Humoral Immune Response Flashcards
Components of mature naive B cell
BCR: IgM, IgD, Ig a & Igβ
Co-BCR: CD19, CD81 & CR2 (CD21)
HLA-Class II
CD40
CD20
Two Types of B-2 cells
Follicular B cells are re-circulating B cells: Majority
Marginal B cells reside in the spleen: blood-borne polysaccharide Ags
What signal allows for migration to the Primary Follicle
CXCR5
First Signal Activation
via mIgs
Must cross link 2 or more BCR
signaling occurs through Igα& Igβcytoplasmic tails
phosphorylation of Syk-B
activate PLCy
leads to inositol triphosphate and DAG
activate Ca2+ dependent enzymes and PKC
Also Activation of RAS and RAC lead to ERK and JNK
All three pathways promote Myc, NFAT, NFkB, and AP-1 which increase
protein synthesis
First signal helping activation signals
Ag bound with C3d binds CR2 and enhances signal 1000 fold. Occurs through: Igα& Igβ, CR2 & CD19 cytoplasmic tails (BCR co-receptor complex*)
also can be TLR signaling
Outcomes of First signal
- Increased survival and proliferation
- Interaction with helper T cells (increased B7 expression)
- Responsiveness to cytokines
- Migration from follicle to T cell area (expression of CCR7)
- Secretion of IgM
what are the two types of Second Signals
- T independent signal- would be the mitogen
- T dependent antigen would be the T helper cell and the CD40/CD40L interaction
Both signals cause the B cell to Proliferate and expand
Once activated by T helper cells B cells will begin to?
Change their chemokine receptor expression (class switch) and affinity maturation
Successful re-arrangements are selected/supported by TFH and follicular dendritic cells
What two things do cytokines released by Th cells promote
- induce H chain class switching
- Augument B cell differentiation and proliferation
Cytokine IL-4 causes activated Isotype switching in B cells to?
IgE
Immunity against Helminths and Mast cell degranulation
Cytokine TGF-beta, APRIL, BAFF causes activated Isotype switching in B cells to?
IgA
Mucosal Immunity
Cytokine IFN-y causes activated Isotype switching in B cells to?
IgG?
Opsonization of phagocytosis and complement activation
Switch Recombination occurs in what region of DNA and by what type of antigen
CD40: CD40L ligation and cytokines in T dependant AG binding (protein)
Occurs in a downstream C region, intervening DNA is deleted
Affinity Maturation
Introduction of Point Mutations in the Variable areas of Ig genes
AID converts C’s to U’s
UNG creates the abasic cites
Ape 1 Endonuclease generates nick ( double strand breaks in DNA)
Idea of Somatic Hypermutation,
Where do the majority of Mutations occur in Somatic Hypermutation
Heavy chain and Light chain V regions,
Mutations mainly occur in secondary and Teritary Antibodies
Characteristics of T follicular Helpers
CD4+ and low levels of CD25 expression
Have ICOS/ICOS-L essential for germinal center reaction
What do T follicular helper cells secrete?
IL-21 to facilitate differentiation to plasma blasts
also provide IFN-y and IL-4 cytokine for switching
What is the selection checkpoint?
Where T Follicular Helper cells and Follicular Dendritic Cells choose the B cell with the highest Affinity to the presented antigen for its necessary survival
Rest of cells Apoptosis
Plasma Cell components?
Terminally differentiated effector B cell
Decrease in CD19 and CD20 expression,
Increase in CD27 cell marker
only secrets its class dependent Antibody
Expansion of ER in Cytoplasm