Module 6: Humoral Response

Question 1

Describe the process of B cell activation (4 steps)

Answer 1

1) BCR stimulation by antigen binding results in NFkB and/or AP-1 activation
2) B cells mature and migrate to lymphoid organs to replicate
3) Some antigens can be presented on MHC II for CD4+ T cell recognition
4) Helper T cell signaling (cytokines and costimulators) allows for differentiation into plasma cells, memory cell production, and germinal center formation

Question 2

What are the 2 mechanisms where B cells can improve the antibodies secreted?

Answer 2

1) Somatic hypermutation
2) Class switching

Question 3

Explain the process of somatic hypermutation

Answer 3

1) Point-mutations are introduced into the V region of antibodies (heavy and light chains) which alter the affinity of the Ig for its antigen
2) B cells that can bind, process, and present more Ag to T follicular helper cells receive cytokine assistance and survive

Question 4

How does class switching occur?

Answer 4

Through DNA splicing of constant regions of the heavy chain, such that the constant region corresponding to a specific isotype remains

Question 5

What are the major differences in function between membrane-bound and secreted antibodies

Answer 5

1) Membrane-bound antibodies function as a receptor for antigens, such that stimulation results in activation of naive B cells and initiation of humoral response
2) Secreted antibodies reside in circulation, tissues, and mucosal sites to neutralize toxins, prevent entry and spread, and eliminate microbes

Question 6

What are the 6 main functions of antibodies?

Answer 6

1) Neutralization
2) Complement activation
3) Opsonization (phagocytosis)
4) ADCC (mediated by NKCs)
5) ADD (parasite expulsion)
6) Agglutination

Question 7

Describe the antibody structure

Answer 7

1) 2 heavy and 2 light chains joined by disulfide bonds, both composed of amino variable (V) region and carboxyl constant (C) region
2) 2 types of light chains: kappa or lambda
3) Variable region of heavy chain contains V, D, J, while the variable region of light chain contains V, J segments

Question 8

What do the heavy chain C regions serve as?

Answer 8

1) Determinant of isotype
2) Mediators of effector functions (binds to Fc receptors, complement, etc.)

Question 9

How do antibodies switch from membrane-bound to secreted form?

Answer 9

Through mRNA splicing

Question 10

Describe the structure and function of IgM

Answer 10

1) Pentameric, no hinge but extra H constant domain, J chain
2) First Ab produced in a primary response
3) Low affinity, high avidity
4) Complement, form dense Ab-pathogen complexes

Question 11

What are the 2 forms of heavy chains?

Answer 11

1) Membrane-bound form of antibody has heavy chains with a C-terminal transmembrane and cytoplasmic portion
2) Secreted forms lack the C-terminal transmembrane segment

Question 12

Describe the structure and function of IgG

Answer 12

1) Monomer, hinge region
2) 4 subclasses (IgG1-4)
3) Bind Fc receptors for enhanced phagocytosis (opsonin), complement

Question 13

Describe the structure and function of IgA

Answer 13

1) Can be monomer or dimer, hinge region, J chain
2) 2 subclasses (IgA1-2)
3) Major isotype in secretions
4) Neutralization

Question 14

Describe the structure and function of IgE

Answer 14

1) Monomer, no hinge but extra H constant domain
2) Major role in allergy, protection against parasites
3) Degranulation by Fc-binding on eosinophils/basophils/mast cells

Question 15

Describe the structure and function of IgD

Answer 15

1) Monomer, hinge region
2) Present on mature B cells along with IgM
3) Function unknown

Question 16

What is affinity?

Answer 16

Strength of all non-covalent interactions between a single antigen binding site and a single epitope (dictated by Ag/Ab fit)

Question 17

What is avidity?

Answer 17

Strength of multiple interactions between a multivalent Ab and Ag (dictated by affinity + number of bindings)

Question 18

What are CDRs (complementarity-determining regions)?

Answer 18

Binding site of antibodies for antigen (CDR1-3), coded for by the variable region of H and L chains

Question 19

What is cross-reactivity?

Answer 19

When one antibody can bind multiple antigens because
1) Different antigens share common epitopes OR
2) The epitopes are different but share common chemical properties

Question 20

What are the benefits and drawbacks of cross-reactivity?

Answer 20

1) Benefit = useful in vaccination (e.g., cowpox used to vaccinate for smallpox)
2) Disadvantage = allergies, autoimmune reaction

Question 21

What is antigen-dependent enhancement (ADE)?

Answer 21

The generation of antibodies from a first infection/vaccine can bind a different but similar pathogen such that the different pathogen is not sufficiently neutralized, rather it results in an enhanced infection rate/spread

Question 22

What are FcRs?

Answer 22

Receptors that bind Fc region of antibodies which can induce activation or inhibiting effects depending on associated motifs

Question 23

Describe the function of F𝛄R

Answer 23

1) Binds IgG, signaling is mostly activating
2) Can induce phagocytosis (macrophages), ADCC (NKCs), and degranulation

Question 24

Describe the function of Fc𝛆R

Answer 24

1) Expressed by granulocytes and binds IgE
2) Triggers release of histamine, proteases, and other inflammatory mediators (allergy)
3) Fc𝛆RI has high affinity for IgE, Fc𝛆RII has lower affinity (on B cells and eosinophils)

Question 25

Describe the function of FcαR

Answer 25

1) Expressed by myeloid cells and binds IgA
2) Triggers ADCC, phagocytosis, and release of inflammatory cytokines, and generation of superoxide free radicals

Question 26

Describe the function of PolyIgR

Answer 26

1) Expressed by epithelial cells and binds IgA and IgM
2) Initiates transport of IgA and IgM from blood to lumen of mucosal tissues (in tears, milk, etc.)

Question 27

What are isotypes?

Answer 27

Isotypes refer to the different subclasses of antibodies (i.e., IgE, IgG, IgA…) and is determined by the constant region of antibody heavy chains

Question 28

What are allotypes?

Answer 28

Antibodies that have the same constant regions but with minor immunologic differences

Question 29

What are idiotypes?

Answer 29

Collection of antigen determinants present in the V region of antibodies, which determines antigen specificity

Question 30

What are Fabs?

Answer 30

Fragment of an antibody that can bind antigens but cannot crosslink/induce an immune response

Question 31

What is F(ab’)2?

Answer 31

Fragment of antibody below the hinge, able to bind and crosslink Ag (generated by pepsin)

Question 32

What is Fc?

Answer 32

The region of the antibody below the hinge which is composed of H chain along and is responsible for effector functions

Question 33

What domains are light chains composed of?

Answer 33

1 variable domain and 1 constant domain

Question 34

What domains are heavy chains composed of

Answer 34

1 variable domain and 3 (IgG, IgA, IgD) or 4 (IgE, IgM) constant domains

Question 35

What is agglutination?

Answer 35

Enhances neutralization and more efficient clearance of pathogens via creation of Ab/Ag complexes