Cellular immune response Flashcards
Cellular immune response:
- provided by?
- provides?
- provided by T cells (Th, Tc)
- provides immunity to: intracellular bact, virus, fungi, protozoa, tumors, parasites
T cells recognize antigen only when it is
presented on the surface of APC by MHC I molecules
T cells must recognize ____ to start immune response
antigens
Infected cells are
killed, activated & destroyed intracellular organism/pathogen
T cell cytotoxicity, 2 mechanisms?
Intrinsic & extrinsic pathway
Intrinsic pathway
- release of enzymes (granzymes & perforins) from cytotoxic T cells
- Granzymes go to mitochondria to produce Cytochrome C
- stimulates caspases which produce DNA fragmentation, cytoskeletal distruption, chromatin disruption
- all leads to APOPTOSIS
Extrinsic pathway
- cytotoxic T cells have CD95L binds w/ CD95 on target cells
- Binding forms DISC (Death Inducing Signaling Complex)
- This produces caspase 8
- leads to APOPTOSIS
Three different types of caspases
initiator-multi-molecular death complexes
effector-break down cellular structures
inflammatory-activated by multimolecular infammasomes
Major morphological features of cell death by apoptosis
- normal cell
- clumping of chormatin, blebbing of cell membrane, loss of organelles
- nuclear fragmentation
- apoptotic bodies
Only 1 type of antigen presenting cell that can trigger cellular/humoral response
dendritic cells –> antigens must be endogenous or intracellular. Only presented on MHC I. Produce increase IL-12
Only molecule that interacts with MHC I is
CD8
CD40/CD154 interaction w/ Dendritic cell. Helper cell –> Th1 w/ CD4. Produce increase IL-2 & IFN-γ. Produce activation of
CD8 T cells. Main activity on target cell –> apoptosis, recognize MHC I & antigen
CD4 produces increase in
IL-12 which produces even more activation of dendritic cells. CCL22 is chemotoxic
CD8+ T cell mediated cytotoxicity
- CAM- “arms” that hold target cell from cytotoxic T cell
- Fas liknks w/ FasL
- CD8 –> MHC I
- Granules move towards cell interaction
- Cytotoxic T cell release Lytic granuales (LG) and induce apoptosis on target cell
When target cell is affected by LG, MHC I
MHC I & CD8 degrade as well
Major pathways that cells of the immune system can kill target cells. (target cells are tumor, or infected cells)
- cytotoxic T cell = MCH restriction
- macrophage = not MHC restricted
- Neutrophil = not MHC restricted
- NK cell = not MHC restricted
What can be released by Th1 cells that activates macrophages and enables them to kill otherwise resistant intracellular bacteria?
IFN-γ and IL-2
____ are very important in activating the macrophage
cytokines
Two pathways by which macrophages can be activated
- one involves IFN-γ production but NK cells & is an innate pathway
- one is mediated by IFN-γ from Th1 cells and is an adaptive response
Depending on their cytokine, macrophages may be ____ activated or ____ activated
- classically (M1 cells)
- alternatively (M2 cells)
What cells have a major regulatory role and are critical to granuloma formation & wound healing? Producing very different cytokine mixtures
M2 cells
Classical activation
IFN-γ, TNF-α (Th1 cells) –> M1 –> Increased IL-1, 6, 12, 23, NO, iNos –> INFLAMMATION
Alternative activation
IL-4,10,13 (Th2 cells, Treg cells) –> M2 –> increased IL-1RA, IL-10, Arginase, TGF-β –> RESOLUTION OF INFLAMMATION- wound repair, cell proliferation
Naive CD8+ T cell differentiates into
- effector CD*+ T cell (killing of infected target cell, macrophage activation)
- memory CD*+ T cell (peripheral tissues)
Effector Memory T cell:
- CD44+
- Increase IL-2 receptor
- Increase adhesion molecules
- Increase IL-4, IFN-γ
- Increase TCR stimulation
- IL-15 –> Tc memory survival
- Human T cell memory survival 8-15 years
T cell cytotoxicity induces apoptosis on the target cell by the activation of caspase cascade (extrinsic and intrinsic) T/F
TRUE
The extrinsic & intrinsic pathways triggers a cascade of enzymes activation to induce apoptosis on the target cell these pathways are activated by the interaction of T cell receptor and the MHC type I antigen. T/F
TRUE
