Chapter 7: Humoral immune responses Flashcards
What are the possible outcomes of activated B cells after differentiation?
- antibody secreting plasma cell
- IgG-expressing B cell
- High-affinity Ig-expressing B cell
- memory B cell
How are B cells activated?
- helper T cells
- other stimuli
What happens during T-dependent B cell activation?
- protein antigen binds to follicular B cell
- helper T cell binds via MHC molecule
- isotype-switched, high-affinity antibodies
- memory B cells and long-lived plasma cells are formed
What happens during T-independent B cell activation?
- polysaccharide antigen binds to IgM antibody on marginal zone B cell (in spleen)
- other signals activate it (complement proteins, microbial product)
- low affinity antibodies
- short-lived plasma cells are formed
What is the lag, peak response, antibody type, and affinity of a primary response?
lag: 5-10 days
peak response: small
antibody type: IgM>IgG
low affinity and more variable
What is the lag, peak response, antibody type, and affinity of a secondary response?
lag: 1-3 days
peak response: large
antibody type: mostly IgG or maybe IgA or IgE under certain situations
high affinity
What decides the antibody type and affinity?
- response to protein antigens
- if a first or second infection
Where are naive B cells located?
peipheral lymphoid tissue
How many receptors must be bound to antigens in order for antigen receptor-mediated signal transduction in B cells?
2 or more
What completment receptor and complement product binds to activate B cells?
complement receptor (CR2) binding by 3Cd bound to microbe
What receptor binds to the PAMP from microbe to activate B cells?
Toll-like receptor
What product of the complement system binds to CR2 to activate B cells?
C3d
What are the functional consequences of antigen receptor-mediated B cell activation?
- increased survival and proliferation
- interaction with helper T cells
- responsiveness to cytokines
- migration form follicle to T cell zone
- antibody secretion
What does CCR7 and CXCR4 do to T cells?
CCR7
- increases to go to T cell zone
CXCR4
- decreases this to go to B cell
What does CCR7 and CXCR4 do to B cells?
CCR7
- increases this to go to B cell zone
CXCR4
- downregulates this to go to T cell zone
What do CCR7 and CXCR4 do to both T cells and B cells?
move them to the germinal center region (space between the B and T cell zones)
What are the steps of antigen presentation by B cells to helper T cells?
- B cell recognizes protein antigen
- receptor-mediated endocytosis of antigen
- antigen processing and presentation via class II MHC complex
- T cell recognition of antigen on B cell
What is required for T cells to activate a B cell besides the MHC complex?
CD40 on B cell
CD40L on T helper cell
Where do B cells proliferate?
germinal center of lymph node
When do B cells leave the germinal center of lymph node?
leave if they are high-affinity antibody-secreting cells and memory B cells
What allows for B cells to be activated to anything other than IgM?
CD40L
cytokines
IL-4 (IgE)
etc.
What is the effector function of IgM?
complement activation
What is the effector function of IgG?
- Fc receptor-dependent phagocyte responses
- complement activation
- neonatal immunity
What is the effector function of IgE?
- immunity against helminths
- mast cell degranulation
What is the effector function of IgA?
- mucosal immunity
What is the mechanism of immunoglobulin heavy-chain isotype switching?
- induction of AID (activation-induced deaminase) which alters nucleotide to they can be cleaved
- switch recombination: Previously formed VDJ exon recombines
to become adjacent to a different
constant region gene - transcription, RNA splicing, and translation
What is the point of activation-induced deaminase?
alters nucleotides so they can be cleaved by other enzymes, allowing S regions to be brought together (isotype switching)
What is switch recombination when isotype switching?
Previously formed VDJ exon recombines to become adjacent to a different constant region gene
Repeated exposure to a protein antigen drives creation of _______ affinity antibodies
higher
Somatic mutations in Ig V genes leads to…
selection of high-affinity B cells
What do follicular dendritic cells do in forming high-affinity B cells?
present antigen via antibodies bound to Fc receptors or complement receptors instead of MHC molecules Antigens are never internalized by FDCs
What are the characteristics of T cell-dependent antigens?
chemical nature: proteins
isotype switching: yes
affinity: yes
life span: long-lived
secondary response: yes
What are the characteristics of T cell-independent antigens?
chemical nature: polymeric antigens (polysaccharides, glycolipids, and nucleic acids)
isotype switching: low level switching
affinity: little or no
life span: short-lived
secondary response: only with some polysaccharide antigens
Humoral response terminated once sufficient quantities of IgG are produced to result in…
inhibition of B cell response
If a antigen-antibody complex binds to 2 different Fc receptors then it does what?
blocks B cell receptor signaling
- antibody feedback
