Lec8 Humoral Immunity Flashcards
Is Fc region heavy or light or both?
Heavy chain
What is function of heavy vs light chain?
Heavy chian = function
Light chain = binding only
5 types of antibodies and major functions
IgA: mucosal immunity
IgD: naive B cell antigen receptor, only expressed B cell surface [not secreted]
IgE: mast cell activation [immediate hypersensitivity] and defense against helminthic parasites, allergic rxns
IgG: opsonization, complement activation, antibody-dependent cell mediated cytotoxitcity, neonatal immunity [can pass placenta], inhibition of B cells, primary antibody of any response
IgM: naive B cell antigen receptor, complement activation
T-dependent antibody response
Protein response = T cells only respond to proteins so T-dependent can only be with proteins
- naive IgM+ IgD+ B cell recognizes protein antigen
- with helper T and other stimuli, B activated to proliferate [T CELL REQUIRED]
- B cells differentiate
- effector cells: secrete IgM antibodies into blood stream
- isotype switching: some cells switch IgM –> IgG
- affinity maturation: higher affinity IgG the more you expose to antigen
- memory B cells: once become memory never go back
Which B cell subpopulations are T cell dependent?
Follicular B cells in spleen and other lymphoid organs
- go through T cell dependent mech with protein antigen
- produce IgG, IgA, IgE, long lived plasma cells
Which B cell subpopulations are primarily T cell independent?
- Marginal zone B cells in lymphoid organs
- B-1 cells in mucosal tissues
- go through T cell independent mech with lipid or polysaccharide antigen
- produce IgM, short lived plasma cells
Primary vs secondary T dependent antibody response
Primary
- lag time: 5-10 days after immunization
- peak response: smaller
- antibody isotope: usually IgM at first, then IgG appears
- Antibody affinity: lower affinity
Secondary
- lag time: 1-3 days after immunization
- peak response: bigger
- antibody isotope: IgG and sometimes IgA/E
- antibody affinity: higher affinity
signal transduction pathway in B cells
- cross-linking of membrane Ig by antigen
- tyrosine phosphorylase events causes:
- activation of PLC-gamma leads to activation Ca dependent enzymes and PKC
- GTP/GDP exchance on Ras, Rac leads to activation ERK, JNK
- get TF: NF-kB, AP-1, NFAT, Myc
B cell activation via complement
- complement activated by microbes and C3d bound to microbe
- microbial antigen binds immunoglobulin receptor [BCR] and C3d binds CR2 on B cell surface –> stimulate B cell activation
- causes B cel to differentiate and proliferate
- occurs in follicle
4 B cell responses to antigen [activation]
- enters cell cycle [get clonal expansion]
- increases expression cytokine receptors [increased responsiveness to cytokines produced by helper T cells]
- migrate out of lymphoid follicles to T-cell rich zones
- secrete low levels IgM [early phase humoral immune response]
B Cell - T Cell interaction pathway
- At infection:
- T cell activated via dendritic APC to CD4 T cell
- B cell primarily activated by microbe to express Class II MHC-Peptide complex - T and B cells migrate toward each other, T cell sees peptide-MHC II on B, binds and cross-stimulate each other [also CD40/CD40L involved]
- T cell tells B cell what kind of antibody to make, allows for T cell dependent antibody response and form extrafolliculrar focus [where early antibody response occurs]
- B cells move back to follicle and set up germinal rxn center [where stronger and more effective antibody response occurs]
B cell vs t cell recognition
- b cell recognizes native epitopes, helper T recognizes peptide fragment of antigen
What drives heavy chain isotype switching of B cells?
No T cell —> IgM
cytokines and CD40L from helper T cells regulate switching:
- IFN-gamma –> IgG
- IL-4 –> IgE
- cyto of mucosal tissue [TGF-B, BAFF, etc –> IgA
Mechanism of B cell class switching
- depends on interaction with T cells
- AID [activation-induced deaminase] changes splicing in switch regions so different function
- get different constant region but same VDJ region
- -> thus specificity of antibody preserved
Mechanism of affinity maturation in B cells
- somatic hypermutation in antigen-binding [CDR] region of V chains [both heavy and light]
- get slight changes in binding site
