Lec8 Humoral Immunity Flashcards

1
Q

Is Fc region heavy or light or both?

A

Heavy chain

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2
Q

What is function of heavy vs light chain?

A

Heavy chian = function

Light chain = binding only

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3
Q

5 types of antibodies and major functions

A

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

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4
Q

T-dependent antibody response

A

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
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5
Q

Which B cell subpopulations are T cell dependent?

A

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
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6
Q

Which B cell subpopulations are primarily T cell independent?

A
  • 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
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7
Q

Primary vs secondary T dependent antibody response

A

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
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8
Q

signal transduction pathway in B cells

A
  • 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
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9
Q

B cell activation via complement

A
  • 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
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10
Q

4 B cell responses to antigen [activation]

A
  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]
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11
Q

B Cell - T Cell interaction pathway

A
  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]
  4. B cells move back to follicle and set up germinal rxn center [where stronger and more effective antibody response occurs]
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12
Q

B cell vs t cell recognition

A
  • b cell recognizes native epitopes, helper T recognizes peptide fragment of antigen
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13
Q

What drives heavy chain isotype switching of B cells?

A

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
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14
Q

Mechanism of B cell class switching

A
  • 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
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15
Q

Mechanism of affinity maturation in B cells

A
  • somatic hypermutation in antigen-binding [CDR] region of V chains [both heavy and light]
  • get slight changes in binding site
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16
Q

Function of germininal reaction center

A

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
17
Q

How is antibody production shut off?

A

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
18
Q

What are ITIM and ITAM? Why do I care?

A

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