12 - B cell Mediated Immunity

Question 1

What do forms do antibodies exist in

Answer 1

1. Membrane-bound antibodies on the surface of B lymphocytes function as antigen receptors
2. Secreted antibodies neutralise toxins, prevent the entry and spread of pathogens, and eliminate microbes.

Question 2

3 hypervariable regions

Answer 2

• Three hypervariable regions of a Variable light domain and the three hypervariable regions of a Variable heavy domain are brought together to create an antigen-binding surface
• Also called complementarity-determining regions (CDRs): CDR1, CDR2, CDR3 (most extensive contact is with CDR#)

Question 3

Dissociation constant (Kd)

Answer 3

Represents affinity of antibody

Question 4

Main antibody functions

Answer 4

• Neutralisation of microbes and toxins
• Opsonisation and phagocytosis of microbes
• ADCC
• Phagocytosis of microbes opsonised with complement fragments
• Inflammation (through complement activation)
• Lysis of microves (through complement activation)

Question 5

Antibody responses in lymphoid tissues

Answer 5

• Develop under direction of Tfh cells
• Antigen is retained for long periods in these complexes as iccosomes

Question 6

What do activated B cells that undergo rounds of mutation and selection for higher affinity mutants in the germinal centre result in

Answer 6

High- affinity antibody-secreting plasma cells and high-affinity memory B cells

Question 7

Half-life of IgE

Answer 7

• Very short (~2 days)
• Although cell-bound IgE associated with the high-affinity IgE receptor on mast cells has a very long half-life

Question 8

Half life of IgA

Answer 8

~ 3 days

Question 9

Half life of IgM

Answer 9

~ 4 days

Question 10

Half life of IgG

Answer 10

21-28 days

Question 11

B cell proliferation and differentiation outcomes

Answer 11

• Antibody secretion
• Isotope switching
• Affinity maturation
• Memory B cell

Question 12

Distributions and functions of immunoglobulin classes

Answer 12

• Antibodies of different classes operate in distinct places and have distinct effector functions.
• Transport proteins that bind to the Fc regions of antibodies carry particular isotypes across epithelial barriers.
• Antibodies can block adherence of bacteria to host cells
• Antibody:antigen complexes activate the classical pathway of complement by binding to C1q.
• Complement receptors are important in the removal of immune complexes from the circulation.

Question 13

High-affinity IgG and IgA

Answer 13

• Can neutralise bacterial toxins.
• Can inhibit the infectivity of viruses.

Question 14

Structure of IgM and IgA

Answer 14

• Can form multimers, in association with an additional polypeptide chain, the J chain
• IgA is dimeric and IgM is pentameric

Question 15

IgG function

Answer 15

• Opsonisation of antigens for phagocytosis by macrophages and neutrophils
• Activation of classical pathway
• ADCC
• Transfer of antibody across placenta and gut

Question 16

IgM function

Answer 16

Activation of classical pathway and antigen receptor of naive B lymphocytes

Question 17

IgA function

Answer 17

Mucosal immunity

Question 18

IgE function

Answer 18

Mast cell degranulation (immediate hypersensitivity reactions)

Question 19

IgD function

Answer 19

Antigen receptor of naive B lymphocytes

Question 20

Secretary dimeric IgA

Answer 20

Binds to the layer of mucous overlaying the gut epithelium and acts as an antigen-specific barrier to pathogens and toxins in the gut lumen

Question 21

Poly Ig receptor

Answer 21

Facilitates transport of dimeric IgA from the lamina proprietor, across the mucosal epithelium and into the lumen

Question 22

What is the dominance of IgA production by intestinal plasma cells due to

Answer 22

Due to selective induction of IgA isotype switching in B cells in GALT and mesenteric lymph nodes

Question 23

How do antibodies neutralise microbes and microbial toxins

Answer 23

• Blocks binding of microbe and infection of cell
• Blocks infection of adjacent cell
• Blocks binding of toxin to cellular receptor

Question 24

What is classical complement pathway initiated by

Answer 24

Binding of the complement protein C1 to IgG or IgM molecules that have bound antigen

Question 25

Which IgG antibodies are more efficient activators of complement

Answer 25

IgG3 and IgG1

Question 26

Form of antibodies that can initiate classical pathway activation

Answer 26

Only antibodies bound to antigens, not free circulating antibodies

Question 27

Do free Ig cross link Fc receptors

Answer 27

NOOOOOOOOOO

Question 28

Opsonisation

Answer 28

- Bacterium is coated with complement and IgG antibody - When C3b binds to CR1 and antibody binds to Fc receptor, bacteria are phagocytosed - Phagosome is formed - Lysosomes fuse with these vesicles, delivering enzymes that degrade the bacteria

Question 29

Neonatal Fc recetor

Answer 29

- Involved in the transport of IgG from the maternal circulation across the placental barrier as well as the transfer of maternal IgG across the intestine in neonates - Does this by recycling IgG to cell surface rather than destroying by lysosomes

Question 30

How are neonatal mammals protected from infection at birth

Answer 30

- Maternally produced antibodies transported across placenta (IgG) - Antibodies in ingested breast milk (IgA and IgG)

Question 31

Mast cell activation

Answer 31

Activated by cross-linking of FcεRI molecules, which occurs by binding of multivalent antigens to the IgE molecules that are attached to the Fc receptors

Question 32

Antibody Dependent Cellular Cytotoxicity (ADCC)

Answer 32

Natural killer (NK) cells and other leukocytes bind to antibody-coated cells by Fc receptors and destroy these cells

Question 33

NK cells and ADCC

Answer 33

- NK cells use their Fc receptor, FcγRIIIA, to bind to antibody-coated cells. - FcγRIIIA (CD16) is a low-affinity receptor that binds clustered IgG molecules displayed on cell surfaces but does not bind circulating monomeric IgG. - Therefore, ADCC occurs only when the target cell is coated with antibody molecules

Question 34

Immune complex removal

Answer 34

Immune complexes bind to CR1 on RBC, which transports them to the liver and spleen, where they are removed by macrophages expressing receptors for both Fc and bound C’

Question 35

Antibody isotope in primary vs secondary response

Answer 35

- Primary: IgM > IgG - Secondary: IgG predominates, and IgA or IgE depending on type of infection