Chapter 9 - Immunity Mediated By B-Cells And Antibodies Flashcards
What is the mechanism for BCR cross-linking?
1) antigen cross-links BCR
2) Clustering of antigen receptors allows receptor associated kinases (Blk, Fyn, Lyn) to phosphorylate ITAMS.
3) SYK binds to phosphorylated ITAMS and is activated.
4) Changes in gene expression in nucleus.
What does B-cell activation require?
- cross linking of B-cell receptors by antigen
- signals from co-receptor
What is the mechanism to generate signals from B-cell co-receptor?
1) Binding of CR1 (on b-cells) to C3b (on pathogen) facilitates the cleavage of C3b by Factor 1 to: iC3b and C3d
2) CR2 on B-cell co-receptor then binds to C3d.
3) Intracellular signals are generated to help activate B-cell.
What subunits is the B-cell co-receptor composed of?
- CR2 = receptor for complement fragments iC3b & C3d
- CD19 = signaling component
- CD81 = brings CD19 to surface and organizes the B-cell co-receptor within the membrane
What will happen if there are defects in the B-cell co-receptor?
- Impaired humoral immunity
- low antibody and very little class switch recombination
Describe movement of B-cell vs T-cell in the lymph node.
B-cell
- naive B cells search for specific antigens displayed by FDC (follicular dendritic cells) in the B- cell area
- antigen-activated B cells move to the boundary region
- B cells present antigen to effector Tfh cells and both form a cognate pair stabilized by adhesive interactions between (B cell ICAM-1 and T cell LFA-1)
- The Tfh will make cytokines (CD40 ligand) that is secreted onto the B cell surface to interact with B cell CD40and activate the cell.
T-cell
- naive T cells search for specific antigen presented by DC (dendritic cells) in T cell area
- antigen activated T cells then proliferate and differentiate into effector Tfh cells and move to boundary region to interact with B cell.
Follicular Dendritic Cell vs Dendritic Cell
- FDC does NOT process antigens. It just holds it so B-cell can see it.
- DC processes antigen and presents it in the context of MHC.
Role of CD69
It keeps S1P receptor inside the cell and prevents cells from leaving the lymph node.
Where is the primary and secondary focus for expansion of antigen-activated B cells?
- primary = medullary cords
- secondary = primary follicle which expands to create the germinal center and is where B cells undergo affinity maturation and isotope switching of antibodies
Describe the areas within a germinal center.
1) centroblasts
- no BCR
- No MHC
- FDC secrete cytokines to induce proliferation
- also where Tfh secretes cytokines and interact with B cells through CD40 for somatic hypermutation and isotope switching with the help of AID
Centrocytes
- increase in BCR and MHC
- affinity maturation
- selection or apoptosis
Mantle Zone
- naive B cells
Bcl-Xl
Expressed by centrocytes in germinal center to prevent apoptosis and ensure the cell’s survival if their receptors have high affinity for the antigen.
Hyper-IgM Syndrome
No germinal centers so none of other Immunoglubulins formed except IgM.
How will centrocytes know whether to differentiate into Plasma Cells or Memory B-cells?
- If the antigen-selected centrocytes mature under the influence of an IL-10-secreting helper Tfh cell -> plasma cell -> fight current infection
- influence of IL-4-secreting helper Tfh cell -> memory B cell -> prevents future infections from causing disease
B-1 cells vs B-2 cells
B-1 cells
- 1st produced in fetus
- primary location = peritoneal and pleural cavities
- self renewing
- IgM secreted, spontaneous prod of Ig
- does NOT need T-cell help (respond to thymus independent antigen)
- NO somatic hypermutation or memory development
B-2 cells
- 1st produced after birth
- primary location = secondary lymphoid organs
- replaced from bone marrow
- IgG secreted
- does need T-cell help
- YES somatic hypermutation and memory development
Role of IgG
IgG is high in the blood, neutralizes pathogen’s that enter the blood, and enters the extracellular space with the help of receptor FcRn to protect tissues
