INNATE IMMUNOLOGY AND INFLAMMATION

Question 1

what are lysozyme chemical barriers?

Answer 1

present in secretions and use hydrolysis to break proteoglycan wall of bacteria cell wall

Question 2

what are defensins?

Answer 2

small, hetergeneous, cationic, antimicrobial peptides (chemical barrier)

Question 3

what do defensins do?

Answer 3

• chemical barrier
• destabilizes membranes and pore formation in bacterial cell walls
• proteolytic degradation of bacterial proteins
• inhibit viral binding and entry
• inhibit virus particle assemble

Question 4

where are defensins stored?

Answer 4

neutrophil granules and secreted by epithelial cells

Question 5

how do defensins kill microbes?

Answer 5

extracellularly –> released when neutrophils die during inflammation
intracellularly –> after a cell phagocytoses a pathogen

Question 6

what are the major phagocytes in the body?

Answer 6

macrophages and neutrophils

Question 7

monocytes –> macrophages

Answer 7

pro-monocytes –> monocytes –> macrophage/ macrophage like cells

Question 8

are macrophages long or short lived?

Answer 8

long lived

Question 9

what are neutrophils?

Answer 9

non-dividing, short lived cells derived from hematopoietic precursors in the bone marrow

Question 10

what is pattern recognition?

Answer 10

immediate recognition for common ‘signs’ of microbial infection

Question 11

what are PRRs

Answer 11

pattern recognition receptors found on phagocytes in response to PAMPs or DAMPs

Question 12

what are some examples of PRRs?

Answer 12

toll-like receptors, nod-like receptors, lectins

Question 13

what responses do PRRs elicit?

Answer 13

phagocytosis and cytokine secretion

Question 14

what are the steps of phagocytosis?

Answer 14

1. PRR binds to a microbe
2. microbe is engulfed by phagocyte –> forms a phagosome
3. microbe killing –> use molecules like ROS, pore forming proteins, hydrolytic enzymes, pH changes
4. microbe remnants are digested and used, or excreted

Question 15

what is a common way for macrophages to kill cells

Answer 15

by synthesizing nitric oxide

Question 16

how do neutrophils kill cells?

Answer 16

use pore-forming molecules within their granules

Question 17

what are some neutrophil granules?

Answer 17

defensins, cathepsin, cathelicidins, lysosomes, lactoferrin

Question 18

what are cathepsin?

Answer 18

a type of protease

Question 19

what are cathelicidins?

Answer 19

pore forming molecule –> cause lysis

Question 20

what are lysozymes?

Answer 20

glycoside hydrolase

Question 21

what granule is best at killing gram +(ve) bacteria

Answer 21

lysozymes

Question 22

what are lactoferrin?

Answer 22

iron binding protein that interferes with iron metabolism in microbes

Question 23

what are NETs

Answer 23

in environments with lots of bacteria, neutrophils can lyse and release their DNA into the ECF

Question 24

what do NETs do?

Answer 24

trap bacteria because they’re sticky and hold them to chromatin –> histones are toxic to many bacteria

Question 25

what are toll like receptors?

Answer 25

transmembrane receptors that make cytokines

Question 26

what inflammatory cytokines do TLRs secrete

Answer 26

inflammatory cytokines (IL-1beta, IL-6, CXCL8, IL-12, TNFalpha)

Question 27

what interferons are secreted by TLRs

Answer 27

IFN alpha, beta, and lambda --> can activate macrophages, NK cells, and inducing antiviral state

Question 28

what is MyD88?

Answer 28

essential adaptor in TLR signaling

Question 29

what is a MyD88 deficiency?

Answer 29

suffer severe bacterial infections but antiviral responses are unaffected

Question 30

what happens when MyD88 is too active?

Answer 30

can develop various blood disorders and cancer because of over production of IgM

Question 31

what are nod like receptors?

Answer 31

intracellular receptors found in cytoplasm

Question 32

what is the main goal of NLRs?

Answer 32

increase cytokine production, recognize DAMP

Question 33

what is the first step in acute inflammation?

Answer 33

- vasodilation: increases blood flow at capillary bed

Question 34

what is used to induce vasodilation?

Answer 34

nitric oxide, histamine, prostaglandins, platelet activating factor, complement (C5a and C3a)

Question 35

how does nitric oxide effect vasodilation?

Answer 35

potent vasodilator at low concentrations, at high concentrations it can kill microbes and host cells

Question 36

what is vascular congestion?

Answer 36

vasodilation and fluid loss due to increased permeability lead to slower blood flow --> helps margination of leukocytes

Question 37

what is chemotaxis?

Answer 37

tells the cell which direction to go to

Question 38

what are important prostaglandins for vasodilation?

Answer 38

PGE2, PGD2, PGI2

Question 39

how are the prostaglandins and leukotrienes for vasodilation produced?

Answer 39

when PLA2 generates arachidonic acid from membrane phospholipids

Question 40

what is LTB4

Answer 40

important chemotactic agent

Question 41

what are lipoxins?

Answer 41

generated from arachidonic acid by 12 lipoxygenase to decrease inflammation

Question 42

what is the second step in acute inflammation?

Answer 42

enhancement of vascular permeability --> capillaries and venules become more leaky because of a number of mediators

Question 43

what mediators enhance vascular permeability

Answer 43

histamine and serotonin, prostaglandins (PGD2, PGE2), leukotrienes (LTC4, LTD4, LTE4), platelet activating factor, C3a, C5a, bradykinin

Question 44

what increases vascular permeability?

Answer 44

contraction of endothelial cells, endothelial damage , transcytosis

Question 44

what is lymphatics?

Answer 44

fluid accumulation during inflammation

Question 45

what is transcytosis?

Answer 45

used to quickly transport antibodies (problem if it occurs accidentally)

Question 46

what is lymphangitis?

Answer 46

when lymphatic vessels become inflamed

Question 47

what is the 3rd step in acute inflammation?

Answer 47

emigration and activation of leukocytes

Question 48

what leukocytes emigrate to site of incident during acute inflammation?

Answer 48

neutrophils, monocytes, eosinophils, basophils

Question 49

what are the steps to leukocyte migration during acute inflammation?

Answer 49

margination, rolling, adhesion, diapedesis, chemotaxis of leukocytes to site of injury

Question 50

what are the two different chemokine families?

Answer 50

CXC and CC

Question 51

what are CXC?

Answer 51

chemokines that attract neutrophils

Question 52

what are CC

Answer 52

chemokines that act on a variety of other leukocytes

Question 53

what are chemokines?

Answer 53

small cytokines that bind to cell-surface receptors and induce movement of leukocytes along chemokine concentration gradient

Question 54

what are E and P selectin used for?

Answer 54

present on endothelium and bind to white blood cells and are responsible for rolling

Question 55

what is responsible for tight binding during the emigration stage of acute inflammation?

Answer 55

integrins: LFA-1, MAC-1, VLAS-4, alpha4beta7 TNF and IL1 and chemokines

Question 56

what agents are produced in higher concentrations on sites of injury?

Answer 56

leukotriene B4, N-formyl-methionine, C5a, chemokines