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Immunology-Nicole > Assignment #8 > Flashcards

Assignment #8 Flashcards

1
Q

What is the site of primary immune response in the CD4+ Thp cells?

A

secondary lymphoid tissues

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2
Q

what is meant by a primary response?

A

first exposure to antigen

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3
Q

what happens when a T cell is engaged with the MHC-peptide complex without TCR present?

A

When a T cell interacts with peptide/MHC complexes in the absence of costimulatory interactions the T cell becomes unresponsive (anergic)
And vice versa for activation

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4
Q

what is the other name for Thp?

A

Naive CD4+ T cell

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5
Q

Thp activation occurs optimally when the T cell receives several signals delivered by an antigen presenting cell. List the interactions that these signals arise from

A

1) peptide/MHC class II w/ TCR
2) MHC class II with CD4
3) B7-1/CD80 with CD28 (costimulatory molecule)
4) B7-2/CD86 with CD28 (costimulatory molecule)
5) CD 40 with counter ligand (CD40L/CD154)
6) Adhesion molecules that were discussed in prior lectures ICAM-1 and ICAM-2 with LFA-1

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6
Q

why is CD80/CD86 interaction with CD28 critical for T cell activation and clonal expansion?

A

triggers signal transduction events that lead to stabilization of mRNA for IL-2

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7
Q

what cytokine and associated receptor induces clonal expansion of antigen stimulated T cells

A

IL-2 and IL-2 receptor

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8
Q

Thp cells differentiate to an intermediate cell, Th0, which secretes what three cytokines?

A

IL-4, IL-2, and IFNgamma

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9
Q

what cytokine contributes to the polarization of the Th0 to Th1 cell?

A

IFNgamma

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10
Q

what cytokine contributes to the polarization of the Th0 to Th2 cells?

A

IL-4

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11
Q

what cytokines are secreted by activated dendritic cells?

A

IL-12, IL-15, IL-18 (IL-15 and IL-18 enhance the effect of IL-12 mediated activation of NK cells to secrete IFNgamma)

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12
Q

what are the two sources of IFNgamma?

A

NK cells (that again have been activated via IL-12) and Th1

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13
Q

what are the two sources of IL-4?

A

Mast cells and Th2 cells

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14
Q

Activated Th1 cells secrete type I cytokines, what are they?

A

IL-2; TNF and IFNgamma

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15
Q

what is the role of TNF in relation to being a Type I cytokine

A

Enhances NADPH oxidase activity and activation of INOS

Role with IL-1 on monocytes, macrophages, and endothelial cells.

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16
Q

what is the role of IL-2 in relation to being a Type I cytokine?

A

Growth factor for T cells expressing IL-2R (CD25)
High in lab converts NK cells to LAK cells (aka enhances activity of NK cells to kill)
Role in differentiation of pre-CTL to CTL (via IFNgamma)

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17
Q

What is the role of IFNgamma in relation to being a type I cytokine?

A

Enhances NADPH oxidase activity and activation of iNOS
Down regulates production of Th2 cytokines
Polarizes differentiation of Th0 to Th1
Role in differentiation of pre-CTL to CTL
Upregulates MHC class I on nucleated cells; class II antigen presenting cells

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18
Q

Activated Th2 cells secrete Type 2 cytokines, what are they?

A

IL-4, IL-5, IL-6, IL-10, IL-13, and TGFbeta

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19
Q

what is the role of IL-4?

A

Required to switch to IgE
down regulation of Th1 cytokines
Down regulation of iNOS( TGFbeta is more effective)
At high polarizes Th0 differentiation to Th2 cells

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20
Q

What is the role of IL-5?

A

Hematopoietic differentiation of eosinophils

chemotatic for eosinophils recruiting to tissues; activation of eosinophils

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21
Q

what is the role of IL-6?

A

Stimulus for secretion of CRP from hepatocytes

role in differentiation of Th0 cells to Th17 in mouse

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22
Q

what is the role of IL-10?

A

Down regulates IL-12 secretion by antigen presenting cells

Down regulates iNOS (TGFbeta is more effective)

23
Q

what is the role of TGFbeta?

A

down regulation of iNOS (critical for differentiation of Th0 to a/i Tregs)
role in differentiation of Th0 cells to Th17

24
Q

what is the role of IL-13

A

Plays a role in allergic asthma and in helminth infections

25
Q

T cell activation can be downregulated in 6 ways, each card will go through the 6 ways, starting with number 1

A

1) Loss of T cell stimulation and Apoptosis –> infectious agent has been eliminated and so peptide/MHC complexes are no longer being presented to T cells

26
Q

T cell activation down regulation number 2?

A

2)Reciprocal regulation of cytokine secretion by Th1 and Th2 cytokines —> IL-4 down regulates Th1 cytokines; IFNgamma down regulates Th2 cytokines

27
Q

T cell activation down regulator number 3?

A

CTLA-4/CD152 interaction —> CD152 has higher affinity for CD80 and CD86 than CD28. Sends negative signal; CD80 and CD86 do not interact with CD 28

28
Q

T cell activation down regulator number 4?

A

CD200R on activated T cells; signaling via CD200R is inhibitory

29
Q

T cell activation down regulator number 5?

A

PD1: PD-LI/PD-L2 –> PD1 is expressed on activated T cells; Interaction with PD-L1 and/or PD-L2 delivers negative signal to T cells.

30
Q

T cell activation down regulator number 6?

A

IL-10 –> down regulates secretion of IL-12 by dendritic cells (affects NK cells and hence Th1 cells and Th1 cytokines)

31
Q

Inactivation of T cells leads to T cell exhaustion which is detrimental in the face of chronic viral infection or cancer. explain what is meant by T cell exhaustion?

A

Exhausted T cells lose the ability to synthesize cytokines, proliferate, or destroy infected cells.

32
Q

what are the two subsets of T cells on which PD1 is expressed?

A

activated CD4+ and CD8+ T cells

33
Q

what type of signal does PD1 receive when PD1 is engaged with its ligand?

A

delivers a negative signal to T cells

34
Q

what are the two ligands for PD1 and what cells are they expressed on?

A

PDL-1 —> constitutively expressed on a number of immune cells and non hematopoietic parenchymal cells
PDL-2 —> expressed on activated monocytes and dendritic cells

35
Q

A big cancer treatment is by blocking these PD1 signals and this leads to tumor regression? How does this process work?

A

blocking PD1 so it cannot bind to its ligands inhibits the negative signal and T cells recover the ability to secrete cytokines, proliferate, and destroy viral infected cells as well as cancer cells

36
Q

Natural T regulatory cells (nTregs) include what three phenotypes?

A

CD4+ ; CD25+ and FOXP3+

37
Q

nTregs source?

A

arise as a separate lineage in the thymus and exit to the periphery

38
Q

what is the role of nTregs?

A

1) dominant players in the control of self reactive T cells that have escaped negative selection —> peripheral tolerance
2) nTregs also negatively control immune responses to allo/non self antigens

39
Q

If you have a depletion of nTregs what effect does this have on the body?

A

Enhances immune responses to pathogens and eventual leads to tumor rejection

40
Q

Genetic mutations in what transcription factor results in deficiency or dysfunction of Tregs?

A

FOXP3

41
Q

dysfunction or deficiency in Tregs leads to what auto immune disorder?

A

IPEX —> immume dysregulation, polyendocrinopathy, enteropathy, x linked syndrome

42
Q

Adaptive-Induced T regulatory Cells (a/iTregs) arise from where?

A

arise in the periphery following activation of Thp and Th0 cells

43
Q

a/iTregs differentiation requires what cytokine?

A

TGFbeta

44
Q

what is the phenotype for a/iTregs?

A

CD4+, CD25+, FOXP3+

45
Q

FOXP3 is a transcription factor that does what?

A

essential for development and function of regulatory T cells

46
Q

what is the role of a/iTregs?

A

control immune responses to both foreign and to self antigens by down regulating the function of effector CD4+ and effector CD8+ T cells

47
Q

In general terms what are CD4+ Th17 cells?

A

effector cells that (in mouse studies) were initially shown to arise from Th0 cells in the presence of TGFbeta and IL-6

48
Q

Differentiation of Th17 cells happens in three stages, what are these stages?

A

1) differentiation (TGFbeta, IL-1/IL-6)
2) Stabilization (IL-23 secreted by dendritic cells and macrophages)
3) amplication (secreted by Th17 cells-growth factor; aka IL-21)

49
Q

what kind of infections are Th1 cells most effective at eliminating?

A

fungal infections

50
Q

Th17 cells play a role in the immune response against extracellular pathogens that are not eliminated by what cells?

A

CD4+ Th1 and CD4+ Th2 effector cells

51
Q

Th17 cells secrete proinflammatory cytokines ?

A

IL-17; IL-21; IL-22

52
Q

Th17 cells induce the secretion of inflammatory mediator from what cells?

A

macrophages and cells that play a role in inflammation

53
Q

What is the difference between a primary immune response and a secondary immune response with respect to T cell activation?

A

in secondary immune response there are memory cells, so when a patient is re-exposed to the initiating agent there is a rapid (1-2 day) response, unlike the seven days required for Thp differentiation to Th1 and Th2 cells

54
Q

7 things that lead to down regulation of activated T cell

A
  1. loss of T cell stimulation since infectious agent is gone so no MHC/peptide complex to present to T cells
  2. reciprocal regulation of cytokine secretion by Th1 and Th2 (think IL-4 and IFNgamma)
  3. CTLA4/CD152 (inhibition of T cell with B7-1/CD80 and B7-2/CD86)
  4. CD200: CD200R interaction (neg signals)
  5. apoptosis
  6. PD-1 interacting with ligands PD-L1/PD-L2
  7. regulatory T cells (a/i Tregs and nTregs)

Immunology-Nicole (20 decks)

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