Lec8 Humoral Immunity Flashcards Preview

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Flashcards in Lec8 Humoral Immunity Deck (18):

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

- lag time: 5-10 days after immunization
- peak response: smaller
- antibody isotope: usually IgM at first, then IgG appears
- Antibody affinity: lower affinity

- 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]

1. enters cell cycle [get clonal expansion]

2. increases expression cytokine receptors [increased responsiveness to cytokines produced by helper T cells]

3. migrate out of lymphoid follicles to T-cell rich zones

4. secrete low levels IgM [early phase humoral immune response]


B Cell - T Cell interaction pathway

1. 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

2. 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]

3. 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]

3. 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


Function of germininal reaction center

Selects for memory b cells with higher affinity so get more efficient memory response
-- b cells with high affinity bind antigen on follicular dendritic cell [FDC = scaffold cells] and present antigen to follicular helper T
-- B cells that bind FDCs selected to survive, others die
-- Antigen is limiting factor so only highest affinity survive


How is antibody production shut off?

When sufficient antibody made:
- Fc receptor on B cell blocs activating signal from antigen receptor, terminates B cell activation
- ITIM, on cytoplasmic part of Fc, binds and inhibits ITAM on cytoplasmic part of Ig receptor


What are ITIM and ITAM? Why do I care?

ITAM = Immunoreceptor tyrosine-based activation motif
- on the cytoplasmic part of Ig receptor in B cell is part of the B cell activation pathway

ITIM = Immunoreceptor tyrosine-based inhibition motif
- on cytoplasmic pat of Tc receptor in B cell, binds and inhibits ITAM to prevent B cell activation