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01/23/2025
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Surface lymphocytes identify lymphocytes as ______
B/T lymphocytes
What does it mean to be clonally distributed?
Specific for each antigen
Antigen receptors (AgR) are assembled during _____
Lymphocyte development
What is the purpose of having multiple checkpoints?
To test developing cells
What is the first checkpoint?
Production of 1 AgR chain
What is the second checkpoint?
Assembly of complete AgR
What are the signals from Pre-AgR and AgR required for?
Survival, proliferation, maturation
What is positive selection?
Facilitates survival of potentially useful lymphocytes
What is negative selection?
Eliminates/changes cells with AgR that bind self too much
What is clonal deletion?
Lymphocytes die by apoptosis
What is receptor editing?
Replacement of heavy/light chain on auto reactive B cells with new rearrangment
What is a Pre-BCR?
Surrogate light chains and u heavy chains
What does the allelic exclusion do?
Shuts off recombination on other chromosome, express heavy chain from 1 inherited parental allele, activates light chain recombination
What gets rearranged first, heavy or light chains?
Heavy
What is BCR (IgM)?
u heavy chain and k light chain
Where does final maturation of B cells happen?
Spleen
A mature B cell consists of the co-expression of _____
IgM and IgD
Where do B cells mature into pre-B and immature B cells?
Bone marrow
Future T cells leave bone marrow and enter the thymus as _____
Double negative cells
Some future T cells may undergo _____
V(D)J recombination
What does a twice unsuccessful B chain result in?
Cell death
What does a successful B chain and pre-Ta result in?
Pre-TCR or Pre-T cells
What does a successful arrangement of the alpha chain result in?
alpha + beta (aB TCR)
What does selection depend on?
Ag recognition, keep useful cells, affinity for self
What does strong binding of self proteins via MHC result in?
Death, negative selection
What results when AgR doesn’t bind/signal?
Death by neglect
What results when there is weak binding through AgR?
Survival, positive selection
If MHC I present antigen, what gets lost?
CD4
If MHC II present antigen, what gets lost?
CD8
What does it mean to be immunocompetent?
Mature lymphocyte capable of recognizing specific antigen and mediating response
What is a naive cell?
Never encountered AgR specific antigen
Which lymphoid tissues do naive lymphocytes circulate between?
2 - spleen and lymph nodes
3 - previously infected tissues
Lymphocytes* migrate across ____ in lymph nodes into paracortex
High endothelial venules
What is the first step of surveillance?
Extravasation/entrance
What drives extravasation?
Sequential activation of surface molecules
What is the second step of surveillance?
Movement
What is the third step of surveillance?
Exit
During step 2 of surveillance, where do dendritic cells go?
Everywhere
During step 2 of surveillance, where do T cells go?
FRC network
During step 2 of surveillance, where do B cells go?
FDC
What is S1P responsible for?
Controlling retention and release of the lymphocytes through lymph nodes
What results in the increase of S1PR1?
No antigen presence
What do lymphocytes use to move through lymph nodes to find antigen?
FDC, FRC, chemokine
CD4+ cells differentiate into ______
Th subsets
Which cell migrates to follicles and helps activate B cells?
Follicular helper T cells
What activates CD8+ cells?
Multicellular interaction
What “licenses” a CD8+ cell?
Activated Th cell
Fully activated CD8+ cells proliferate and differentiate into _____
Effector CTLs and memory cells
B cells detect antigens in ____
Follicle
B cells get help from _____
Ag-specific T cells
Memory B cells differentiate into ______ and produce ______
Plasma cells; IgM
Memory cells can form ____
Germinal center
What is the purpose of germinal center?
Makes better antibodies, binds antigen, improve biological function
To initiate a response, what gets unregulated and what gets downregulated?
S1PR1; L-selectin
Where do early IgM producers go to?
Lymph node medulla
Where do IgG go to?
Bone marrow
Where do IgA go to?
Mucosal immune tissues
Effector and memory T cells follow _____
Chemokine cues
How long does it take for contraction/resolution to happen?
10-14 days
What are the 2 mechanics within contraction/resolution?
Fas-FAsL and regulatory T cells