Lecture 8 & 9- Cytokines and Naive T cell Activation Flashcards
Which cell types produce IL-1? Why do they produce it?
Mononuclear phagocytes (main) Leukocytes Fibroblasts Vascular endothelial cells (ECs) In response to LPS, TNF, IL-1 or CD4+ T cell stimulation
What does IL-1 do?
Increases IL-2 synthesis Promotes leukocyte adhesion to EC Systemically - cachexia
Give three functions of TNF alpha
Any of: - Increases expression of adhesion molecules on leukocytes and vascular ECs - increases permeability of endothelium - activates microbicidal activity of macrophages and neutrophils - induces release of IL-1, IL-6, itself - increases class I and II MHC expression - increases core body temp (systemic) - induces acute phase protein synthesis - can cause circulatory collapse and DIC if excessive levels
What induces TNFalpha release?
TNFalpha signaling, or LPS binding TLR4
What stimulates IL-6 release?
IL-1 and TNFalpha signalling
What does IL-6 do?
Stimulates acute phase protein synthesis, promotes B cell differentiation
What is the main function of IL-8? Give one cell type that makes it.
Chemotaxis and activation of neutrophils e.g antigen-activated T cells, LPS activated phagocytes, fibroblasts, ECs, platelets
What is the main function of IL-12? Name the cell types that produce it.
Macrophages and dendritic cells Induces Th1 differentiation, activates NK cells
What are the two main functions of IL-17? Which cell types makes it?
Th17 cells (in response to IL-23 from dendritic cells) Recruit macrophage and neutrophils to site of inflammation Release of IL-1, IL-6, TNF alpha from macrophage
What part of the bacteria does C reactive protein bind? What function does this promote?
Binds phosphocholine on bacterial surface Promotes phagocytosis (opsonisation)
Which are the type 1 interferons? Which cell types produce them?
IFN alpha and IFN beta Most cells
What event induces type 1 IFN synthesis and release?
Binding of TLR3 by dsRNA Or, type 1 IFN signaling
Give 4 intracellular effects of type 1 IFN signaling
- Mx protein induced, traps viral proteins for degradation 2. Protein kinase R initiates antiviral signaling pathways 3. RNase cleaves viral RNA 4. MHC I expression increased to boost CD8+ T cell function
What effect does type 1 IFN have on NK cells?
Activates them
Which cells produce IL-2?
CD4+ and CD8+ T cells
What major effect does IL-2 have on T cells?
If they express the high-affinity IL-2-R, it induces proliferation
What are four other effects of IL-2?
IFN-gamma release by T cells TGFbeta release by T cells B cell stimulation NK cell stimulation
Which cell types produce IL-4? Which inflammatory pathway absolutely requires it?
Produced by CD4 T cells, NK cells, mast cells Required by B cells for class switching to IgE
Name one cell that produces TGFbeta. What are two functions?
Treg cells Stimulates angiogenesis, inhibits T cell proliferation, required for class switch to IgA
Which cell types produce IFN gamma? In response to what?
Th1 and CD8 T cells, in response to antigen encounter and IL-2
List four functions of IFNgamma
Any of: - potent activator of phagocytes and neutrophils - induces synthesis of enzymes of the respiratory burst - induces TNFalpha secretion - activates NK cells - increases MHC I and II expression - promotes B cell differentiation - promotes IgG2a synthesis (opsonising)
Which cell types produce IL-5? Which inflammatory pathway is it important for?
Th2 and mast cells Stimulates eosinophil growth; important for helminth immunity
How are chemokines classified?
Based on configuration of two cysteine residues at the N terminus
What are the five types of cytokine receptors?
- Immunoglobulin superfamily 2. Class 1 cytokine receptors (haematopoetin family) 3. Class 2 cytokine receptors (interferon family) 4. TNF receptors 5. Chemokine family receptors (G protein coupled)
Give two examples where viruses make cytokine-like molecules.
Vaccinia and cowpox produce an IL-1beta binding protein Poxviruses produce soluble IFNgamma receptor
What are the five attributes of cytokine function?
Pleitrophy Redundancy Synergy Antagonism Cascade induction
List five cytokines secreted by activated macrophages
IL-1beta TNFalpha IL-6 IL-8 IL-12
List three cytokines that cause fever
IL-1beta IL-6 TNFalpha
Which cytokines induce acute phase protein synthesis?
IL-1, TNFalpha, IL-6
When, other than bacterial infection, might phosphocholine be present in the body?
Cell damage - usually only present on the inside of the plasma membrane. If on the outside, indicates cell damage. Bound by C-reactive protein from liver, promoting complement lysis of damaged cell.
What are three pathological, systemic effects of TNFalpha?
Insulin resistance Thrombosis Low cardiac output
What cell signaling pathway is used by IFNalpha signalling?
JAK1/ STAT2 for IFNalpha JAK1/STAT1 for IFN gamma
What event must occur before an activated T cell can proliferate?
Maturation of the IL-2 receptor (synthesis and insertion of alpha subunit) and stimulation (autocrine) by IL-2
What is the signal that leads to stabilisation of IL-2 mRNA and increased IL-2 secretion by the T cell?
CD28 from T cell - B7 from macrophage interaction (signal 2 of T cell activation)
What is the pathway by which the IL-2 receptor matures?
Antigen recognition by receptor >> NF AT binds IL-2 promoter region >> get IL-2 R alpha expression
Which intracellular signaling pathway does IL-12 use to drive Th cell development? What is the transcription factor that is important, and which molecule induces it? Which Th cell results?
IFNgamma signaling > Tbet expression IL-12 signalling via STAT4 dependent pathway Get Th1
Which intracellular signaling pathway does IL-4 use to direct Th cell development? Which transcription factor is also important? Which Th cell results?
IL-4 > STAT6 pathway GATA-3 needed Th2 results
Name the cells.
If the purple cell is a naive CD8+ T cell, what are the two circled molecules? What about the soluble molecule in the second picture?
