Inflammation Flashcards by Monica Fatorma

Hypersegmented neutrophils (> 5 segments) are thought to be pathognomonic of what class of anemias?

megaloblastic anemias (vit B12 or folate deficiencies)

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What is the difference between selectins and integrins?

selectins: weak binding; initiate rolling
integrins: stable binding and adhesion

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Lactoferrins purpose in secondary granules of PMNs?

to chelate iron

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What are the steps in neutrophil margination and adhesion?

Step 1: the endothelial cells at sites of inflammation have increased expression of E- selectin and P selectin, due to elaboration of cytokines by resident tissue macrophages

Step 2: neutrophils weakly bind to the endothelial selectins and roll along the surface

Step 3: neutrophils are stimulated by chemokine to express their integrins

Step 4: binding of the integrins to cellular adhesion molecules (ICAM-1 and VCAM-1) allows the neutrophils to firmly adhere to the endothelial cell.

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Name some endothelial selectins.

P-selectin
E-selectin
GlyCam-1/ CD34

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Name some endothelial integrins.

ICAM-1
VCAM-1

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Name some leukocyte selectins?

Sialyl-Lewis X & PSGL -1 (bind to P and E selectins)

L-selectin (binds to GlyCam-1 CD-34)

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What are some leukocyte integrins?

LFA-1 & MAC-1 (with ICAM-1)
VLA-4 (with VCAM-1)

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What are some conditions in which defects of adhesion can be seen?

DM
corticosteroid use
acute alchohol intoxication
Leukocyte adhesion deficiency Type 1

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Defects in phagocytosis and degranulation of neutrophils can be seen in what condition?

Chediak-Higashi

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Is Chediak Higashi an AR or AD condition?

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LAD type 1 (leukocyte adhesion deficiency type 1) is due to a defiency of what?

defiency of B2 integrin subunit (CD18) responsible for synthesis of LFA1

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LAD type 1 is an AR or AD condition?

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What are characteristic features when one has LAD Type 1 that can be evidenced?

recurrent bacterial infection (non pyogenic)
delay in umbilical cord sloughing

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Be able to draw out the O2 dependent killing involved. in a phagocyte vacuole.

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Describe oxygen dependent intracellular killing.

respiratory burst require O2 and NADPH oxidase and produces superoxide (O2-) hydroxyl radicals (OH) and hydrogen peroxide (H2O2)
myeloperoxidase require H2O2 and halide (Cl-) and produces HOCl (hypochlorous acid)

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What does Oxygen-independent killing involve. (What enzymes/substances etc.)?

lysozyme, lactoferrin, acid hydrolases, bactericidal permeability increasing protein (BPI), and defensins

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What are some conditions that are caused by deficiency in O2 dependent killing? Explain.

Chronic granulomatous disease of childhood

marked by deficiency of NADPH oxidase, lack of superoxide and hydrogen peroxide

myeloperoxidase deficiency

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Inheritance pattern of CGD of childhood?

can be X-linked or autosomal recessive

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What will the nitro blue tetrazolium test be in a patient with myeloperoxidase deficiency?

positive (purple blue)

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Inheritance pattern of myeloperoxidase defiency?

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What are those with myeloperoxidase deficency commonly infected by?

candida

What is the NBT test?

Nitroblue Tetrazolium Test

Normally, the white blood cells turn blue when NBT is added. This means that the cells should be able to kill bacteria and protect the person from infections.

If the sample does not change color when NBT is added, the white blood cells are missing the substance needed to kill bacteria. This may be due to chronic granulomatous disease.

What converts prekallikrein to kallikrein?

activated Hageman factor (factor XII)

Name some mediators of pain.

Bradykinin Prostaglandins (E2)

Thromboxane A2 is produced by what cells in the body?

platelets

Thromboxane A2 actions

cause vasoconstriction and platelet aggregation

What are the actions of PGI2?

produced by vascular endothelium and causes vasodilation and inhibition of platelet aggregation

Which prostaglandins cause vasodilatation?

PGE2, PGD2, and PGF2, PGI2

LTB4 has what major actions in the body?

causes neutrophil chemotaxis

LTC4/D4/E4 have what action in the body?

cause vasoconstriction

Which cytokines are involved in the fever response?

IL-1, TNF-a, IL-6

Which interleukin is an important chemoattractant produced by macrophages?

IL-8

Describe the appearance of the eosinophil.

bi-lobed nucleus with large granules (pink)

Describe the appearance of basophils?

bilobed nucleus, large granules (blue)

Describe the appearance of neutrophils.

lobed nucleus, small granules

Lifespan of macrophages.

about 60 - 120 days

What is the eosinophilic chemokine?

eotaxin

What is a major role eosinophils play a role in?(what type of organisms do they typically attack)

They typically play a role in ridding the body of parasitic infections

What is included inside of eosinophilic granules that helps them rid the body of parasites?

major basic protein

Basophils and mast cells play an important role in what type of responses?

IgE mediated rxns (allergies and anaphylaxis)

Describe what chronic granulomatous inflammation is.

a specialized form of chronic inflammation characterized by small aggregates of modified macrophages (epitheloid cells and multinucleate giant cells) usually populated by CD4+ Th1 lymphocytes

Name cells that compose granuloma formation.

epitheloid cells multinucleate giant cells lymphocytes and plasma cells

Why does central necrosis occur in those with granuloma formation?

occurs in granulomas due to excessive enzymatic breakdown also blood not able to reach center

Central necrosis or necrotizing granulomas are commonly found in what conditions?

M. tuberculosis infections

What are epithelioid cells?Where are they located in the granuloma? How do they appear?

located centrally they form when IFN-y transforms macrophages to epitheloid cells. They are enlarged cells with abundant pink cytoplasm

What are multinucleate giant cells? Where is their location in granuloma formation?

Located centrally in granuloma, are formed by fusion of epitheloid cells.

Name some conditions that are termed granulomatous diseases.

TB (caseating granulomas) cat scratch fever, syphilis, leprosy, fungal infections (e.g coccidioidomycosis), parasitic infections (e.g, schistosomiasis) foreign bodies, beryllium, sarcoidosis

Exudative inflammation. (Also give examples)

acute inflammatory response with neutrophils. (e.g. bacterial meningitis, bronchopneumonia, and abscess)

Necrotizing Inflammation. (Also give examples)

occurs when a virulent organism produces severe tissue damage and extensive cell death (e.g. necrotizing fasciitis and necrotizing pharyngitis)

Granulomatous inflammation what is a characteristic of organisms that cause this type of granuloma formation? (Also give examples)

granulomatous response predominates with slow growing organisms e.g. mycobacteria, fungi, and parasites

Interstitial inflammation (Also give examples)

a diffuse mononuclear interstitial infiltrate that is common response to viral infectious agents. Examples include myocarditis (Coxsackie virus) and viral hepatitis

Cytopathic/cytoproliferative. (Also give examples)

refers to inflammation in which the infected/injured cell is altered. Changes may include intranuclear/cytoplasmic inclusions (cytomegalic inclusion disease, rabies (Negri body), syncytia formation (RSV and herpes virus) and apoptosis (Councilman body in viral hepatitis)