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Immunology
Lima2 - Innate Immune System
26
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Kindergarten
01/14/2013

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Term
Innate cells use _______ to recognize _______ on invaders?
Definition
-Pattern recognition receptors, pathogen associated molecular patters (PAMPs)
Term
What are the some major pattern recognition receptors and what PAMPs do they pair with? (5)
Definition
Toll-like receptor;
-double stranded RNA
-unmethylated CpG DNA islands
-lipopolysaccharides (LPSs) in gram- bacteria
-teichoic acids in gram+ bacteria
-(many other molecules on microbes but not our cells)

N-formyl-methionyl receptor
-N-formylmethionine (special tRNA in bac that initiates protein synthesis)

Mannose receptor;
-Mannose rich oligosaccharides

Scavenger receptor
-Oxidized lipoproteins

Glucan receptor (macrophages)
-glucan
Term
What is it called when white cells squeeze through the walls of blood vessels?
Definition
-diapedesis or extravasation (extravasation is just a little more specific while diapedesis encompasses the whole migratory process)
Term
Which is the cell type that does the rolling along blood vessels and how does it work?
Definition
-Neutrophils have s-Lex (sialyl-Lewisx) which weakly and transiently interacts with selectin on endothelium
-s-Lex---selectin (nice ring to it)
Term
If the rolling cell sticks to the endothelium, how's that work?
Definition
-Neutrophils have integrins (such as LFA-1) which stick to endothelial adhesion molecules (like ICAM-1)
-Expression of the adhesion molecules is caused by cytokines such as CXCL8 (IL-8)

-So CXCL8 --(+)--> ICAM-1 --(binds)--> selectin (on neutrophil)
Term
Professional vs. non-professional phagocytes
Definition
-Non-professional are epithelial cells, endothelial cells, fibroblasts, and mesenchymal cells. Phagocytosis is not their normal function, although they can do it
-Professional phagocytes are just the normal ones; monocytes, macrophages, neutrophils, tissue dendritic cells and mast cells.
Term
Neutrophil life, abundance, and function? Appearance?
Definition
-live only about a day
-are the predominant white cells
-arrive first on the scene to phagocytose bacteria
-Multi-lobed nucleus
Term
Macrophage/monocyte life, abundance, and function? Appearance?
Definition
-Long-lived
-Macrophages are in tissues, moncytes in blood
-Arrive later scene, but are more potent because they can be activated
-Have a shaggy membrane as macrophage and a bean shaped nucleus as monocytes
Term
What is CD14?
Definition
-Marker for macrophages
-It is LPS receptor
Term
What do macrophages have to recognize compliment?
Definition
-CR3 (compliment receptor 3)
Term
What is the chain of events leading to ROSs?
Definition
-NADPH oxidase coverts O2 to superoxide ion (O2-)
-Then superoxide dismutase takes that to hydrogen peroxide
-Finally, peroxidases use iron to make hypochlorite and hydroxy radicals

-In both macrophages and neutrophils
Term
What is the Fc region?
Definition
-The fragment crystallizable region (Fc region) is the tail region of an antibody that interacts with cell surface receptors called Fc receptors on cells like macrophages
Term
What is C3?
Definition
-It is a protein of the compliment system that allows it's activation
-It is also able to function in opsonization as C3b and has compliment component 3 (C3) receptors on cells like macrophages
Term
Chronic granulomatous disease?
Definition
-From a bad NADPH oxidase
-Patients cannot generate respiratory burst (rapid release of ROSs from cells)
-Patients are immunodeficient
Term
What do natural killer cells recognize, what do they use to do it, and how are they activated? Give a cytokine they produce?
Definition
-They recognize the absence of MHC using KIR (killer cell Ig-like receptor) or lectin-like (in compliment) CD94:NKG2
-They activated by IL-2 and IFN-γ (interferon; released when pathogen is present)
-They produce IFN-γ
Term
What are the major cytokines of the innate immune system? (7)
Definition
-IL-1,6,8,12
-IFN-α,β (interferon)
-TNF-α

-All are produced by macrophages, all but IL-1 are produced by dendritic cells
Term
In general, what do TNFs, ILs, and IFNs do?
Definition
-tumor necrosis factors (TNFs) cause apoptosis and alter vascular endothelial cells (for inflammation)
-interleukins (IL's) means literally "between leukocytes" and function in general communication
-interferons "interfere" with viral replication by being produced by host cells
Term
What is the producer, target, and effect of IL-1 & IL-6?
Definition
-IL-1 is produced by macrophages and keratinocytes
-IL-6 is produced by macrophages and dendritic cells
-Both of them act on lymphocytes and the liver
-Enhance responses and stimulate acute-phase protein secretion in liver
-Also helps mediate inflammation
Term
What is the producer, target, and effect of CXCL8?
Definition
-AKA IL-8
-It is produced by macrophages and dendritic cells
-It is a chemoattractant for neutrophils
-Stimulates epithelial cells to express adhesion proteins (like ICAM-1)
Term
What is the producer, target, and effect of IL-12?
Definition
-Produced by macrophages and dendritic cells
-Act on naive T cells to help them differentiate to Th1 cells (activate cellular immunity, CTL)
Term
What is the producer, target, and effect of TNF-α?
Definition
-Produced by macrophages and dendritic cells in response to LPS activation
-Acts on vascular endothelium to stimulate inflammation
-Also stimulates apoptosis, fever, sepsis
-Too much will cause septic shock
Term
Septic shock?
Definition
-Caused by an abundance of LPS in the blood activating macrophages
-Macrophages then secrete large amounts on TNF-α, which causes a whole body inflammation reaction and fever
-Eventually there is widespread endothelial injury and then activation of the coagulation system culminating in disseminated intravascular coagulation (DIC) (basically just clots)
-organ failure eventually results
-Typically from gram- bacteria
Term
What chemokines attract neutrophils, macrophages, and granulocytes?
Definition
-IL-8 (CXCL8); neutrophils
-Macrophage Chemotactic Protein; Macrophages
-Macrophage inflammatory protein (MIP); Granulocytes
Term
What is the acute phase response and how is it activated? Name four of the major proteins?
Definition
-It is the rapid change in plasma protein levels in response to trauma or infection
-It is activated by IL-6 (& 1)

-CRP (C reactive protein) increases; a non specific opsonin
-α-macroglobulin
-Fibrinogen
-Mannose binding lectin (an opsonin)
Term
What is an opsonin?
Definition
-Any molecule that targets an antigen for an immune response
-However, the term is usually used in reference to molecules that act as a binding enhancer for the process of phagocytosis, especially antibodies
Term
What is a lectin?
Definition
-Sugar-binding proteins
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