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T Cells 2 Flashcards

1
Q

What type of cells express Fas and CD40 ligands?

A

CTLs, some effector CD4+ cells, and B cells

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2
Q

are Fas and CD40 ligands expressed on naive T cells?

A

no

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3
Q

when are Fas and CD40 ligand genes induced?

A

genes included in the group of genes that are induced after signals 1,2,3

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4
Q

what type of ligands are Fas and CD40?

A

transmembrane

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5
Q

what type of cytokines are Fas and CD40?

A

TNF

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6
Q

what type of interaction are Fas and CD40 ligands involved in?

A

cell-to-cell

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7
Q

what type of cells is Fas ligand expressed on and where on the cell?

A

expressed on the surface of effector CD8+ cells and TH1 cells

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8
Q

how is Fas ligand used by CD8+ T cells?

A

to exert cytotoxic effect and kill infected cells

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9
Q

where does Fas ligand bind?

A

binds Fas on surface of infected cells in the periphery/site of infection

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10
Q

when do cells express Fas?

A

when they are stressed/damaged

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11
Q

what type of cells express CD40 ligand?

A

TH1, TH2, TH17, TFH cells

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12
Q

where does CD40 ligand bind?

A

binds CD40 on B cells and innate immune cells

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13
Q

what is the role of CD40 ligand binding to CD40?

A

activates target cells –> allows for DC licensing (cross-presentation) and expression of more co-stimulatory molecules

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14
Q

what are the 3 signals for generating CTLs?

A
  1. TCR binds MHC I
  2. co-stimulatory signal transmitted by CD28-B7
  3. IL-2 induces proliferation and differentiation into CTL
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15
Q

why don’t CD8+ T cells require polarizing cytokines?

A

there is only 1 type of effector CD8+ T cell so don’t need to be directed to specific types

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16
Q

what are 3 CD8+ specific considerations?

A
  1. CD8+ T cells require more co-stimulation than CD4
  2. IL-2 can be autocrine AND paracrine (from neighbouring TH1 or TH17)
  3. Requires help of effector CD4+ T cells
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17
Q

how do CTLs recognize and kill infected/tumour cells?

A

using their TCR

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18
Q

what is the simplest and most rare method for CD8+ cell activation?

A

DCs present antigen on MHC I with co-stimulatory molecules

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19
Q

what is the most common method for CD8+ T cell activation?

A

CROSS-PRESENTATION –> licensed by CD4+ effector T cells

20
Q

what are the general steps leading to cross-presentation?

A

PRR on DC recognizes viral PAMP as exogenous peptide –> MHC II –> cross presented to MHC I –> CD8+ T cell activated

21
Q

what are the 2 types of cross-presentation for CD8+ T cell activation?

A
  1. sequential
  2. simultaneous
22
Q

describe SEQUENTIAL cross-presentation

A
  1. CD40 on APC interacts with CD40 ligand on CD4+ T cell
  2. APC is licensed
  3. CD4+ T cell leaves, CD8+ T cell comes
  4. CD8+ T cell activated
  5. CD8+ T cell produces IL-2 for proliferation then differentiation
23
Q

describe SIMULTANEOUS cross-presentation

A
  1. CD40 on APC APC interacts with CD40 ligand on CD4+ T cell
  2. APC is licensed
  3. CD8+ T cell is already there and interacts with APC before CD4+ T cell can leave
  4. CD8+ T cell activated
  5. CD4+ and CD8+ both produce IL-2 to induce proliferation
24
Q

what is the role of CD40 signaling?

A

causes DC licensing and expression of more co-stimulatory molecules for cross- presentation

25
what 3 things need to happen to CD4+ T cells in order for CD8+ T cell activation to occur?
1. find peptide - MHC II match 2. receive all 3 signals 3. expression of CD40 ligand that binds to CD40 on APC
26
what 5 things need to happen to DCs to allow them to present antigen to both CD4+ and CD8+ T cells?
1. encounters a PAMP 2. travels to secondary lymphoid organ (lymph node) 3. presents antigen on MHC II to CD4+ T cell 4. licensed thru CD40 binding 5. presents exogenous antigen on MHC I to CD8+ T cell
27
what occurs during activation of CD4+ T cell?
1. IL-2 secretion 2. CD40 ligand expression
28
what 2 things does APC licensing by CD40 cause?
1. increased expression of co-stimulatory ligands CD80/86 2. induction of 4-1BBL
29
what is the role of 4-1BBL?
provides co-stimulatory molecules (along with CD80/86) to further activate CD8+ T cells
30
Assistance by CD4+ T cells is critical for _____
Assistance by CD4+ T cells is critical for generating memory CD8+ T cells
31
what is required for producing memory CD8+ T cells?
cross-presentation
32
how do CTLs kill infected cells in the periphery?
thru interaction of TCR with pMHC I and presence of CD8 co-receptor
33
why are CTLs able to kill periphery cells?
all nucleated cells have MHC I and CTLs kill via TCR interaction with MHC I
34
what are the 2 effector functions of CTL?
1. induces apoptosis to kill infected cells 2. secrete cytokines to direct the immune response
35
what are the 2 ways that CTLs induce apoptosis?
1. Fas-Fas ligand 2. granules
36
how do CTLs target infected cells?
Initial interaction is via non-specific adhesion molecules to anchor itself - if pMHC isn't a match --> CTL moves on - if CTL recognizes pMHC --> cell has been infected then infected cell is killed
37
describe Fas-FasL mediated killing
- effector CTL expresses Fas ligand - infected cell expresses Fas 1. Fas binds FasL and induces signaling cascade 2. procaspases cleaved to caspases 3. target cell undergoes apoptosis
38
describe granule-mediated killing
- specific recognition via TCR:pMHC - reorganization of cytoskeleton and cytoplasmic contents so that granules get closer to infected cell - granules released at point of cell contact
39
what are the 2 types of proteins in CTL granules?
1. perforin 2. granzymes B
40
what are CTL granules?
cytotoxins
41
what does perforin do?
helps to deliver contents of granules into cytoplasm of target cell by making pores
42
what does granzyme B do?
it is a serine protease that cleaves things to activate apoptosis once in the cytoplasm of the target cell
43
describe granzyme/perforin-mediated cytolysis
1. TCR on CTL binds pMHC 2. intracellular signaling is triggered 3. leads to reorganization of cytoplasm and cytoskeleton 4. PERFORIN punches holes in the membrane 5. GRANZYME B enters cytoplasm and causes proteolytic cleavage of procaspases 6. leads to cell fragmentation and cell death
44
what is membrane blebbing?
cytoskeleton breaks and membrane bulges outward, a sign of apoptosis
45
besides infected cells, what other type of cells can CTLs kill?
tumour cells
46
what are the 2 types of CTL pathways and where do they converge?
1. Perforin/granzyme pathway 2. Fas/FasL pathway both converge on CASPASE 3 activation, leading to apoptosis
47
how does CTL kill cells that are close to one that it has already killed?
- CTL killing does not affect neighbouring cells, so it must undergo the exact same process for the next cell kills 1 cell, dissociates, then restart by looking at other cells via non-specific binding

MIMM 214 (33 decks)

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