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SFM IMMUNO > T-Cell Mediated Immunity And Effector Mechanisms > Flashcards

T-Cell Mediated Immunity And Effector Mechanisms Flashcards

1
Q

What cell can activate a mature, naive T cell?

A

Only Dendritic Cells

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2
Q

What cell type(s) can activate memory T cell?

A

B cells, macrophages, and DCs can activate memory T cells

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3
Q

What general functions do activated T cells perform?

A

CD4+ T cells “help” activate B cells and macrophages

CD8+ T cells initiate cell death of infected or transformed cells

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4
Q

You will find _______ dendritic cells in the peripheral and secondary lymphoid tissues.

A

You will find (immature) dendritic cells in the peripheral and secondary lymphoid tissues.

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5
Q

Immature DCs in peripheral tissues express LOW levels of ______, ______, and ______ on their surface and HIGH levels of ______.

A

Immature DCs in peripheral tissues express LOW levels of (surface MHC Class II, co-stimulatory molecules, and CCR7 (chemokine receptor)) on their surface
and HIGH levels of (CCR1 (chemokine receptor)).

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6
Q

Mature DCs in secondary lymphoid tissue express LOW levels of ______ on their surface and HIGH levels of ______, ________, and ________.

A

Mature DCs in secondary lymphoid tissue express LOW levels of (CCR1 (chemokine receptor) on their surface and HIGH levels of (MHC Class II, co-stimulatory molecules, and CCR7 (chemokine).

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7
Q

What changes occur to DCs once they are activated in the peripheral tissues?

A

Activated peripheral DCs: lose adhesive markers and up-regulate expression of CCR7 which allows the activated DCs to leave peripheral tissue and begin migrating to secondary lymph tissues and also begin to mature.

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8
Q

What surface expression changes occur as activated DC migrates to lymph tissue?

A

DCs mature as they migrate and INCREASE expression of MHC/HLA Class I and II, CD80(B7) (co-stimulatory ligand), and LFA-1.

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9
Q

Why do activated DC’s increase expression of CCR7?

A

CCR7 is a chemokine receptor for chemokine, CCL21, secreted in secondary lymph tissue. This signal allows the DCs to move to the lymphoid tissue and induces maturation as they migrate.

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10
Q

The cytokines secreted by APCs help naive T cells to ________

A

The cytokines secreted by APCs help drive differentiation of naive T cells, especially differentiation of T helper cells into their specific class of helper T cells.

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11
Q

List and Describe the function of receptors found on surface of mature, naive T Cytotoxic Cells

A

TCR/CD3 signaling complex including zeta (signaling chain)
CD8+ (binds MHC Class I)
MHC/HLA Class I (bc nucleated)
CD28+ (constitutively expressed, co-stimulatory receptor)
LFA-1 (late-functioning antigen; integrin= adhesion molecule)
L-selectin (helps migrate leukocytes into areas of acute inflammatory response, expressed on activated endothelium; cell adhesion molecule helps cell slow down and bind to surface of HEV)

LFA-1, CCR7, and L-selectin help move mature naive T cell into lymphoid tissue

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12
Q

List and Describe the function of receptors found on surface of mature, naive T helper Cytokine Secreting Cells

A

TCR/CD3 signaling complex including zeta chain
CD4+ (binds with MHC/HLA Class II)
MHC/HLA Class I (because nucleated)
CD28+ (co-stimulatory receptor)
LFA-1 (late-functioning antigen; integrin adhesion molecule)
CCR7 (chemokine receptor- brings cell into lymphoid space)
L-selectin (helps migrate leukocytes into areas of acute inflammatory response, expressed on activated endothelium; helps cell slow down in HEV)

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13
Q

Describe the migration of a naive T cell to lymph tissue

A

Naive T cell is released from thymus into circulation (needs to get to lymph node to be activated)
They enter LN across High Endothelium venules (HEV) in the cortex.
T cell sample antigen presented by APC
If does not encounter specific Ag, T cell leaves node through lymphatics and travels down chain to next LN. Repeats sampling.
(circulate entire body once/24 hours)

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14
Q

Describe surface interactions between T cell and endothelial cells of the HEV

A

As T cell enter the HEV interaction of L-selectin and CCR7 on T cell with PNAd and CCL19/CCL21 on endothelial cell slows down the movement of the cell.
Binding of T cell LFA-1 with endothelial ICAM-1 causes stable arrest of their entrance on high endothelial venule in LN

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15
Q

T cells that encounter antigen ______

A

T cells that encounter antigen will proliferate and differentiate into effector T cells:
CD4+ T cells increase 100x to 1000x
CD8+ T cells increase 100,00x

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16
Q

Describe the receptor/ligand interactions between T cell and APC at the immune synapse
(signal transduction, antigen recognition, adhesion)

A

(Ag recognition): TCR <————————–>Peptide presented on MHC/HLA Class I or II (of APC)
(Signal Transduction): CD4+ or CD8+ of TC <————>MHC/HLA Class II or I (respectively)
CD3 complex, signaling through ITAM & zeta
(Signal Transduction): CD28+ (costim recept) <———> CD80/B7-1/B7-2 (of APC)
upon activation - T cell expression of CTLA-4 <———> CD80/B7-1/B7-2
upon activation - T cell expression of PD-1 (program death) <——> PD-L1/PD-L2
(cell adhesion): LFA-1 <———————————> ICAM-1

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17
Q

What is the first signal of T cell activation? What binds at immune synapse?

A

First signal is binding of the TCR on T cell to the peptide displayed on the MHC/HLA of DC.
- Either CD4+ or CD8+ of T cell binds to invariant portion of MHC/HLA on DC

Binding causes signaling through T cell CD3 zeta chain —- leads to activation induced part of activation

(Don’t forget CD28 is present on T cell and CD40 is present on DC)

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18
Q

Formation of the _____________ initiates the intracellular signaling leading to COMPLETE T cell activation.

A

Formation of the (immune synapse) initiates the intracellular signaling leading to COMPLETE T cell activation.

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19
Q

What is the second signal of T Cell activation?

A

Upon binding of TCR to Peptide/MHC/HLA complex - Co-stimulation occurs:

T Cell increases expression of CD40L which then binds to CD40 (constitutively expressed) on DC
Binding of CD40L –CD40 stimulates DC to up-regulate expression of B7 (CD80) and increase cytokine secretion.
B7(CD80) on DC binds to CD28 (constitutively expressed) on T cell
Cytokines secreted from DC bind to T cell —-> enhances activation, proliferation and differentiation of T cell

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20
Q

TCR/HLA antigen recognition triggers conformational change of integrin (LFA-1) on T cells from _______ affinity to ______ affinity. This is important because …….

A

TCR/HLA antigen recognition triggers a conformational change in integrin (LFA-1) on T cells from (low) affinity to (high) affinity.
This is important because it creates a firm adhesion of the immune synapse and binds T cell and DC tightly together. This tight binding ensures that the cytokines secreted from DC, which are essential for robust T cell activation, are received by the T cell.
ensures robust activation

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21
Q

Why is there a 2 pronged approach to T cell activation?

A

It ensures that the T cell being activated is highly specific to the epitope presented so that when clones are made they maintain that specificity…..Clonal Selection

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22
Q

After T cell is activated, Clonal Selection occurs through a signaling cascade (via PI-3 kinase/Akt; RAS/MAP-kinase) which results in _______, __________, _____________, and ___________.

A

After T cell is activated, Clonal Selection occurs through a signaling cascade (via PI-3 kinase/Akt; RAS/MAP-kinase) which results in:
Increased production 0of Bcl-X and Bcl-2 —–> cell survival
Increased secretion of IL-2 and expression of IL-2R ——> Cell proliferation
Increased Cyclins and decreased Cell cycle inhibitors —–> DNA synthesis/Cell proliferation
Multiple signaling pathways —–> Differentiation to effector and memory cells

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23
Q

Formation of the immune synapse occurs through activation of ___________

A

Formation of the immune synapse occurs through activation of immunoreceptor tyrosine-based activation motifs (ITAMs)

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24
Q

Binding of CD4+/CD8+ to the TCR-MHC/HLA/Peptide complex triggers the activation of CD4+/CD8+ associated intracellular kinase _____ . Activated ________ phosphorylates and activates the _______ on the C3 complex zeta chain which then activates kinase _________, leading to downstream signaling inducing protein and DNA synthesis as the new cell starts to clone itslef.

A

Binding of CD4+/CD8+ to the TCR-MHC/HLA/Peptide complex triggers activation of CD4+/CD8+ associated intracellular kinase (Lck). Activated (Lck) phosphorylates and activates the (ITAMs) on the C3 complex zeta chain which then activates kinase (ZAP-70), leading to downstream signaling inducing protein and DNA synthesis as the new cell starts to clone itself.

25
Q

Within 5-12 hours of activation, T cells are producing/expressing large amounts of: (3 things)

A

CD40L (membrane effector molecules)
IL-2 (cytokine)
IL-2Ra=CD25 (cytokine receptor)

26
Q

Activated CD4+ Th cells start expressing _______ and _____ for immune regulation.

A

Activated CD4+ Th cells start expressing (CTLA-4) and (PD-1) for immune regulation.

27
Q

Activated CD8+ T cells start expressing _______ for immune regulation.

A

Activated CD8+ T cells start expressing (PD-1) for immune regulation.

28
Q

Within hours-days of activation T cells begin secreting cytokines: _______, _______, ______ depending on the differentiation of T helper cells.

A

Within hours-days of activation T cells begin secreting cytokines:
IL-2
IFN-gamma
IL-4
depending on the differentiation of T helper cells.

29
Q

______ is an autocrine survival signal for newly activated T cells.

A

(IL-2) is an autocrine survival signal for newly activated T cells.

30
Q

______ is constitutively expressed on mature, naive T cells as a ______ affinity receptor minimizing proliferation.

A

(IL-2R beta gammaC) is constitutively expressed on mature, naive T cells as a (LOW) affinity receptor minimizing proliferation.

31
Q

Upon activation, the T cell up-regulates expression of additional high affinity chain in ______ called _____

A

Upon activation, the T cell up-regulates expression of an additional high affinity chain in (IL-2R) called (alpha chain/CD25)

32
Q

What does IL-2R alpha beta gamma C do?

A

Binding of IL-2 to high affinity IL-2R alpha beta gamma C promotes T cell proliferation and differentiation

33
Q

What happens to CD8+ T cells after activation?

A

CD8+ T cells leave LN immediately after activation to carry out effector function in peripheral tissue

34
Q

What happens to CD4+ T cells after activation?

A

CD4+ T cells are helper T cells- trapped in lymph tissues for several days after activation to help B cells before they can leave and go to peripheral tissues

35
Q

How are CD4+ T cells trapped?

A

Transient expression of CD69

36
Q

Gamma Delta T cells-
where are they?
what are they?
why are they special?

A

Have TCR that is made up of gamma/delta chains NOT alpha/beta
less than 5% of T cells
Mainly found in epithelial boundaries: Gut mucosa, urethra, lungs
Have Toll-like receptors
**Non-HLA restricted (Can recognize Ag through HLA pathway but don’t need to be)
*** Can recognize NON-Protein
Pleiotropic responses; Cytokines secretion profile as T helper 1, Th17, Th2, and Tregs
Also have cytolysis ability - release granzymes, perfornin, TRAIL (like NK cells or CD8+)

37
Q

Surface Expression of Effector T cytotoxic Cells

A

TCR/CD3 signaling complex including zeta
CD8+
MHC/HLA Class I
CD28+
CD25+
FasL - shut off at end of immune response
PD-1 - shut off at end of immune response
LFA-1/VLA-4 - allows to migrate to peripheral tissue to site of infection
CXCR3 - allows to migrate to peripheral tissue to site of infection
E- and P- selectin - allows to migrate to peripheral tissue to site of infection

38
Q

Surface expression of Effector T helper cells

A

TCR/CD3 signaling complex w/ zeta
CD4+
MHC/HLA class I
CD28+
CD25+
CTLA-4 - shut off at end of immune response
PD-1 - shut off at end of immune response
LFA-1/VLA-4 - allows to migrate to peripheral tissue to site of infection
CXCR3 - allows to migrate to peripheral tissue to site of infection
E - and P- selectin - allows to migrate to peripheral tissue to site of infection

39
Q

what is the major difference between an effector T cell and a resting naive T cell?

A

Effector T cell is able to response to specific antigen without need for co-stimulation via B7(CD80)-CD28+ interaction
**DOES NOT NEED CO-STIMULATION

40
Q

T helper 1 Cells:

  • Stimulated by
  • Secretes
  • Role
  • Defense against
  • Patholoyg
A

T helper 1 Cells:
Proliferation stimulated by IL-12 and IFN-gamma (secreted by Macrophage, NK cells, DCs)
Unique transcription factor: T-bet - in response to IFN-gamma - opens IFN-gamma genes for secretion during development
Secretes: IFN-gamma, TNF-alpha
Role: Classical macrophage activation (M1) (via IFN-gamma)
Defense: Intracellular pathogens
Pathology: Chronic Inflammation

41
Q

T helper 1 IFN-gamma activities

A
  • increases Macrophage response to INTRACELLULAR MICROBES (classical M1 pathway)
  • stimulates B cells to class switch to IgG during activation (opsonization)
  • stimulates class II MHC antigen presentation and B7 (CD80) expression
  • inhibits Th2 and Th17 production
42
Q

T helper 1 IFN-gamma activities

A
  • increases Macrophage response to INTRACELLULAR MICROBES (classical M1 pathway)
  • stimulates B cells to class switch to IgG during activation (opsonization)
  • stimulates class II MHC antigen presentation and B7 (CD80) expression
  • inhibits Th2 and Th17 production
43
Q

CD4+ T helper Cell

  • Proliferative stimulation
  • Transcription factor
  • Secretes
  • Role
  • Defense
  • Pathology
A

T helper 2 Cells

  • Proliferative stimulation response to IL-4 (secreted by Mast cells, basophils, Th2 cells in immediate surroundings)
  • Transcription factor: GATA-3
  • Secretes: IL-4, IL-5, IL-13
  • Role: Eosinophil, mast cell, ALTERNATIVE macrophage activation
  • Defense: Helminths, big worms
  • Pathology: Allergy (Type 1 hypersensitivity)
44
Q

T helper 2 cytokine activities: IL-4, IL-5, IL-13

A
  • stimulate B cells class switch to IgE
  • IL-13: Increased production of mucus (mucus contraction) in epithelial cells (gut, airway
  • IL-5: Increased eosinophil migration and activation
  • Support alternative macrophage development (M2)
  • Inhibits Th1 development and effector responses
45
Q

Classically activated macrophage produces:

A

Classically activated macrophage (M1) - activated by T helper 1
Secretes: ROS, NO, lysosomal enzymes —-> Microbicidal actions: phagocytosis and killing of bacterial and fungi
Secretes: IL-1, IL-12, IL-23 —> INFLAMMATION

46
Q

Alternatively activation Macrophage Results

A

Alternatively activation macrophage (M2) - activated by T helper 2 cells
Secretes: IL-10 and TGF-B —-> ANTI-INFLAMMATORY effects, wound/tissue repair, fibrosis
Cancels out activity of M1

47
Q 
T helper 17 
Proliferative Stimulus:
Secretes:
Unique transcription factor:
Role:
Defense:
Pathology:
A

T helper 17 cells:
Proliferative Stimulus: response to IL-1, IL-6 (from DCs)
Secretes: IL-17, IL-22
Unique transcription factor: ROR gamma t
Role: Neutrophil activation
Defense: Extracellular bacteria and Fungi
Pathology: Autoimmunity, inflammation

48
Q

T helper 17 cytokine activity: IL-17, IL-22

A

IL-17: INFLAMMMATORY

  • recruitment of pro-inflam. leukocytes\
  • increases pro-inflam cytokine and chemokine production
  • stimulates anti-microbial peptide (defesins) production

IL-22: PROTECTIVE (immounoreg roles)

  • promotes regenerative responses within epithelial barrier
  • stimulates anti-microbial peptide (defensins) production
49
Q

T helper 17 immunity roles

A

destruction of extracellular bacterial and fungi by inducing neutrophilic inflammation

  • important in barrier function
  • role in inflammatory autoimmune diseases including Multiple sclerosis, inflammatory bowel disease, rheumatoid arthitis
  • role in cancers such as breast and lung
50
Q

Where do all CD4+ helper cells work?

A

All CD4+ helper T cells perform effector functions in the periphery NOT lymphoid tissues

51
Q

Where do CD8+ cells go after activation?

A

Immediately leave lymphoid tissue and enter circulation - circulate until they find inflammatory molecules — allows them to migrate to peripheral tissues at site of infection

52
Q

What do CD8+ Cytotoxic T cells recognize/bind?

A

CD8+ cytotoxic t cells recognize MHC/HLA Class I and altered-self peptides

53
Q

Effector function of CD8+ cytotoxic T cells:

A

Effector function is killing of cells infected with INTRACELLULAR PATHOGENS or TUMOR-TRANSFORMED cells by release of lytic enzymes (main mechanism) or Fas/FasL induced death (not all have Fas/FasL)
Proliferation, differentiation, and clonal expansion enhance by Th1 cells via release of IL-2

54
Q

How do CTLs kill?

A

Ag recognition and immune synapse formation
Directional release of enzymes and targeted killing of infected/altered cells – endocytosis of perfornin and granzymes (same as NK cells)

55
Q

What does perforin do?

A

Perforin (released by CTLs and NK cells) pokes holes in endocytic vesicle membrane and allows granzymes to enter cytosol and induce apoptosis

56
Q

How do CTLs kill by Fas/FasL induction?

A

Effector CTLs express Fas ligand (FasL) which binds to the death receptor Fas expressed on many cell types —> activation of caspases and apoptosis of Fas-expressing altered target cells

57
Q 
CD4+ T Regulatory Cells (T regs)
Stimulated by:
Surface expression:
Unique transcription factor:
Secretes:
Pathology:
A

Stimulated by: IL-2, IL-10, TGF-B (all immunosuppressive)
Surface expression: constitutively express CTLA-4 and CD25 (high affinity alpha chain)
Unique transcription factor: FOXp3
Secretes: IL-10, TGF-B “shut it down-okines”
Pathology: peripheral tolerance

58
Q

How does T regs having CD25 on surface at all time lead to immune homeostasis environment?

A

Allows circulating T regs to react with any IL-2 that is in lymphoid tissue where newly activated T cells are secreting IL-2 and allows T regs to use it up and secrete inhibitory cytokines as they do it

SFM IMMUNO (6 decks)

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