1.Humoral Immunity2.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

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

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 proteins are present on the surfaces of most vertebrate

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

Difference between antibodies & T cell receptors :

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

AIDS : Helper T cell destruction

Autoimmune diseases are produced as the immune system fails to:

This failure results in TWO things:

recognise & tolerate self antigens

1. activation of T cells

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

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

Why is it difficult to develop a vaccine?

- lacks proofreading function

This leads to mutant viruses

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:

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 / 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

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

Antigen (agglutinogen)

on RBC membrane

Agglutinin(antibody)in plasma

Blood group

A b AB a B

AB nil ABnil ab O

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:

RecipientDonor