[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
Describe the Germinal center reaction.
DFC produce IL-6, IL-15, 8D6, and Baff(cytokines) which induce B cells to divide rapidly and become centroblasts-create the germinal center
What is AID?
Tfh interaction at the CD40 receptor causes b cells to produce AID which is essential for hypermutation and isotype switching
What is responsible for swelling ~1 week after infection?
Primary follicle turning into a secondary follicle which causes swelling of lymph nodes
What is the mantle zone?
area where naive B-cells passing through the lymph node
What is the dark zone?
a compact area of densely-packed centroblasts
What are centroblasts?
cells that give rise to centrocytes
What are centrocytes?
slowly dividing cells that begin to express surface immunoglobulins again (mutated and isotype switching)-centrocytes are short-lived unless they encounter antigen and bind Tfh
What is the light zone?
a low density of centrocytes and high density of FDCs and Tfh cells
What does somatic hypermutation lead to?
creates diversity-high and low affinity
What type of centrocytes will survive?
centrocytes with the highest affinity for antigen on FDCs
Which cells will live longer, those that home in bone marrow or in lymph node?
bone marrow
- lymph node is short lived
What is Affinity maturation?
refines the response to this pathogen
During infection, which cytokine is produced by Tfh cell?
IL-10 ; induces centrocytes to differentiate into plasma cells
After infection, which cytokine is produced by Tfh cells?
IL-4; induces centrocytes to become memory B cells
What is IgM antibody?
- first IgM produced by plasma cells (10 binding sites
- lowest affinity
- binds microorganisms and particulate antigens and activates the complement cascade
- bulky and has limitation in passively leaving the blood
What is IgG?
produced by isotype switching and affinity maturation
- two high-affinity binding sites
- better able to infiltrate tissue than IgM
IgG-dominant blood-borne antibody (one of the highest in the blood)
prevent blood-borne infections and spread of microorganisms
What is IgA?
produced by isotype switching and affinity maturation
- two high-affinity binding sites
- better able to infiltrate tissue than IgM
Monomeric IgA-made by B-cells in lymph node and spleen
- prevent blood-borne infections and spread of microorganisms
How is IgG able to bind with FcRn receptor?
The acidic environment protects IgG from proteolysis, once the IgG gets to the basolateral face of the endothelial cell, the basic pH of the extracellular fluid dissociates IgG and FcRn
What is dimeric IgA?
- protects the mucosal epithelial surfaces
- made in patches of mucosal-associated lymphoid tissue
- antibody-secreting mucosal cells are on one side of mucosal epithelium and pathogen is on the other
- driven by transcytosis
How do you neutralize antibodies?
high-affinity antibodies that prevent microbial attachment to target cells-coat pathogen and prevent infection of the target cell
eg. IgA
What antibodies can neutralize some microbial toxins and animal venoms?
IgG and IgA
- to neutralize Ab must be high affinity, bind irreversibly, and penetrate tissue to reach the toxin
What antibody activates the complement system?
IgG
can either bind to the antigen on pathogen surface or on multivalent antigen which will initiate C-reative pathway (C1q)
What cells facilitate the removal of immune complexes from the blood?
Erythrocytes
Why are phagocytes important in the process of breaking down Ab-coated pathogen?
phagocytes uptake and breakdown Ab-coated pathogen by surrounding bacteria and having lysosomes fuse with the phagosome
How do NK cells break breakdown IgG coated target cells?
signal target cells to die by apoptosis
What is IgE?
used as cell surface receptor for antigens-cross-linking on mast cells results in granule release of inflammatory mediators (histamine)
- mast cells secrete mediators that cause sneezing, vomiting, coughing, diarrhea-to expel pathogens from the respiratory and GI tract
Where is IgG most commonly found solely in comparison to the other antibodies?
placenta
Where is dimeric IgA found and not the others?
mother’s milk-passive transfer
When are low levels of IgG mostly found in child development?
3 months to 9 months
