Acute and chronic inflammation

Question 1

Inflammation

Answer 1

Reaction to injurious agents that limits damage and promotes repair, mediated by vessels and blood cells, tightly regulated chain of molecular and cellular events, categorized as acute or chronic based on duration of response and types of cells involved

Question 2

Neutrophils

Answer 2

Major constituent of white blood cells
Segmented nuclei
Motile, granular phagocytes
Primary responder in acute inflammation

Question 3

Leukocytes

Answer 3

Single nucleus, scant cytoplasm
Divided into B cells, T cells, NK cells
Produce antibodies, cytokines, toxic granules
Primary cell type in chronic inflammation

Question 4

Macrophages

Answer 4

Motile phagocytes

Bridge innate-> acquired inflammation by recognizing opsonized particles and presenting via MHC Class II receptors

Question 5

Macrophage activation

Answer 5

Non-immune: activation by endotoxin, fibronectin, chemical mediators of inflammation
Also activated by cytokine IFN-y

Question 6

Eosinophils

Answer 6

Bi- or tri-lobed nucleus, cytoplasm with eosinophilic granules
Granules contain histamine, proteolytic enzymes, major basic protein
Involved in inflammatory reactions to allergens and parasites

Question 7

Basophils (mast cells)

Answer 7

Bilobed nucleus obscured by basophilic granules containing histamine, proteoglycans, proteolytic enzymes

Question 8

Granulocytes

Answer 8

Neutrophils, eosinophils, basophils

Question 9

Mononuclear cells

Answer 9

Lymphocytes, macrophages

Question 10

Steps in acute inflammation

Answer 10

1. changes in vascular flow and permeability
2. leukocyte recruitment and activation (adhesion, transmigration, activation, phagocytosis, release of products)
3. Sequelae of inflammation (resolution, scar formation, chronic inflammation)

Question 11

Vasoactive mediators of vascular permeability

Answer 11

histamine, bradykinine, substance P, IL-1, TNF, IFN-y

Question 12

Leukocyte adhesion

Answer 12

Stasis, margination, adherence (selectins on endothelium loosely bind to S-L X mod glycoprotein then ICAM1/ VCAM1 on endothelium loosely bind to intigrins)

Question 13

Leukocyte chemotactic agents

Answer 13

exogenous agents, C5a, LTB4, IL-8

Question 14

Phagocytosis: regognition

Answer 14

mannose and fucose residues on microbial cell walls but not host cells; opsonization by IgG or C3b aids

Question 15

Phagocytosis: killing

Answer 15

• oxygen dependent: NADPH oxidation produces hydroxyl radical that is converted to hypochlorite by myeloperoxidase
• oxygen independent: substances in leukocyte granules

Question 16

regurgitation during feeding

Answer 16

phagolysosome remains open to outside after fusion

Question 17

frustrated phagocytosis

Answer 17

leukocyte attaches to immune complexes fixed on tissues, so they cannot be phagocytosed

Question 18

cytotoxic release

Answer 18

leukocyte ingests a substance that damages its cell membrane (ex uric acid crystals)

Question 19

exocytosis

Answer 19

lysosomal granules secreted to outside of cell

Question 20

serous inflammation

Answer 20

thin watery transudate exuded at site of injury

Question 21

fibrinous inflammation

Answer 21

clear fluid plus fibrinogen escapes the vessel causing polymerization to form a thick fibrin coat. characteristic of inflammation of lining of body cavities

Question 22

suppurative/ purulent inflammation

Answer 22

production of pus composed of neutrophils, necrotic cells, and edema fluid. characteristic in infection with pyogenic bacteria

Question 23

pseudomembranous inflammation

Answer 23

characteristic overgrowth of colonic C diff or fungi (secondary to antibiotics/ immunosuppression) causing a film over mucosa made up of inflammatory cells, necrotic epithelium, fibrin, mucus

Question 24

ulcer

Answer 24

destruction of an epithelial lining due to ischemic damage or infection

Question 25

gangrene

Answer 25

tissue necrosis secondary to interruption of blood supply due to trauma, infection, or thrombosis

Question 26

non-specific chronic inflammation

Answer 26

mononuclear cell infiltration, tissue destruction, fibrosis

Question 27

granuloma

Answer 27

collection of activated macrophages ("epithelialized") surrounded by a collar of lymphocytes with or without central caseation and giant cells - limited ddx: TB, leprosy, brucellosis, cat scratch disease, fungi, foreign insoluble objects, sarcoidosis

Question 28

Complement system: classical pathway

Answer 28

antigen-antibody complex activates C1, initiating complement cascade

Question 29

Complement system: alternative pathway

Answer 29

microbial surface molecules or Factor XII directly activate C3

Question 30

Complement system: lectin pathway

Answer 30

plasma lectin bound to mannose on bacterial surface activates C1, initiating the complement cascade

Question 31

C5a

Answer 31

chemotactic; causes vasodilation by stimulating histamine release

Question 32

C3a

Answer 32

causes vasodilation by stimulating histamine release

Question 33

C3b

Answer 33

opsonin

Question 34

kalikrein

Answer 34

converts high molecular weight kininogen to bradykinin; directly activates C5 to C5a; activates Factor XII (autocatalytic amplifiers)

Question 35

thrombin

Answer 35

links the clotting cascade and inflammation: causes mobilizaation of selectins, change in endothelial cell shape, production of chemokines, induction of arachidonic acid pahtway, production of platelet factor and NO

Question 36

plasmin

Answer 36

fibrinolytic and inflammatory roles: - directly cleaves C3 to form C3a - activates Factor XII, promoting kinin and clotting cascades - forms fibrin split products by breaking fibrin, which augment vascular permeability

Question 37

platelet activating factor

Answer 37

- derived from phospholipids, produced in platelets, macrophages, neutorphils, basophils, endothelial cells - cause platelet aggregation, vasodilation, bronchoconstriction, leukocyte adhesion, chemotaxis, degranulation, oxidative burst, potentiation of arachidonic acid metabolism

Question 38

primary lysosomal granules

Answer 38

contain myeloperoxidase, definsins, elastase, lysozyme, acid hydrolases, collagenases. release contents into lysosomes

Question 39

secondary lysosomal granules

Answer 39

contain lysozyme, gelatinase, histaminase, alkaline phosphatas, collagenase, lactoferrin, plasminogen activator release to extracellular space more readily than primary granules

Question 40

defects in leukocyte adhesion

Answer 40

- genetic deficiencies LAD types 1 and 2 --> recurrent bacterial infection, impaired wound healing

Question 41

Chediak-Higashi syndrome

Answer 41

- neutropenia, defective granulation, delayed microbial killing - abnormalities in melanocytes (albanism), nerve cells, platelets (bleeding disorders) - giant lysosomal granules in neutrophils

Question 42

chronic granulomatous disease

Answer 42

defects in oxygen-dependent microbicidal activity due to defect in genes encoding for NADPH oxidase-> recurrent bacterial infection

Question 43

Complement C3 deficiency

Answer 43

increased susceptibility to infection; inability to form MAC-> unable to clear infection by Neisseria

Question 44

paroxysmal nocturnal hemoglobinuria

Answer 44

- mutation in genese controlling complement activation | - recurrent complement-mediate intravascular hemolysis, hemolytic anemia

Question 45

hereditary angioneurotic edema

Answer 45

- genetic deficiency of C1 inhibitor | - edema of skin and mucosa of larynx and GI tract provoked by emotional stress or trauma

Question 46

a1-antitrypsin deficiency

Answer 46

- a1-antitrypsin is a major inhibitor of elastase, proteases from neutorphils - lack of antiprotease-> digestion of extracellular tissue-> emphsema, cholestatic hepatitis leading to cirrhosis, variable expression