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MIMM 214 > T Cells 2 > Flashcards

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
Q

what 3 things need to happen to CD4+ T cells in order for CD8+ T cell activation to occur?

A
  1. find peptide - MHC II match
  2. receive all 3 signals
  3. expression of CD40 ligand that binds to CD40 on APC
26
Q

what 5 things need to happen to DCs to allow them to present antigen to both CD4+ and CD8+ T cells?

A
  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
Q

what occurs during activation of CD4+ T cell?

A
  1. IL-2 secretion
  2. CD40 ligand expression
28
Q

what 2 things does APC licensing by CD40 cause?

A
  1. increased expression of co-stimulatory ligands CD80/86
  2. induction of 4-1BBL
29
Q

what is the role of 4-1BBL?

A

provides co-stimulatory molecules (along with CD80/86) to further activate CD8+ T cells

30
Q

Assistance by CD4+ T cells is critical for _____

A

Assistance by CD4+ T cells is critical for generating memory CD8+ T cells

31
Q

what is required for producing memory CD8+ T cells?

A

cross-presentation

32
Q

how do CTLs kill infected cells in the periphery?

A

thru interaction of TCR with pMHC I and presence of CD8 co-receptor

33
Q

why are CTLs able to kill periphery cells?

A

all nucleated cells have MHC I and CTLs kill via TCR interaction with MHC I

34
Q

what are the 2 effector functions of CTL?

A
  1. induces apoptosis to kill infected cells
  2. secrete cytokines to direct the immune response
35
Q

what are the 2 ways that CTLs induce apoptosis?

A
  1. Fas-Fas ligand
  2. granules
36
Q

how do CTLs target infected cells?

A

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
Q

describe Fas-FasL mediated killing

A
  • 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
Q

describe granule-mediated killing

A
  • 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
Q

what are the 2 types of proteins in CTL granules?

A
  1. perforin
  2. granzymes B
40
Q

what are CTL granules?

A

cytotoxins

41
Q

what does perforin do?

A

helps to deliver contents of granules into cytoplasm of target cell by making pores

42
Q

what does granzyme B do?

A

it is a serine protease that cleaves things to activate apoptosis once in the cytoplasm of the target cell

43
Q

describe granzyme/perforin-mediated cytolysis

A
  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
Q

what is membrane blebbing?

A

cytoskeleton breaks and membrane bulges outward, a sign of apoptosis

45
Q

besides infected cells, what other type of cells can CTLs kill?

A

tumour cells

46
Q

what are the 2 types of CTL pathways and where do they converge?

A
  1. Perforin/granzyme pathway
  2. Fas/FasL pathway

both converge on CASPASE 3 activation, leading to apoptosis

47
Q

how does CTL kill cells that are close to one that it has already killed?

A
  • 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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