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This 2 page Class Notes was uploaded by Mary-elizabeth Notetaker on Thursday September 8, 2016. The Class Notes belongs to bio 390 at University of Louisville taught by Shira Rabin in Fall 2016. Since its upload, it has received 7 views. For similar materials see Intro to Immunology. in Biology at University of Louisville.
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Date Created: 09/08/16
Week 3 Thursday, September 1, 2016 1:04 PM • Cytokines- communication marker ○ secreted from one cell, target cell w cytokine receptor takes it & signals something to happen ○ Soluble mols- ligand ○ Interleukins(inter leukocytes)…not all ○ Chemokines- chemical that induces mobilization of other immune cells to bring them to the cell ○ Mediate effector functions of immune system Endocrine action- produced by cell very far from target cell Paracrine action- nearby target cells Autocrine cells- target cell is self ○ 4 diff ways for cell to act on other cell: Pleitrophy- 1 cytokine can act on multiple cells to do diff things □ TH cell(t helper) CD4+… produces IL4… can act on b cell, CD8+ t cell, mast cell, or b cell and cause diff things Redundancy- 1 cell □ CD4+ helper t cell produces 3 IL's that do same thing Synergy- more than additive, put 2 things together and works much more intensly □ IL4 w IL5 causes mass Class switching Antagonism- can block something □ IFN-y can block IL4 ○ Cascade induction- one thing to few to many to lots ○ iis(Innate immunity): IL1 & TNF-a- can be made by either type of immune cell but target only iis cells ○ Sis (specific/Adaptive immunity): IL2 & IL4 (" " " " " ") ○ What kind of cytokines does the cd4+ t cell make? (Det's cytokines and how response goes from there) TH1- cytotoxic immune resp ---> acts on macrophagess and CD8+ cytotoxic t cells □ Makes IL12 & IFNy □ Leads to inflammatory cytotoxic response TH2- humoral immune system resp---> acts on b cells(make antibodies) □ Makes IL4 & IL5 □ Leads to antibody mediated(humoral) repsonse TH17- inflammatory state---> acts on macrophages & neutrophils □ IL17 □ No specific immune cells… majority are innate cells--> leads to massive inflammation • Specificity: ○ Cytokines don’t activate t cells nonspecifically bc: Activated cell alters cytokine Receptors Concentrated btwn secreting & target cells □ Low half life- just enough to send message Signaling thru multiple receptors □ 20 receptors for 50 chemokines Enzymes diff w/in target cells--> diff downstream events • 6 families of cytokines Based on: □ stx of ligand and receptor □ Nature of signaling pathways induced ○ Interleukin 1 □ Stimulated by viral, parasitic, or bacterial antigens □ Pro-inflammatory(fever/swelling/pain) □ Secreted early by macs and DCs Sis response □ Acts locally to bring WBCs to infected tissues □ Acts systematically to produce fever IL1- pro-forms(caspase1 activates it by cleaving IL1pro to IL1) □ Binds IL-1R1 & IL-1RAcP receptor in immunoglobulin receptor Come together in intermembrane region □ TIR domains- starts activation of MAPK & NF-kB pathways MAPK- signaling downstream of ITAMS …cascade pathway… involved in proliferation NF-kB: TF.. In nucleus, changes transcriptome □ Inhibit: IL1-Ra- binds IL-1R1 and prevents IL-1RAcP from binding so blocks cascade IL-1R2- binds IL1 in place of IL-1RAcP.. Receptor w/out activation ◊ No TIR domain so signal cant go in cell IL18- redundant- uses IL1 receptor family and expressed w macs & DCs Early iis cells □ IL-18Ra Bio 390 Page 1 □ IL-18Ra □ IL-18Rb □ Inhibited w soluble receptor(IL-1F7 & IL-18BP) IL33- smooth muscle and bronchial epithelia □ Induces TH2 cytokines--> activates B cells and mast cells □ Implicated in asthma, allergies, and bowel diseases □ Soluble inhibitors ○ TNF family TNF-a: proinflamm & produced by activated macrophages & other cell types TNF-b: from activated lymphocytes □ Activation, increased MHC, adhesion □ "present more" Receptors: □ Soluble, in memb Signaling- can lead to many diff things □ Fas receptor & Fas-L---> apoptosis & immune system shut down □ Fas receptor: Fas-L interacts w receptor to induce trimerization ◊ Adaptor protein FADD recruited Binds Fas & makes death domain which activates caspase ◊ Caspase cascade (caspase 8 cleaved to activate procaspase 3 & 7 inactive that activates caspace 3&7) ◊ apoptosis ○ Hematopoeitin (class 1) family- originate from and affect b & t differentiation, activation, & Ab secertion IL2- tells cell to grow(proliferation) □ Receptors have low/med/high affinity forms Inacitve- intermediate affinity ( y & b) ◊ NK cells(resting t cells) Activated- low(a) & high affinity form (y, b, & a) Activated CD4+ & CD8+ t cells, & activated b cells Many low affinity, few high affinity…lots of IL2, t cell will bind a lot w low affinity and few w high affinity – Reduces local concentration to keep other inactivated t cells in the area from being unnecessarily activated IL3/IL5/GM-CSF- antagonism, both signals at same time will inhibit each other □ All Binds a subunit, b subunit is shared signal-transdsucing protein btwn all a chains (usually not enough b chains) □ Proliferation unless too much cytokine- saftey mech ○ Interferon(Class 2) family Type 1 interferon- a & b □ Antiviral affects □ Secreted by viral-infected cells(not necessarily WBCs) □ If cell 1 infected, can make interferons & secrete so cell 2 picks them up and makes antiviral proteins, so cell 2 can withstand virus & survive Type 2 interferon- y □ Produced from activated T cells & NK cells □ Leads to TH1 response(CD4+ T cell)--> cytotoxic/inflamm response □ Inc MHC(increased presentation by iis cells) lvls on cells □ Intracellular pathogens(viruses, some bac) ○ IL17 family- pro-inflamm Expressed by variety of cells Receptors found on neutrophils, keratinocytes(on skin) Innate & adaptive immunity boundary • JAK kinase- allow signals to get into cell • STATS- adaptor mols that bring signals further in ○ Chemokine family- cause mobilization Secreted by cell Direct leukocyte migration Have highly conserved disulfide bonds..very small Many cystines in mols Signaling- chemokine receptors help cell move locations □ G protein activated- 3 subunits(aby), a dissociated when signal received then binds other mols to move cell □ GPCRs- chemokine receptor in membrane Bio 390 Page 2
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