Module 6: Humoral Response Flashcards
Describe the process of B cell activation (4 steps)
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
What are the 2 mechanisms where B cells can improve the antibodies secreted?
1) Somatic hypermutation
2) Class switching
Explain the process of somatic hypermutation
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
How does class switching occur?
Through DNA splicing of constant regions of the heavy chain, such that the constant region corresponding to a specific isotype remains
What are the major differences in function between membrane-bound and secreted antibodies
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
What are the 6 main functions of antibodies?
1) Neutralization
2) Complement activation
3) Opsonization (phagocytosis)
4) ADCC (mediated by NKCs)
5) ADD (parasite expulsion)
6) Agglutination
Describe the antibody structure
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
What do the heavy chain C regions serve as?
1) Determinant of isotype
2) Mediators of effector functions (binds to Fc receptors, complement, etc.)
How do antibodies switch from membrane-bound to secreted form?
Through mRNA splicing
Describe the structure and function of IgM
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
What are the 2 forms of heavy chains?
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
Describe the structure and function of IgG
1) Monomer, hinge region
2) 4 subclasses (IgG1-4)
3) Bind Fc receptors for enhanced phagocytosis (opsonin), complement
Describe the structure and function of IgA
1) Can be monomer or dimer, hinge region, J chain
2) 2 subclasses (IgA1-2)
3) Major isotype in secretions
4) Neutralization
Describe the structure and function of IgE
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
Describe the structure and function of IgD
1) Monomer, hinge region
2) Present on mature B cells along with IgM
3) Function unknown
What is affinity?
Strength of all non-covalent interactions between a single antigen binding site and a single epitope (dictated by Ag/Ab fit)
What is avidity?
Strength of multiple interactions between a multivalent Ab and Ag (dictated by affinity + number of bindings)
What are CDRs (complementarity-determining regions)?
Binding site of antibodies for antigen (CDR1-3), coded for by the variable region of H and L chains
What is cross-reactivity?
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
What are the benefits and drawbacks of cross-reactivity?
1) Benefit = useful in vaccination (e.g., cowpox used to vaccinate for smallpox)
2) Disadvantage = allergies, autoimmune reaction
What is antigen-dependent enhancement (ADE)?
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
What are FcRs?
Receptors that bind Fc region of antibodies which can induce activation or inhibiting effects depending on associated motifs
Describe the function of F𝛄R
1) Binds IgG, signaling is mostly activating
2) Can induce phagocytosis (macrophages), ADCC (NKCs), and degranulation
Describe the function of Fc𝛆R
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)
