14 - Class Switching And Generation Of Diversity And Memory

Question 1

Light and heavy chain structure in antibodies at domain level

Answer 1

• they are composed of repeating Ig domains
• N-terminal domains of both chains are called variable (V) domains
• the remaining domains are constant (C) domains

Question 2

Antigen binding site structure

Answer 2

Made from VL and VH domain interactions

Question 3

How do heavy chain structures of IgM differ

Answer 3

• H chains have a CH4 domains
• multiple disulphide bonds, and H chains heavily N-glycosylated
• contain N-glycans - complex carbohydrates
• N-glycans are large, so hold domains apart
• allow exposure of functional motifs (e.g. complement binding sites)

Question 4

How heavy chain structures differ considerably: IgG

Answer 4

Different domains have different functions:
Cy1, Cy2: bind complement components
Cy2, Cy3: bind Fc receptors on neutrophils
Cy3: binds Fc receptor on macrophages and NK

Question 5

Heavy chain structures differ: IgE

Answer 5

• Multiple N-glycans make this a stiff rigid molecule
• good for targeting large pathogens
• but cannot cross-link small targets

Question 6

IgA differences in heavy chain

Answer 6

• IgA is very flexible
• good cross-linker
• valency = 4

Question 7

Class switching

Answer 7

…

Question 8

Clonal expansion theory recap

Answer 8

• antigen activates only those lymphocytes already committed to respond to it
• lymphocyte committed to an antigen displays cell surface receptors that specifically recognise antigen
• even if antigen has never been encountered before
• T- cell receptors and B-cell receptors are membrane-bound antibodies
• millions of different clones of lymphocytes in human immune system
• before encountering antigen, only a few of each clone are present
• when encounter antigen to which are committed to, lymphocytes undergo clonal expansion and differentiation

Question 9

Clonal selection and Clonal expansion and Clonal deletion recap

Answer 9

Clonal selection:
- following infection, individual clones selected by antigen
- based on how well antigen and receptor fit together
- result is pathogen-specific lymphocytes are selected from pools of B and T cells

Clonal expansion:
- selected clones undergo mitosis, proliferate and differentiate into effector cells

Clonal deletion:
- lymphocytes that react inappropriately with ‘self’ antigens are destroyed

Question 10

How does diversity in lymphocytes, B and T cells, arise in cells - recap

Answer 10

• antigen activates only the lymphocytes already committed to respond to it
• so there is pre-existing diversity built into adaptive immune system

How this occurs:
- antigen-specific receptors (TCR and membrane bound antibodies for T and B cells respectively) are encoded by unusual segmented genes

• these genes assembled from a series of gene segments by an unusual form of recombination
• called somatic gene recombination
• somatic gene recombination used for class switching
• though, a slight change leads to massive pre-existing diversity

Question 11

Generation of primary antibody diversity