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Immunology > Week 4: T Cell Activation Part 2 > Flashcards

Week 4: T Cell Activation Part 2 Flashcards

1
Q

Describe the function of co-simulatory signals?

A

Required for optimal T cell activation and proliferation

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2
Q

What are signals for naive T cell activation?

A
  1. Antigen specific TCR engagement (activation)
  2. Contact with co-stimulatory ligands (survival)
  3. Cytokines directing T cell differentiation into distinct effector cell types (differentiation)
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3
Q

What is required for T cell activation?

A

Cell to cell contact

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4
Q

What is immunologic synapse?

A

The interface between the APC and the naive T cell

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5
Q

How is immunologic synapse initiated?

A

TCR recognition of MHC and stabilized by interaction of the T cell co-receptor (CD 4 and 8) with MHC

Additional interactions strengthen and stabilize the synapse

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6
Q

What interactions occur between TCR and MHC in stage 1?

A
  1. DC, macrophages, or B cells provide signal to activate T cells
  2. DC are effective when activating naive CD4 T cells because they express co-stimulatory molecules and MHCII
  3. Macrophage MHC II expression is inducible
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7
Q

What are positive costimulatory receptors?

A

Facilitate activation

CD28 and ICOS

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8
Q

What are negative costimulatory receptors?

A

Help turn activation off

CTLA4, PD1, BTLA

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9
Q

Describe the characteristics of CD28?

A
  1. Expressed on majority of T cells
  2. Enhances TCR induced proliferation and survival
  3. Binds to B7-1 (CD80) and B7-2 (CD86) expressed by APCs
  4. involved in initial activation events in T cells
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10
Q

Describe the characteristics of ICOS?

A
  1. Inducible costimulator, binds to ICOS ligand on activated APS
  2. Expressed on memory and effector T cells
  3. May help maintain activity of already differentiated cells
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11
Q

Describe the characteristics of CTLA4 (CD152)?

A
  1. Induced within 24 hr after activation, peaks 2-3 days post stimulation
  2. Binds to B7-1/B7-2 with higheraffintiry than CD28 but shuts down signaling pathways (brakes)
  3. Biologic drug mimics their interactions (abatacept)
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12
Q

Describe the characteristics of PD-1 (CD279) ?

A
  1. PD1 help to mediate T cell tolerance in non-lymphoid tissues
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13
Q

Describe the characteristics of BTLA (B and T lymphocyte attenuator)

A

Down regulates inflammatory and autoimmune responses

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14
Q

What helps regulate T cell activation in the periphery?

A
  1. cell surface adhesion molecules
  2. co-receptors
  3. cytokine receptors
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15
Q

What are cell adhesion molecules?

A

Promote T cell homing to specific tissues by binding ligands on vascular endothelial cells

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16
Q

What are integrins (LFA-1)?

A

Mediate homing of the lymphocyte to the site of infection and inflammation

Helps with binding of the T cell to the APC

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17
Q

What are the functions of co-receptros?

A

Induced and recruited to the immunological synapse between TCR and MHC on the APC

CD8 binds to MHCI
CD4 binds to MHCII

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18
Q

What provides signal 3?

A

Cytokines which can be stimulatory or inhibitory

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19
Q

What is IL2?

A

Growth factor for activated CD4 and CD8 T cells (autocrine)

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20
Q

What are super antigens?

A
  1. Viral/bacterial proteins that bind to specific Vb regions of TCRs and a chain of class II MHC
  2. Short circuits needed for co-stimulation
  3. Procudes dramatic cytokine secretion by inappropriately activated T cells
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21
Q

What can produce super antigens?

A

Staphylococcus associated with food poisoning and toxic shock syndrom

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22
Q

Do effect T cells need to be costimulated?

A

No if they already encountered their specific antigen

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23
Q

What happens once a naive T cells is activated?

A

Leads to clonal expansion and differentiation into effector and memory cell subsets

  1. Initial activation leads to induction of signals 1 and 2
  2. Clonal expansion (rust proliferation)
24
Q

How does signal 1 and 2 respond to intial activation?

A
  1. T cell activation
  2. Upregulation of pro-survival genes
  3. Transcription of IL2 and IL2R genes
25
What is clonal expansion?
Production of memory and effect clonal cell populations
26
How are memory T cells formed?
During adaptive immune response and persist in the absence of their antigen that induce them
27
Describe differentiation of CD8?
1. CTLs are selective and serial killers of cells at the site of infection. 2. TCR binds to MHC class I molecules 3. Immunological synapse is formed. 4. CTLs kill their target cells by inducing apoptosis by perforin-granzyme release
28
What are polarizing cytokines?
(lineage specifying cytokines) determine which subset of helper T cell will be produced from a naïve CD4+ T cell Send a polarizing signal to the T cell that leads to activation of unique transcription factors that determine which cytokine genes are expressed
29
What pathway is associated with polarizing cytokines?
JAK-STAT pathway
30
What are TH1?
Mediates cellular immunity to intracellular microbial pathogens by secreting cytokines that eradicate microbes that can survive in macrophages
31
What causes TH1 differentiation?
IL12 and IFN-y
32
What are the products of of TH1 and what do they do?
TNF-a and IFN-y 1. Leads to class switching to IgG classes that support opsonization and complement fixation 2. Supports differentiation of antiviral CD8+ cytotoxic T cells 3. Activates other T cells, NK cells, and macrophages
33
What is TH2?
Promotes humoral immunity to extracellular microbial pathogens by producing cytokines that activates B cells
34
What promotes TH2?
IL-4
35
What is produced after the activation of TH2?
IL-4, IL5, IL13
36
What is the function of IL4?
Induces class switching to IGE which helps other cell types to release anti-parasite inflammatory mediator molecules eventually promoting the activation of eosinophils, mast cells, and basophils
37
What is the function of an activated TH17?
1. Controls fungal and extracellular bacterial infections by enhancing the neutrophil response and amplifying inflammation 2. Promotes B cell class switching to IgG to promote opsonization response 3. Enhances the production of antimicrobial peptides by epithelial cells within mucosal surfaces
38
What is IL17?
Associated with chronic inflammatory and autoimmune resposnes
39
What activates a TH17?
IL1, IL6, IL23, TGFb
40
What is secreted by TH17?
IL17, IL22
41
What are the polarizing cytokines?
IL6 and IL21
42
What is the function of Tfh?
1. Help B cells produce antibodies against most foreign pathogens 2. Cause rapid proliferation and differentiation of B cells into plasma cells
43
Where are Tfh found?
Secondary lymphoid tissues in B cell zones (tonsils, spleen, lymph nodes (tonsils, spleen, lymph nodes)
44
What is secreted by plasma cells?
IL4 and 21 that promote B cell differentiation and class switching
45
What is Treg?
1. Inhibit immune responses 2. Arise during activation of T cells in the presence of IL2 and TGFb 3. Contributes to self-tolerance
46
What is secreted by T reg?
IL10 and TGFb
47
What is the function of IL10 and TGFb?
Downregulate inflammation (inhibits APCs) and suppress activation of T cell cytokines
48
What are the inhibitory cytokines?
IL10 and TGFb
49
What is self-tolerance?
Failure to respond to self-antigens and commensal microbes
50
What are the cytokines that cause negative regulations of CD4 development?
1. Under homeostatic conditions, TGF-b secreted by TREG cells inhibits TH1 and TH2 responses. 2. IL-4 (TH2) or IFN-g (TH1) can inhibit TH17 development. 3. IFN-g produced by TH1 can inhibit TH2 responses. 4. IL-4 produced by TH2 can inhibit TH1 differentiation.
51
What are the characteristics of memory T cells?
1. Arise from effector T cells and are maintained through IL-7 and IL-15 stimulation 2. Heterogenous
52
How does memory T cells defer from naive T cells?
1. Cell surface expression of proteins 2. Responses to stimuli 3. Gene expression
53
What are the memory t cells?
1. Central 2. Effector 3. Tissue resident
54
What are central t cells?
Reside in the T cell zones of secondary lymphoid tissue
55
What are effector memory t cells?
Circulate in the blood and can be rapidly enter inflamed tissues and contribute to first line defenses upon re-stimulation
56
What are tissue resident memory T cells?
Do not migrate and live long term in various epithelial sites
57
What is the difference between effector and cytotoxic T cells?
C; Important in eliminating virally infected cells M: Quickly activates and responds upon subsequent encounter with their antigens

Immunology (17 decks)

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