(10) B-cell mediated Response Flashcards
What is the 1st step in B cell activation?
- B cell encounters antigen and Ig-alpha:Ig-beta crosslink and transduce a signal to the nucleus indicating the cognate determinant has been found
- CR2 binds C3d (from C3b) which confirms the pathogenic nature of the initial Ig-alpha:Ig-beta signal
**Note: this alone is not sufficient to activate the B-cell
What is the function of CD19?
- CD81?
CD19 amplifies the transmission of the Ig-alpha:Ig-beta signal
Differentiate T-dependent and T-independent reactions of a B-cell?
T-dependent requires binding of cognate AS WELL AS T-cell binding
- This leads to proliferation
T-independent reactions require B-cell Receptor (BCR) and a PRR on the B-cell be bound by cognate and PAMP respectively
**THIS DOES NOT LEAD TO GERMINAL CENTER RXNS
What are the two types of T-independent antigens?
- how do they differ?
T-independent 1 (TI-1)
- binds PAMP and BCR to initiate B-cell response
T-independent 2 (TI-2)
- bind Polysaccharides (repetitive structures in general)
What are mitogens?
T-independent 1 (TI-1) antigens
Determine if binding of TI-1 causes the following:
- Germinal Center Reaction
- Class Switching
- Proliferation
- Antibody Release
Germinal Center reaction:
- NO, B-cell activation by TI-1 (or TI-2) does not lead to a germinal center reaction
Class Switching:
- NO, not really… some switching to IgG, but mostly just IgM produced
Proliferation:
- YES!!! cell still proliferates
Antibody Release:
- YES
What happens if a huge number of Mitogens (TI-1) are encountered?
B-cells proliferate in a polyclonal fashion aka a NON-SPECIFIC RESPONSE
What are antigens that might elicite a TI-1 response?
LPS
Pokeweed
What constitutes a TI-2 antigen?
- how does it work?
- what (cell type) does it work on?
TI-2 antigen:
- Repetitive structure like polysaccharides
How:
- Repetitive structures and cause a lot of cross-linking of BCRs
What:
- Works mostly on B1 B cells
Which of the following antigens can elicit and antibody response in the absence of Cognate T cells?
- TI-1
- TI-2
- TD
YES:
- TI-1
- TI-2
NO:
- TD
**This is the definition of a T-cell dependent reaction
Which of the following antigens can cause antibody production in congenital athymic individuals?
- TI-1
- TI-2
- TD
YES:
- TI-1
- TI-2
NO:
- TD
**The thymus is needed for T-cell production, if people lack a thymus they can’t do T-dependent activation, but should have no problem with T-dependent activation
Which of the following antigens can elicit and antibody response in infants?
- TI-1
- TI-2
- TD
YES:
- TI-1
- TD
NO:
-TI-2
**TI-2 can’t elicit a response in infants because these antigens mainly affect B1 B cells, which aren’t finished maturing until we are about 5 y/o
Which of the following antigens can activate T cells?
- TI-1
- TI-2
- TD
YES:
- TD
NO:
- TI-1
- TI-2
**If the antigen is T-dependent it must also be able to bind T-cells
Which of the following antigens induces immunological memory?
- TI-1
- TI-2
- TD
YES:
- TD
NO:
- TI-1
- TI-2
Which of the following antigens can activate non-specific B-cells?
- TI-1
- TI-2
- TD
YES:
- TI-1
NO:
- TD
- TI-2
**remember TI-1 also known as mitogens which can induce a nospecific response in high enough concentrations
Which of the following antigens REQUIRES repeated epitopes?
- TI-1
- TI-2
- TD
YES:
- TI-2
NO:
- TD
- TI-1
**This defines TI-2 binding
What type of response would you expect to be initiated by the presence of flagellin?
- TI-1 or TI-2
TI-2 this is because flagellin is highly repetitive
What type of response would you expect to be initiated from:
- LPS?
- Polysaccharides?
LPS = TI-1
Polysaccharides = TI-2
What cell types are involved in the germinal center?
B and T HELPER cells
What happens during a germinal center reaction?
- B cell receives both of its signals in 2˚ lymph. tissue (TH1 or TH2 binding and antigen binding)
- activated cell proliferates and undergoes somatic HYPERMUTATION
- Positively selected cells undergo isotype switching
What actually creates the germinal center?
After the germinal reaction some B cells and T cells that were positively selected will migrate back into B cell zone to proliferate to create germinal center
**NOTE: B cells that do not reenter will be Plasma cells
Describe what happens to a B cell proceeding the germinal reaction to the point where it undergoes isotype switching?
- What is going on and where??
- B cells hypermutate in germinal center (via somatic hypermutation)
- B cells here = CENTROBLASTS - B cells move toward periphery
- B cells here = CENTROCYTES - B cells encounter FDCs (follicular dendritic cells) which positively select for high affinity B cells (AFFINITY MATURATION)
- B cells enter T-cell zone and T cells promote ISOTYPE SWITCHING
How do follicular dendritic cells work in the process of affinity maturation?
They expression lots of:
- Fc receptors:
- Traps things bound by antibody
- Complement Receptors
- Traps things bound by complement
*It presents the shit that its bound and sees which B cells want it the most, those that do are given survival signals, those that don’t DIE
What is the difference in FDCs and normal dendritic cells?
Normal dendritic cells present peptides to Naive T cells to induce differentiation.
What 4 very important things happen in the germinal center?
- B and T cell proliferation
- Somatic Hypermutation
- affinity maturation - Isotype Switching
- B cell differntiation into:
- plasma cells
- memory B cells
What are the weakly opsonizing antibody isotypes in humans?
IgG2 and IgG4
T or F: cyokines (IL’s, TGF’s etc.) inhibit class switching to the isotypes that oppose the isotypes that they promote
TRUE,
TH1:
Induces: IgG1 and IgG3
Inhibits: IgG2 and IgG4, IgA, and IgE
TH2:
Induces: IgA and IgE, IgG2, and IgG4
Inhibits: IgG1 and IgG3
T or F: once an antigen is encountered a plasma cell can undergo isotype switching.
FALSE, plasma cells cannot do isotype switching only resting B cells can do this?
What is the biggest difference between a resting B cell and a circulating plasma cell?
Resting B cell has receptors and can still recognize antigens so that it can be induced to grow and hypermutate and isotype switch
Plasma cells have none of these characteristics because they are not longer necessary it ONLY SECRETES ANTIBODIES
Determine if each of the following applies to a resting B cell or plasma cell?
- Surface Ig
- Surface MHC class II
- Lots of Ig secretion
- Growth
- Somatic Hypermutation
- Isotype Switching
Resting B cell:
- Surface Ig
- Surface MHC class II
- Growth
- Somatic Hypermutation
- Isotype Switching
Plasma Cell:
Lots of Ig secretion
Where are each of the following found?
- IgG
- IgM
- IgA
- IgE
IgG:
Extracellular Spaces and Serum
IgM:
Primarily in the blood
IgA (monomer) :
- Serum
IgA (dimer):
- ALL mucus membranes
IgE:
Skin and linings of the GALT and MALT
What does IgE bind to?
- how does this account for its normal blood concentration?
Binds to FceRI receptor on MAST CELLS
- It does this very quickly accounting for IgE’s extremely low blood concentration
What process actively transports antibodies into secretions or into extravascular spaces?
- how is this done?
Transcytosis
- Antibodiy binds to a specific receptor and is endocytosed and transported from the basolateral side of the cell to the apical surface
What receptor binds antibodies allowing them to transcytose?
- what antibodies have high affinity for them?
- Poly-Ig Receptor
- Can bind IgA or IgM with high affinity by IgM is too hard to pull through
Where do most plasma cells that make IgA migrate?
- what does this imply about the location of the Poly-Ig Receptor
To mucosal lining of the respiratory and GI tract (GALT and MALT)
- Poly-Ig receptor is located on the Epithelial surfaces of these same tissues
Why is a piece of Poly-Ig Receptor left attached to the IgA after it has transcytosed?
- what is the purpose of this?
- It stabilizes the IgA multimers (increasing their half-life)
- Its called the secretory component
What is the Brambell receptor (FcRB/FcRn) and what does it do?
Moves IgG across VASCULAR endothelium and into extravascular spaces
**This applies to the placenta too!
What is the imporantace of IgG transport by the Brambell receptor (FcRB/FcRn) in fetal life?
- what does this mean for a newborn?
Brambell (FcRB):
- Allows for transport accross the placental barrier
This confers the fetus with passive immunity for the 1st 6 to 9 months of life VIA IgG
T or F: like the poly-Ig receptor the Brambell receptor increases the lifespan of the antibody that it secretes
True, the Brambell receptor increases the lifespan of IgG
Brambell Receptor:
- move things from…to….
- what allows for this movement
Moves IgG from endothelial lumen (capillary) to Extracellular space
- opening of the vesicle depends on pH change from endothelium to extracellular space
***What is Natural vs. Passive immunity?
Natural:
- from mother to child via placental barrier, breast milk, or colostrum
Passive:
- transfer of antibody, immune serum, or T cells from one person/animal to another person
What is the first newly synthesized antibody to peak after birth?
IgM (peaks at about 1 year of age)
*SEE NOTES FOR COMPLETE GRAPH
What are the two main neutralizing types of antibodies?
IgA and IgG2 and IgG4
What Fc receptor has the highest affinity for the antibody that it bind?
- what are the consequences of this?
Fc(epsilon)RI receptor
**Binds orders of magnitude harder than others and can bind IgE without IgE even being bound to its cognate
Fc(gamma)RIII
- what does it bind?
- what cells is it most important to?
- what process is it important in?
Binds IgG1
NK cells and FDC express this opsonization receptor
Important in CELL MEDIATED IMMUNITY
Fc(epsilon)RI
- what does it bind?
- what cells is it most important to?
Binds IgE
Mast Cell and FDC cells express this opsonization receptor
What types of cells TYPICALLY express opsonizing receptors?
Macrophages, Neutrophils, Eosinophils, dendritic cells
Is opsonization more important in cell mediated or humoral immunity?
Humoral, because it is dependent on antibodies binding
T or F: opsonization via antibodies is an important process to ridding the body of a capsular pathogen
False, antibodies don’t recognize the capsule, the complement cascade and C3b
T or F: like antibody binding, C3b binding to the cell surface is reversible.
False
Explain Mast cell degranualation.
- Mast cell has thousands of IgE that are NOT bound to cognate on their surface. this is allowed because of Fc(epsilon)RI is so high affinity.
- Bound IgE essentially serves as a receptor
- Once these IgE’s bind a sufficient amount of pathogen degranulation is triggered.
What other cell steals IgE from the blood to use it as a receptor?
Eosinophils because they also express Fc(epsilon)RI receptors too
What is the major role of esosinophils in the immune response?
- Kill multicellular parasites
What is a hybridoma?
- what’s the point?
Cloned B cell line that has been fused with a tumor cell
**B cells die quickly in culture but Cancer lives forever so we fuse a myeloma to a B cell so that it lives longer
What are monoclonal antibodies?
- how are these made?
Antibodies with a SINGLE specificity
- made from antibodies that were secreted from a cloned hybridoma
What are polyclonal antibodies?
- are all the isotypes the same for these?
Antibodes that were secreted by different B cell lineages
- These have DIFFERENT ISOTYPES (all types likely except IgD)
- Represent a conglomeration of antibodies that were created for MULTIPLE DETERMINANTS on a specific antigen
