(L25) Humoral (B cell) Immune Response Flashcards
What surface molecules do B cells have?
L24 S9
- BCR (IgM/IgD)
- Igα and Igβ
- CD19, CD81, and CD21 (CR2)
- MHC class II
- CD40
- CD20
What are the types of B cells and where are they found?
L25 S7
B-1 cells:
- found in mucosa
- limited Ag specificity
B-2 cells: -follicular B cells (majority) —circulating B cells marginal B cells —found in marginal zone of spleen —secrete Abs for polysaccharides
What causes B cells to migrate to the lymph follicles?
L25 S8
CXCR5 expressed on B cells which is a receptor for CXCL13, a chemotactic factor produced by the spleen and lymph nodes.
When they are partially activated they need to go to medulla to become fully activated thus will express CCR7.
What responses do B cells have to binding of Ag to BCRs?
L25 S12
Increased survival and proliferation signals
Expression of B7 (CD80/86) for interaction with T helper cells
Expression of cytokine receptors
Expression of CCR7 for migration to follicle
Secretion of IgM
What signals are involved in T-dependent B cell activation?
L25 S15
Binding of Ag to BCR results in generation of signals for B cell activation and internalization of Ag/presentation on MHC class II
Interaction upregulates expression of CD80/86 (B7) on B cell
CD80/86 binds CD28 (constitutive) on T cells, upregulating expression of CD40L and release of cytokines
Binding of CD40L to CD40 (constitutive) on B cells generates remaining signals needed for activation
Cytokine receptors and CD40 generate signals needed for somatic hypermutation and class switching
What is somatic hypermutation and by what process does it occur?
L25 S20
T-dependent activation causes expression of (activation-induced cytidine deaminase)
AID causes deamination of cytosine to uracil
Native enzyme cleave the uracil base from the DNA backbone.
Apurinic endonuclease (APE) causes a double-stranded break.
Double-stranded break is repaired and possible change is DNA sequence occurs that could change the affinity of the Ab produced.
How does class switching occur?
L25 S19
These double stranded breaks are made at the ends of VDJ segment and in C region of desired heavy chain isotype.
Double stranded breaks are ligated together with desired heavy chain isotype next to VDJ segment. Intervening DNA is deleted
What selection occurs following somatic hypermutation?
Why and how does it happen?
L25 S25
B cells have changed their affinity follow somatic hypermutation.
Follicular DCs and Tfh cells test B cell for affinity with Ag.
Only B cells with high affinity are given survival signals and proceed to become antigen secreting plasma cells.
What signals are involved in T-independent B cell activation?
L25 S27
Extensive cross linking of BCRs to polysaccharide Ag
Can be be supplemented with binding of bacterial PAMPs to B cell TLRs
Activation mechanism of marginal zone B cells and B-1 cells
What causes contraction of B cell response?
L25 S31
Binding of IgG to FcγRIIB (IgG specific) on B cells prevents PIP3 formation attenuating B cell activation signals
What are the characteristics of primary and secondary antibody responses? (timing, strength of response, Ab type, affinity)
L25 S35
Primary:
- slow response time (5-10 days)
- weaker response
- mostly IgM
- lower affinity
Secondary:
- fast response time (1-3 days)
- larger response
- mostly IgG or class switched
- higher affinity
What are the effector mechanisms of Abs?
L25 S36
- neutralization
- opsonization via Fc region
- antibody-dependent cellular cytotoxicity (ADCC)
- inflammation
- opsonization via complement (C3b)
- lysis via MAC
How do Abs neutralize microbes and toxins?
What Abs are capable of this?
L25 S43
Works with any Ab
Microbes:
- coats microbe preventing penetration of epithelium
- coats microbe preventing binding/infection of cells
Toxins:
-binds toxins preventing effector mechanism
How do Abs opsonize microbes?
What Abs are capable of this?
L25 S44
Fc region of IgG binds FcγRI (CD64) of phagocytes, activating them
What is ADCC and how do Abs regulate it?
What Abs are capable of this?
L25 S46
Antibody-dependent cellular cytotoxicity, effector mechanism of NK cells, caused by binding of IgG to NK cell FcγRIII (CD16)
