Lecture 14 Evolution of Antibodies

Question 1

BCR/Antibody Structure

Answer 1

Variable region with two binding sites which determine the ANTIGEN SPECIFICITY

Fvregion

Fc region –constant region which determines the CLASS of the antibody and thereby the FUNCTION

Question 2

Antibodies are made by B cells

Answer 2

• Start off as cells with the receptor on the surface of the cell (BCR).

-The receptor recognises whole antigen

-ANTIBODY can bind to whole pathogens and facilitate a range of functions –depending on its Fc region

-Differentiate into plasma cells that secrete the receptor as ANTIBODY

Question 3

Antibody is important because it

Answer 3

Neutralisestoxins and viruses by blocking their interaction with cells

Opsonises pathogens to promote phagocytosis and killing activity by other cells

Activates thecomplement cascade which helps kill pathogens

Agglutinatesparticles (pathogen debris, viruses etc)

Mediates Antibody dependent cell-mediated cytotoxicity (ADCC)

Question 4

How many different B cell receptors (Antibodies) do we need for diversity?

Answer 4

*Human genome is 3 billion base pairs
*Much DNA is intergenic
*The total estimated number of human genes is only 20,000-25,000
*Estimates of diversity in microbes are difficult, but tend to be in the order of half a million different species

Question 5

patter recognition problem

Answer 5

We can’t make enough pattern recognition receptors to deal with all pathogens, especially since many pathogens can evolve faster than us

Question 6

BCR/Antibody Structure

Answer 6

where is the

heavy chain

light chain

2 identical heavy chains and light chains

Question 7

Antibody variable region

Answer 7

Variable regions of the antibody are made up of two or three gene segments –VJ or VDJ depending on whether it is the light chain or the heavy chain

DNA—RNA—–PROTEIN

Question 8

what happens to our antibody repertoire as we grow older

Answer 8

As we grow older and are exposed to more antigens………………..then our antibody repertoire evolves to reflect the immune challenges it has seen

But another level of evolution is at the individual antibody level……called “Affinity Maturation”

SELECTION of the best
Somatic hypermutation
*DELIBERATE mutation of Ig genes

Question 9

what happens as B cells expand?

Answer 9

As B cells expand they mutate their Ig genes

The best ones are kept

Question 10

what is the germinal centre

Answer 10

A germinal centre in the spleen

In a Germinal Centre reaction:

*B cells divide and mutate their antibody genes
Then they die (no Bcl2)UNLESSThey can be rescued by T cells
*To get T cell help they need to show the T cell some processed antigen
*Antigen is in limiting supply
*So only the B cells with the highest affinity antibodies can win some antigen to give to the T cell and get the survival signa

Question 11

Changing the function of an antibody

Answer 11

Variable region with two binding sites which determine the ANTIGEN SPECIFICITY

Fc region –constant region which determines the ISOTYPE of the antibody and thereby the FUNCTION

Question 12

Classes and subclasses of Antibody

Answer 12

IgA
IgM
IgG- IgG1, IgG2, IgG3, IgG4
IgD
IgE

Question 13

“Second hand antibodies”

Answer 13

Already evolved to bind one target

Can take part in a reaction to another target, and further evolve.

Question 14

IgD

Answer 14

Membrane-bound form of Immunoglobulin on Naïve B cells (B cells early in development before they see antigen)

Question 15

IgM

Answer 15

*The default immunoglobulin that B cells start with in development.
*The Fc region enables the molecules to form pentamers –which is useful in forming immune complexes, but which means that the molecules are too large to diffuse into tissues or cross the placenta.
*Very efficient at activating complement through the classical activation pathway

Question 16

IgG

Answer 16

*IgG is the main antibody secreted into the blood after class switching.
*It is very good at opsonisation –coating pathogens so that phagocytic cells can recognise them.
*Pathogens coated in IgG also become targets for killing by Natural killer cells –antibody-dependent cellular cytotoxicity
*There are 4 subclasses of IgG (IgG1,IgG2 etc

Question 17

IgA

Answer 17

*Is the mucosal antibody –produced by B cells at mucosal surfaces and secreted into breast milk
*It is actively secreted across mucosal surfaces
*It can form a dimer, which helps protect it from enzymatic breakdown (such as occurs in the gut), but generally exists in monomeric form in the plasma
*There are two Subtypes (IgA1, IgA2)

Question 18

IgE

Answer 18

*IgEis important in parasitic infection.

*It binds to the surface of Mast cells via its Fc receptor –even in the absence of antigen
*Antigen cross-linking of IgEon Mast cells causes the mast cells to degranulate
*Usually low in concentration, but higher in cases of allergy –especially immediate hypersensitivity