T-cell activities Flashcards

1
Q

Naive T-cell enters lymph node via?

A

2 routes

  1. Blood vessel–> HEV
  2. Afferent lymph vessel from upstream lymph node
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2
Q

Naive t-cell gets directed into lymph node…..

A
  1. **Rolling interaction: **L-selectin (t-cell) :: GlyCAM-1 and CD34 (endothelial cell)
  2. Chemokine interaction: CCR7 (naive t-cell)::SLC/ ELC on endothelial cell
  3. **Tight binding: **LFA-1 :: ICAM 1
  4. **Diapedesis **
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3
Q

**Interactions bewteen CD4 and MHC ___ **

(x5)

What’s the end result?

A

Interactions bewteen CD4 T cell:: MHC II

  • **Adhesion: **LFA-1 :: ICAM1/2
  • **Adhesion: **CD2: LFA-3
  • **Activation Part 1: **CD4 (Lck):: MHC II
  • Activation Part 2: CD3 (TCR):: MHC II antigen
  • **Coactivation: **CD34:: B71/2

Activation T-cell CD45 Tyrosine kinase–> activation of transcription factors.

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4
Q

**Interaction between CD8+ and MHC ___. **

**End result is? **

A

Interactions bewteen CD8 T cell:: MHC I

  • Adhesion: LFA-1 :: ICAM1/2
  • **Adhesion: **CD2: LFA-3
  • **Activation Part 1: **CD8 (Lck):: MHC I
  • **Activation Part 2: **CD3 (TCR):: MHC I antigen
  • **Coactivation: **CD34:: B7-1/2

**Activation of T-cell CD45 tyrosine kinase–> PIP II/ DAG/IP3 cascade **

**notice this is identical to CD4 except for CD4 and MHC parts and final cascade**

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5
Q

What receptor changes depending on whether or not the T-cell is activated? What does that receptor bind and do in active/inactive T-cells?

A

Inactive/Naive T-cells: CD28 bind B7 on APC==> ++ activation of T-cell

Active T-cell: CTLA-4 binds B7==> LIMITS activation and proliferation.

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6
Q
  • What happens if the APC doesn’t have B7? What’s the purpose of this response?
  • Why doesn’t it have it?
    *
A
  • B7 only expressed by ACTIVATED professional APC
  • T-cell + antigen w/o B7==> Anergy
  • If an APC has an antigen but no B7, it’s likely presenting a self-antigen.
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7
Q

What induces APC maturation/activation?

A

Inflammatory cytokines, TLR ligands

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8
Q

What are the professional APC’s

A
  • Dendritic cells, b-cells, macrophages
  • Their distribution varies

THESE ARE THE ONLY CELLS THAT WILL EXPRESS B7!!

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9
Q

These cells are especially important for T-cell activation in the lymph nodes!

A

Dendritic cells.

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10
Q

**B-cells **

  1. Antigen uptake
  2. MHC expression
  3. B7
  4. Antigen presentation
  5. location
A
  1. Antigen uptake==> Ag specific receptor holds ag
  2. **MHC expression: * ***++ to ++++ (increases with activation, but always active)
  3. Stimulation/actvity- Inducible – to +++
  4. **Antigen presentation: **Soluble Ag, toxins, viruses
  5. **location: **blood, lymph
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11
Q

**Macrophages **

  1. Antigen uptake
  2. MHC expression
  3. B7
  4. Antigen presentation
  5. location
A
  1. Antigen uptake==> phagocytosis
  2. MHC expression: **inducible by bactera and cytokines
  3. Stimulation/actvity- Inducible – to +++
  4. **Antigen presentation: **particulate ag, extracellular and intracellular pathogens
  5. **location: **lymph, CT, body cavity
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12
Q

Dendritic cells

  1. Antigen uptake
  2. MHC expression
  3. B7
  4. Antigen presentation
  5. location
A
  1. Antigen uptake==> macropinocytosis/phagocytosis
  2. MHC expression: low in tissues, high in lymph nodes
  3. Stimulation/actvity- always active
  4. **Antigen presentation: **peptides, viral antigens, allergens
  5. **location: **Lymph, CT, epithelia
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13
Q

These cells are pretty good at activating T-cells at the site of infection and inflammation

A

Macrophages- they present EC bacteria

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14
Q

These present soluble antigens

A

B-cells

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15
Q
  1. Immature dendritic cells lack
  2. Mature dendritic cells lakc
A
  1. Immature= No co-stimulatory Ag activity
  2. Mature= no phagocytic abilities
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16
Q
  • What induces differentiation of dendritic cells?
  • What do the mature dendritic cells gain (receptors/markers?)
A
  • LPS, cell wall products, TNF alpha (and other inflammatory cytokines?)
  • Gain B7 and CCR7 markers.
17
Q

Things IL-2 Does

A
  1. T-cell prolifarion, increased cytokine produciton (IL-4, IFN gamma)
  2. B-cell proliferation and Ab production
  3. NK proliferation and cytolytic activity
18
Q

T-cell expresses different things when naive vs activated. What TWO things change?

A
  1. L-selectin in NAIVE cell, VLA-4 in MATURE cell
  2. CD45RA in NAIVE, CD45R0 in Mature

VLA= very late antigen

19
Q

Type 1 cytokines promote ____. They are ___ and are released by? ?

A

Type 1= cell mediated =IFN-gamma, IL-2

Released by TH1 cells

20
Q

Type 2 cytokines promote, are released by, are/

A

Type II= Humoral immunity= IL2,3,4,5,9,13

Released by TH2 cells

21
Q

TH17 cells release?

A

IL-17 and 22 = promotion of inflammation

22
Q
  1. To promote TH1 (over TH2)
  2. To inhibit TH1?
A
  1. Pro TH1: IL-12, IFN-gamma
  2. Anti TH1: IL-4, IL-10
23
Q
  1. Pro TH2
  2. Anti TH2
A
  1. Pro TH2= IL4
  2. Anti TH2= IFN-gamma
24
Q
  1. Pro TH17
  2. Anti TH17
A
  1. IL-1, IL-6 IL-23
  2. IL-4, IFN gamma
25
Q

Humoral response can be stimulated by?

A

BOTH Th1 and Th2 cells.

Th2= acivation of b-cells to make Ab (general)

Th1= Activation of opsonizing Ab like IgG1

26
Q

TH2

  1. Induction
  2. cytokines produced
  3. effect
A

TH2

  1. Induction: IL-4 (basophils) ==> GATA3 ON= committed
  2. **cytokines produced: **IL-4, IL-5, IL13 (IL-10?)
  3. effect: increased pdt of neutralizing Ab (IgG4), IgE, Basophil, eosinophil and mast cell activation.

BIG FOR PARASITES

27
Q

TH1

  1. Induction
  2. cytokines produced
  3. effect
A

TH1

  1. Induction: IL-2 (macrophages, DC), IFN-gamma (NK cells)==> T-BET turns on= committed TH1 cell
  2. **cytokines produced: **IL-2, TNF-apha, IFN-gamma, IL3, CXCL2. GM-CSF
  3. effect:
  • IL2=self proliferation, t-cell proliferation
  • TNF-alpha- Endothelial activation (adhesion and diapedesis enhanced)
  • **IFN-gamma- **macrophage activation
  • **CXCL-8- **draws macrophages to site of infection
  • GM-CSF/ IL3= macrophage differentiation in bone marrow and spleen
28
Q

Functions of the Cell-mediated response?

A
  1. Control of intracellular pathogens and tumors
  2. transplant rejection
  3. type 4 hypersensitivity
  4. contribute to granuloma formation
  5. contribute to chronic inflammation
29
Q

TFH Cells

A

Release IL21, IL4 and IFN gamma to activate B-cells, switch asotybe and increase antibody affinity.

30
Q

TH17

  1. Precursor cell
  2. Induction
  3. **Inhibition **
  4. **Cytokines released? **
A
  1. Precursornaive CD4+ or CD8+ t-cells
  2. Induced by IL1, IL-6, IL-23
  3. Inhibited by : Il2, IL4, IFN-gamma
  4. **Releases: **
  • IL-17= induces G-CSF expression, chemokines to attract neutrophil
  • IL-22= Antibacterial proteins
  • IL 21, 26
31
Q

T-regulator Cells

A

**AKA Tregs, FoxP3+ cells **

  • TFG-beta, IL-10, IL-35
  • Suppresses activity of the other T-effector cells.
  • Expersses: CD25, CTLA4
32
Q

TC cells- cytokines and main objective

A

Release TNF beta, porforin, granzymes and Fas-induced apoptosis= serial killer cell.

33
Q

Activation of CD8+ cells

A
  1. CD8+ cell needs CD28 from APC to become active/effector CD8+ cell
  2. Effector cell proliferates and differentiates with IL-2 that it makes or TH cell makes
  3. Effector CD8+ T-cell can kill cells expressing antigen in MHC I WITHOUT CD28 signal.

But, at first, needs the CD28 signal.

34
Q

How do we detect cell killing activity of CD8 T cells?

A

51Cr in cells, when they get killed the release it

35
Q

Granulomas

A
  • defense mechanism to prevent spread of infection
  • aggregation of infected cells (lymphocytes, neutrophils, eosinophils, multinucleated giant cells, fibroblasts, collagen)
  • can be from poor TH1 activation
36
Q

How does the CNS regulate the immune system?

A

SNS, PNS, pituitary, neuroendocrine output.

Stress= immunosupressant

37
Q

Immune system regulation on CNS?

A

IL1,6, TNF alpha = fever, sleepiness, fatigue, loss of appetite, decreased libido.

38
Q

Immune system and liver?

A

Induces synthesis of acute phase proteins= sickness behavior