Path VII: chronic inflammation

Question 1

What are some common settings in which we see chronic inflammation?

Answer 1

1. persistent bacterial or viral infection
2. prolonged exposure to foreign bodies, toxic agents, or trauma
3. autoimmune disease

Question 2

What are three common histologic findings seen in chronic inflammation?

Answer 2

1. predominance of macrophages
2. evidence of tissue destruction
3. concomitant attempts at tissue repair

Question 3

Why do we usually see evidence of tissue destruction in chronic inflammation?

Answer 3

-prolonged toxic effects of inciting agent or prolonged exposure to the released cotnents of lysosomal granules, proteases, and other toxic metabolites.

Question 4

What are 3 important events that happen during tissue repair?

Answer 4

fibroblast proliferation, collagen deposition, and vascular proliferation/angiogenesis

Question 5

What are 4 major sources of macrophages in chronic inflammation?

Answer 5

1. resident macrophages
2. recruitment of monocytes to the site of inflammation
3. prolif of macrophages
4. immobilization of macrophages

Question 6

lymphocytes: what do they do?

Answer 6

cell-mediated and antibody mediated immune response

Question 7

lymphocytes: who recruits them? what activates them? What do they produce?

Answer 7

recruited by macrophage products. activated by antigen binding or IL1 and TNF-a by macrophages.
produce: IFNgamma, which stimulates destructive pwrs of macrophages

Question 8

How would eosinophils be recruited to a site of inflammation?

Answer 8

via eotaxin produced by macrophages

Question 9

Why might I see neutrophils in chronic inflammation?

Answer 9

macrophages may continue to recruit them in some conditions.

Or, persistence of organisms or tissue damage

Question 10

What are examples of times when granulomatous inflammation is particularly likely?

Answer 10

infection with Microbacterium tuberculosis, M. leprae, sarcoidosis

Question 11

What is a granuloma?

Answer 11

aggregation of epithelioid macrophages surround by a collar of lymphocytes and fibroblasts

Question 12

What are epithelioid macrophages (functional definition)

Answer 12

epithelioid macrophages are macrophages that have been transformed by the continuing presence of IFN gamma and are immobile but have a high capacity for O2 radical production and lysozymal production.

Question 13

What do epithelioid macrophages look like?

Answer 13

paile pink finely granular cytoplasm and indistinc cell boundaries on H&E stains.

Question 14

What is a giant cell?

Answer 14

fused epithelioid macrophage

Question 15

What is the defining cell of the granuloma?

Answer 15

epithelioid macrophage

Question 16

What kind of immunity is necessary for granuloma formation and why?

Answer 16

T-lymphocyte imunity necessary because IFN-gamma released by T-lymphocytes is responsible for macrophage transformation

Question 17

What are two common outcomes of granuloma infection?

Answer 17

lifelong granuloma

resolution with a calcified scar

Question 18

What is the lymphatic system

Answer 18

system of channels within tissues which drain to lymph nodes and help balance extravascular tissue fluid.

Question 19

What roles do lymphatics play during infection?

Answer 19

1. help drain edema from fluids entering the extravascular spaces during inflammation
2. transport macrophages, lymphocytes, and tissue debris
3. also transport toxins, bacteria, and other infectious agents. can help spread disease, but also increases APCs’ exposure to antigen

Question 20

What is the word for when lymphatics themselves become inflamed? What about when the lympho nodes get inflamed and painful?

Answer 20

lymphatic inflammation: lymphangitis

lymph node inflammation: lymphadenitis

Question 21

What three factors are most important for establishing fever?

Answer 21

IL-1, IL-6, and TNF-a

Question 22

IL-1, IL-6 and TNF-a promote fever by producin what in which part of the brain?

Answer 22

IL-1, 6 and TNF-a stimulate production of PGE2 within the hypothalamus.

Question 23

What happens to the body when PGE2 is produced in the hypothalamus?

Answer 23

fever:

peripheral vasoconstriction, decr. sweating, incr. shivering

Question 24

Leukocytosis: what factors mediate this? What is leukocytosis?

Answer 24

mediated by IL-1 and TNF-a. this means elevated WBC counts.

Question 25

How do IL-1 and TNF-a promote leukocytosis? What is one effect of leukocytosis?

Answer 25

induction of accelerated release of leukocytes from the bone marrow. may result in “left shift” in the WBC differential count (less mature cells, esp. of the neutrophil series). In severe rxns, this will look like leukemia- this is called a leukemoid rxn.

Question 26

What factor mediates the anorexia observed in chronic inflammation?

Answer 26

TNF-a is a direct appetite suppressant

Question 27

Why might you see anemia in a chronically inflamed person?

Answer 27

acute phase reactant hepcidin reduces iron availability.

Question 28

What are acute phase proteins?

Answer 28

plasma proteins whose concentrations increase in response to inflammation. examples: completment, C-reactive protein, transferrin, coagulation protein, serum amyloid A

Question 29

What factors promote the release of acute phase proteins from the liver?

Answer 29

IL-1, TNF-a, IL6

Question 30

What are two diseases involving defects in leukocyte adhesion?

Answer 30

leukoctye adhesion deficiencies type I and II

Question 31

What is leukocyte adhesion deficiency type I: inheritance, manifesation, molecular defect

Answer 31

lack of b-chain LFA-1 and MAC-1 integrins leads to less firm adhesion.
manifestation: recurrent skin and periodontalo infections, granulocytosis, delayed separation of the umbilical stump.
autosomal recessive

Question 32

What is leukocyte adhesion deficiency type II? molec defect and manifestations

Answer 32

fucose metab defect: lack of sialyl=LewisX. reduced rolling and attachment of leukocytes to endothelail cells.
manifestation: recurrent skin and periodontal infections, granulocytosis, umbilical stump probs. less severe than type II

Question 33

What is chediak-Higashi syndrome?

Answer 33

neutrophils and monocytes with large granules. They have problems with membrane fusion, leading to poor formation of phagosomes and lysomsomal fusion.
recurrent skin and periodontal infections, esp. with S. aureus. associated albinism, neuropathy, and intellectual disability.
autosomal recessive

Question 34

What is chronic granulomatous disease? inheritance? manifestations?

Answer 34

missing compoents of the NADPH oxidase system. may be autosomal recessive (cystosolic component) or sex-linked recessive (plasma membrane component). severe recurrent infections of skin, liver, lung, bones, esp. with catalase pos. organisms.

Question 35

What is neutrophil specific granule deficiency? molec, manifestations, inheritance

Answer 35

lack of neutrophil-specific granules and abnormal eosinophils and platelts. autosomal recessive. recurrent infections of skin, ears, sinuses, delayed wound helaing, and bleeding tendency.

Question 36

What is myeloperoxidase deficiency?

Answer 36

autosomal recessive. defective production of myeloperoxidase. fairly midl disorder. mostly flares when pts are immunocompromised or diabetic. fungal infection common