lecture 3b

Question 1

pathogen capture

Answer 1

1. chemotaxis (pathogen drawn to neutrophil)
2. adherence -> NETS (neutrophil extracellular traps - sticky and have enzymatic activity)
3. opsonization (phagocytose bacteria - in presence of antibody that bind to bacteria = enhanced pathogen uptake through opsonization, complements increase opsonization)

Question 2

pathogen killing mechanisms

Answer 2

1. ingestion: after opsonization (phagocytosis)
2. destruction!

options: lysozyme, defensins, lactoferrin, collagenase, gelatinase, ELASTASE, cathepsin B, beta glucuronidase, myeloperoxidase

oxidative mechanism (phagosomsomes)
oxidative mechanism (phagolysosomes)
non oxidative mechanism (phagolysosomes)

Question 3

O2 dependent killing in phagosome

Answer 3

TNFa activates NADPH oxidase on membrane, this converts NADPH + 2O2 -> NADP+ + H+ (which will lower pH - oh no!) + 2O2- radical (superoxide anion - oh no!) + 2H -> (superoxide dismutase) O2 + H2O2 (also kills bacteria

Chronic granulomatous disease in doberman pinscher (defect in NADPH oxidase - bacterial infection resulting from animal incapable of killing bacteria through NADPH oxidase)

Question 4

O2 dependent killing in phagolysosome

Answer 4

same reaction as in phagosome…. H2O2 + Cl- -> (myeloperoxidase) H20 + 0CL- (hypochlorous acid - oh no!)

Question 5

non O2 killing in phagolysosome

Answer 5

1. proton pump adds H+ ions and they accumulate
2. enzymes: acid hydrolases (lysozyme) damages bacterial cell membranes, proteases, DNAses and RNAses
3. antibacterial peptides (defensins) create holes in the bacterial membranes (fluid gets in!)

Question 6

neutrophilia

Answer 6

increase [neut] in the blood compared to reference interval
caused by:
acute inflammation
stress/excitement
leukocyte adhesion deficiency
myeloid leukemia

Question 7

neutropenia

Answer 7

decreased [neut] in the blood compared to reference interval
caused by:
long term inflammation & chemotaxis to tissue - depleting the circulating pool (CP-> MP-> tissues)
destruction of PMNs (immune mediated)
genetic defect in myelopoiesis (cyclic neutropenia in gray collies)
bone marrow damage (distemper virus K9, drugs (estrogen) - hematopoesis compromised)

Question 8

acute inflammation

Answer 8

causes neutrophilia
>1.5-5x [neut] of reference interval
release mature neutrophils from bone marrow into the blood

Question 9

stress/excitement

Answer 9

causes neutrophilia
marginating pool travels to circulating pool
>1.5x [neut] of reference interval
cortisol release (stress) decreases the expression of adhesion molecules
epinephrine (excitement) increases blood flow and decreases adhesion

Question 10

leukocyte adhesion deficiency

Answer 10

causes neutrophilia
>10-20x [neut] of reference interval
marginating pool travels to circulating pool
neutrophils are unable to stick to endothelium to enter places of infection so increase in floating around in blood

autosomal recessive trait - no CD18 integrin so CD11/18 heterodimer not expressed - holsteins and irish setters
characterized by: recurrent bacterial infections, persistent and extreme neutrophilia

Question 11

myeloid leukemia

Answer 11

causes neutrophilia
release immature neutrophils from bone marrow
>20-100x [neut] reference
IMMATURE!

Question 12

canine cyclic neutropenia

Answer 12

gray collie syndrome
genetic defect in myelopoiesis (-AP3 beta 1)
autosomal recessive trait in border collies
dilution of skin pigmentation
cyclic fluctuations in leukocyte numbers (penia->philia)
enteric disease, respiratory infections and gingivitis - bc neutrophils are incapable of killing bacteria
can do blood transfusion, genetic testing and prophylactic medications w antibodies against the above symptoms