topic 6 Flashcards
What is the general process of b cell activation? What are the two different types of b cells?
Antigen is recognized
B cell is activated (maybe by Th cell or by other stimuli)
Clonal expansion
Differentiation-
Antibody secretion, class switching, affinity maturation, memory b cells
What are the different subsets of b cells and what do they respond to and how?
Follicular b cells respond to protein antigen and helper t cells (in germinal center) and leads to various isotypes (igG, IgA, igE) and long lived plasma cells
Marginal Zone B cells are in the spleen, respond to polysaccharides, lipids, etc. and lead to IgM and short lived plasma cells
B-1 B cells are found in the mucosa, respond to polysaccharides, lipids, etc. and lead to IgM and short lived plasma cells
What are some differences between primary and secondary antibody response? What are the different antibodies involved in each? How does the antibody effect differ in both?
Primary-peak response smaller, igM>igG, lower average antibody affinity
secondary-peak response larger, igG has a relative increase and sometimes igA or igE are involved (heavy chain class switching. There is a higher average antibody affinity (affinity maturation).
What are some specific steps of antigen recognition and b cell activation?
Ags are delivered to primary follicles of peripheral LN via lymphatics or also by macrophages or DCs. In the spleen they can be delivered to the b cells via blood, or in DC or macrophages
The Ag is recognized using Ig receptors.
When the Ag forms an antibody, Ig-alpha and Ig-beta are brought into close proximity to form the BCR complex which then undergoes tyrosine phosphorylation through its ITAM
This leads to a signalling cascade which results in transcription factors being formed which leads to proliferation and differentiation.
How do complement (C) and TLRs play a role in b cell activation?
C binds to microbe which leads to a signal cascade resulting in activation.
TLR binds to a PAMP from the microbe and then sends a signal leading to activation.
How does activation differ between Ti and Td Ag
For Ti Ag, the activation results directly in proliferation and differentiation and thus more crosslinking of receptors occurs and C’ is activated more strongly.
For Td Ag, the activation simply prepares the cells to be fully activated by Th
How are Td’s prepared for Th’s?
Activation of these b cells leads to clonal expansion, increased expression of cytokine receptors, decreased chemokine receptors (migration to t cells), and secretion of low levels of IgM.
How and where do b cells meet?
B cells lose chemokine receptors and migrate from follicle into t cell zones.
When b cells bind with an antigen, they phagocytose it and cut it up and present it on the membrane in a class II MHC. The T cell recognizes to epitope/MHC.
T/B cells enter into a germinal center in the lymphoid follicle
After recognition, how do Th cells activate b cells?
Upon binding, CD40 on the b cell recognizes the CD40 ligand (expressed upon binding) on the t cell. When they bind, the t cell releases cytokines which are recognized by cytokine receptors on b cells. This leads to differentiation and proliferation.
What is heavy chain class switching? Which cytokines lead to b cell proliferation? Which cytokines lead to the specific isotypes?
Heavy chain class switching is how different isotypes are accomplished. Different cytokines cause different receptors (ABs) to be expressed.
IL-2,4,5 lead to be cell proliferation in general.
IL-2,4,5 lead to IgM
IL-4,6,2 and IFN-gamma lead to IgG
IL-5 and TGF-beta lead to IgA
IL-4 leads to IgE
What is the molecular/genetic mechanism for class switching?
Activation induced deaminase causes differential splicing which leads to different isotypes being transcribed.
How they are spliced depends on which cytokines are received.
What is the main factor that determines which isotype is needed?
It is largely based on site. Where a b cell will dwell determines which function is needed most and thus determines the isotype.
How does Affinity maturation work?
Once the Th/B cells are into the germinal center, proliferation begins, and random mutations occur very frequently in the CDR regions (areas in V gene). This is referred to as somatic hypermutation. Mutations that lead to a really good fit with the antigen are selected. Thus as time goes on, the cells bind to the antigen with much higher affinity.
How are high affinity b cells selected?
B cells that are able to recognize antigen are able to bind to the antigen on follicular dendritic cells and then present the antigen to helper t cells. B cells that can do this receive survival signals. B cells that have mutated the wrong way don’t receive survival signals and die.
What is the difference between t independent and dependent b cells
t dependent is what we studied in detail. In t independent, polymeric antigens are recognized because they can be recognized by multiple receptors on a b cell and thus cross-link receptors which leads to a fairly strong activation. They have little or no class switching and thus only IgM and some IgG and little or no affinity maturation. memory b cells are only produced when dealing with some antigens, not all.
