Immunology Lecture 3 (Ti): Innate Immunity

Front 1

Which type of immunity has a broad spectrum and is non-specific?

Back 1

innate immunity

Front 2

Innate immunity is the ? ? of defense?

Back 2

first line of defense

Front 3

What kind of memory and lasting protective immunity does innate immunity have?

Back 3

none

Front 4

How many different recognition molecules does innate immunity have?

Back 4

a limited repertoire

Front 5

innate immunity responses are ? ancient.

Back 5

phylogenetically (result of evolution)

Front 6

Name the different arms of adaptive immunity?

Back 6

1. humoral (B-cells)

2. cell-mediated (T-cells)

Front 7

Response time of innate immunity vs. adaptive immunity?

Back 7

innate = minutes/hours

adaptive = days

Front 8

specificity of innate vs adaptive immunity?

Back 8

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

Front 9

Diversity of innate immunity vs. adaptive immunity?

Back 9

innate = limited # of germ line encoded receptors

adaptive = highly diverse, a very lg number of receptors arising from genetic recombination of receptor genes

Front 10

Memory responses of innate immunity vs. adaptive immunity?

Back 10

innate = none

adaptive = persistent memory, with faster response of greater magnitude on subsequent infection

Front 11

Self/nonself discrim. of innate vs. adaptive immunity?

Back 11

innate = perfect, no microbe-specific pattern in host

adaptive = very good, occasional failures of self/nonself disc. result in autoimmune disease

Front 12

Soluble components of blood or tissue fluids of innate vs adaptive immunity?

Back 12

innate = many antimicrobial peptides and proteins

adaptive = antibodies

Front 13

Major cell types of Innate immunity? (3)

Back 13

1. phagocytes (monocytes, macrophages, and neutrophils)

2. natural killer (NK) cells

3. dendritic cells

Front 14

Major cell types of adaptive immunity? (3)

Back 14

1. T-cells

2. B-cells

3. Ag presenting cells

Front 15

6 innate barriers to infection?

Back 15

1. skin

2. mouth and upper alimentary canal

3. stomach

4. small intestine

5. lg. intestine

6. airway and lungs

Front 16

What is secreted in the alimentary canal?

Back 16

saliva secretes IgA

Front 17

What is the skin assoc. with that is a hostile environment for bacteria?

Back 17

oil

Front 18

Connections b/n innate and aqd immunity do what?

Back 18

protect against pathogens

Front 19

What detects the invading pathogens?

Back 19

sensors

Front 20

What is a PRR?

Back 20

a pattern recogniton receptor (type of sensor that detects invading pathogens)...recognizes PAMPS (pathogen assoc. molecular pattern, ie, sugars, proteins, nucleic acids)

Front 21

What ability is inherited from our ancestors?

Back 21

the ability to recognize any Ag they ever encountered

Front 22

Inflammation an be ? or ?.

Back 22

acute or chronic

Front 23

Acute inflammation is a response to what?

Back 23

tissue damage (cut or burn...also knee injuries)

Front 24

What does acute infl. combat?

Back 24

early stages of infection and leads to repair of damaged tissues

Front 25

Chronic inflammation is a response to what?

Back 25

a response to dmg leading to osteoarthritis, continued dmg to tissue...occurs when the immune system does "shut off"

Front 26

What does chronic inflammation require?

Back 26

pharmacotherapy (NSAIDS, COXI/COXII inhibitors, etc.)

Front 27

What does osteoarthritis lead to?

Back 27

hip/knee replacements, etc

Front 28

The 4 cardinal signs of inflammation?

Back 28

1. swelling (tumor)

2. redness (rubor)

3. heat (calor)

4. pain (dolor)

Front 29

what is pus?

Back 29

dead neutrophils

Front 30

4 steps of inflammation?

Back 30

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

Front 31

Leukocyte extravasation is highly what?

Back 31

regulated

Front 32

leukocyte extravasation is necessary for what?

Back 32

the movement of leukocytes to site of infection

Front 33

What do inflammatory mediators act on?

Back 33

the endothelium of blood vessels

Front 34

What do the terms rolling and extravasation refer to? (give the 4 steps)

Back 34

how leukocytes become activated

1. rolling

2. activation

3. arrest/adhesion

4. transendothelial migration

Front 35

What is responsible for the adhesion of a neutrophil/leukocyte?

Back 35

integrin on the cell binds to ICAM on the tissue ("anchor") (if it didn't adhere bl. flow would just carry it away)

Front 36

Give 3 steps for the initiation of extravasation?

Back 36

1. selectin-mucin intrxns mediate rolling

2.chemokines/chemoattractants induce change in integrins

3. integrins adhere firmly to ICAMS

Front 37

Name 3 other soluble factors in the innate immune system?

Back 37

1. defensins

2. cathelicidins

3. interferons

Front 38

What is a defensin?

Back 38

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)

Front 39

Where are paneth cells seen?

Back 39

in the pancreas and kidney

Front 40

What kind of activity do interferons have?

Back 40

antiviral

Front 41

Where are all the soluble factors of the innate immune system produced?

Back 41

at the site of infection...and all act locally

Front 42

What are the sol. factors of innate immunity predominantly produced by?

Back 42

endothelium (but some are from neutrophils)...but always at the site of infection

Front 43

What is the role of the mediators of inflammation?

Back 43

to trigger or enhance both the innate and aqd immune response

Front 44

What 3 cells release mediators of inflammation?

Back 44

1. tissue mast cells

2. platelets

3. leukocytes

Front 45

the 3 mediator families?

Back 45

1. chemokine mediators

2. lipid inflammatory mediators

3. plasma enzyme mediators

Front 46

4 plasma enzyme mediators?

Back 46

1. kinins

2. clotting factors

3. fibrinolytic system

4. complement

Front 47

What are chemokines?

Back 47

cytokines that activate or attract leukocytes...( but not all chemoattactants are chemokines)

Front 48

Chemokines are usually composed of how many AAs?

Back 48

65-120

Front 49

What are chemokines released by?

Back 49

a wide variety of cells in response to viral or bacterial infection

Front 50

Some chemokines play a role in what?

Back 50

angiogenesis

Front 51

What is angiogenesis?

Back 51

the development of a blood supply (as in a tumor)

Front 52

What does APR stand for?

Back 52

acute phase response

Front 53

When was APR discovered?

Back 53

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+)

Front 54

What is the phyiologcal significance of APRs?

Back 54

not well understood...made by the liver...induced by TNF-alpha, IL-1, IL-6

Front 55

Innate immunity uses a variety of receptors to detect infection. Name 4 of them? (receptor,location)

Back 55

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)

Front 56

The target of the complement receptors of the innate immune system?

Back 56

microbial cell wall components

Front 57

The target of the CRP receptors of the innate immune system?

Back 57

phosphatidylocholine, pneumococcal polysacch

Front 58

The target of the toll-like receptors of the innate immune system?

Back 58

microbial components not found in hosts

Front 59

The target of the NOD receptors of the innate immune system?

Back 59

bacterial cell wall components

Front 60

What is a TLR?

Back 60

toll-like receptor

Front 61

The discovery of what TLR was important?

Back 61

TLR-4 was the first evidence that immune responses were conserved between the fruit fly and the human

Front 62

How many TLRs are in humans?

Back 62

11 (but functions only known for 9 of them)

Front 63

Where are TLRs located?

Back 63

they are transmembrane spanning proteins (leucine rich regions)

Front 64

TLRs are gradually becoming a what?

Back 64

a more popular target for drugs in development

Front 65

TLRs can detect a ? ? of pathogens?

Back 65

wide variety

Front 66

TLRs on cell surfaces recognize what?

Back 66

extracellular ligands

Front 67

TLRs that are found intracellularly recognize what?

Back 67

intracellular ligands, such as viral RNA or bacteril DNA frag.s

Front 68

What do neutrophils specialize in?

Back 68

phagocytosis and killing

Front 69

Neutrophils are the first cell to do what?

Back 69

arrive at the site of infection

Front 70

Neutrophils are well weaponized. List 3.

Back 70

1. display TLR-2 and TLR-4

2. ROS (reactive O2 species)

3. RNS (reactive nitrogen species)

Front 71

What are ROS and RNS?

Back 71

noxious substances that neutrophils "shoot" at pathogens

Front 72

What does phox stand for?

Back 72

NADH phagosome oxidase

Front 73

ROS and RNS mechanisms are generated by what?

Back 73

by phox

Front 74

What can a defect in phox cause?

Back 74

chronic granulomatous disease...increased susceptibility to fungal and bacterial infection

Front 75

4 species of ROS (reactive oxygen species) arm?

Back 75

1. O2- (superoxide anion)

2. OH- (hydroxyl radical)

3. H2O2 (hydrogen peroxide)

4. ClO- (hypochlorite anion, BLEACH)

Front 76

3 species of the RNS (reactive nitrogen species) arm?

Back 76

1. NO (nitric oxide)

2. NO2 (nitrogen dioxide)

3. ONOO- (peroxynitrite)

Front 77

What is the strongest of the antimicrobial species generated from oxygen and nitrogen?

Back 77

HClO- (hypochlorite)(bleach)...kills almost everything

Front 78

Is nitrogen dioxide (NO2) toxic to bacteria?

Back 78

to some bacteria

Front 79

Macrophages have several what?

Back 79

antipathogen mechanisms

Front 80

What is iNOS?

Back 80

inducible nitric oxide synthetase...expressed in high levels by macrophages...converts L-arginine to L-citrulline and releases NO (nitric oxide)

Front 81

NO has what?

Back 81

potent antimicrobial activity (it is an antipathogen mechanism of macrophages)

Front 82

Besides iNOS and NO what else is secreted by macrophages that act as an anitpathogen mechanism?

Back 82

a variety of cytokines