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69 Cards in this Set

  • Front
  • Back
Is Ig by itself destructive?
no
Do all isotypes of Ig initiate the same signal transduction cascade?
yes
What is the step of antigen activating BCR?
1)antigen binds to BCR
2) tyrosine kinases blk, lyn and fyn become activated
3) blk, fyn, lyn phosphorylate ITAM on Ig&B; and Igα
4)Syk docks on Igβ
5) signal transduction
What are the three components of the BCR co-receptor?
CD-81
CR 2 /CD 21
CD19
What are the complement receptors on B cells? Which one of the complement receptors is in the Co-BCR?
CR = complement receptor
CR1
CR2 in co-BCR
How is the mechanism of how complement works in B cell activation?
1) CR1 binds factor C3b --> iC3b+C3d
2) CR2 binds C3d
How does the BCR and co-BCR work together?
1)CR2:C3d interaction juxtaposes BCR and Co-BCR
2)BCR lyn tyrosine kinase can posphorylate CD19
3)CD 19 amplifies signal of BCR 100X
What are the two types of signals B cells can recieve for activation?
1) thymus dependent (TI-1, TI-2)
2) thymus independent
How do TI-1 antigens activate B cells?
via the innate immune sytem
What are examples of the way TI-1 works?
1) LPS - specific and non specific
2) Bacterial DNA - specific
What is the mechanism for TI-1 LPS B cell activation?
1) Specific - anti-LPS mIgM binds LPS, LPS activates TLR4
2) Non specific - anti-another surface molecule IgM and LPS activates TLR<b>4</b>
What is the mechanism for Bacterial DNA activation of B cells via TLR4
mIg binds DNA
DNA activates TLR<b>9</b>
What is the mechanism for how TI-2 antigens work?
1) antigens have uniform highly repetitive epitopes
2) they crosslink strongly with BCR and co-BCR
3)generate strong signal
Which B cell activation type is produced in congientially athymic individual?
TI-1, TI-2
What B cell antigen is found to prime T cells?
TD only
Which B cell antigen activates polyclonal B cells?
TI-1
Which B cell antigen requires repeating epitopes?
TI-2 antigen
How does T-dependent response work?
1) B cell uses CAMS and integrins to get to T dependent area
2) B cell picks up antigen
-----meanwhile
3)T cell meets up with dendritic cell and gets antigen
4) T cell waits for a B cell with antigen in MHC II
5)cognate interaction occurs
6)T cell has CD40L and B cellhas CD40 receptor
7) T cell sends cytokines to B cell to activate it
What is cognate interaction?
T and B cell recognize same antigen but different epitopes
What cytokines are released from T cell to B cell that stimulate differentiation and proliferation?
proliferation- IL4
differentiation - IL5, IL6
What do the B and T cell need to do inorder for the T cell to secrete the cytokines to the B cell?
T cell needs to reorient its cytoskeleton and secretory apparatus towards the B cell
What structure forms after the B:T cell conjugation occurs?
Primary focus forms in the T cell
When a B cell is in the primary focus what two things can occur?
1) B cell matures to plasma cell and goes to bone marrow
2) B cell enters follicle along with T cell to form a secondary focus
How is a secondary focus formed?
1)A secondary focus is formed when FDCs bind intact antigen
2)FDCs bind antigen using the CR1 and CR2 to bind to 3cd from degradation of complement
3)retain them for long periods of time
4)T cells also help drive the secondary focus formation
What is located in the germinal center?
1)rapidly dividing B cells in dark zone called centroblasts undergoing somatic hypermutation
2)centroblasts differentiate into centrocytes and move to the light zone
How does a helper T cell influence centrocyte fate?
Centrocyte without high affinity BCR: T cell interaction will die by apoptosis
Germinal center centrocyte with high affinity surface Ig is cross-linked and antigen is presented to helper T cell
What directs isotype switching in B cell?
CD40-CDL interaction
cytokines like IL-4, IL-5, INF&gamma;, TGF-&beta;
What is hyper IgM syndrome?
no germinal centers
What causes the lack of germinal centers?
T-cells
CD-40L
What cytokine directs whether a cell will become a memory cell or a plasma cell?
memory cell - (IL 4)
plasma cell - (IL-10)
What are the characteristics unique to plasma cells?
dfasd
What characteristics does a resting B cell have that a plasma cell does not? (5)
-Surface Ig
-Surface MHC class II
-Growth
-Somatic hypermutation
-Isotype switching
What characteristics does a plasma cell have that a resting B cell does not?
high rate Ig secretion
Which Ig can cross the placenta?
IgG
When does a infant start making their own Ig?
6 months
Where are the different types of Igs located in the body? (3)
IgM and IgG: plasma
IgE:epithelial surface
IgA: mucosal secretion
What determines the anatomical location and functions of isotypes?
Fc portions
How does IgG get into the extracellular space?
Bramble Receptor=FcRn
What is the mechanism of IgG exocytosis? (4)
1)FcRN on endothelial wall
2) IgG binds to it and gets into a endocytotic vesicle
3) acidic pH of vesicle causes association with IgG with FcRn protecting it
4)basolateral surface basic pH causes IgG to dissociate from FcRn
What two Igs are transported across epithelial cells?
IgA, IgM
What is the mechanism of IgA/IgM transcytosis?
1)poly Ig receptor on basolateral surface of epithelial cell
2) receptor mediated endocytosis
3) transport to apical phase
4) cleavage of receptor
What is transcytosis?
unidirectional xport of macromolecules through a cell
Is neutralization isotype specific?
no
How do neutralizing antibodies work?
block ability of toxin to bind receptor on cell surface and get endocytozied
What are the two types of Ig that are best able to activate complement?
IgG and IgM (especially IgG3)
How does IgM activate complement?
1)pentameric IgM
2) binds C1
3) classical C3 convertase to C3a and C3b
What is special about IgM activating complement?
since it is a pentamer only 1 IgM molecule is needed
What does C1 bind?
pentameric proteins like IgM pentamer and CRP of innate immune response
What is the problem with the IgM and complement response?
IgM activates complement efficiently but has limited access to tissues and low affinity
What happens once you have a antibody:antigen complex?
1) C1 binds
2) classical pathway occurs because C1 activates C4bC2a
3)C3b is made which activates more complement deposition
How does IgG activate complement?
2 molecules of IgG are needed they bind C1q of C1
Does IgG have higher or lower affinity than IgA
higher affinity
How do erythrocyte help with clearing immune complexes?
CR1 on ethryocyte binds C3b
RBC carries complex to liver or spleen where a macrophage gets rid of it
What are the advantages and disadvantages of the IgG flexibility?
adv: bind two epitopes
disad: hinge is non globular and susceptible to protease degradation
Which IgG is the best activator of complement?
IgG3
What is the least abundant isotype of IgG?
IgG4
What happens to IgG4 in serum?
heavy and light chain exchange so IgG becomes monomeric and therefore non-inflammatory
What two effects does IL4 have on isotype switching?
promote switching to IgE and IgG4
What is the high affinity receptor for IgG?
Fc&gamma;RI
&alpha; chain binds with high affinity IgG1 and IgG3
&gamma; chain activates signaling cascade
Where is the FC&gamma;RI receptor found?
monocytes
macrophages
dendritic cells
What is the purpose of the FCR receptors?
interact with coated IgG to increase efficiency of phagocytosis
Are all FCRs activating?
No some FcRs are inhibitory and have ITIMs on cytoplasmic domains instead of ITAMs
How do NK cells use Igs to kill infected cells?
1)IgG1 binds target cell
2) FcRIII(CD 16) on NK cell binds IgG1
3) NK gets activated to kill
How is IgE releated to the allergic response?
IgE crosslinking on Fc&epsilon;R results in release of granule
Which FcR activates almost all cells? inhibits almost all cells?
Fc&gamma;RIIIA (excitatory)
Fc&gamma;RIIIB2 (inhibitory)
What is the common activating signal in the FcR?
&gamma; chain
What Ig do most FcRs interact strongest with?
IgG1
What are the exceptions to the fact that most FcRs react strongest with IgG1?
Fc&epsilon; (IgE)
Fc&alpha; (IgA)
Do FcRs have restricted expression?
yes, most types of FcR are on macrophages and neutrophiles