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Flashcards in Helper T cells and cytokines Deck (14)
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1

Outline function of cytokines

- Secreted single chain proteins regulating the amplitude and duration of immune response
- Produced locally and transiently ((short- lived)
- Very potent
- Binds to specific cell-receptors triggering intracellular pathways
- Can activate cells in local microenvironment or activate themselves
- Sends signalling cascade into cell so it is activated and carries out effector function

2

Outline some common cytokines

- Interleukin
- Tumour necrosis factor
- Interferons (IFN)
- Colony- stimulating factors
- Chemokines- important in cell recruitment due to chemotaxis (some interleukins are chemokines e.g. IL8)

3

Explain the cytokine mode of action

1) Cytokine receptors consist of 2 chains, the cytoplasmic domains of which bind to JAKs
2) Cytokine binding dimerises the receptor, bringing together the cytoplasmic JAKs, which activate each other and phosphorylate the receptor
3) Transcription factors (STATs) bind to the phosphorylated receptors and are, in turn, phosphorylated by the activated JAKs
4) Phosphorylated STATs form dimers that move into the nucleus to initiate gene transcription
5) Therefore the cell carries out its effector function

4

Outline the 3 signals between the helper T cells and APC triggering activation of APC and differentiation of T cell

Signal 1: T Cell protein recognises peptide presented on HLA
If presented on HLC class 1 APC will have CD8 as coreceptor and if presented on HLA class 2 APC will have CD4 as coreceptor
- if only signal 1 will become anergic (switched off)
2: CD28 on surface of T cell binds to B7 molecules on APC (B7.1 and 7.2)- become upregulated when dendritic cell has engulfed something and become activated
- Now T cell properly switched on/ activated
3: T helper0 cell- naïve T cell- not decided what T helper cell it is going to become/ its function
- Makes this decision based on signal 3 and cytokines that are secreted or that are in the local microenvironment when the T cell becomes activated

5

Explain what the different cytokines in the local environment do in terms of T cell differentiation

IL-12 or IFN- gamma (interferon gamma)- T helper 1 cell
- produces own set of cytokines (IFN gamma and IL2) that drive cell- mediated immune responses like activating macrophages

IL4- T helper 2 cell
Produces IL 4, IL10, IL5-
Activate B cells to make antibodies and drive class switching

IL6, TGF- beta (transforming growth factor- beta)- T helper 17 cell '
Produces IL-17 causing inflammation

IL10, IFN-alpha, TGF- beta (transforming growth factor beta)- T regulatory cell
Produces TGF-beta, IL10- involved in regulation

6

Explain how interleukins produced by Th2 cells are involved in B cell activation

- B cell or dendritic cell will recognise, internalise, process and present peptides from antigen on MHC class 2
- Binding to T cell receptor on naïve T cell (and CD4 coreceptor- as presented on MHC-II), B7 binds to CD28 on T cell so APC activated and cytokines released- in this case IL4
- This causes the naïve T helper cell to differentiate into a T helper 2 cell and produce its won cytokines- IL4
- This triggers B cell to class stitch and generate many antibodies against the same target

7

Why are cytokines important? How can they cause disease?

Cytokines keep us healthy by ensuring correct T cell made to produce response e.g. Cell mediated response or B cell response and antibody formation
Sometimes overstimulation can lead to too many cytokines being produced- causing disease
This can occur due to:
- Lack regulation
- Or chronic stimulation of immune system
- Too many can lead to organ failure

8

2 types of infections that need T helper cells and explain why they are needed

- Extracellular infection- need phagocytes (phagocytosis), complement, antibodies (for opsonisation and lysis) and eosinophils (extracellular digestion)
Need T helper 2 cells for production of antibodies
- Intracellular vesicular infection- need T helper 1 cells for cell- mediated responses activate macrophage and help better digest pathogen

9

Explain Th 1 and macrophage activation

1) Via phagocytosis macrophage takes up the pathogen (e.g. bacteria)
2) Processes and presents on MHCII
3) Recognised by T cell receptor which due to cytokine environment at the time is T helper I cell
4) This produces interferon- gamma (important in intracellular digestion of vesicular pathogen)

10

How can bacteria evade the immune system

Th1 cells produce interferon- gamma to activate and help the macrophage better intracellularly digest the pathogen
Some mycobacteria produce mediators (lipoarabinomannan) that stop macrophages being able to respond to the interferon gamma produced and hence preventing activation

11

What happens if the TH1 cells cannot clear the pathogen

- Granulomatous inflammation
- Expression of too many cytokines (continuous stimulation) by CD4 helper 1 cells cause chronic over stimulation of macrophages
- Rather than the immature macrophages becoming activated macrophages that are able to better digest pathogen we see epithelioid cell production
- Fusion of these form a multinucleate giant cell/ granulomatous formation
- Causes further tissue damage

12

What is a clinical manifestation of granulomatous inflammation in the lungs

- Tuberculosis is caused by a bacteria- mycobacterium tuberculosis
- Overstimulation of the macrophages can lead to epithelioid cells--> granulomous formation (giant multinucleate cells) in the lungs
- This causes further tissue damage

13

Explain granulomas formation in the skin

- Chronic overstimulation of macrophages in the skin can cause leprosy

- 2 types: (2 polar forms but many intermediate- based on cytokines produced in response to infection)
- Tuberculoid leprosy- over stimulation of cell mediated immune response- so normal T cell responsiveness specific to Mycobacterium leprae (intracellular pathogen), and normal serum immunoglobulin levels, hence causing macrophage activation and better intracellular digestion so organisms to be present at low levels and low infectivity but granulomas and local inflammation as well as peripheral nerve damage
- Lepromatous leprosy- antibody mediated response activated causing hypergammaglobulinemia (XS gammaglobulin in blood) but no T-cell response, and antibodies cant access intracellular mycobacteria, hence organisms flourish in macrophages , high infectivity and disseminated infection (spreads from 1 part of the body to another)- present in bone, cartilage and causes diffuse nerve damage

14

What cytokine patterns do we see in both forms of leprosy?

In tuberculoid- Th1 cells produced so they make IL2, IFN- gamma and (TFN- beta)
In lepromatous- Th2 cells make IL4,IL5 and IL10