Lecture 18 - T cell function and destruction of cell associated invaders Flashcards
Two CD8 functions
- cytotoxic/regulatory
- memory
Cytotoxic T lymphocytes are CD_
CD8+
What do CD8+ T cells recognize antigens on
MHC I
What happens once CD8+ T cells recognize antigen on MHCI
clonally expand, differentiate, and develop a killing machinery in their cytoplasm
When do CD8+ T cells kill a cell
kill cells that have the antigen it recognizes bound to an MHC I molecule
CD8+ T cells are important in
protection from intracellular microbes that cause the synthesis of foreign proteins in the cytoplasm such as viruses
Apoptosis
programmed cell death or cell suicide that involves the controlled dismantling of intracellular components while avoiding inflammation and damage to surrounding cells
Initiator caspases activate
executioner caspases that subsequently coordinate their activities to demolish key structural proteins and activate other enzymes
What are the morphological hallmarks of apoptosis
DNA fragmentation and membrane blebbing
What are the hallmarks of necrosis
membrane degradation, release of cytoplasmic contents, inflammation, involvement of larger area
2 major pathways of apoptosis
- intrinsic or mitochondrial
- extrinsic or death receptor pathway
What is the role of caspases in inflammation and apoptosis
endopeptidases that are important in maintaining homeostasis through regulating apoptosis and inflammation
What do initiator caspases do
activated by multimolecular death complexes
What do effector caspases do
break down cellular structures
What do inflammatory caspases do
activated by multimolecular inflammasomes
What are the initiator caspases
2, 8, 9, 10, 14
What are the effector caspases
3, 6, 7
What are the inflammatory caspases
1, 4, 5, 11
How does caspase get activated intrinsically
cell stress, DNA damage->granzymes->release cyt c from mitochondrion->apoptosome->activate caspase 9->activate effector caspase->DNA frag, cytoskeleton disruption, chromatin disruption->apoptosis
How does capsase get activated extriniscally
CD95L->DISC->caspase 8 activation->activate effector caspase->DNA frag, cytoskeleton disruption, chromatin disruption->apoptosis
List the characterisitcs of apoptosis in order
- normal cell
- clumping of chromatin, blebbing, loss of organelles
- nuclear fragmentation, apoptotic bodies
- apopotic bodies
Steps of apoptosis with cytotoxic T cell responses
- antigen recognition and binding of CTL to target cell
- CTL activation and granule exocytosis
- apoptosis of target cell
Cytotoxic T cell responses occur in 5 stages:
1. Activation of ______ by a DC in _____
2. ___ and ____ of the activated CTL cell into daughter cells called ____
3.____ of a pre-CTL in an inflammatory site into an “____” CTL
4. ______ of the armed CTL by encounter with specific _____ presented by _____ on a target cell
5. ______ of the target cell as well as other cells displaying the identical _____
- naive CTL, secondary lymphoid tissue
- Proliferation, differentiation, Pre-CTLs
- armed
- Activation, non-self peptide, MHC Class I
- CTL-mediated destruction, pMHC
Unlike naive T cells, to activate armed CTL, what is needed and what is NOT needed
only engagement of single TCR by a single specific pMHC is needed, no costimulation needed
Perforin pathway of cell killing
1. After conjugate formation, ___ of the CTL reorganizes to bring cytotoxic ___ to the site of ____ contact.
* The granules fuse with ____ and their contents are directionally ___ towards the target cell membrane.
* ___ & ___ are major contents of these granules.
* Perforin is a ___ and the granzymes are a family of ____
- cytoskeleton, granules, CTL-target cell
- CTL membrane, exocytosed
- perforin, granzymes
- pore-forming protein, serine proteases
What is CD95 or Fas
transmembrane death receptor that is widely expressed on mammalian cells
What do naive cytotoxic T cells NOT express, what do they express after activation and conjugate formation
Fas-ligand (FasL/CD95L); FasL on CTL surface
Engagedment of Fas on a target cell by FasL or CD95L expressed by armed CTL results in
death of the target cell by apoptosis
What does the CD95L-CD95 system regulate
T cell survival
What happens to do unwanted surplus or self-reactive T cells
eliminated once they have served their functions
Killing target cells using immune pathways MHC restricted or not??
1. cytotoxic T cell
2. Macrophage
3. Neutrophil
4. NK cell
- yes
- no
- no
- no
What is the most efficient pathway of killing target cells
cytotoxic T cell
What are activated macrophages capable of killing
resistant intracellular bacteria
How can macrophages be activated
- infection
- phagocytosis
- TNF a
- IL-12->Th1 cell
- IFNy, IL-2
- fully activated macrophage
What can lead to an incompletely activated macrophage vs a fully activated macrophage
NK cell; Th1 cell
M1 macrophages are activated by what activation
classical activation
Describe classical activation
- Th1 cells
- IFNy, TNF a, IL-2
- M1
- increases IL-1, 6, 12, 23, NO, INOS
M2 macrophages are activated by what activation
alternative activation
Describe alternative activation
- Th2 cells, Treg
- IL-4, 10, 13
- M2
- Increases IL-1RA, 10, Arginase, TGF B
Function of M1 macrophages
increased antimicrobial activities
Functions of M2 macrophages
wound healing and immune regulation
Cytotoxic extrinsic pathway includes ___ while the instrinsic pathway includes ____
- perforins, granzymes
- Fas, ligand
Some bacteria and parasites may evade destruction by living within the ____ of phagocytic cells, especially macrophages.
The elimination of these intracellular organisms is mediated by activation of ___ macrophages by ____ produced by ___ cells.
- endosomes
- M2
- IFNy
- Th1
