B Cell Immunity Flashcards
What is unique about the properties of B1 and MZ cells?
- behave innate-like
- first line of defense
Describe the following characteristics related to B1 cells:
- time of production
- diversity
- mode of renewal
- antigen
- T cell involvement
- produced in the fetus
- not so diverse b/c no N regions
- self-renewing
- yes to CHO, sometimes to protein
- no T cells
Describe the following characteristics related to B2 (conventional) cells:
- time of production
- diversity
- mode of renewal
- antigen
- T cell involvement
- produced after birth
- very diverse
- regenerated from the bone marrow
- mostly protein, sometimes CHO
- requires T cell (adaptive immunity)
Describe the following characteristics related to MZ B cells:
- time of production
- diversity
- mode of renewal
- antigen
- T cell involvement
- produced after birth
- somewhat diverse (has N regions, but limited Vs)
- long-lived (no renewal)
- both CHO and protein
- sometimes interacts with T cells
What has increased immunogenicity:
- size
- dose
- composition
- form
- adjuvants
- large
- intermediate dose
- complex composition
- insoluble
- slow release adjuvants, bacterial adjuvants
Why are intermediate doses given for an immune response?
- low dose might not generate a response
- high dose can cause tolerance
Why do insoluble antigens have more immunogenicity?
b/c when solubilized it is harder for phagocytic cells to take them up
Define adjuvant.
molecule or peptide used to enhance the immune response to a particular antigen
What is the most common adjuvant?
- alum (aluminum hydroxide)
How does alum work?
- alum is insoluble and when combined with a soluble antigen => precipitated aggregate => easier to uptake
- instigates inflammasome reaction
- delayed antigen release
What signals are required for B cell activation?
- TCR:MHC:CD4
2. CD40L:CD40
Describe thymus-dependent antigen reactions.
- mostly peptide antigens
1. TCR:MHC:peptide
2. T cell secretes stimulatory cytokines: IL-4, IL-5, IL-6
3. T cell expresses CD40L => CD40
4. B cell activated to proliferate
5. B cell differentiates into a memory cell or a plasma cell
How can you immunize an infant, who cannot produce T-independent immune responses, against a polysaccharide antigen?
NOTE: T cells and B cells must recognize the same antigen
1. attach a protein (tetanus toxoid) to the polysaccharide (H. influenza) structure
2. polysaccharide antigen will bind to its specific B cell
3. B cell processes the antigen
4. antigen presentation only occurs with the peptide fragment because polysaccharides cannot bind to the MHC antigen-binding cleft
5. T cell recognizes MHC and peptide => gives B cell the okay to proliferate and make memory/plasma cells
6. B cell produces the SAME antibody it had on its surface = the one against the polysaccharide structure
Thus, the antibodies produced are against the polysaccharide even though the T cell recognized only the peptide
Differentiate primary and secondary antibody response.
Primary
- slow
- IgM
Secondary
- rapid
- IgG
- more antibody (higher titer)
- increased affinity
How and when does an isotype switch occur?
- How: rearrange the remaining heavy chain constant region genes by looping out DNA
- When: T-dependent responses, regulated by T-cell cytokines
What are some examples of T cell cytokines that induce isotype switch?
- IL4 causes switch from IgG to IgE
- TGFB causes switch to IgA
- IFNg causes switch to IgG3
Recall the mechanism for isotype switching.
- enzyme AID (activation-induced cytidine deaminase)
1. recognizes switch regions in front of the remaining C genes of the heavy chain
2. loops out the DNA in between => excised => ligated
3. you are left with a new C region on the DNA
NOTE: only possible if there are C regions left on the 3’ end of theW DNA after the original VDJ-C rearrangement
What activities occur in the germinal centers?
- B cell proliferation
- isotype switch
- somatic hypermutation
- development of memory or plasmablast cells
- forms during immune response*
What are the possible results of somatic hypermutation?
- creation of a high affinity surface Ig => memory or plasma cell
- creation of a low affinity surface Ig or a totally different specific affinity Ig => apoptosis b/c no activation from Thelper cells in the GC
Define somatic hypermutation.
occurs after B cell is activated to proliferate
- purpose: generate a high specificity antibody against the antigen
- mutations occur in the V regions
Describe the mechanism of somatic mutation.
- activated B cell undergoes somatic hypermutation in the GC via AID enzyme
- follicular dendritic cell present an antigen-antibody complex to test the affinity of the new antibody
- if the new antibody is specific enough, the T cell will be activated again and stimulate the B cell to become a plasma or memory cell
- if the new antibody is not specific => apoptosis
What enzyme is used in hypermutation?
AID
What happens in patients with AID deficiency?
can only make IgM
no somatic diversity
What happens to hypermutation with time?
as time goes on, more and more mutations occur, creating more specificity
