[EXAM 2] Lecture 6 (B-cell Mediated Immunity) Flashcards
B-cell Mediated Immunity
What is the function of Tfh cells?
to activate naive B-cells to develop into mature antibody producing plasma cells
- they remain in secondary lymph tissue
1st priority-speed of production-IgM antibody- low affinity
2nd priority-improve quality
1- increase the affinity of the antibody through somatic hypermutation
2- change the isotype of the antibody-recruit effector cells and mechanisms that can clear infection
How are B cells activated?
- ) surface IgM moleculescross-links BCR-clustering
- ) activation of tyrosine kinases
- ) Ig alpha and IGBeta-associated with IgM cytoplasmic tails are phosphorylated (contain ITAMS)- Blk, Fyn, and Lyn (bind Ig alpha
- ) Syk now binds IgB tail-signaling cascade and changes in gene expression
What components make up the B cell co receptor?
CD21 or CR2 ( recognizes iC3b and C3d on pathogens w/ CR1)
CD19 (signaling portion)
CD81 (brings CD19 to surface; organizes B-cell and co-receptor interaction)
Why is CR1 important?
binds C3b on pathogen, leading to cleavage by factor I to iC3b and C3d
What happens to Lyn when when BCR and co-receptor engage the pathogen?
Lyn phosphorylates CD19 (Lyn is bound to Ig alpha)
- can bind to pathogen directly or bind to optimized antigen
What are follicular dendritic cells?
- secondary lymphoid organs- stromal cells of fibroblast-like origin, not hematopoietic origin
- organize the B cell area of the lymph node into primary follicle-interdigitating dendrites
- have entensive surface area-large quantities of antigen can accumulate
- antigen can be presented on surface for long periods b/c not phagocytic
What does CR1 bind to when taking up antigens from lymph?
C3b
What does CR2 bind to when taking up antigens from lymph?
C3d
How is CR2 able to “fish” for antigens?
long “stalks” allow CR2 to get antigen from subcapsular sinus
How are Naive B cells attracted to lymph node?
By CCL21 and CCL19 and into the B cell follicle by CXCL13
What happens to B cells if no antigen is encountered?
naive B cells enter follicle and “search” for FDCs for antigen
What happens to B cells if B cell is encountered?
B cells express CD69-no S1P receptor expression
What receptor binds to CCL21 and CCL19 in naive B cells?
CCR7, when B cells move to the boundary between B- and T- cell areas-will interact with Tfh
What happens to the expression of CCR7 as Tfh cell interact with B cell?
Tfh cells decrease the expression of CCR7 as they move to boundary
- if conjugate pair is formed, T cells are induced to express Cd40 ligand, which binds CD40 on B cell transcription of Nf-KB and ICAM-1-synapse formed
What is the primary focus event between B cell/Tfh cells that occurs?
B-cell/Tfh conjugate pairs move into the medullary cords and begins to divide
**lasts several days and gives rise to dividing B-cells secreting IgM-antibidy leaves via the efferent lymph and Is delivered to the blood to be carried to the site of infection
What happens to B cells when they enter the medullary cord?
They differentiate into plasma cells due to IL-5 and IL-6 secreted by Tfh-cells
What is BLIMP-1?
transcription factor that induces B-cells to stop dividing and increase immunoglobulin chain synthesis and secretion
What are plasma cells also known as?
antibody factories\
~ 20% of protein production is immunoglobulin-rough ER
Do all B-cells become plasma cells?
no, some move to primary follicles of B cell area with Tfh attached