Path VII: chronic inflammation Flashcards
What are some common settings in which we see chronic inflammation?
- persistent bacterial or viral infection
- prolonged exposure to foreign bodies, toxic agents, or trauma
- autoimmune disease
What are three common histologic findings seen in chronic inflammation?
- predominance of macrophages
- evidence of tissue destruction
- concomitant attempts at tissue repair
Why do we usually see evidence of tissue destruction in chronic inflammation?
-prolonged toxic effects of inciting agent or prolonged exposure to the released cotnents of lysosomal granules, proteases, and other toxic metabolites.
What are 3 important events that happen during tissue repair?
fibroblast proliferation, collagen deposition, and vascular proliferation/angiogenesis
What are 4 major sources of macrophages in chronic inflammation?
- resident macrophages
- recruitment of monocytes to the site of inflammation
- prolif of macrophages
- immobilization of macrophages
lymphocytes: what do they do?
cell-mediated and antibody mediated immune response
lymphocytes: who recruits them? what activates them? What do they produce?
recruited by macrophage products. activated by antigen binding or IL1 and TNF-a by macrophages.
produce: IFNgamma, which stimulates destructive pwrs of macrophages
How would eosinophils be recruited to a site of inflammation?
via eotaxin produced by macrophages
Why might I see neutrophils in chronic inflammation?
macrophages may continue to recruit them in some conditions.
Or, persistence of organisms or tissue damage
What are examples of times when granulomatous inflammation is particularly likely?
infection with Microbacterium tuberculosis, M. leprae, sarcoidosis
What is a granuloma?
aggregation of epithelioid macrophages surround by a collar of lymphocytes and fibroblasts
What are epithelioid macrophages (functional definition)
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.
What do epithelioid macrophages look like?
paile pink finely granular cytoplasm and indistinc cell boundaries on H&E stains.
What is a giant cell?
fused epithelioid macrophage
What is the defining cell of the granuloma?
epithelioid macrophage
What kind of immunity is necessary for granuloma formation and why?
T-lymphocyte imunity necessary because IFN-gamma released by T-lymphocytes is responsible for macrophage transformation
What are two common outcomes of granuloma infection?
lifelong granuloma
resolution with a calcified scar
What is the lymphatic system
system of channels within tissues which drain to lymph nodes and help balance extravascular tissue fluid.
What roles do lymphatics play during infection?
- help drain edema from fluids entering the extravascular spaces during inflammation
- transport macrophages, lymphocytes, and tissue debris
- also transport toxins, bacteria, and other infectious agents. can help spread disease, but also increases APCs’ exposure to antigen
What is the word for when lymphatics themselves become inflamed? What about when the lympho nodes get inflamed and painful?
lymphatic inflammation: lymphangitis
lymph node inflammation: lymphadenitis
What three factors are most important for establishing fever?
IL-1, IL-6, and TNF-a
IL-1, IL-6 and TNF-a promote fever by producin what in which part of the brain?
IL-1, 6 and TNF-a stimulate production of PGE2 within the hypothalamus.
What happens to the body when PGE2 is produced in the hypothalamus?
fever:
peripheral vasoconstriction, decr. sweating, incr. shivering
Leukocytosis: what factors mediate this? What is leukocytosis?
mediated by IL-1 and TNF-a. this means elevated WBC counts.
How do IL-1 and TNF-a promote leukocytosis? What is one effect of leukocytosis?
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.
What factor mediates the anorexia observed in chronic inflammation?
TNF-a is a direct appetite suppressant
Why might you see anemia in a chronically inflamed person?
acute phase reactant hepcidin reduces iron availability.
What are acute phase proteins?
plasma proteins whose concentrations increase in response to inflammation. examples: completment, C-reactive protein, transferrin, coagulation protein, serum amyloid A
What factors promote the release of acute phase proteins from the liver?
IL-1, TNF-a, IL6
What are two diseases involving defects in leukocyte adhesion?
leukoctye adhesion deficiencies type I and II
What is leukocyte adhesion deficiency type I: inheritance, manifesation, molecular defect
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
What is leukocyte adhesion deficiency type II? molec defect and manifestations
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
What is chediak-Higashi syndrome?
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
What is chronic granulomatous disease? inheritance? manifestations?
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.
What is neutrophil specific granule deficiency? molec, manifestations, inheritance
lack of neutrophil-specific granules and abnormal eosinophils and platelts. autosomal recessive. recurrent infections of skin, ears, sinuses, delayed wound helaing, and bleeding tendency.
What is myeloperoxidase deficiency?
autosomal recessive. defective production of myeloperoxidase. fairly midl disorder. mostly flares when pts are immunocompromised or diabetic. fungal infection common
