Block 1 Lecture 7 -- B Cells and Antibodies Flashcards
What Abs bind exist as dimers?
IgA
What Abs exist as pentamers?
IgM
What Abs exist as monomers?
IgD IgG monomeric IgA IgE IgM
What makes a B-cell response thymus dependent?
if Ag is protein
What are the effects of a helper-T cell response on a B cell?
1) isotype switching
2) affinity maturation
3) memory B cell response
What makes a B-cell response thymus-independent?
polymeric Ag (polysaccharides, glycolipids, nucleic acids)
What Abs are produced in response to PEG in 10-25% of patients?
IgM (T-independent)
What are the effects of a thymus-independent B cell response?
little isotype switching (maybe IgG)
no affinity maturation
no memory response
Describe the immunological synapse proteins between a T-B cell interaction.
B cell: pMHCII to TCR
- CD40 to CD40L
- CD80/86 to CD28
What are the effects of the T-B interaction?
1) T’s produce Tfh cells
2) IL2,4,5 = proliferation of B and short-lived plasma cells
Where does affinity maturation, memory response, and isotype switching take place?
in the germinal center of the lymph node (B cell follicle)
What cytokine from Th helps produce IgG?
IFN-y (from Th1)
What cytokine from Th helps produce IgE?
IL-4 (from Th2)
What cytokine helps produce IgA?
mucosal tissue and TGF-beta
What is the half-life of IgG?
23 days
What Ab has the shortest half-life?
IgE (2 days)
Function of IgA?
mucosal immunity
Function of IgD?
naive B cell Ag receptor
Function of IgE?
helminth immunity, allergy
Function of IgG?
opsonization
complement
ADCC
neonatal immunity
Function of IgM
naive B cell Ag receptor, complement activation
What are examples of overactive B cell disorders?
leukemia, lymphoma, autoimmunity
How are overactive B cell disorders treated?
1) Rituximab
2) Immunosuppressants
3) Cell therapy
How does rituximab work?
targets CD20 on B cells to stimulate ADCC
What is ADCC?
Ab-dependent cell-mediated toxicity (performed by macrophage, monocyte, or NK)
What are CAR-T cells?
treatment for ALL, etc.
modified T cells include Ab that kills all B-cells
What are examples of underactive B cell disorders?
XLA (X-linked agammaglobulinemia)
XHM (X-linked immunodeficiency with hyper IgM)
CVID (common variable immunodeficiency)
What are therapies for underactive B cells?
IV Ig
What is IV Ig?
pooled Abs from healthy donors
readminister q3-4 weeks (igG has 23 day t1/2)
How are B cells activated (pathways)?
1) Ag
2) Complement
How is a B cell activated by Ag?
BCR dimerization -- Src-TK phosphorylate stuff -- PLC = Ca + DAG, PKC -- Ras pathways generation of TFs
How is a B cell activated by complement?
Microbe-C3d
- recognized by IgM and CR2 receptors
- kinase pathways
Describe B cell development.
Stem – Pro – Pre – Immature – Mature
Characteristics of pro-B cells
proliferation, beginning of mutations
Characteristics of pre-B cells
1-chain Ag receptor
Characteristics of immature B cells
2-chain Ag (undergoes positive or negative selection)
What is a Complimentarity Determining Region
area of hypermutation in DNA of the Ag-binding regions of an Ab
How many disulfide bonds in an Ab?
4
What changes occur in the antigen-binding region of an antibody?
1) somatic hypermutation
2) VDJ recombination
What changes occur in the Fc portion of an antibody?
isotype switching (heavy chain selection)
What is the fx of FcRn
neonatal immunity and longer t1/2
What is the mechanism of FcRn?
recycles IgG after endocytosis
