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7. The Innate Immune System
BrownMed
58
Chemical Engineering
Graduate
11/10/2010

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Term
first line of defense (3)
Definition
barriers: physical, chemical and environmental, and biological
Term
first immunological line of defense
Definition
innate immune system
Term
a soluble means of protection against pathogens that evade cellular contact
Definition
complement system
Term
how do you know complement system is important? (3)
Definition
1. sea urchins have them 2. it develops in humans in the first trimester, 3. hereditary disorders are associated with disseminated recurrent infections
Term
complement components are made where and present where
Definition
made in liver, present in blood and tissues
Term
t/f complement system only functions in the innate immune system
Definition
false - also in the adaptive
Term
native complement protein components
Definition
C1-9, B, D, P
Term
what component is central to all pathways
Definition
C3
Term
3 complement activation pathways
Definition
alternative, lectin, and classical
Term
C3 cleavage activates _ by what mechanism
Definition
activates C5-9 via all 3 complement activation pathways
Term
opsonization (2)
Definition
coats bacterial surfaces, enhancing phagocytosis. by C3b
Term
how does complement system cause inflammation
Definition
stimulates histamine release (binds to mast cells and allows them to degranulate), increased blood vessel permeability, chemotactic attraction of phagocytes
Term
direct killing via complement system
Definition
attach to invader, form complex, drill holes
Term
indirect killing via complement system
Definition
mark invader for destruction by macrophages, attract phagocytes to the area and increase phagocytosis
Term
C3a
Definition
small soluble fragment, leads to vacular increased permeability and recruitment and activation of phagocytes
Term
when is classical pathway triggered
Definition
when IgM or IgG bind to antigens on microbial cell surface; Fc regions become accessible to complement proteins, and two or more Fc regions come close together
Term
C1
Definition
binding of C1q results in activation of C1r, which in turn activates C1s = activated C1qrs, an enzyme that cleaves C4 and C2
Term
C4b
Definition
binds to membrane and combines with C2b whereas C4a/C2a is released.
Term
C3 convertase
Definition
C4b2b complex; C3b joins, making C5 convertase
Term
C1 esterase inhibitor
Definition
C1 INH, C1 inhibitor. is a protease inhibitor that blocks the activation of C1.
Term
hereditary angioedema
Definition
tissue swelling that looks like allergic reaction, caused by deficiency of C1-INH
Term
MBL pathway
Definition
lectin pathway=mannose-binding lectin pathway. MBL+mannan+MASP1and2>complex>activation of the MASPs and cleavage of C4 and C2
Term
lectin
Definition
protein that is able to bind to a carbohydrate molecule found at surface of common pathogens (innate)
Term
MBL / produced/stored where
Definition
a protein that specifically binds to mannans (mannose-containing polysaccharides, found on surfaces of bacteria). produced in liver, found in blood and tissues
Term
binding of MBL to a pathogen results in
Definition
the physical association of two MBL-associated serine proteases (MASPs). MASP1=C1r, 2=C1s, MBL=C1q
Term
alternative pathway / technical
Definition
also innate, unlike classical. natural breakdown of plasma C3 via spontaneous cleavage of the highly reactive thioester bond (now located on C3b) allows C3 to attach to any nearby host or foreign surface unless that surface is protected. / C3b+B > C3bBbP (this is C3 convertase and that reaction happened through the catalyst D) > C3bBb3bP (this is C5 convertase)
Term
how to regulatory proteins on host cells protect them
Definition
by inactivating C3b
Term
t/f spontaneous cleavage is the only innate way to cleave C3
Definition
false - a variety of enzymes also do it
Term
C3b can bind to _ because it's very reactive (2)
Definition
amino or hydroxyl groups; many bacterial cell walls have these
Term
if C3b doesn't react with anything in 60 microseconds
Definition
it is neutralized by water
Term
alternative pathway C3 convertase is stabilized by
Definition
properdin = factor P
Term
DAF
Definition
decay accelerating factor = a protein on the surface of human cells that accelerates breakdown of the convertase C3bBb by other proteins in the blood (decays complement)
Term
CD59
Definition
human cell surface protein that kicks "almost finished" MACs off before they can make holes
Term
"grenade"
Definition
C3b
Term
complement regulatory proteins
Definition
are present on human cells but not microbial cells
Term
terminal complement inhibitor proteins
Definition
are anchored to RBC surface by GPI tails; are crucial in protecting blood cells from inappropriate destruction.
Term
PNH / symptoms
Definition
paroxysmal nocturnal hemoglobinuria: disease caused by lack of host cell protection from complement / anemia, fatigue, dark colored urine
Term
"smart bombs"
Definition
lectin activation pathway
Term
phagocytes
Definition
eat invader + fuse with lysosome to destroy invader. produce cytokines that call more leukocytes into the area, inducing inflammation
Term
how does the innate immune system know what to kill?
Definition
PAMPs (pathogen associated molecular patterns), using a limited number of PRRs or pattern recognition receptors
Term
PAMPs / 2 examples
Definition
sugars, NAs, lipids, proteins or combos of any of these; widely expressed on viruses and bacteria. / bacterial LPS (lipopolysaccharide) on gram-negative bacteria, peptidoglycans on gram-positive
Term
Toll-like receptors
Definition
TLRs mediate recognition of diverse pathogens. after binding to PAMPs > enhanced activation of genes encoding cytokines in the nucleus of the invader (and other molecules involved in antimicrobial activity). result: synthesis and secretion of cytokines that promote inflammation and the recruitment of leukocytes to the site of infection
Term
NK / how do they kill
Definition
kills virus and cancer. functions in production of cytokines. / insertion of perforin and granzymes
Term
MHC I
Definition
molecules sending a "kill" signal to CTLs. NK cells however kill based on absence of a "don't kill" signal as well as presence of a "kill" signal
Term
neutrophil
Definition
= part of the innate system, multi-lobar nucleus
Term
lymphocyte
Definition
adaptive, big round nucleus
Term
major players of adaptive immune system
Definition
B, T, and APC
Term
T lymphocytes
Definition
CD8 (CTL) and CD4 (T helpers: Th1 = CMI, Th2 = Humoral)
Term
physical barriers
Definition
skin, mucous, cilia
Term
chemical and environmental barriers
Definition
sweat, stomach and vagina acids; digestive enzymes; microbicidal substances on skin and mucous
Term
biological barriers
Definition
=commensal organisms: skin, GI tract, vagina
Term
innate immunity
Definition
complement, NK, phagocytes (neutrophils and macrophages)
Term
sequential activation
Definition
of complement components results in release of fragments important in inflammation and in formation of MAC
Term
lytic pathway
Definition
=terminal pathway, = attachment of C5b to the bacterial membranes leads to the addition of components C6, C7, and C8. this facilitates addition of multiple C9 molecules to form a pore in the membrane
Term
what does C1 INH inactivate other than C1
Definition
fibrinolytic, clotting and kinin pathways
Term
"pigtail"
Definition
=GPI tail on RBCs that binds to DAF to protect against complement. deficiency = PNH.
Term
CTLs kill by same mechanism as _, but
Definition
NK, but CTL is adaptive instead of innate
Term
expression of MHC-I molecules is often _ by virus/cancer, = _
Definition
depressed / loss of don't kill signal
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