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IMMUNOLOGY: CMOD-Week 2 > (09) T Cell Effector Mechanism > Flashcards

(09) T Cell Effector Mechanism Flashcards

1
Q

In what 2 ways do a fully differentiated effector T cell differ from that of a naive T cell?

A
  • Effector T cells do not require co stimulation (no B7)

- Express many adhesion molecules that direct them to the correct tissue

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2
Q

What are the differences in the adhesion molecule expression profile of an activated T cell and an Naive T cell?

A

Activated T Cell:

  • increases: LFA-1, VLA-4, CD2, CD44 and CD45RO
  • decreases: L-selectin (CD8 only) and CD45RA
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3
Q

Why do activated CD4 T cells not lose their L-selectin as they mature?

A

L-selectin is needed to enter 2˚ lymphoid tissue. CD4 effector cells MUST enter 2˚ tissue to serve as the secondary activator of antigen-specific B cells

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4
Q

Why can’t CD8 T cells express L-selectin on their surface?

A

They would enter the 2˚ Lymph tissue and destroy all of the APCs

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5
Q

What does L-selectin bind?

A

Glycam-1 and CD34

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6
Q

What does VLA-4 do?

A

Binds to VCAM-1 found on activated endothelial cells so facilitate diapedesis

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7
Q

what is CD45RA?

A
  • Marker found on naive T cells
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8
Q

What is CD45RO?

A
  • Marker found on activated and memory T cells
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9
Q

What are the 3 main types of effector T cells?

A
  1. CD8 effector (killers)
  2. CD4 helper TH1
  3. CD4 helper TH2
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10
Q

What are the main effector molecules used by CD8 T cells?

A
  • Fas Ligand
  • IFN-gamma
  • Perforin
  • Granzymes
  • Granulysin

(other cytokines - see drawing)

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11
Q

What is the primary effector role of BOTH types of effector helper T cells (CD4)?

A
  • Supply the secondary activation stimuli needed to activate an antigen-specific B cell and drive their differentiation
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12
Q

What additional function do TH1 helper cells have?

A

They activate macrophages to make them more bactericidal and phagocytic

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13
Q

T or F: for Treg cells to perform their effector function they simply must be present in the blood

A

FALSE, Tregs must be present and attached to the same AP cell to prevent self-reactive T cells from functioning

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14
Q

Which regulators are secreted by Tregs to suppress self-reactive Tcells?

A

TGF-ß and IL-10

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15
Q

What do TH17 cells do?

A

**NOTE these are both indirect actions that are actually carried out by endothelial cells

Induced production of chemtractants for Neutrophils (IL-17)

Induce antimicrobial peptide formation (IL-22)

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16
Q

What 2 things must happen for a naive T cell to become activated?

A
  1. Recognition of cognate determinant on MHC by TCR

2. CD28 (T cell) binding to B7 on APC

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17
Q

What molecule is produced after the 2 activation conditions are satisfied for Naive T cells?

A

IL-2, the autocrine growth factor

**This leads to proliferation and differentiation

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18
Q

What happens to T cells after IL-2 has finished promoting proliferation and differentiation?

A

They move out of the secondary lymph tissue and into inflamed tissue.

  • They now act as effector cells
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19
Q

What 3 molecules are secreted by CD8 effector cells to perform their effector function?

A
  • Perforins
  • Granulysin
  • Granzymes
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20
Q

how do each of the following help CD8 cells perform their effector function?

  • Perforins
  • Granulysin
  • Granzymes
A

Perforin - puts holes in the effector cell membrane (similar to MAC)

Granulysin - puts holes in membrane of host (and may have antimicrobial properties)

Granzymes - INITIATE APOPTOTIC PATHWAY if they get into host cytoplasm

**Note: the 1st two perform their function so that granzymes can enter an perform its function

21
Q

What size holes do perforins put in the membrane?

  • why does this conflict with info. about how granzymes enter the cell?
  • how can we reconcile this?
A
  • Perforin (and granulysin) create 16nm holes (NOT EVEN CLOSE TO BIG ENOUGH FOR GRANZYME)
  • We can reconcile this because affected cells endocytose areas affected by pore formation. When they do granzymes enter too.
22
Q

What enzyme is activated by granzymes causing apoptotic death?

A

caspases

23
Q

Besides perforins, granzymes, and granulysins what do CD8 effectors have that helps them perform their effector function and what do these molecules do?

A

INF-gamma
- Drives TH0 differentiation toward TH1 which aids in elimination intracellular infection

Fas-ligand
- binds to Fas and kills host cells

24
Q

What do granzymes bind to on the outer cell surface?

A

Cation-independent mannose 6-P receptors (CI-MPR)

25
Q

What end product of the Fas cascade ultimately leads to cell death?

A

DNA fragments produced by CAD

26
Q

Give an overview of the steps in the Fas cascade.

A
  1. Fas ligand (T cell) binds THREE Fas domain (host)
  2. Caspase 8 binds Fas and activates caspase 3 (via cleavage)
  3. Caspase 3 cleaves ICAD away from CAD
  4. CAD is released and starts chopping up DNA
27
Q

What does ICAD stand for?

A

Inhibitor of CAD

28
Q

T or F: CD8 cells apoptose along with the cells that they kill

A

NO, they simply release granules with killer contents in them

  • They can continue to kill throughout their entire lifespan
29
Q

How do CD8 cells prevent their granule contents from expelling everywhere causing innocent cell death?

A
  • Polarized granulation - this means the granules go to where the MHC is bound to release their contents (this happens quickly)
30
Q

What are some common intracellular bacteria?

A
  • *Mycobacterium Tuberculosis
  • Listeria monocytogenes
  • Salmonella typhi
  • Francisella tularensis
  • Burkholeria pseudomallei
  • Yersinia pestis
31
Q

What type of T cell responds to a macrophage that is infected with an intracellular bacterium (like TB)?

A

TH1 (CD4 helper cells)

32
Q

How does Macrophage activation occur via TH1?

A

TH1 recognizes its cognate ligand on the macrophage

  1. CD40 Ligand on T cell binds CD40 on macrophage
  2. INF-gamma from T cell binds to INF-gamma receptors on macrophage
33
Q

What is the result of macrophage activation?

A
  • Macrophage becomes better at presenting antigens (MHC I and II upregulated) and becomes more bactericidal
34
Q

What specifically are the molecules upregulated by Macrophage activation?

A

Better APC:

  • B7
  • MHC class I
  • MHC class II

More bactericidal:

  • More NO
  • MORE O2-

More inflammation:

  • TNF-alpha
  • THF-alpha receptor
35
Q

Are the general effects of these (3 of 6) cytokines secreted from activated TH1 cells?

  • INF-gamma and CD40 ligand
  • Fas ligand or LT
  • IL-2
A

INF-gamma and CD40 ligand
- activates macrophages to destroy engulfed bacteria

Fas Ligand or LT
- Kills chronically infected macrophages, releasing bacteria to be destroyed by healthy macrophages

IL-2
- Induces T cell proliferation, increasing the number of effectors

36
Q

Are the general effects of these (3 of 6) cytokines secreted from activated TH1 cells?

  • IL-3 and GM-CSF
  • TNF-alpha and LT
  • CXCL2
A

IL-3 and GM-CSF
- Induce macrophage differentiation in bone marrow

TNF-alpha and LT
- Activates endothelium to induce macrophage adhesion and exit form the blood vessel at the site of infection

CXCL2
- Causes macrophages to accumulate at the site of infection

37
Q

What is the most important function of CD4 effector T cells?

A

Supplying secondary activation signals to naive B cells

38
Q

What two signals are needed for B cells to become activate?

A
  1. Must be bound to cognate antigen

2. CD40-ligand (T cell) binding to CD40 on the B cell

39
Q

What brings effector CD4 (TH1 or TH2) T cells into close enough proximity to allow CD40 binding?

A

MHC present it cognate peptide that is present AFTER the B cell (antibody) receptor brings in the molecule for endocytosis

**NOTE: because they are CD4 T cells and b/c of the method its most likely to present the antigen on MHC class II

40
Q

T or F: TH1 AND TH2 cells can activate B cells

A

True

41
Q

What is the the difference in TH1 and TH2 binding to a B cell?

A

TH1:
- typically fights intracellular infection so it promotes the B cell to produce IgG1 and IgG3 (strong OPSONIZERS)

TH2:
- typically fights extracellular infection so produces weakly opsonizing antibodies (IgG2, IgG4, IgA, and IgE)

42
Q

What is Histoplasma capsulatum?

A

A fungus that lives intracellularly (inside macrophages)

43
Q

***Why does granuloma formation occur with infections of Mycobacterium TB and Histoplasma capsulatum?

A

Even activated macrophages can’t kills these infections so Macrophages fuse and get surrounded by TH1 CD4 effector T cell

**this forms a wall preventing DISSEMINATION

44
Q

Why are people with immune deficiency of T cells at increased risk for systemic infection by TB?

A

Granulomas don’t form because THEY REQUIRE T CELLS

  • Infection can disseminate and cause systemic disease
45
Q

If a Treg is bound to a cell, what can you almost guarantee about the cell?

A

Its a SELF cell, because Tregs are pick specifically because they do recognize self

46
Q

What requirements must be met before a Treg can become activated?

A
  1. It recognizes self antigen (on MHC II)

2. CTLA-4 (Treg) binds to B7 on APC

47
Q

What is released after Treg binds to MHC II (self) and CTLA-4:B7?
- why these?

A

IL-10 and TGF-beta are released, these down regulate any T cells nearby and decrease inflammation

48
Q

What happens if you suffer from a Treg deficiency?

A

Autoimmune disease

IMMUNOLOGY: CMOD-Week 2 (11 decks)

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