Immunogenetics

Front 1

Immunogenetics

Back 1

Study of genetic basis of immunity

Front 2

Immune Response and Immunity

Back 2

Such response = immune response

Protection provided = immunity

Front 3

Body defense mechanisms

Back 3

Front 4

Innate immunity

Back 4

Anatomical barriers - Skin & mucous membranes, Acidity of stomach
Washing affect of Tears, Saliva, mucous secretion entraps foreign microorganisms (Lysozymes destroy bacterial cell wall)
Cilia propels mucous entraped microorganisms.

Front 5

Innate immunity - after enter the body

Back 5

Phagocytose - kill, and digest whole organisms.

- Blood monocytes,
- Neutrophils and
- Tissue macrophages

Front 6

Phagocytosis diagram

Back 6

1. Pathogens entering the wound.
2. Blood clotting
3. White blood cells enter the injured space
4. phagocytosis

Front 7

Phagocytic Cells

Back 7

Monocytes, neutrophils (white blood cells) and tissue macrophages (monocytes differentiate into macrophages)

- Internalization of whole micoorganism and formation of phagosomes.
- Fusion of phagosomes with lysosome
- Digestion of microorganism by lysosomal enzymes

Front 8

Phagocytosis process

Back 8

Front 9

difference between pathogens and antigens

Back 9

A pathogen is any organism capable of producing disease.

An antigen refers to the protein on the surface of a cell (bacterium, fungus or virus) that our bodies recognize as a foreign substance and triggers the immune system into producing antibodies specific to that antigen. This means that if in the future the same antigen is again introduced, our immune system will recognize, remember and produce the right antibodies to "deal" with the intruders.

Pathogens have antigens on their surface.

Front 10

How do lysosomes destroy microbes?

Back 10

Front 11

Lymphocytes (specialized white blood cells)

Back 11

originate in the bone marrow stem cells - migrate to Thymus and become T lymphocytes (T cells)
some remained in Bone marrow and become B lymphocytes
- mature into plasma cells
- Produce large quantities of antibody

Front 12

Lymphocyte classes

Back 12

Front 13

Lymphocytes show specificity

Back 13

T and B lymphocytes recognize and respond to particular microbes and foreign molecules - specificity

Front 14

immunogen

Back 14

A foreign molecule that elicits a specific response by lymphocytes is called an immunogen

Front 15

antigen

Back 15

A foreign molecule that binds specifically to an antibody, a B cell or a T cell receptor.

Front 16

Cell mediated inmmunity

Back 16

Development of various T cells after stimulation of antigen
- cytotoxic T cells, secrete toxic substances, responsible for the death of virus-infected and foreign cells.
- helper T cells, secrete growth factors (cytokines), help the action of B cells and other T cells

- T cells giving rise to lymphokines, soluble factors, enhance destructive action of other white cells e.g. macrophages

Front 17

Humoral Immunity

Back 17

B-lymphocytes produce Immunoglobulin (=antibodies).
- mature to plasma cell
- produce antibodies
- triggered by the presence of antigen
Antigens may be infinite
- viruses,bacteria,foreign molecules of any kind, blood cells from other animals

Front 18

foreign substance initiates

Back 18

- antibody produced against it is directed against specific structure on the surface of the cell or particle (surface antigen)

Front 19

when the animal is attacked by the same antigen

Back 19

- antibody binds with the antigen
- forms antigen-antibody complex

result :
a) agglutination (clumps of inactivated cells)
b) precipitation (clumping of soluble antigen)
c) cell death (series of reactions leading to cell lysis)

The protection arising from the production of antibodies is called humoral immunity.

Front 20

Antibodies

Back 20

attach to surface of B-cells or in blood plasma called immunoglobulins (IG)

A basic antibody molecule consists of
- 4 chains of AA: 2 identical light (L) chains and 2 identical heavy (H) chains

Each chain consists of a variable (V) region and a constant (C) region

Variable region differs from one antibody to the next.

Front 21

Antibodies diagram

Back 21

Front 22

Antibodies properties

Back 22

Being polypeptides – antibodies are the products of genes.

L- and H- chains – produced from different clusters of genes

Each different antibody – produced by a different clone of B lymphocytes

Binding of antigens to antibodies triggers immune respone

Front 23

Blood transfusion

Back 23

animals do not normally carry antibodies to red-blood-cell antigens (Red-cell antigens), unless they have been specifically challenged with appropriate foreign red blood cells.
Because of this – it is often assumed that blood transfusions in animals can be conducted safely with any available blood – and there is normally no need for blood typing before transfusion.

Front 24

Blood transfusion cross-match

Back 24

If untyped donors must be used – a simple cross-match should be conducted

Front 25

Transplant rejection

Back 25

Organ and tissue transplants and skin grafts
- usually rejected by the recipient.
Chance of rejection considerably reduced if the donor is a close relative of the recipient.
Obvious that there is genetic basis to transplant rejection.

Rejection is the result of an immune response determined by naturally occurring cell-surface antigens

Front 26

haplotype

Back 26

A haplotype is a collection of specific alleles (particular DNA sequences) in a cluster of tightly-linked genes on a chromosome that are likely to be inherited together

Front 27

What is MHC

Back 27

group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances

Both classes – surface antigens

Front 28

What does HTC do?

Back 28

Ok, so when there is a pathogen (foreign particle) in your body, the first cells to act are the phagocytic cells (macrophages, neutrpphils...). They engulf the pathogen and partially digest it, then present part of the pathogen on the surface of their cell with the MHCII complex. Another cell, the helper T cell, can now recognize the presentation to activate the cytotoxic T cells. The cytotoxic T cells then destroy any other remaining pathogens. Another way for a pathogen to be recognized is by the B cells, which have antibodies on their surface to recognize the pathogen, then they take the pathogen in and digest it, and present a portion of the antigen on their MHCII complex for the helper T cells to recognize. The helper T cell can then stimulate the B cell to make an increased amount of antibodies to kill the remaining pathogen. All nucleated cells in the body have a MHCI complex on their surface. This is how the body can recognize 'self' from 'nonself' cells. Another cell called the natural killer cell will destroy any cell that has a missing or abnormal MHCI complex

Front 29

Major Histocompatibility Complex

Back 29

Many loci whose gene products play a role in compatibility between tissues (histocompatibility).

One group of tightly-linked loci play much more important role than others
Because of its major role – these loci are major histocompatibility complex (MHC)

MHC in mammals
- includes many genes
- 3 regions

Front 30

MHC Diagram

Back 30

Front 31

Class I region

MHC Class I

Back 31

Contains many genes, each of which codes for a polypeptide which combines with another polypeptide β2-microglobulin (Transport to cell surface)

Class I histoglobulin

expressed on almost all nucleated cells

Tells immune cells that its not a foreign body (self cells)

Front 32

MHC Class I diagram

Back 32

Front 33

MHC Class I Pathway

Back 33

Front 34

Class II region

MHC Class II

Back 34

Contains genes that encode 2 types of polypeptide (α and β chains) which unite to form a class II histoglobulin

limited distribution – mainly on lymphocytes, macrophages, and dendritic cells

Front 35

MHC Class II diagram

Back 35

Front 36

MHC Class I Pathway

Back 36

Front 37

class I and class II MHC Pathways

Back 37

Front 38

Class III region

Back 38

contains a mixture of genes having a wide range of functions only some of which involve in immune response

Front 39

Determining phenotype and genotype at the MHC

Back 39

To determine the role of MHC in immunity to disease
Need to
-identify the types of histoglobulin present in the individual
-determine the potential difference of histoglobulins between donor and recipient

Front 40

Determining phenotype and genotype at MHC Methods

Back 40

1. Tissue typing
- use of sera containing polyclonal antibodies which distinguish between histoglobulins
- it identifies the phenotype (tissue type) of corresponding allele

2. Molecular technology
- genotypes can be determined directly (nucleotide sequence)
- almost all different alleles – occurs on exons 2 and 3 in Class I MHC
- Exon 2 in Class II MHC
- identification by RFLP (restrication fragment length polymorphism)

Front 41

MHC polymorphism

Back 41

Many alleles at most loci

The chance of choosing any two individuals having the same set of MHC alleles – exceedingly small
This is the reason for difficulty to find suitable donor for tissue transplant
crossing-over of MHC genes – very rare due to closeness of their locations