T Lymphocyte Activation

Question 1

give the 3 aspects of the TCR complex and their functions

Answer 1

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

Question 2

when are the signals from CD3 sent?

Answer 2

after TCR binds to MHC/antigen complex

Question 3

what type of MHC does CD4 bind?

Answer 3

MHC II

Question 4

what type of MHC does CD8 bind?

Answer 4

MHC I

Question 5

what do adhesion molecules do?

Answer 5

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

Question 6

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

Answer 6

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

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

Question 7

do adhesion molecules send signals?

Answer 7

no; they just keep the T cell and APC together

Question 8

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

Answer 8

provide extra signals for activation

Question 9

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

Answer 9

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

Question 10

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

Answer 10

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

Question 11

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

Answer 11

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

Question 12

give the timeline of generation of effector helper T cells

Answer 12

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

Question 13

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

Answer 13

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

Question 14

what does the master gene regulator do?

Answer 14

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

Question 15

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

Answer 15

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

Question 16

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

Answer 16

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

Question 17

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

Answer 17

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

Question 18

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

Answer 18

1. activates eosinophils

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

Question 19

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

Answer 19

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

Question 20

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

Answer 20

promotes inflammation by increasing neutrophil and monocyte activity

Question 21

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

Answer 21

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

Question 22

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

Answer 22

activates B cells

Question 23

where are induced Treg cells generated?

Answer 23

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

Question 24

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

Answer 24

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

Question 25

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

Answer 25

suppress the immune response

Question 26

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

Answer 26

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

Question 27

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

Answer 27

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

Question 28

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?

Answer 28

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

Question 29

what must T helper cells be activated by?

Answer 29

professional APCs

Question 30

what must cytotoxic T cells be activated by?

Answer 30

licensed APCs

Question 31

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

Answer 31

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

Question 32

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?

Answer 32

1. Tc1: the majority of CTLs, secretes IFN-gamma | 2. Tc2: secrete IL-4 and IL-5; both kill infected cells

Question 33

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

Answer 33

the kiss of death

Question 34

describe the 6 steps of the kiss of death

Answer 34

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

Question 35

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

Answer 35

1. with perforin and granzyme | 2. FasL

Question 36

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

Answer 36

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

Question 37

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

Answer 37

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

Question 38

what are the 4 subsets of T memory cells?

Answer 38

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

Question 39

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

Answer 39

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

Question 40

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

Answer 40

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

Question 41

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

Answer 41

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

Question 42

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

Answer 42

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