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surface Ig other name
BCR
Secreted Ig other name
antibody
antigen
anything antibody binds to
somatic recombination
mixing and matching of VDJ segments
RAG1/RAG2
recombination enzyme complex
combinatorial diversity
diversity from V,D,Js
Junctional Diversity
added nucleotides, not from inherited gene, nucleotides, n-nucleotides
p-nucleotides
RAG1/RAG2 adds (junctional diversity)
n-nucleotide
TDT enzyme adds (junctional diversity)
B-cells
what develops in BM
HSC
stromal cell promotes growth of
steps of B-cell development
HSC, pro-B, Large Pre-B, Small Pre-B, immature B
self tolerance
removing or inactivating self-reactive T+B cells
Central self-tolerance purpose
to kill or inactivate self-reactive B-cells
central self tolerance location
during development in BM and thymus is location of what
B-cell doesn’t bind anything
good, can leave BM
Binds antigen on surface of another cell (ex.stromal)
apoptosis or retry LC rearrangement if unsuccessful, undergo apoptosis
BCR binds soluble antigen
anergy, lives but inactivated
peripheral self-tolerance purpose
killing / inactivation after T&B cells are mature and in circulation
TCRs
peptides presented by MHC molecules interact with what
which TCR region rearranges first?
Beta chain (VDJ)
which TCR region rearranges second?
alpha chain (V-J)
CD4
MHCII binds which T-cell
CD8
MHC I binds which T-cell
MHCI
which MHC is found on all cells
on macrophages, dendritic cells
where is MHCII found?
Dendritic cells
bridge between innate and adaptive system, presenting antigens to T cells and activating them, activate adaptive
through phagocytosis and pinocytosis (sample fluid) dendritic
how do DC get peptides?
Dendritic cell
Antigen Presenting Cells (APC) is the job of
combo of MHC and peptide
how do TCR bind?
MHCI
endogenous peptides (here’s what’s inside of me) is presented by
MHCII
exogenous cells (“here’s what I found outside of me") is presented by
MHCI
TAP, proteosome used in which antigen processing
MHCII
lysosome used in which antigen processing
invariant chain
blocks MHCII so no MHCI peptides bind
No
can MHC be on surface without a peptide?
T-cells
thymus is where what develop?
3 steps of t-cell
gene rearrangement, positive selection, negative selection
steps of T-cell -/+
DN, DP, SP
proteins that starts T-cell signal transduction
CD3 - 6 protein cluster
proteins that starts B-cell signal transduction
IG-alpha, IG-beta
cortical epithelial cells
positive selection, MHCI, MHCII on surface, all peptides are self for positive selection
where does positive selection occur?
cortex
where does negative selection occur
medulla
what cells are involved in negative selection?
medullary epithelial cells, MØ, DC
Negative selection
Is TCR self reactive?
Why does T-cell selection need to be so strong?
they activate B-cells
positive selection ideal outcome
interacts with MHCI or MHCII
what do medullar epithelial cells express?
AIRE
AIRE
causes expression of proteins that are normally only in specific tissue
what does AIRE help do
helps eliminate self-reactive T-cells
what happens in an AIRE deficiency?
widespread multi-target autoimmunity
human MHC
HLA: human leukocyte antigen
MHCI varities
HLA-A, HLA-B, HLA-C, coexpressed
MHC varities
HLA-DP, HLA-DQ, HLA-DR, co-expressed
organ donor compatibility is based on what?
HLA compatibility
relationship between HIV and MHC diversity
more diversity = slower onset
HIV impact on cells
kills CD4 T-cells
Mature naive T&B
stage when leave BM, thymus but hasn’t encountered antigen
when are memory cells created?
after activation from encountering an activating pathogen
where do naive cells go?
enter blood, home to 2º lymphoid organs
lymph
clear fluid that drains out of blood and back into lymphatic vessels, moved by bodily movement
high endothelial venue
blood vessel that runs through lymph node, how b and t cells arrive at lymph node
chemokines involved in adhesion process in lymph nodes
CCL19, CCL21
adhesion molecule for naive t and b cells
L-selectin
FDC
follicular dendritic cells
what does FDC do?
secrete CXCL13 to attract B-cells
dendritic are activated…now what
increase MHC, express B7, migrate through lymphatic vessels
chemokine expressed by DC
CCL18
how are T-cells activated
TCR/MHC peptide binding AND B7/CD28 binding
clonal expansion
low affinity IL-2 receptor becomes high affinity upon activation, IL-2 expressed, signals back to itself to divide
why don’t non-activated t-cells clone?
their IL-2 receptors are low affinity, so don’t bind