Cytokines - Lecture notes Immunology PDF

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Physiological Systems and Immunology...

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Cytokines Cytokines • secreted, low MW (~ 30kDa) proteins • white blood cell derived • usually in response to stimulus • Functions? • cell - cell communication • innate and specific immunity • haematopoeisis How? • bind specific receptors – induces cell signaling • local effect - carefully regulated i) high affinity to receptors - so need low amounts ii) not stored - transient production

Cytokines influence a network of cells • large number of receptors • large number of different cytokines produced cytokines = Interleukins (WBC derived IL1- IL37) + chemokines (IL8) + interferons (I/II) cytokines exhibit • pleiotropy – same cytokine has different effects on different cells • redundancy – 2 or more cytokines have similar effects • synergy – combined effects of 2 cytokines is greater than the sum of each alone • antagonism – effects of one cytokine opposes another

• cascade – a cytokine stimulates a target cell- to produce another cytokineetc

T helper cell subpopulations Th cells exert function through cytokines need appropriate effector function to eliminate particular pathogen Th cells - Th1 IFN gamma - Th2 IL4, 5,6 and 13 - Th17 IL17 Th1 - cell mediated functions eg. DTH and Tc Th2 - helper for B cell activation of IgE synthesis

Th17 - defence against certain pathogens eg Klebsiella and fungi and induce autoimmunity Th1 cytokines = IL-2 and IFN (interferon) Th2 cytokines = IL-4, IL-5, IL-13

innate anti-bacterial cytokine responses • TNF - increase adhesion (low conc) molecules on endothelium - increase cytokine secretion - activate leukocytes to kill microbes •

IL-6 •

- increase vascular permeability Chemokines eg IL-8 - chemotaxis and adhesion

anti-viral cytokine responses Type 1 • IFNab - inhibit viral replication - increase NK cell activation /lysis - increase MHC I expression - activate mf • IL-12

- activates NK cells + T cell to produce IFNg - differentiates T cells to Th1 -> IFNg - increases NK and Tc cytotoxicity (->cell lysis) Aquired • IFNg - increases MHC class I and II expression - increases NK cell killing + mf killing - suppresses Th2 cells and Th17 cells IL-15 – Increase proliferation NK Cells

Cytokines and Disease Some diseases occur due to an imbalance in Th1 or Th2 cells Asthma Th2 SLE Th2 MS Th1 Leprosy (tuberculoid) Th1 Leprosy (lepromatous) Th2 Some diseases are caused by over-expression of certain cytokines

Cytokine or receptors

Presentations

IL-5

Hyper eosinophilic syndrome

IL-6

Multiple myeloma

IL-13

Hodgkins disease

TGFβ

Keloid; tissue fibrosis

TNF

Septic shock

Some diseases are caused by under-expression of certain cytokines

Defect in Cytokine or receptors

Presentations

G-CSF

Congenital neutropenia

IFN γR, IL-12R

Enhanced susceptibility to mycobacterial disease

IL-2Rγ chain

X-linked SCID

CD40L

Hyper-IgM syndrome, increased infections

Th1 cytokines

Increased susceptibility to infections

(CCR5

Resistance to HIV infection)!

Summary Cytokines are low MW proteins, derived from leukocytes. They bind to Rs and have a transient local effect.

They are involved in homeostasis and cell communication and can stimulate via paracrine, autocrine or endocrine action. They exhibit redundancy, pleiotropy, syngergy and antagonism Cytokines can cascade via several cell types. Different cytokine signatures are released by Th1 and Th2 cells, during viral immunity and innate bacterial immunity. Imbalances of Th1 and Th2 cytokines are associated with some diseases. Loss or gain of specific cytokines or their receptors is also associated with disease....