8/29/13 Flashcards
What is the difference in antibody location between a naive B-cell and a mature B-cell?
Naive B-cells have antibodies on their cell surface while mature B-cells secrete antibodies
Which antibody is secreted first in the humoral response system?
IgM
What are the 3 subsets of B-cells and what do they respond to?
Follicular B-cells–> they respond to protein antigens and are the source of antibodies to T-cell dependent protein antigens
Marginal Zone B-cells–>Blood borne Non-protein antigens
B-1 cells–> Non-protein antigens in the mucosa and peritoneum
How can you tell new infections from repeat infections?
IgM to IgG ratio–> antibody switch
For B-cell activation, does the antigen have to be processed?
No
Describe the B-cell signal transduction pathway
Accessory molecules Ig alpha and Ig beta contain ITAM–> cluster together when antigen is attached–> ITAM phosphorylated–> BLK/Lyn/Fyn phosphorylated–> Syk phosphorylated that leads to the activation of the PLC pathway and RAS/RAC pathway described for T-cells
Which molecules of B-cells are synonymous with CD28 and CD40L?
CR2 and TLR–> stimulate activity but do not participate in the signal cascade like accessory moclecules (CD3, zeta for Tcells/Ig alpha, Ig beta for B-cells)
How do T-cells and B-cells come to interact with each other in lymph nodes?
CD4 T-cells switch from CCR7 to CXCR5 when activated and thus migrate towards the follicle. B-cells switch from CXCR5 to CCR7 when they are activated and thus move outside the follicle. The T-cells and B-cells meet just outside the follicle.
What are the helper T-cell signals that confer antibody switching in B-cells?
CD40L signal to switch and cytokines signal which isotype to switch to (germinal center reactions)
T-helper cell—cytokine—antibody
TH1—IFNgamma—IgG1 and IgG3
TH2—IL-4— IgE
TH17— TGB beta, BAFF—IgA
Describe how cytokines and CD40L initiate antibody switching
Cytokines initiate RNA transcription at one of the S regions–> CD40L induced enzyme AID can act on the more open conformation
Which chain stays constant during antibody switching (Heavy chain, light chain)
Light chain
The reason average affinity of Ab increases with repeated exposures to T-dependent antigens
Affinity maturation
What is the difference between non protein and protein antigen in B-cell stimulation
Non-protein antigen does not stimulate Ab switching, affinity maturation, or memory cells
Which receptor on B-cells stimulates humoral response down-regulation?
FcRIIB
Order of antibodies in serum from highest to lowest
G, M, A, E, D
What receptor helps extend the half life of IgG antibodies and where are they expressed throughout life?
FcRn, expressed in endosomes of the endothelium
Which antibody is confined mainly in the blood
IgM
List the effector function of antibodies
Neutralization of toxins, Opsonization, antibody dependent cellular cytotoxicity, complement activation (lysis, opsonization, and inflammation)
IgA mainly has this type of effector function
neutralization
Multiple/ single FCr on the phagocytes must be engaged by Fc portions of antibodies for successful opsonization
Multiple
Fc receptors for opsonization
FcgammaRI (high affinity), FcgammaRIIa (low affinity)
FcgammeRIIB leads to what
down-regulation of B-cells
Fc receptor for antibody dependent cellular cytoxcity
FcgammaRIIIA
FcepsilonRI
degranulation of mast cells and basophils
In the classical pathway of complement recognition, what are the components of the C3 convertase?
C4b, C2b
Which antibody is the best at complement activation?
IgM
Describe the classical pathway for complement activation
C1q binds to two or more antibodies–> reveals binding sight for C1r and C1s–> C4 binds to C1q and is cleaved by C1r2s2–> C4b binds to the antigenic surface and antibodies–>C2 binds to C4b and is cleaved by C1s making C2b–> C3 convertase cleaves C3 to C3b–> C3b binds to the convertase and antigen sruface–> the complex cleaves C5 and leads to MAC formation
How does Factor I affect complement regulation
It cleaves C3b to C3bi (cofactor is factor H) and converts C4b to C4bi with C4 binding protein as cofactor
How does factor H affect complement regulation
It catalyzes the disassociation of C3bBb
How does C4 binding protein affect complement regulation?
It catalyzes the disassociation of C4bC2b
IgA form dimers with the aid of
J-chain
How does IgA cross in to the lumen
Dimer forms–> Poly Ig receptor at Fc–>IgA dimer cleaved and actively transported to lumenal side–> secretory component remains on the lumenal side
three ways microbes evade humoral immunity
Antigenic variation, inhibition of complement, resistance to phagocytosis
