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82 Cards in this Set

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Which type of immunity has a broad spectrum and is non-specific?
innate immunity
Innate immunity is the ? ? of defense?
first line of defense
What kind of memory and lasting protective immunity does innate immunity have?
none
How many different recognition molecules does innate immunity have?
a limited repertoire
innate immunity responses are ? ancient.
phylogenetically (result of evolution)
Name the different arms of adaptive immunity?
1. humoral (B-cells)

2. cell-mediated (T-cells)
Response time of innate immunity vs. adaptive immunity?
innate = minutes/hours

adaptive = days
specificity of innate vs adaptive immunity?
innate = specific for mol.s and molecular patterns assoc. with pathogens

adaptive = highly specific, discriminate even minor differences in molecular structure, details of microbial or nonmicrobial structure recognized with high specificity
Diversity of innate immunity vs. adaptive immunity?
innate = limited # of germ line encoded receptors

adaptive = highly diverse, a very lg number of receptors arising from genetic recombination of receptor genes
Memory responses of innate immunity vs. adaptive immunity?
innate = none

adaptive = persistent memory, with faster response of greater magnitude on subsequent infection
Self/nonself discrim. of innate vs. adaptive immunity?
innate = perfect, no microbe-specific pattern in host

adaptive = very good, occasional failures of self/nonself disc. result in autoimmune disease
Soluble components of blood or tissue fluids of innate vs adaptive immunity?
innate = many antimicrobial peptides and proteins

adaptive = antibodies
Major cell types of Innate immunity? (3)
1. phagocytes (monocytes, macrophages, and neutrophils)

2. natural killer (NK) cells

3. dendritic cells
Major cell types of adaptive immunity? (3)
1. T-cells

2. B-cells

3. Ag presenting cells
6 innate barriers to infection?
1. skin

2. mouth and upper alimentary canal

3. stomach

4. small intestine

5. lg. intestine

6. airway and lungs
What is secreted in the alimentary canal?
saliva secretes IgA
What is the skin assoc. with that is a hostile environment for bacteria?
oil
Connections b/n innate and aqd immunity do what?
protect against pathogens
What detects the invading pathogens?
sensors
What is a PRR?
a pattern recogniton receptor (type of sensor that detects invading pathogens)...recognizes PAMPS (pathogen assoc. molecular pattern, ie, sugars, proteins, nucleic acids)
What ability is inherited from our ancestors?
the ability to recognize any Ag they ever encountered
Inflammation an be ? or ?.
acute or chronic
Acute inflammation is a response to what?
tissue damage (cut or burn...also knee injuries)
What does acute infl. combat?
early stages of infection and leads to repair of damaged tissues
Chronic inflammation is a response to what?
a response to dmg leading to osteoarthritis, continued dmg to tissue...occurs when the immune system does "shut off"
What does chronic inflammation require?
pharmacotherapy (NSAIDS, COXI/COXII inhibitors, etc.)
What does osteoarthritis lead to?
hip/knee replacements, etc
The 4 cardinal signs of inflammation?
1. swelling (tumor)

2. redness (rubor)

3. heat (calor)

4. pain (dolor)
what is pus?
dead neutrophils
4 steps of inflammation?
1. tissue dmg causes release of vasoactive and chemotactic factors that trigger a local increase in bl. flow (brings in neutrophils, causes swelling, and pain) and capillary permeability

2. permeable capillaries allow an influx of fluid (exudate) and cells

3. phagocytes migrate to site of infl. (chemotaxis)

4. phagocytes and antibacterial exudate destroy bacteria
Leukocyte extravasation is highly what?
regulated
leukocyte extravasation is necessary for what?
the movement of leukocytes to site of infection
What do inflammatory mediators act on?
the endothelium of blood vessels
What do the terms rolling and extravasation refer to? (give the 4 steps)
how leukocytes become activated

1. rolling

2. activation

3. arrest/adhesion

4. transendothelial migration
What is responsible for the adhesion of a neutrophil/leukocyte?
integrin on the cell binds to ICAM on the tissue ("anchor") (if it didn't adhere bl. flow would just carry it away)
Give 3 steps for the initiation of extravasation?
1. selectin-mucin intrxns mediate rolling

2.chemokines/chemoattractants induce change in integrins

3. integrins adhere firmly to ICAMS
Name 3 other soluble factors in the innate immune system?
1. defensins

2. cathelicidins

3. interferons
What is a defensin?
a soluble factor in the innate immune system...a small peptide...kills a wide variety of bacteria rapidly ("not picky")...associated with neutrophils...also secreted by paneth cells (GI)
Where are paneth cells seen?
in the pancreas and kidney
What kind of activity do interferons have?
antiviral
Where are all the soluble factors of the innate immune system produced?
at the site of infection...and all act locally
What are the sol. factors of innate immunity predominantly produced by?
endothelium (but some are from neutrophils)...but always at the site of infection
What is the role of the mediators of inflammation?
to trigger or enhance both the innate and aqd immune response
What 3 cells release mediators of inflammation?
1. tissue mast cells

2. platelets

3. leukocytes
the 3 mediator families?
1. chemokine mediators

2. lipid inflammatory mediators

3. plasma enzyme mediators
4 plasma enzyme mediators?
1. kinins

2. clotting factors

3. fibrinolytic system

4. complement
What are chemokines?
cytokines that activate or attract leukocytes...( but not all chemoattactants are chemokines)
Chemokines are usually composed of how many AAs?
65-120
What are chemokines released by?
a wide variety of cells in response to viral or bacterial infection
Some chemokines play a role in what?
angiogenesis
What is angiogenesis?
the development of a blood supply (as in a tumor)
What does APR stand for?
acute phase response
When was APR discovered?
during the research to control pneumococcal pneumonia...serum protein obtained during recovery or before death...related to C-reactive protein (CRP) which is a pentraxin (binding to ligand is Ca2+)
What is the phyiologcal significance of APRs?
not well understood...made by the liver...induced by TNF-alpha, IL-1, IL-6
Innate immunity uses a variety of receptors to detect infection. Name 4 of them? (receptor,location)
1. complement (bloodstream, tissue fluid)

2. C-reactive protein (CRP)(bl. stream, tissue fluids)

3. toll-like receptors (cell surface or internal compartments)

4. NOD family receptors (intracellular)
The target of the complement receptors of the innate immune system?
microbial cell wall components
The target of the CRP receptors of the innate immune system?
phosphatidylocholine, pneumococcal polysacch
The target of the toll-like receptors of the innate immune system?
microbial components not found in hosts
The target of the NOD receptors of the innate immune system?
bacterial cell wall components
What is a TLR?
toll-like receptor
The discovery of what TLR was important?
TLR-4 was the first evidence that immune responses were conserved between the fruit fly and the human
How many TLRs are in humans?
11 (but functions only known for 9 of them)
Where are TLRs located?
they are transmembrane spanning proteins (leucine rich regions)
TLRs are gradually becoming a what?
a more popular target for drugs in development
TLRs can detect a ? ? of pathogens?
wide variety
TLRs on cell surfaces recognize what?
extracellular ligands
TLRs that are found intracellularly recognize what?
intracellular ligands, such as viral RNA or bacteril DNA frag.s
What do neutrophils specialize in?
phagocytosis and killing
Neutrophils are the first cell to do what?
arrive at the site of infection
Neutrophils are well weaponized. List 3.
1. display TLR-2 and TLR-4

2. ROS (reactive O2 species)

3. RNS (reactive nitrogen species)
What are ROS and RNS?
noxious substances that neutrophils "shoot" at pathogens
What does phox stand for?
NADH phagosome oxidase
ROS and RNS mechanisms are generated by what?
by phox
What can a defect in phox cause?
chronic granulomatous disease...increased susceptibility to fungal and bacterial infection
4 species of ROS (reactive oxygen species) arm?
1. O2- (superoxide anion)

2. OH- (hydroxyl radical)

3. H2O2 (hydrogen peroxide)

4. ClO- (hypochlorite anion, BLEACH)
3 species of the RNS (reactive nitrogen species) arm?
1. NO (nitric oxide)

2. NO2 (nitrogen dioxide)

3. ONOO- (peroxynitrite)
What is the strongest of the antimicrobial species generated from oxygen and nitrogen?
HClO- (hypochlorite)(bleach)...kills almost everything
Is nitrogen dioxide (NO2) toxic to bacteria?
to some bacteria
Macrophages have several what?
antipathogen mechanisms
What is iNOS?
inducible nitric oxide synthetase...expressed in high levels by macrophages...converts L-arginine to L-citrulline and releases NO (nitric oxide)
NO has what?
potent antimicrobial activity (it is an antipathogen mechanism of macrophages)
Besides iNOS and NO what else is secreted by macrophages that act as an anitpathogen mechanism?
a variety of cytokines