Innate Immunity Patho

Question 1

Describe Physical Barriers of Defense

Answer 1

tightly associated epithelial cells to prohibit passage of microorganisms into underlying tissue (skin)

Question 2

Describe Mechanical Barries of Defense

Answer 2

normal cell turnover/”washing” of surfaces (skin sloughing off, mucous being excreted)

Question 3

Describe some biochemical barriers of defense

Answer 3

epithelial-derived chemicals - substances secreted to trap or destroy microorgansisms (mucus, earwax, sweat, saliva, tears, sebaceous glands)

Question 4

what is a normal microbiome

Answer 4

colonization of surface where there is a mutualistic relationship and does not normally cause disease (can be disrupted by antibiotics)

Question 5

How does normal microbiome contribute to defense against pathogens

Answer 5

the microbiome offers innate protection through outcompeting pathogens for nutrients

Question 6

What are first lines of defense?

Answer 6

Physical, Mechanical, Biochemical, and Microbiome

Question 7

What are second lines of defenes?

Answer 7

non-specific innate immunity - ie inflammation, fever

Question 8

What is a mast cell?

Answer 8

most important cellular activator of the inflammatory response - contains granules that are released or synthesized when activated

Question 9

What is mast cell degranulation

Answer 9

release of mast cell granules (histamine, chemotactic factors, cytokines)

Question 10

What is mast cell synthesis

Answer 10

new production and release of of mediators (leukotrienes, prostaglandins, platelet-activating factors) slower acting

Question 11

What is the function of histamine

Answer 11

1.causes temporary constriction of smooth muscle lading to vasodilation & increased blood flow to area
2. causes increased vascular permeability through retraction fo endothelial cells & increased adherence of leukocytes to endothelium
3.H1 = proinflammatory, augments neutrophil chemotaxis and activates mast cells and neutrophils
4. H2 = antiinflammatory, opposite of H1

Question 12

What are the functions of Platelet Activating factor

Answer 12

1.endothelial retration –> increased permeability
2.leukocyte adhesion to endothelial cells
3. platelet activation

Question 13

What are the functions of prostaglandins

Answer 13

1. increase vascular permeability
2. smooth muscle contraction
3. Works with bradykinin on nociceptors to induce pain
4. can suppress release of histamine from mast cells and lysosomal enzymes from neutrophils to inhibit inflammation

Question 14

What are the functions of leukotrienes

Answer 14

*similar to histamine but slower acting and has prolonged effect
1.smooth muscle contraction
2.increased vascular permeability
3.neutrophil/eosinophil chemotaxis

Question 15

What are the function of Chemotactants

Answer 15

directs movement of cells along a chemical gradient
1. Neutrophil CF
2. Eosinophil CF of anaphylaxis
3. Leukocyte chemotaxis

Question 16

What are the functions of growth factors

Answer 16

help with tissue regeneration and angiogenesis
ex) VEGF (endothelial cell proliferation) and PDGF (connective tissue and smooth muscle proliferation)

Question 17

What are the three plasma protein systems essential to inflammatory response?

Answer 17

Complement, Clotting, and Kinen

Question 18

Describe the Complement System

Answer 18

1. bacteria activate complement cascade
2. Proteins form a membrane attack complex (MAC) that break off and form a pore in bacterial membranes, leading to cell lysis and death

Question 19

What three pathways lie within the Complement System?

Answer 19

Classical, Alternative, and Lectin

Question 20

Describe the Classical Complement pathway

Answer 20

antibodies activate the first complement component

Question 21

Describe the Alternative Complement pathway

Answer 21

bacterial products activate cascade, antibodies not required

Question 22

Describe the Lectin Complement pathway

Answer 22

mannose-binding lectin bind to bacterial polysaccharides containing mannose, activating the cascade

Question 23

Describe the Clotting System

Answer 23

activated by both intrinsic (within the vessel) or extrinsic (TF, damaged endothelium) pathways, the clotting cascade results in clot formed by fibrin mesh adn platelets to plug damaged vessels, stop bleeding, and trap microorganisms. Leads to leukocyte migration, chemotaxis, and increased vascular permeability

Question 24

Describe the Kinin system

Answer 24

initiated by clotting system, factor 12 –>factor 12a -> prekallikrein and results in production of bradykinin, which increases vascular permeability and leukocyte - augments inflammation and leads to pain

Question 25

Describe macrophage activation

Answer 25

monocytes --> macrophages; PRRs (including TLRs) expressed on surface recognize pathogens, when bind to PAMP or DAMPs this activates the macrophage, which causes it to release cytocines and chemokines

Question 26

What is a PRR

Answer 26

pattern recognition receptor

Question 27

What is a TLR

Answer 27

toll-like receptor

Question 28

Define PAMPs and DAMPs

Answer 28

pathogen-associated and damage associated molecular patterns

Question 29

what is the function of a chemokine?

Answer 29

induce leukocyte chemotaxis

Question 30

what is the function of a cytokine?

Answer 30

intercellular signalling to regulate innate and adaptive immunity, can be pro on anti inflammatory

Question 31

what is the function of a TLR

Answer 31

recognize fungal, viral and bacterial patterns --> initiates intracellular signlaing to activate macrophages release chemokines and cytokines

Question 32

what are the most important proinflammatory cytokines?

Answer 32

TNF, IL, and IFN

Question 33

What is the function of TNF

Answer 33

promotes innate immune response to injury or infection, including chemotaxis, adherance of neutrophils, phagocytosis, and cell proliferation

Question 34

What is the function of ILs

Answer 34

regulate cell adhesion molecules, attract leukocytes (chemotaxis), proliferation of leukocytes in bone marrow, and enhance or suppress inflamation

Question 35

What is the function of IL-1

Answer 35

growth factor, pyrogen (fever inducing) that reacts with hypothalamus

Question 36

what is the function of IL-6

Answer 36

induces hepatocytes to produce proteins needed for inflammation and stimulates growth and differentiation of blood cells in bone marrow and growth of fibroblasts required for wound healing

Question 37

What is the function of IFN

Answer 37

produced and released by virally infected cells, induce antiviral proteins in neighboring healthy cells, can activate Macrophages

Question 38

define anti-inflammatory cytokines

Answer 38

diminish and control inflammatory response, IL-10 and TGF-b

Question 39

define the role of dendritic cells

Answer 39

APC, recognized invaders by PRRs adn phagocytose them. Unlike macrophages they migrate through lymphatic vessels

Question 40

What is the vascular response to injury or infection

Answer 40

vasodilation, increased vascular permeability, diapedesis (leukocyte adherence to inner vessel walls)

Question 41

What is the cellular response to injury or infection

Answer 41

neutrophils & macrophages perform phagocytosis, eosinophils defend against parasites and regulate mediators released by mast cells phagocytosis: recognition and adherence of phagocyte to target through PRRs, engulfment, fusion with lysosomal granuels, adn destruction of target

Question 42

What are four cardinal signs of inflammation

Answer 42

redness, heat, swelling, and pain

Question 43

What events lead to swelling/edema

Answer 43

increased vasodilation and capillary permeability lead to plasma leaking into interstitial space, caused by mast cell degranulation

Question 44

what causes redness/heat?

Answer 44

histamines, leukotrienes, and prostaglandins cause smooth muscle to relax leading to vasodilation --> increased blood flow

Question 45

what causes fever?

Answer 45

IL-1 and TNF through hypothalamus stimulation

Question 46

what causes function loss due to inflammation?

Answer 46

injury, edema, swelling close to joint

Question 47

What causes pain during inflammation

Answer 47

edema and badykinins activate nociceptors

Question 48

define acute inflammation

Answer 48

resolves in 8-10 days, self-limiting

Question 49

What are three systemic manifestations of inflammation?

Answer 49

1. Fever 2. Leukocytosis (>leukocytes in blood) 3. Increase in circulating plasma proteins (increased fibrinogen leads to increased ESR)

Question 50

What are the four stages of a successful inflammatory response

Answer 50

1. initiation 2. cell recruitment 3. debris removal 4. repair and regeneration

Question 51

What is a granuloma?

Answer 51

dense infiltration of lymphocytes and macrophages that the body tries to isolate cause by chronic macrophage-t cell interations

Question 52

what are examples of dysfunctional inflammatory responses

Answer 52

1.adhesions (excessive bleeding & fibrin) 2. keloids (raised scar outside boundaries) 3. hypertrophic scar (raised scar within boundaries) 4. contractures

Question 53

What 2 characteristics of the neonatal immune system make them more susceptible to infection?

Answer 53

-depressed inflammatory function (neutrophils and monocytes incapable of efficient chemotaxis) -deficient in collectins

Question 54

what are considerations that must be taken in regards to the aging population and inflammation?

Answer 54

-may be on steroids due to chronic illness -more susceptible to bacterial infections of lungs, urinary tract, and skin -cellular components of innate response deficient (macrophage) or have diminished activity (chemotaxis, phagocytosis)