Lecture 13 T cell mediated immunity Flashcards
Why do we need adaptive immunity?
- immunological memory, specificity, flexibility, respond to evolution, efficiency
Why are T cells necessary as part of adaptive immunity?
- induce B cell response
- cell mediated response (cancer)
T cell targets given antigen only in the presence of ____
self
cytotoxic T cells recognize ___ aa peptides in context of MHC I (genes: ____)
8-10; AB&C
helper T cells recognize ___ aa peptides in context of MHC II (genes: ___)
12-25; DP, DM, DO, DQ, DR
What are the three developments of the immune response?
- nonspecific, innate
- central (priming) phase
- T cell effector phase
The central (priming) phase occurs in _______ and T cells are primed by ___
central lymph node; APC
The T cell effector phase (______ _______) is directed at _______ and makes the area inflammatory
secondary activation; target tissue
T helper cell types
1, 2, 17, follicular
Priming stage starts by initial ___ recognition of antigen by _____
TCR; professional APC
The priming stage is _____
afferent
The effector stage refers to ______ recognition by effector T cells. It requires signal __
invader/source; 3
T cell priming occurs in the _______ which is why there is ______ after vaccination
draining lymph node; swelling
T cells enter lymph node cortex via _____ and meet up with DCs in _______. DCs enter via lymphatics.
high endothelial venules;
paracortex
Describe how T cells are trafficked into draining lymph node
- rolling (L-selectin binds CD62L)
- activation by CCR7
- adhesion via LFA-1 and ICAM (integrins)
- diapedesis CCR7 responds to CCL21, CCL19, CXCL12
_____ is a lipid chemoattracant and would cause the T cell to get out of the lymph node. ____ downregulates this factor so they are stuck. This is an activation marker, showing they’ve been activated by DC.
S1PR1; CD69
If T cells are not activated by DCs, they will not exhibit ____, so they will
CD69; GTFO
DCs present to ____ T cells
naive
Macrophages and B cells present to _______ T cells. The ____ results in function (autophagic/antibody production)
effector;
CD40L
______ discovered DC
Ralph Steinmann
______ DC produce buckets of IFN-alpha
plasmacytoid
Mature DCs express more
CCR7, CD80/86, CD40, MHC, CD25, ICAM
DCs can pick up antigens via
receptor-mediated endocytosis, macropinocytosis, viral infection, cross presentation after uptake, or transfer from incoming DC to resident
TLR signaling induces _____ expression so that DCs migrate to the ________ upon maturation
CCR7; lymph node via draining lymphatics
Resident DCs have a tendency to interact with ____ first. Migratory DCs tend to interact with ___ first
CD8+; CD4+
T cell: APC binding
Supermolecular activation complex (SMAC)
first LFA-1:ICAM (pSMAC)
then TCR binds MHC/antigen (cSMAC), signals LFA-1 to keep binding,
CD8/4 facilitate binding, CD28 binds CD80/86 (cSMAC)
What happens during polarization of T cell?
CD45 moves distal (dSMAC)
TCR, CD28 closes in
Signal 1
TCR: MHC
tells the identity of the problem maker
Signal 2
CD28: CD80/86
impacts survival of T cell and magnitude of activation/response
tells how dangerous the problem is
Signal 3
cytokines to TCR,
tells this is what you are supposed to do
What occurs in signal 2 only (no signal 1)
no effect
What occurs in signal 1 only (no signal 2)
anergy/deletion of T cell (decreased TCR signaling through induction of GRAIL and activation of Cbl)
so that you don’t kill yourself
An activated T cell expresses ____, the alpha chain that increases affinity for ____ so the cell is now susceptible as an autocrine factor
CD25; IL-2
