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Veterinary Immunology > Lecture 18 - T cell function and destruction of cell associated invaders > Flashcards

Lecture 18 - T cell function and destruction of cell associated invaders Flashcards

1
Q

Two CD8 functions

A
  1. cytotoxic/regulatory
  2. memory
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2
Q

Cytotoxic T lymphocytes are CD_

A

CD8+

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3
Q

What do CD8+ T cells recognize antigens on

A

MHC I

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4
Q

What happens once CD8+ T cells recognize antigen on MHCI

A

clonally expand, differentiate, and develop a killing machinery in their cytoplasm

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5
Q

When do CD8+ T cells kill a cell

A

kill cells that have the antigen it recognizes bound to an MHC I molecule

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6
Q

CD8+ T cells are important in

A

protection from intracellular microbes that cause the synthesis of foreign proteins in the cytoplasm such as viruses

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7
Q

Apoptosis

A

programmed cell death or cell suicide that involves the controlled dismantling of intracellular components while avoiding inflammation and damage to surrounding cells

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8
Q

Initiator caspases activate

A

executioner caspases that subsequently coordinate their activities to demolish key structural proteins and activate other enzymes

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9
Q

What are the morphological hallmarks of apoptosis

A

DNA fragmentation and membrane blebbing

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10
Q

What are the hallmarks of necrosis

A

membrane degradation, release of cytoplasmic contents, inflammation, involvement of larger area

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11
Q

2 major pathways of apoptosis

A
  1. intrinsic or mitochondrial
  2. extrinsic or death receptor pathway
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12
Q

What is the role of caspases in inflammation and apoptosis

A

endopeptidases that are important in maintaining homeostasis through regulating apoptosis and inflammation

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13
Q

What do initiator caspases do

A

activated by multimolecular death complexes

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14
Q

What do effector caspases do

A

break down cellular structures

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15
Q

What do inflammatory caspases do

A

activated by multimolecular inflammasomes

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16
Q

What are the initiator caspases

A

2, 8, 9, 10, 14

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17
Q

What are the effector caspases

A

3, 6, 7

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18
Q

What are the inflammatory caspases

A

1, 4, 5, 11

19
Q

How does caspase get activated intrinsically

A

cell stress, DNA damage->granzymes->release cyt c from mitochondrion->apoptosome->activate caspase 9->activate effector caspase->DNA frag, cytoskeleton disruption, chromatin disruption->apoptosis

20
Q

How does capsase get activated extriniscally

A

CD95L->DISC->caspase 8 activation->activate effector caspase->DNA frag, cytoskeleton disruption, chromatin disruption->apoptosis

21
Q

List the characterisitcs of apoptosis in order

A
  1. normal cell
  2. clumping of chromatin, blebbing, loss of organelles
  3. nuclear fragmentation, apoptotic bodies
  4. apopotic bodies
22
Q

Steps of apoptosis with cytotoxic T cell responses

A
  1. antigen recognition and binding of CTL to target cell
  2. CTL activation and granule exocytosis
  3. apoptosis of target cell
23
Q

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 _____

A
  1. naive CTL, secondary lymphoid tissue
  2. Proliferation, differentiation, Pre-CTLs
  3. armed
  4. Activation, non-self peptide, MHC Class I
  5. CTL-mediated destruction, pMHC
24
Q

Unlike naive T cells, to activate armed CTL, what is needed and what is NOT needed

A

only engagement of single TCR by a single specific pMHC is needed, no costimulation needed

25
Q

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 ____

A
  1. cytoskeleton, granules, CTL-target cell
  2. CTL membrane, exocytosed
  3. perforin, granzymes
  4. pore-forming protein, serine proteases
26
Q

What is CD95 or Fas

A

transmembrane death receptor that is widely expressed on mammalian cells

27
Q

What do naive cytotoxic T cells NOT express, what do they express after activation and conjugate formation

A

Fas-ligand (FasL/CD95L); FasL on CTL surface

28
Q

Engagedment of Fas on a target cell by FasL or CD95L expressed by armed CTL results in

A

death of the target cell by apoptosis

29
Q

What does the CD95L-CD95 system regulate

A

T cell survival

30
Q

What happens to do unwanted surplus or self-reactive T cells

A

eliminated once they have served their functions

31
Q

Killing target cells using immune pathways MHC restricted or not??
1. cytotoxic T cell
2. Macrophage
3. Neutrophil
4. NK cell

A
  1. yes
  2. no
  3. no
  4. no
32
Q

What is the most efficient pathway of killing target cells

A

cytotoxic T cell

33
Q

What are activated macrophages capable of killing

A

resistant intracellular bacteria

34
Q

How can macrophages be activated

A
  1. infection
  2. phagocytosis
  3. TNF a
  4. IL-12->Th1 cell
  5. IFNy, IL-2
  6. fully activated macrophage
35
Q

What can lead to an incompletely activated macrophage vs a fully activated macrophage

A

NK cell; Th1 cell

36
Q

M1 macrophages are activated by what activation

A

classical activation

37
Q

Describe classical activation

A
  1. Th1 cells
  2. IFNy, TNF a, IL-2
  3. M1
  4. increases IL-1, 6, 12, 23, NO, INOS
38
Q

M2 macrophages are activated by what activation

A

alternative activation

39
Q

Describe alternative activation

A
  1. Th2 cells, Treg
  2. IL-4, 10, 13
  3. M2
  4. Increases IL-1RA, 10, Arginase, TGF B
40
Q

Function of M1 macrophages

A

increased antimicrobial activities

41
Q

Functions of M2 macrophages

A

wound healing and immune regulation

42
Q

Cytotoxic extrinsic pathway includes ___ while the instrinsic pathway includes ____

A
  1. perforins, granzymes
  2. Fas, ligand
43
Q

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.

A
  1. endosomes
  2. M2
  3. IFNy
  4. Th1

Veterinary Immunology (20 decks)

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