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Biology Of The Immune System > L5: T Cell Activation > Flashcards

L5: T Cell Activation Flashcards

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1
Q

How is clonal proliferation of naive T cells triggered?

A

By cells making contaact with specific Ag and APC in secondary lymphoid tissue

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2
Q

What effector cells do naive T cells differentiate into?

A
  • cytotxic T cells (CD8+) which kills infected cells

- helper T cells (CD4+) which secretes cytokines

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3
Q

What happens in lymphoid tissue?

A
  • T cells recognise Ag/MHC on APC

- T cells reside prior to activation

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4
Q

Where can APC be found?

A

In lymphoid tissue e.g. lymph nodes, spleen, tonsils

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5
Q

What must happen for naive T cells to survive?

A

They must encounter Ag

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6
Q

Explain the process by which T cells become activated

A
  1. Enter lymph node from blood via high endothelial venules
  2. Moves into ‘T cell area’ which is rich in dendritic cells and macrophages (APC)
  3. APC presents Ag and delivers other activation signals
  4. T cells that aren’t activated leave lymph node via cortical sinuses and lymphatic vessels, where they re-enter circulation and are recycled. If they are still unable to activate they die
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7
Q

What is the function of chemokine receptors on the T cell surface?

A

Chemokine receptors bind ligands (chemokines) expressed or released by other cells

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8
Q

How are cell/cell interactions mediated?

A

Using cell adhesion molecules (CAMs) once close to other cells

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9
Q

T cells contact APC using CAMs then TCR scans APC peptide/ MHC complexes. What 2 outcomes can occur?

A
  1. No recognition- disengages
  2. Recgonition- signal from TCR complex (CD3) sent, increasing affinity of CAMs interactions.
    - T cells divide
    - Progeny differentiate into effector cells and exit forming the T cell mediated response
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10
Q

Explain the T cell mediated response

A
  1. T cells bind APC through low affinity LFA 1/CAM 1 interactions
  2. Subsequent bnding of TCR signals LFA 1
  3. Conformational change in LFA 1 increases affinity and prolongs cell/cell contact, which is the start of the singalling cascade T cell receives
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11
Q

What molecule does the first signal of the T cell signalling cascade involve?

A

The CD3 zeta chain

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12
Q

What do naive T cells require for activation

A

3 signals

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13
Q

After T cell activation what proteins are expressed?

A

ICOS (Inducible T-cell COStimulator) & CTLA 4

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14
Q

What is the job of ICOS

A

It binds ICOSL on APC to induce cytokine secretion by T cells

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15
Q

What is the job of CTLA-4

A

Binds to B7, stronger than CD28 which it is highly related to, which delivers a -ve signal to the activated T cell (is antagonist to that of CD28)

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16
Q

What is the purpose of the -ve signal sent to T cell after CTLA-4 binding?

A

It dampens down/ limits T cell response

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17
Q

CTLA mutations are associated with what type of diseases?

A

Autoimmune diseases

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18
Q

Give an example of a clinical use of CTLA

A

It can be used to treat cancer patients by blocking negative signaling from the B7-CTLA-4 interactions, to enhance immune (B cell) response

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19
Q

Name 2 co-stimulatory molecules involved in the T cell response

A
  • CD80 (B7.1)
  • CD86 (B7.2)
    They both seem important but their functional differences aren’t clear yet
20
Q

What states can CD80 and CD86 be found in?

A
  • Constitutive on mature dendritic cells

- Inducible on macrophages/ B cells

21
Q

What triggers co-stimulation on APC?

A

Activation of APC by pathogens so APC can provide 2nd signal to activate T cells

22
Q

What is the 2nd T cell activating signal also known as?

A

The danger singal

23
Q

How is the danger signal activated?

A

APC expresses receptors for microbial molecules (PPR) and bind these pathogen- associated molecules. This ensures this signal only occurs during infection

24
Q

What does the danger signal trigger?

A

The APC upregulation of MHC and co-stimulatory molecules

25
Q

What will happen if a T cell receives signal 1 without signal 2?

A

It becomes functionally inactivated (anergic) and will not respond. This ensures only pathogen activated APC can activate T cells

26
Q

How is signal 3 delivered?

A

It is provided by cytokines and delivered by APC

27
Q

What is the role of signal 3 in T cell activation?

A

It dictates the differentiation of activated CD4 cells into different subseets of effector cells

28
Q

What is the function of dendritic cells as an APC?

A

To present Ag and is crucial for the activation of naive T cells

29
Q

What are the functions of macrophages and B cells?

A

They present Ag in order to receive help from effector T cells

30
Q

What 2 types of dendritic cells exist?

A

Plasmacytoic (pDC, DC6) and myeloid (convential DC (DC2/3)

31
Q

Explain the function of plasmacytoic dendritic cells

A

They are important in viral infection and secrete several type 1 alpha and beta interferons which express TLR 7 and 9 (these sense viral Ags)

32
Q

Explain the function of myeloid dendritic cells

A

They are involved in the activatin of naive T cells.

  • immature form found in epithelia and are macropinocytic (endocytose) & phagocytic
  • they don’t express B7.1/2 until activated
  • are induced to mature and migrate to lymph node following danger signal activation
33
Q

Once activated where can mature DCs be found?

A

In T cell areas of lymphoid tissue

34
Q

What happens to DC MHC class I and II molecules once activated?

A

They are loaded with peptides from pathogens they encountered in peripheral tissues
- their level of co stimulatory molecules will be very high so will express high levels of adhesion molecules

35
Q

Why do some DCs (DC I) process exogenous Ag and present it via MHC I molecules?

A

It allows DC to activate CD8 T cells which can then kill other infected but non-APC cells that are expressing viral Ags on class I without co stimulatory molecules

36
Q

Name key features of macropahges

A
  • highly phagocytic
  • express MHC II and B7 which increase T cell helpers
  • reside in many tissues at peripheral sites, lymphoid tissues and others
  • once activated secrete many inflammatory cytokines
37
Q

B cells are good at phagocytosis. True or false?

A

False, they are very poor.

38
Q

Explain the working mechanisms of B cells

A

They internalise soluble Ag for processing and presenting by BCR
- Ag binding to BCR upregulates B7 thus B cells are able to provide signal 2 required to activate T cells

39
Q

What is Interlukin-2 (IL-2)

A

It’s a key cytokine for T cell survival and a potent autocrine T cell growth facyor

40
Q

How does T cell affinity alter when the cell becomes activated?

A

Naive T cell expresses low affinity for IL2R but once activated this becomes high and IL-2 is secreted

41
Q

What causes lots of T cell poliferation?

A

IL-2 bindng on activated T cells

42
Q

What is the function of IL-2?

A

Allows rapid division of T celles, expands population of Ag specific activated T cells and is the target of immunosuppresive drugs

43
Q

Following activation by APC T cells differentiation into which effector cells?

A

CD8+: cells acquire cytotoxic activity (kills cells expressing peptide/ MHC class I complexes)

CD4+: cells function by secreting cytokines, effecting on other cell types recognising peptide/ MHC class II complexes

44
Q

What dictates the type of effector cell generated?

A

Signal 3 (cytokines) from APC + environment/ pathgen

45
Q

How are CD8+ T cells activated?

A

Either directly by infected or cross presnting APC or may require additional help from CD4+ T cells

Biology Of The Immune System (9 decks)

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