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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
Q

What is clonal expansion?

A

Production of memory and effect clonal cell populations

26
Q

How are memory T cells formed?

A

During adaptive immune response and persist in the absence of their antigen that induce them

27
Q

Describe differentiation of CD8?

A
  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
Q

What are polarizing cytokines?

A

(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
Q

What pathway is associated with polarizing cytokines?

A

JAK-STAT pathway

30
Q

What are TH1?

A

Mediates cellular immunity to intracellular microbial pathogens by secreting cytokines that eradicate microbes that can survive in macrophages

31
Q

What causes TH1 differentiation?

A

IL12 and IFN-y

32
Q

What are the products of of TH1 and what do they do?

A

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
Q

What is TH2?

A

Promotes humoral immunity to extracellular microbial pathogens by producing cytokines that activates B cells

34
Q

What promotes TH2?

A

IL-4

35
Q

What is produced after the activation of TH2?

A

IL-4, IL5, IL13

36
Q

What is the function of IL4?

A

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
Q

What is the function of an activated TH17?

A
  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
Q

What is IL17?

A

Associated with chronic inflammatory and autoimmune resposnes

39
Q

What activates a TH17?

A

IL1, IL6, IL23, TGFb

40
Q

What is secreted by TH17?

A

IL17, IL22

41
Q

What are the polarizing cytokines?

A

IL6 and IL21

42
Q

What is the function of Tfh?

A
  1. Help B cells produce antibodies against most foreign pathogens
  2. Cause rapid proliferation and differentiation of B cells into plasma cells
43
Q

Where are Tfh found?

A

Secondary lymphoid tissues in B cell zones (tonsils, spleen, lymph nodes (tonsils, spleen, lymph nodes)

44
Q

What is secreted by plasma cells?

A

IL4 and 21 that promote B cell differentiation and class switching

45
Q

What is Treg?

A
  1. Inhibit immune responses
  2. Arise during activation of T cells in the presence of IL2 and TGFb
  3. Contributes to self-tolerance
46
Q

What is secreted by T reg?

A

IL10 and TGFb

47
Q

What is the function of IL10 and TGFb?

A

Downregulate inflammation (inhibits APCs) and suppress activation of T cell cytokines

48
Q

What are the inhibitory cytokines?

A

IL10 and TGFb

49
Q

What is self-tolerance?

A

Failure to respond to self-antigens and commensal microbes

50
Q

What are the cytokines that cause negative regulations of CD4 development?

A
  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
Q

What are the characteristics of memory T cells?

A
  1. Arise from effector T cells and are maintained through IL-7 and IL-15 stimulation
  2. Heterogenous
52
Q

How does memory T cells defer from naive T cells?

A
  1. Cell surface expression of proteins
  2. Responses to stimuli
  3. Gene expression
53
Q

What are the memory t cells?

A
  1. Central
  2. Effector
  3. Tissue resident
54
Q

What are central t cells?

A

Reside in the T cell zones of secondary lymphoid tissue

55
Q

What are effector memory t cells?

A

Circulate in the blood and can be rapidly enter inflamed tissues and contribute to first line defenses upon re-stimulation

56
Q

What are tissue resident memory T cells?

A

Do not migrate and live long term in various epithelial sites

57
Q

What is the difference between effector and cytotoxic T cells?

A

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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