Immunology: Inflammation/innate Immunity/pathology

Front 1

What chemical mediators in acute inflammation are responsible for the cardinal signs of inflammation?

Back 1

Rubor/calor: histamine-mediated vasodilation of arterioles
Tumor: histamine-mediated increase in permeability of venules
Dolor: PGE2 sensitizes nerve endings to the effects of bradykinin

Front 2

Describe the sequential vascular events that occur in an acute inflammation that enable leukocytes to reach an infection.

Back 2

1) Neurogenic reflex (vasoconstriction). 2) Vasodilation (histamine, NO). 3) Increased permeability of venules (histamine, IL-1, TNF). 4) Edema (outflow of fluid > lymphatic drainage

Front 3

Describe the sequential cellular events that occur in an acute inflammation that enable leukocytes to reach an infection.

Back 3

1) Margination (neutrophils move to the periphery). 2) Rolling (selectin adhesion molecules). 3) Adhesion (B-integrins on neutrophils, CAMs on ECs). 4) Diapedesis (neutrophils dissolve BM with IV collagenase, edema carries opsonins). 5) Chemotaxis (C5a, LTB4, IL-8)

Front 4

Which molecules activate neutrophil adhesion molecules in actue inflammation?

Back 4

C5a and LTB4 activate B2-integrin on neutrophils. B2-integrin binds to ICAM and VCAM on endothelial cells.

Front 5

What is the most common exogenous agent on bacteria that acts as a chemoattractant?

Back 5

N-formyl-methionine terminal amino acid

Front 6

What are the three main steps of phagocytosis?

Back 6

Opsonization (IgG, C3b, C-reactive protein), ingestion (phagolysosome formation), killing.

Front 7

Which leukocytes can produce bleach? Describe the oxidative burst.

Back 7

Neutrophils and monocytes (not macrophages). NADPH oxidase oxidizes NADPH to NADP while reducing molecular oxygen to form superoxide free radicals. These free radicals are then converted to peroxide via superoxide dismutase. MPO combines peroxide with Cl ions to form bleach.

Front 8

What molecule neutralizes hydrogen peroxide?

Back 8

Glutathione peroxidase.

Front 9

Name the oxygen-independent compounds used for bacterial killing.

Back 9

Acids, lysosomes (degrades bacterial peptidoglycan: acid-N-acetyl-glucosamine), lactoferrin (iron chelator), defensins (cytoxoic to microbes), major basic protein (from eosinophils and cytotoxic to parasites)

Front 10

What is arachodonic acid metabolism?

Back 10

In response to several stimuli, cells use membrane lipids to generate biologically active lipid mediators (autocoids, short acting hormones) that aid in inflammation and hemostasis.

Front 11

What essential acid is arachadonic acid made from? What are arachadonic metabolites also known as?

Back 11

Linoleic acid. Metabolites are eicosanoids.

Front 12

What are the arachadonic acid metabolites and what enzymes form them?

Back 12

Phospholipase A2 converts membrane phospholipids to arachadonic acid.
COX converts AA to PGG2, PGH2, PGE2. PGH2 is converted to PGI2 (prostacyclin synthase) and TXA2 (thromboxane synthase).
Lipoxygenase converts AA to LTB4, LTC4, LTD4, LTE4.

Front 13

What are the functions PGE2? PGI2? LTB4? LTC,D,E?

Back 13

PGE2: VD, pain, fever, keeps ductus areteriosus open)
PGI2: VD, inhibit platelet aggregation
LTB4: chemotaxis, activates neutrophil adhesion molecules
LTC,D,E: VC, increase vessel permeability, bronchoconstriction

Front 14

Complement pathways differ initially, but both form C3 and C5 convertase and ultimately MAC. What are the complement pathways?

Back 14

Alternate pathway: activated by microbial surfaces (LPS, teichoic acid)
Classical pathway: activated by Ag-Ab
Mannose-lectin pathway

Front 15

What are the important cleavage products in the complement system?

Back 15

C3b and C4b – opsonize
C3a and C5a – chemotaxis (neutrophils, monocytes)
C3a and C5a (anaphylotoxins) – release of mediators from mast cells/basophils (histamine, serotonin, PG's)

Front 16

Name the types of acute inflammation.

Back 16

Purulent: pus-forming organisms
Fibrinous inflammation: deposition of a fibrin exudate
Pseudomembranous inflammation: bacterial toxin-induced damage of mucosal lining (C. difficile, C. diphtheriae)

Front 17

What is the significance of a fever in inflammation?

Back 17

Right-shifts O2-binding curve. More O2 available for oxidative burst.

Front 18

What is granulation tissue?

Back 18

Highly vascular tissue composed of new blood vessels (angiogenesis) and activated fibroblasts. Essential for normal wound healing. Converted to scar tissue.

Front 19

What is the key adhesion glycoprotein in ECM required for granulation tissue?

Back 19

Fibronectin.

Front 20

A special type of chronic inflammation is known as granulomatous inflammation caused by infections or noninfections (sarcoidosis, Crohn's). What is the morphology of a granuloma?

Back 20

Pale, white nodule with/without caseous necrosis. Epithelioid cells (activated macrophages) surrounded by CD4 helper T cells, Th1. Multinucleated giant cells are formed by the fusion of the epithelioid cells.

Front 21

In tuberculous granuloma, macrophages present Ag to CD4 T cells and then secrete what in order to stimulate Th1 formation/activation. Subsequently, Th1 cells release what factors to control macrophage activity?

Back 21

Macrophages secrete IL-12 for Th1 formation and IL-1 for fever.

Th1 cells release IL-2 (stimulate Th1 proliferation), gamma-interferon (activate macrophages), MIF (migration inhibitory factor which causes macrophage accumulation).

Front 22

In fibrosis, what collagen is initial produced? Metalloproteinases replace type III collagen with _____ collagen.

Back 22

Type III collagen. Metalloproteinases replace type III collagen with type I collagen.

Front 23

Of the three types of cells, which can undergo cell regeneration? Labile, stable, permanent.

Back 23

Labile (stem cells) and stable (e.g. fibroblasts) can replicate. Permanent (cardiac and striated muscle) cannont.

Front 24

What cells in the lung are responsible for repair?

Back 24

Type II pneumocytes which replace both type I and type II.

Front 25

What is gliosis?

Back 25

Astrocyte proliferation in the brain in response to an injury (brain infarction).

Front 26

What are some causes of neutrophil leukocytosis?

Back 26

Infection, sterile inflammation with necrosis (acute MI), drugs inhibiting neutrophil adhesion molecules: corticosteroids, catecholamines, lithium.

Front 27

What is a 'left shift' of leukocytes referring to?

Back 27

Defined as greater than 10% band (stab) neutrophils or the presence of earlier precursors.

Front 28

What are azurophilic granules?

Back 28

Primary lysosomes (contains MPO, lysosomes, defensins, etc)

Front 29

Patient presents with recurrent bouts of swelling in his face and oropharynx. What is the diagnosis and pathophysiology?

Back 29

Hereditary angioedema. Autosomal disorder with deficiency of C1 esterase inhibitor which leads to increase in anaphylatoic activity.

Front 30

What is the most common complement deficiency?

Back 30

C2 deficiency. Associated with septicemia and lupus-like syndrome in children.

Front 31

Child presents with disseminated Neisseria gonorrhoeae. Last month he was infected with N. menignitidis. What disorder could he have?

Back 31

C6-C9 deficiency. No MAC complex which normally kills unencapsulated gram negative bugs.

Front 32

Patient presents with hemoglubinuria and anemia. You determine his condition is related to a missing membrane protein. What is it?

Back 32

Decay accelerating factor (DAF) normally degrades C3 and C5 convertase on hematopoietic cell membranes. The patient has paroxysmal nocturnal hemoglobinuria.

Front 33

If there is a decrease in factor B, what complement pathway is activated?

A decrease in C4 or C2 indicates activation of which pathway?

Back 33

Alternative pathway

Classical pathway

Front 34

A child presents with severe gingivitis, poor wound healing, peripheral blood and neutrophilic leukocytosis. Additionally, his mother says that his umbilical cord took an abnormally long time to separate. What is the diagnosis?

Back 34

Leukocyte adhesion deficiency (LAD). An autosomal recessive disorder. LAD1 is deficient in CD11a:CD18 (integrin). LAD2 is deficient of a selectin that binds to the neutrophils.

Front 35

Patient presents with recurrent infections, photophobia and pale skin. A staining of his leukoctyes show giant azurophilic granules. What is the diagnosis?

Back 35

Autosomal recessive Chediak-Higashi syndrome which is a defect in membrane fusion. Characterized by defects in chemotaxis, degranulation, and bacteriocidal activity (cant form secondary phagolysosomes).

Front 36

A patient who suffered from psychomotor retardation died at age 9. His lysosomes contained no hydrolytic enzymes. What is the pathophysiology of his disease?

Back 36

I cell disease: Defect in phosphorylation of mannose in glycoproteins that target proteins to lysosomes. Inclusion bodies accumulate in cytosol.

Front 37

What are some clinical features of I cell disease?

Back 37

Skeletal abnormalities, coarse features, restricted joint movement, psychomotor retardation.

Front 38

What is the adult form of I cell disease?

Back 38

pseudo-Hurler polydystrophy.

Front 39

What type of mutation causes Tay-Sach's disease?

Back 39

Frameshit: four base insert results in the synthesis of a defective lysosomal enzyme (hexosaminidase).

Front 40

Patient also present with dysarthria, dysphagia, ataxia, and spasticity.

Back 40

Tay-Sachs disease. GM2 ganglioside build up to toxic levels within nerve cells of the brain.

Front 41

What two disease result in a build up of mucopolysaccharides (dermatan and heparan sulfate)?

Back 41

Hurler's (autosomal recessive) and Hunter's (X-linked). L-iduronidase deficiency. Characterized by multiple organ involvement, coarse facial features, retardation, corneal clouding, and coronary artery disease

Front 42

What lysosomal storage disease is deficient in glucocerebrosidase? What characteristic cells are present?

Back 42

Gaucher's disease (adult type I) is characterized by fibrillar appearing macrophages.

Front 43

Notice the soap-bubble appearance of the macrophage. What is accumulating?

Back 43

Sphingomyelinase. Niemann-Pick disease .

Front 44

Red headed patient presents with severe eczema and very elevated IgE.

Back 44

Job's syndrome aka hyper-IgE syndrome.

Front 45

Boy presents with Staphylococcus and Burkholderia infections. WBC profile and serum antibody levels in the high-normal range. Neutrophils failed to reduce NBT. Diagnosis?

Back 45

The boy has chronic granulomatous disease.

Front 46

What is the genetic basis of chronic granulomatous diease?

Back 46

65% are X-linked and 35% are autosomal recessive.

Front 47

How come CGD often presents with recurrent staph infections but no streptococcal infections?

Back 47

Streptococcus are catalase negative. The bacteria provides hydrogen peroxide to the phagocyte which then produces HOCl (hypochlorite)

Front 48

What are the common infections in chronic granulomatous disease?

Back 48

Aspergillus, Candida, Staph aureus, Serratia, Burkholderia cepacia.

Front 49

What cells release IFN-gamma?
What are some functions of IFN-gamma?
What phagocytic disorder can it be used to treat?

Back 49

Th1, NK cells. IFN-gamma enhances the activity of macrophages, inhibits Th2 response, and upregulate expression of MHC molecules. Its used to treat CGD, because it increases macrophage ability to kill bacteria.

Front 50

What infections are patients with IFN-gamma receptor deficiency susceptible to?

Back 50

Defective IFN-gamma receptor prevents macrophage activation and killing of intracellular pathogens. These patients can have disseminated, severe mycobacterial infections.