Cytokines Flashcards
(47 cards)
What are cytokines?
Proteins/polypeptides secreted by cells of innate & adaptive immunity
When are cytokines produced?
In response to microbes/Ags in immune/inflammatory reactions
What is the nomenclature of cytokines based on?
Based on cellular sources previously
- “Monokines = produced by mononuclear phagocytes
- Lymphokines = by lymphocytes
- Interleukin = by leukocytes & act on other leukocytes
What are the general properties of cytokines?*
- Cytokine secretion is a BRIEF, SELF-LIMITED event
- Synthesis is initiated by new gene transcription (not stored as preformed molecules)
- Synthesis are transient & rapidly secreted when needed - Cytokine actions are often “PLEIOTROPIC & REDUNDANT”
- Pleiotropism: 1 cytokine can act on different cell types = diverse effects
- Redundancy: multiple cytokines have same effects. Hence, antagonist against “a cytokine” = not effective because other cytokines could compensate - Cytokine actions can be LOCAL and SYSTEMIC
- Act on same cell (autocrine) or on nearby cell (paracrine)
- Enter circulation & act at a distance from production site (endocrine) ➔ e.g. TNF-a - SYNERGY & ANTAGONISM
- Synergy - IFN-gamma & TNF = increased expression of class I MHC
- Antagonism - eg. IFN-gamma activated MO while IL-10 inhibits MO activation - Cytokines initiate their actions by binding to target cell receptors
- Expression of cytokine receptors:
- Regulated by external signals (eg. Ag stimulates T/B cells ➔ increase cytokine receptors)
- Also regulated by cytokines themselves (+ve amplification or -ve feedback) - Cellular responses to cytokines:
- Changes in gene expression in target cells
- Leads to new functions & target cell proliferation (eg. Switching of Ab isotypes in B cells, Th cells differentiated Th1 or Th2 subsets)
- TIGHTLY REGULATED to turn down these responses (eg. Cytokine induction of genes encoding inhibitors of the cytokine receptors)
There are two types of cytokine receptors. What are they and what are they for?
Cytokine receptors consist of 1 or more transmembrane proteins
- Extracellular portion: for cytokine binding
- Cytoplasmic portions: for initiating signalling pathways
What are the signalling pathways for cytokines activated by?
Receptor clustering
➔ bringing together the cytoplasmic portions of 2 or more receptors
What is the classification of cytokine receptors based on?
Based on structural homologies of the extracellular cytokine binding domains & shared intracellular signalling mechanisms
What are the different classifications of cytokine receptors?
- Type I cytokine
- Type II
- IL-1 family - IL-1
- TNF - TNF-alpha
- Seven-transmembrane a-helical -
What are the cytokine Type I receptors for?
IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-11, IL-12, IL-13, IL-15, GM-CSF, G-CSF
Except 1, 8, 10, 14
What are the cytokine type II receptors for?
IFN-a/b, IFN-g, IFN-λ, IL-10, IL-20, IL-24, IL-26
What are the cytokine IL-1 family receptors for?
IL-1, IL-18
What are the TNF receptors for?
TNF-a, TNF-b (lymphotoxin), CD40, Fas, nerve growth factor
What are seven transmembrane a-helical receptors for?
Chemokines
Receptors for different cytokines activate distinct signalling pathways. What are the different types of cytokine signalling based on their receptors?
- Type I & II receptor family (most ILs & IFNs)
- Involve Janus Kinases (JAK - enzyme) & Signal Transducers & Activators of Transcription (STATs - transcription factors)
- JAK-STAT: best defined signal transduction pathway - TNF family - cytokine responses depends on particular receptor & cell type
- pro-inflammatory responses = new gene response
- TNF-R1 & Fas: cell death signals - Seven transmembrane receptor (for chemokine): involves G protein & the signalling mechanism engages GTP activating various cellular enzymes
- Ig receptors: involves receptor-associated tyrosine kinase
What are the 3 main functional categories of cytokines?
- Mediators & regulators of innate immunity
- Mediators & regulators of adaptive immunity
- Stimulators of hematopoiesis
In innate immunity, what are cytokines produced by? How do cytokines mediate and regulate innate immunity?
Produced by mononuclear phagocytes (NK cells) in response to infectious agents
- LPS binds to TLRs on macrophage cell surface ➔ synthesis & secretion of impt cytokines of innate immunity (IL-1, IL-12, TNF-a, IFN-g)
- The same cytokine (IFN-g) may also be secreted by macrophage activated by Ag-stimulated T cells (part of adaptive response)
What is the source of tumor necrosis factor (TNFa)? What is the stimulus for the secretion of this cytokine?
Activated macrophages
LPS - most potent stimulus
What is the function of TNFa?
Recruits neutrophils & monocytes to infection sites ➔ activate these cells to eradicate microbes
What does TNFa act on?
Acts on EC & leukocytes: critical for local inflammatory responses to microbes
What is bad about the secretion of TNFa?
It can injure the host, ex. autoimmune diseases like RA
What is the source of IL-12?
Macrophages and activated dendritic cells
When is interleukin-12 produced?
Is an important link between innate and adaptive immunity*
- Produced during early innate immune reactions against intracellular microbes & promoting adaptive immune response to these microbes
Which receptor family does IL-12 interact with? Via what pathway?
Interacts with type I cytokine receptor family
via Jak-STAT pathway
What is the function of IL-12?*
Enhances the cytotoxic functions of activated NK cells & CTLs
- Stimulate IFN-g production by T & NK cells*
- IL-12 + IFN-g promote Th1 differentiation*
