T Lymphocyte Activation Flashcards

1
Q

give the 3 aspects of the TCR complex and their functions

A
  1. TCR with alpha and beta chains: binds to antigen/MHC complex
  2. CD3: signal transducing compound that doesn’t bind anything, but whose signals are required for T cell activation
  3. CD4 or CD8: bind MHC
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2
Q

when are the signals from CD3 sent?

A

after TCR binds to MHC/antigen complex

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3
Q

what type of MHC does CD4 bind?

A

MHC II

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4
Q

what type of MHC does CD8 bind?

A

MHC I

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5
Q

what do adhesion molecules do?

A

help sustain the signals between the antigen-presenting cell and the T cell during activation

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6
Q

what are the 2 types of adhesion molecule interactions involved in T helper cell activation?

A
  1. LFA-1 on T cell binds ICAM-1 or ICAM-2 on APC

2. CD2 on T cell binds LFA-3 on APC

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7
Q

do adhesion molecules send signals?

A

no; they just keep the T cell and APC together

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8
Q

what do co-stimulatory molecules do in Thelper cell activation?

A

provide extra signals for activation

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9
Q

describe the co-stimulatory molecules interactions/signals in T helper cell activation (2)

A
  1. CD28 on T cell binds to either CD80 or CD86 on APC, resulting in full activation
  2. within 24 hours of this activation, T cell expresses CTLA-4, which also bids to CD80 or CD86 on the APC and provides an inhibitory signal which inactivates the T cell and prevents overactivation
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10
Q

provide a summary of T helper cell activation signalling steps (3)

A
  1. signaling via TCR complex, which happens when TCR binds antigen/MHC complex
  2. signaling via CD28 (costimulatory interactions), where CD28 binds to either CD80 or CD86
  3. signaling via cyotkines
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11
Q

describe signaling via cytokines in T helper cell activation (2)

A
  1. T cell will secrete IL-2, which performs autocrine signaling and results in proliferation of the T cell/clonal selection of T cell specific for activating antigen
  2. APC also secretes cytokines, as well as other nearby cells that stimulate T cell differentiation, causing the T cell to differentiate into the type of T cell needed to combat the pathogen
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12
Q

give the timeline of generation of effector helper T cells

A
  1. activation through engagement with APC after approximately 6-8 hours of being stuck together by adhesion molecules
  2. 1-2 days later, proliferation occurs, takes so long because cell needs to process the signals it received
  3. proliferation continues for 4-5 days, which results in a population of effector T cells that are all identical
  4. effector T cells travel to tertiary lymphoid tissue or remain in secondary lymphoid tissue to regulate response
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13
Q

what does each subset of effector T helper cells have and what does this do?

A

each subset has distinct polarizing cytokines that induce the expression of a master gene regulator

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14
Q

what does the master gene regulator do?

A

regulates gene expression for effector cytokines that are produced when T helper cells are fully differentiated

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15
Q

give the polarizing cytokines that cause differentiation, the master gene regulator, and the effector cytokines of TH1

A

polarizing cytokines: IL-12, IFN-gamma, and IL-18
master gene regulator: T-Bet
secretes effector cytokines: IFN- gamma and TNF-B

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16
Q

what is the role of the effector cytokines (IFN-gamma and TNF-B) secreted by TH1?

A

activation of macrophages and cytotoxic T cells in viral responses or infection

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17
Q

give the polarizing cytokine that causes differentiation, the master gene regulator, and the effector cytokines of TH2

A

polarizing cytokine: IL-4
master gene regulator: GATA3
secretes effector cytokines: IL-4, IL-5, and IL-13

18
Q

what is the role of the effector cytokines (IL-4, IL-5, and IL-13) secreted by TH2? (2)

A
  1. activates eosinophils

2. causes class switch of B cells to IgE to generate a specific type of antibody

19
Q

give the polarizing cytokines that cause differentiation, the master gene regulator, and the effector cytokines of TH17

A

polarizing cytokines: IL-6, IL-23, and TGF-B
master gene regulator: RORyt (y is gamma)
secretion of effector cytokines: IL-17A, IL-17F, and IL-22

20
Q

what is the result of the effector cytokines (IL-17A, IL-17F, and IL-22) secreted by TH17?

A

promotes inflammation by increasing neutrophil and monocyte activity

21
Q

give the polarizing cytokines that cause differentiation, the master gene regulator, and the effector cytokines of TFH (follicular T helper cell)

A

polarizing cytokines: IL-6 and IL-21
master gene regulator: Bcl-6
secretes effector cytokines: IL-4 and IL-21

22
Q

what is the result of the effector cytokines (IL-4 and IL-21) secreted by TFH?

A

activates B cells

23
Q

where are induced Treg cells generated?

A

in the secondary lymphoid organs instead of the thymus like all other T helper cells

24
Q

give the polarizing cytokines that cause differentiation, the master gene regulator, and the effector cytokines of induced Treg cells

A

polarizing cytokines: IL-2 and TGF-B
master gene regulator: FoxP3
secretion of effector cytokines: IL-10 and TGF-B

25
Q

what is the role of the effector cytokines (IL-10 and TGF-B) secreted by induced Treg cells?

A

suppress the immune response

26
Q

what are the 4 steps of activation of cytotoxic T cells? broad for now

A
  1. generation of TH1 cells
  2. TH1 cell interacts with professional APC
  3. APC begins to express MHC I
  4. licensed APC activates CD8+ cell
27
Q

describe the 2 ways, both of which must happen, that the TH1 cell interacts with a professional APC in cytotoxic T cell activation

A
  1. TCR complex interacts with MHC II/antigen on APC, where the TCR interacts with the MHC II/antigen
    and the CD4 of the TH1 interacts with just the MHC II
  2. CD40L on the TH1 binds to CD40 on the APC
28
Q

when the APC begins to express MHC I in cytotoxic T cell activation, what is this called and what is the APC referred to as?

A

it is called cross-presentation when the APC expresses BOTH MHC I and MHC II and the APC is considered a licensed APC

29
Q

what must T helper cells be activated by?

A

professional APCs

30
Q

what must cytotoxic T cells be activated by?

A

licensed APCs

31
Q

describe the fourth step of cytotoxic T cell activation, where the licensed APC activates the CD8+ cell (4)

A
  1. TCR complex interacts with MHC I/antigen on APC, where the TCR binds the MHC/antigen and the CD8 binds just MHC I
  2. adhesion molecules interact
  3. costimulation occurs where CD28 of T cell binds to CD80/86 on APC
  4. secretion of IL-2 results in proliferation of activated CD8+ cells
32
Q

what are the 2 major types of effector cytotoxic lymphocytes (CTLs) and what effector cytokines do they secrete? what do both kinds of CTLs do?

A
  1. Tc1: the majority of CTLs, secretes IFN-gamma

2. Tc2: secrete IL-4 and IL-5; both kill infected cells

33
Q

what is the formation of the immunological synapse between CTL and infected cell also called?

A

the kiss of death

34
Q

describe the 6 steps of the kiss of death

A
  1. engagement of TCR with antigen/MHCI
  2. ring of adhesion molecules bind around TCR/antigen/MHC I
  3. centrosome of CTL polarizes to area of synapse
  4. cytotoxic contents are released into the synapse and directed at the infected cell
  5. apoptosis is inititated in infected cell
  6. CTL dissociates from infected cell and can now go kill another infected cell
35
Q

what are the 2 methods that CTLs killed infected cells via apoptosis?

A
  1. with perforin and granzyme

2. FasL

36
Q

describe how CTLs use perforin and granzyme to kill infecged cells via apoptosis (4)

A
  1. engagement of TCR complex with infected cell MHC I/antigen causes rise of intracellular calcium
  2. this results in exocytosis of CTL granules
  3. perforin insert into infected cell membrane and polymerize, forming cylindrical holes
  4. granzyme enters infected cell and initiates apoptosis
37
Q

describe how CTLs use FasL to kill infected cells via apoptosis (2)

A
  1. engagement of TCR with infected cell results in localization od FasL to immunological synapse
  2. FasL binds to Fas on infected cell, initiating apoptosis
38
Q

what are the 4 subsets of T memory cells?

A
  1. Tcm: central memory
  2. Tem: effector memory
  3. Trm: resident memory
  4. Tscm: stem cell memory
39
Q

what is the function of Tcm (central memory) cells? where found?

A

reside in secondary lymphoid tissues and are long-lived as they undergo division and differentiation

40
Q

what is the function of Tem (effector memory) cells? where found?

A

travel in tertiary lymphoid tissues (sites of infection) and already exhibit effecto functions so do not undergo differentiation upon a secondary exposure to a pathogen, just allow for the immediate response of the body to a specific pathogen the second time

41
Q

what is the function of Trm (resident memory) cells? where found?

A

permanent residents of tertiary tissue; are activated and differentiate upon secondary exposure, making the adaptive response quicker to an invader

42
Q

what is the function of Tscm (stem cell memory) cells? where found?

A

found in secondary lymphoid tissue and are self-renewing so the body has T memory cells long-term