Ch. 7 Humoral - Activation B-cells and Ig production

Question 1

Antigen receptors on naive B-cells are:

Answer 1

IgM and IgD

- they recognize antigens and lead to B-cell clonal expansion

Question 2

T-dependent/independent B-cell response

Answer 2

• T-dependent - B-cells need t-cells for protein antigens
  
  • allows Antigen Maturation, and Heavy Chain isotype switching
  • B-cells have a very weak response to proteins on their own
• t-cell independent - all other antigens (polysach, lipids)
  
  • no Heavy Chain switching or Affinity maturation for T-cell-independent

Question 3

Components of BCR

Answer 3

• antigen receptor (IgM or IgD)
• Ig-alpha, Ig-beta

> 2 bind antigens near each other - tyr immunoreceptor ITAMs etc. same as T cell cascade

• PLC-gamma - PI3 - Ca2+ NFAT
  - DAG - NF-kB
• RasGTP - ERK, JNK (MAPK) - AP-1

Question 4

2nd signal for B-cells

Answer 4

• C3d binds microbes
• when antigen binds to Ig on B-cell, the C3d coating it binds to type 2 receptors (CR2, CD21)
• this is required to initiate the signal transduction pathway

Question 5

B-cell activation by T-cell cell-cell interaction

Answer 5

• B-cell presents protein antigen on MHC-II
• TCR recognizes the antigen and expresses CD40L
  
  • T-cell secretes cytokines
• CD40 on B-cell binds CD40L on ligand
  CD40 + ligands activate B cell for proliferation and differentiation
• allows for heavy chain switching
  
  • the specific class is specified by the cytokines released

Question 6

X-linked hyperIgM syndrome

Answer 6

• mutation in the CD40L gene of t-cells
• they can’t bind to macrophages or B-cells
• B-cells can’t do heavy chain switching - leads to only IgM producion

Question 7

Activation-induced deaminase

Answer 7

• cuts the DNA to includes a certain C region leading to the different heavy chain isotypes

Question 8

switch recombinase

Answer 8

AID cuts the DNA to splice the VDJ antigen specific region to a C region to create different heavy chain isotypes (IgG, IgM, IgD etc)

Question 9

(Th1 response) INF-gamma affect on Macrophages and B-cell

Answer 9

• INF-gamma induces IgG production because IgG is good for opsonization, and phagocytes recognize the Fc of IgG
• INF-gamma activates macrophages to phagocytose things - they have the FcR that binds IgG

Question 10

Th2 response on target cells

Answer 10

Th2 produces IL-4 which activates IgE

• IgE binds to helminths
• Eosinophils have FcR’s for IgE
• eosinophils kill the helminths
• Th2 produces IL-5 that activates eosinophils
• Helminths produce Th2 responses

Question 11

IgA

Answer 11

• IgA can go thru mucosal linings
• it is the main Ig made at mucosal lymph organs
• B-cells specialize in making IgA there
• T-cells there secrete cytokines that lead to IgA response

Question 12

Affinity Maturation

Answer 12

• Affintiy of antibodies to antigen increases with prolonged or repeated exposure to antigen
• only with T-cell dependent protein antigens
• mutations in the hv region of the V of the antibodies
• hypermutation (due to AID) in the rapidly dividing B-cells in the follicular region of lymph nodes
• then the affinity is checked by antigen presenting follicular dendritic cells - if they do not recognize and antigen they will die by apoptosis b/c don’t get survival signal here in germinal center
• occurs in germinal centers

Question 13

antibody feedback

Answer 13

• antigen is bound by IgG antibody to form a complex
• complex comes into contact with B-cell type that made it
• while antigen binds to BCR, the Fc-gamma receptor on the B-cell binds the Fc region of the IgG
• this leads to negative feedback
• stops the antigen signalling thru B-cell and stops production of antibodies
• turns off the humerol response when infection is taken care of - enough antibodies