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Activation of naive T cells Flashcards

1
Q

Where do naive T cells encounter antigen?

A

During recirculation through secondary lymphoid organs

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2
Q

T cell antigen encounter process

A

T cells enter a lymph node across high endothelial venules in the cortex –> T cells monitor antigen presented by macrophages and DCs –> T cells which do not encounter specific antigen leave the node via efferent vessel –> T cells that encounter specific antigen proliferate and differentiate to effector cells

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3
Q

If an DC is mature, then it is expressing _____ and ______

A

High levels of MHC; co stimulatory molecules

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4
Q

Role of cell adhesion molecules in the generation of immune responses

A
  • migration of naive T cells through the lymph nodes
  • initial interactions with APC
  • migration of the effector T cells into the peripheral tissues
  • interactions with target cells
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5
Q

Adhesion molecules are ______ and _____ T cell contacts with APC

A

Initiating and controlling
- T cells initially bind DC through low affinity LFA-1: ICAM-1 interactions –> subsequent binding of T cell receptors signals LFA-1 –> conformational change in LFA-1 increases affinity and prolongs cell-cell contact

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6
Q

First signal

A

Specific, T cell receptors and MHC-antigen interactions

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7
Q

Difference between TCR and TCR complex

A

CD3 complex does not recognize antigen, only signaling function

TCR is capable of recognizing antigen, but not signaling

TCR+CD3 can provide signaling and antigen presentation

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8
Q

MHC-CD4/8 interactions

A

Binding of TCR and its co receptors CD4/8 to the peptide:MHC class 2/MHC class 1 complex on the DC delivers a signal

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9
Q

Second signal

A

Co-stimulatory

  • binding of the T cell CD28 to B7 expressed on DC delivers a signal
  • T cell tolerance to antigens expressed on nonprofessional APC results from antigen recognition in the absence of the co stimulatory signal
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10
Q

Co stimulatory signal alone

A

Without antigen recognition, co stimulatory will not do anything to the T cell

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11
Q

Specific signal alone

A

If antigen reception is not supported by signal 2, then it will not respond and just float in the circulation
- anergy

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12
Q

B7-1

A

CD80

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13
Q

B7-2

A

CD86

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14
Q

Co stimulatory signal is important for ___ and _____ of naive T cells

A

proliferation; survival

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15
Q

Specific signal recognition, initiation of signal transduction

A
  • clustering of TCR and accessory molecules together on the cell surface
  • phosphorylation of cytoplasmic portions of CD3 and z chains
  • activation of adapter proteins and biochemical intermediates
  • concentration of intracellular signaling molecules around the receptors
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16
Q

What does signal transduction lead to?

A

Clonal expansion and differentiation

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17
Q

What is the one important step in signal recognition and transduction (is the first signal)?

A

Antigen recognition

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18
Q

Transmission and amplification of the signal

A

Activation of certain intracellular enzymes

- diacylglyceral (DAG) and inositol trisphospate (IP3)

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19
Q

IP3

A

Increases intracellular calcium concentration, activating a phosphatase, calcineurin

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20
Q

Transmission of the signal to the nucleus

A

Transcriptional activation of genes that are silent in resting T lymphocytes
- NFkB, NFAT, and AP-1 change the pattern of gene expression

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21
Q

Last step in signal transduction

A

Cell division, proliferation and differentiation to effector T cells

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22
Q

Cyclosporin tacrolimus

A

Only targets calcineurin

- will deactivate entire chain

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23
Q

Activated T cells secrete and respond to ______

A

Inerleukin 2 (IL-2)

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24
Q

T cells and IL-2

A
  • resting T cells express moderate affinity IL-2 receptor (IL-2Rbeta and gamma)
  • activated T cells express high affinity IL-2 receptor (IL-2R alpha, beta, and gamma) and secrete IL-2
  • binding of IL-2 to its receptor signal T cell to enter mitosis
    = induces T cell proliferation
25
Q

Rapamycin (sirolimus)

A

Affects interactions of IL-2 and IL-2 receptor

26
Q

Effector T cells do not depend on ______

A

Co stimulatory signals

- they just need to recognize an antigen to fulfill effector function

27
Q

What is the 3rd signal?

A

Cytokines!!

- involved in T helper differentiation

28
Q

IL-12 and IFN-gamma

A

Creates Th1 cell

  • receptors: IFN-gamma, IL-2, and TNF alpha and beta
  • target cell: macrophages
29
Q

IL-2, IL-4, IL-33, Notch L

A

Creates Th2 cell

- receptors: IL-4, IL-5, IL-13, IL-25

30
Q

IL-6, and IL-21

A

Creates T follicular helper cell

- IL-21, and IL-17

31
Q

IL-6 and TGF-beta

A

Creates Th17 cell

  • receptors: IL-17, IL-17F, IL-22, IL-21
  • promotes inflammation
32
Q

IL-2, and TGF-beta

A

Creates Treg cell

- receptors: TGF-beta, IL-10, IL-35

33
Q

Th2 cells are involved in _____

A

Helminth infections

34
Q

Th1

A

Primary targets are macrohages

- activates infected macrophages if T cell has been primed to the same pathogen

35
Q

Partial macrophage activation

A

Defect in signal, or macrophage is not responding well

- leads to granuloma formation that is surrounded by T cells (helps limit inflammation)

36
Q

Complete macrophage activation

A
  • Th1 cell and infected macrophage come together
  • T cell binds to, and activates macrophage = killing of intravesicular bacteria
  • CD40 and IFN-gamma are the 2 signals
37
Q

IFN-gamma

A
  • induces B cell proliferation and differentiation
  • macrophage activation
  • complement binding and opsonizing antibodies
38
Q

Fas ligand (TNF-beta)

A

Kills chronically infected cells, releasing bacteria to be destroyed by fresh macrophages
- Th1 cell

39
Q

IL-2

A

Induces T cell proliferation, increasing numbers of effector cells
- Th1 cell

40
Q

TNF-alpha + TNF-beta

A

Activates endothelium to induce macrophage binding and exit from blood vessel at site of infection (diapedisis)
- Th1 cell

41
Q

Th2 cells stimulate the proliferation and differentiation of _____

A

Naive B cells

- IL-4!!! helps with IgE neutralization and mast cell degranulation

42
Q

What cytokine activates eosinophils?

43
Q

What types of stimuli induce Th2 responses?

A
  • allergens (pollen, food, vaccine)

- parasites, viruses, bacteria (peptidoglycans or lipopolysaccharides)

44
Q

T follicular helper cells

A

CD4+ T cells that enter the germinal center to mediate their helper function for antibody production
- needs cooperation between DC and B cells to function

45
Q

BCR roles in B cell activation

A
  • signals to the B cell’s interior when antigen is bound
  • delivers bound antigen to intracellular sites, where it is degraded to peptides that are presented on B cell surface by MHC class 2
  • peptice: MHC complexes are recognized by antigen-specific Th cells that have already differentiated in response to the same pathogen
46
Q

B cell activation by antigen and helper T cells

A

–> antibody secretion by plasma cells = neutralization, opsonization, and complement activation

47
Q

Linked recognition

A

A given B cell can only be activated by its cognate T cell (Th2 or Thf that respond to the same antigen)

48
Q

Do T and B cells recognize identical epitopes on the same protein?

A

NO. Peptide recognized by T cell should be physically close with the peptide recognized by B cells, so that after B cell internalization of the antigen you can still get recognition by both T and B cells

49
Q

Requirement of link recognition

A

Self tolerance

- autoimmune response will occur only if both a self reactive T and B cell are present at the same time

50
Q

Bystander effect

A

Activation of lymphocytes that are not specific for the antigens of the infectious agent

51
Q

What happens with activation of a B cell by a Th2 cell that is not primed by the same antigen

A

Tissue destruction by the infection, followed by availability of the self antigen, pro inflammatory cytokines IL-1 and IL-6 inhibit Tregs

52
Q

Effects of Th17 derived IL-17

A
  • neutrophil accumulation
  • monocyte accumulation
  • increased mucin secretion
  • synergy with IL-1beta, IL-6, TNF-alpha, adn GM-CSF –> augmentation of inflammation
53
Q

What are the target cells for Th17?

A

Neutrophils and monocytes

54
Q

Cellular and humoral adaptive immune responses are initiated and controlled by _______

A

Effector T cells (CD4 Th and CD8 cytotocxic cells)

55
Q

T cell activation is accomplished by ____

A

Dendritic cells

56
Q

Activation of T cell leads to production of _____, which drives proliferation and differentiation

57
Q

Co stimulatory signals are required for naive T cell activation through interaction of ____ on naive T cell with _____ on DC

58
Q

The third signal for T cell activation comes from the _____ in the form of _____

A

APC; IL-12

59
Q

CD4 T cell functions

A
  • help B cells make antibody
  • induction/control of Ig class switching and somatic hypermutation
  • enhance priming and maintain response of CD8 T cells
  • regulate macrophage and enhance neutrophil response
  • adjust immune response magnitude and persistence
  • controls autoimmunity
  • highly important mediators of immunologic memory

Immunology (28 decks)

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