T Cells/TCR Flashcards
What initiates the adaptive immune response?
APCs
What are 2 things a naive T cell can differentiate into after activation
Effector T cells or Memory T cell
What do effector T cells do?
Produce Cytokines (like IL-4 and IFN-gamma)
What do memory T cells do?
Long lived (weeks/months/years); “protective immunity”: antigen specific; respond quickly if re-exposed to same antigen–> rapid production of effector molecules/fxns
Clonal Selection Hypothesis
1) Lymphocyte clones mature in generative lymphoid organs in absence of antigens.
2) Clones of mature lymphocytes specific for diverse antigens enter lymphoid tissues (e.g. spleen and lymph nodes)
3) Antigen-specific clones are activated (“selected”) by antigens.
4) Antigen-specific immune responses occur. (Anti-X antibody)
What is “protective immunity”?
effector T cells and antibodies persist for weeks after exposure to antigen
What is “immunological memory”?
second exposure to same antigen that produces a much faster resposne
How are dendritic cells activated?
Innate immune system signaling (Toll-like Receptors) –> activate DCs –> cause maturation
How are DC antigens presents?
0) immature DC is in epidermis (Langerhans cell)
1) antigen is captured by DC and then DC is activated/matured
2) DC migrates via lymphatics
3) in the lymph nodes, the mature dendritic cell presents the antigen to the native T cell
What to T cell Receptors recognize?
The MHC complex WITH the peptide. (need to see both)
What two signals are necessary to fully activate a T cell (co-stimulation)?
1) binding of TCR to antigen-HLA(MHC) complex on dendritic cell
2) binding of CD28 (T cell) to B7 (expressed by DC) molecules
**Also causes up-regulation of B7 = fundamental for activiation
What happens if a naive T cell binds to an antigen (on TCR) but CD28 can’t find a B7?
No response or anergy (tolerance)!
It’s co-stimulator deficient so it senses that what it is binding to is NOT not-self (eg: it could be self) –> therefore needs to shut down that T cell (for days/weeks/always) so you don’t have an autoimmune response.
What is the role of IL-12
Co-stimulatory for T cell proliferation (but can’t surpass need for B7 interaction)
What is the normal mechanism of T cell response?
DC’s B7 and MHC+antigen bind to CD28 and TCR (respectively) to activate effector and memory T cells
Why are tumors hard to clear?
May be presenting lots of MHC but are recognized as “self” (no B7 so corresponding T cells are lost)
Native CD8 T cells specific for TRA (tumor restricted antigen) cannot be activated by the tumor cells and may be rendered anergic
( lack co-stimulation, which inhibits T cell responses –> tumor grows)
