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91 Cards in this Set
- Front
- Back
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tissue necrosis is always followed by? |
acute inflammation -- increase in neutrophils
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What is the goal of acute inflammation? |
eliminate pathogen (infection) or clear necrotic debris (necrosis) |
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Describe pathway of TLR's
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Pathogen Associated Molecular Patterns(PAMPs) activate TLR's on macrophages/lymphocytes causing upregulation of NF-kB which is a nuclear transcription factor that activates immune response genes leading to production of multiple immune mediators |
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How do macrophages deal with gram negative bacteria? |
the CD14 receptor (a TLR) on macrophages recognize LPS (a PAMP) on outer membrane of all gram negs |
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TLR on B-cells importance |
They cross link enough receptors to NOT need a second signal! |
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Where is arachadonic acid cleaved from and what enzyme is used?
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Arachidonic Acid released from cell membrane by phospholipase A2.
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List the classes and specific examples of Arachidonic Acid Metabolites from the COX pathway. What do they have in common structurally?
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1. prostaglandins (PGE2, PGD2)
2. prostocyclins (PGI2) 3. thromboxanes(COX). They all have a cyclic group in the middle of the hydrocarbon |
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List the mnemonic for the COX pathway.
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Why are you so COX IDE-ed?
(PGI, PGD, PGE from the COX pathway) |
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How do the prostaglandins/prostacyclins function?
What is the extra function of PGE2? |
They mediate vasodilation at the precapillary arteriole sphincter and increase vascular permeability.
PGE2 additionally mediates fEver and pain. |
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List the Arachidonic Acid Metabolites from the 5-lipoxygenase pathway. What do they have in common structurally?
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1. leukotrienes (LTB4, LTC4, LTD4, LTE4)
They all have an oxidized group on their hydrocarbon part. (Lipo-oxygenase) |
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What happens at the level of the lung with aspirin induced allergic reaction? |
The COX pathway is inhibited so there is more production of leukotrienes. This can cause symptoms of anaphylaxis.
all the result of SM contriction (pericytes contraction causes vasodilation) |
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What is the leukotriene with a special function? What does it do? |
LTB4. It is chemotaxic for neutrophils. |
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Mast cells activated by (3)
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1. tissue trauma (if the ship is damaged in any way)
2. complement proteins C3a, C5a (owls and mews coming to alert) 3. cross linking by IgE (If it's masts get messed up, which is another form of injury) |
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Mast cell immediate response
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INCREASE INFLAMMATION! |
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Mast cell delayed response
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WALL THINGS OFF AND TELL THE SUPERTROOPERS TO COME TO THE EXACT SPOT!
release AA metabolites, especially leukotrienes which will constrict blood vessels and attract neutrophils. |
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Decribe the difference between the initial recogniztion mechanism in the three pathways of the Complement System
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Classical Pathway -- C1 binds IgG or IgM that's bound to antigen
Alternative pathway -- microbial products directly activate Mannose binding lectin pathway - MBL binds to mannose on microorganisms and activates complement |
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Review Complement pathway in your head dummy
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Draw it out, check
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Why are you more predisposed to Neisserial infections with a deficit in the complement proteins? (especially MAC complex)
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Neisserial bacteria are encapsulated and are resistant to phagocytosis, but very susceptible to being killed with the MAC complex.
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Where is the Hageman produced and stored?
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It is produced in the liver and circulates inactive in the blood.
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How is Hageman factor activated?
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By tissue injury. Specifically through exposure to subendothelial or tissue collagen.
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What does Hageman factor activate?
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1. Coagulation and fibrinolytic system (by the intrinsic system)
2. Complement system 3. Kinin system |
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Who is Hageman? And what does he like to do?
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He is a burly 12 (Factor XII) year old lumberjack who likes to cleave things.
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What is hemostasis?
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The process which causes bleeding to stop.
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Review Coagulation pathway in your head dummy
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Draw it out, check
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Give the mnemonic of Hageman factor and bradykinin.
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Hageman factor is asleep on the highway (bloodstream) until there is a missing part of the rail and his car veers off the road.
Then he feels the need to fix the highway by chopping up logs to rebuild it. This includes lumber from passing trucks (fibrinolytic system) as well as a log cabin he finds, which is home to the deadly Brady Bunch (bradykinin). Ironically, this log cabin was a previous HMWK assignment for him. And he will also fix toys for the complement systen (C1 activation) because that is a skill he has. |
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What does Bradykinin do?
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The same thing as histamine (cannonball) except that it also brings the pain!
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What two factors mediate pain and how do they do this?
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PGE2 and bradykinin by sensitizing nerve endings
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What enzyme causes DIC? How does it do this?
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Hageman Factor(Factor XII)
It is over activated and will cause clots to form all over the vasculature. This depletes clotting factors in the blood and results in inability to clot when it is really needed. Even tiny things will produce bleeding. |
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What does DIC present as?
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A lot of bleeding, specifically purpura pattern rashes.
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What are the three phases of acute inflammation?
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1. Edema and blood flow in phase
2. Neutrophil phase 3. Macrophage phase |
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Cardinal Signs of inflammation (4)
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1. Redness (rubor)
2. Warmth (calor) 3. Swelling (tumor) 4. Pain (dolor) |
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What are the key mediators of redness and warmth? (3) Which is the most important?
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1. Histamine (most important)
2. Prostaglandins (PGI2, PGD2, PGE2) 3. Bradykinin |
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What are the two key mediators of tissue swelling and what are their mechanisms?
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1. Histamine that changes the endothelial cells
2. Tissue damage that actually lets blood in physically |
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What is the pathway by which fever is created starting from the pyrogen all the way to raising the temperature set point?
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Pyrogen --> Macrophage releases IL-1 and TNF ---> They act on the perivascular cells of the hypothalamus --> COX activity is upregulated and local PGE2 is produced ---> PGE2 raises the temperature set point
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What are the seven steps of neutrophil coming from the blood to leaving the tissue?
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1. Margination
2. Rolling 3. Adhesion 4. Transmigration and Chemotaxis 5. Phagocytosis 6. Destruction of phagocytosed material 7. Resolution |
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Leukocyte margination occurs through?
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postcapillary venules! Cells marginate from the being in the center of the bloodflow to the periphery due to the slow of blood flow from vasodilation
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Leukocyte rolling occurs via?
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P and E selectin speed bumps upregulated in endothelial cells.
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How are P selectins expressed?
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Induced by histamine
Released from small, preformed Weibel-Palade bodies |
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What else is the Weibel-Palade bodies of endothelial cells?
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von Wilebrand Factor
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What does the von Wilebrand Factor (vWF) do?
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It is released during endothelial damage and serves to attract platelets to initiate the coagulation cascade.
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What are E-selectins induced by?
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TNF and IL-1
(Think back to Dr. Najeeb and his hooks!) |
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What does selectin on endothelial cells bind on leukocytes(neutrophils, macrophages, etc.) to induce rolling?
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Sialyl Lewis X
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Leukocyte adhesion to endothelial cells occur via?
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Binding of Cellular adhesion molecules (CAMs) on endothelial cells to integrins on leukocytes.
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What are the two types of CAMs?
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ICAM and VCAM
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What causes upregulation of adhesion molecules on endothelial cells?
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IL-1 and TNF
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What induces integrin upregulation on neutrophils?
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C5a and LTB4
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What are the chemotaxic factors for neutrophils? (4)
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1, C5a (owls)
2. LTB4 (3 armed albino Boy) 3. IL-8 (V8) 4. Bacterial products |
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What specific compenent is missing in Leukocyte Adhesion Deficiency?
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CD18 subunit of the leukocyte integrin
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What are the clinical findings of leukocyte adhesion deficiency? (3) Explain each.
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1. Delayed separation of the umbilical cord (lack of inflammation to clear up dead cells after necrosis of the umbilical cord)
2. Increased circulating neutrophils (the neutrophils in the marginated pool in the lung endothelium cannot stick onto those walls) 3. Recurrent infections that lack pus (neutrophils can't migrate in and eat the pathogens) |
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What do neutrophils phagocytize and how is this regulated?
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They kind of eat everything, but eating is enhanced by opsonins including C3b and IgG.
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How are ingested cells digested by leukocytes?
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They are taken in by pseudopods and taken in as a pagosome. The phagosome will follow the cytoskeleton down to meet a lysosome where they will fuse into a phagolysosome and kill the contents.
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What is Chediak-Higashi syndrome?
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The railroad system of microtubules (due to defect in LYST gene) is defective so it is hard to kill the pathogens.
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What are 6 clinical features of Chediak-Higashi Syndrome?
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i. Increased risk of pyogenic infections
ii. Neutropenia (due to intramedullary death of neutrophils) iii. Giant granules in leukocytes (due to fusion of granules arising from the Golgi apparatus that can't go anywhere) iv. Defective primary hemostasis (due to abnormal dense granules in platelets also not being able to go anywhere) v. Albinism vi. Peripheral neuropathy |
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Why is there an increased risk of pyogenic infections?
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The phagosomes cannot fuse with the lysosomes so well.
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Why is there neutropenia?
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There is trouble with dividing up cellular components in neutrophils during mitosis since that is mediated by microtubules. Therefore there is decreased production.
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Why is there giant granules in leukocytes?
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There is a lot of production of protein granules from the golgi and no rail system to ship them around the cell. These granules accumulate and look giant.
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Why is there defective primary hemostasis?
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The platelets also have important clotting granules that they need to distribute around. The rail system is also defective here and make problems.
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Why is there partial albinism?
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Usually one melanocyte creates enough melanin for 25 keratinocytes and ships it out to each one through a microtubule system. If this is missing, then you have albinism.
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Why is there peripheral neuropathy?
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peripheral neurons need to go a very long way (as long as 2 feet). If there is not a suitable microtubule track delivering nutirents to the peripheral part, then they die off.
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How can I remember Chediak-Higashi syndrome through menomics?
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A very sickly, partially albino, prone to bleeding, japanese che guevara.
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What do I often confused Chediak Higashi syndrome with?
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Budd-Chiari Syndrome
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What are the two ways in which destruction of phagocytosed material is destroyed?
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1. O2 dependent
2. O2 independent (through enzymes) |
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What enzyme turns O2 into O2.-?
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NADPH oxidase
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What enzyme turns superoxide into hydrogen peroxide?
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superoxide dismutase
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What enzyme turns hydrogen peroxide into bleach? What color is it?
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Myeloperoxidase. Green.
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Where do NADPH oxidase deficiencies come from?
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Genetics. it is either autosomal recessive or x-linked.
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How come most bacteria can still be killed even though a person may be deficient in NADPH oxidase and cannot produce much H2O2?
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Bacteria produce some of their own H2O2. Myeloperozidase can just grab these and turn them to bleach and usually this is sufficient to kill them.
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What bacteria are the exception to this rule and why?
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Catalase positive bacteria because catalase is much stronger than myeloperoxidase and will break the H2O2 down to H2O and O2 first.
Catalase negative bacteria usually have slower mechanisms for breaking down H2O2. |
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What happens when someone with NADPH oxidase deficiency gets infected with a catalase positive organism?
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They develop granulomas to deal with it.
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What is this disease called?
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Chronic Granulomatous Disease
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What are some common catalase positive organisms? (5) Which is the most common? Which is the most commonly tested?
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1. S. Aureus (most common)
2. Pseudomonas cepacia (most commonly tested) 3. S. marcescens 4. Nocardia 5. Aspergillus |
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What does the Nitroblue tetrazolium test? How is it tested and what does it look like?
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a yellow chemical that turns blue when blood is dripped in if NADPH oxidase activity is intact. The more blue it turns, the more activity there is.
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What happens when a person is deficient in myeloperoxidase (MPO)?
Why? |
They have increased risk of Candida albicans infections.
Otherwise, they do not seem immunosuppressed. This is because there is a lot of redundancy for MPO function. |
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What is a major enzyme in the O2-independent pathway of phagocytic digestion? Where is it stored?
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Lysozyme. It is stored in the secondary granules of leukocytes.
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How do neutrophils leave the tissue?
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they undergo apoptosis and are eaten up by macrophages.
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How long does it take for neutrophils to be cleared out after resolution?
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24 hours.
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How long does it take neutrophils to arrive on scene after the inflammatory cascade starts?
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24 hours.
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how long does it take for macrophages to peak in activity after inflammation begins?
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2-3 days
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How do macrophages migrate into the tissues?
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The same way that neutrophils do
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How do macrophages destroy ingested particles?
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By enzyme dependent killing with lysozyme.
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What role do macrophages take on when they get to the infection site?
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They take on the role of managers and decide whether to resolve the inflammation or continue on with it.
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What are the 4 pathways that macrophages can direct the immune response towards when they arrive? (don't list cytokines yet)
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1. Resolution and healing
2. Continued acute inflammation 3. Abscess formation 4. Chronic inflammation |
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What cytokines do macrophages secrete to resolve inflammation? (2)
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1. IL-10
2. TGF-b |
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What cytokines do macrophages secrete in order to continue on with acute inflammation? (1)
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1. IL-8
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What is the hallmark of acute inflammation?
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Neutrophils and pus formation
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How can macrophages mediate abscess formation? Why would they do this?
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If they sense that the immune system can't handle the infection, they will wall it off. They do this by surrounding the infection site and forming giant cells.
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What is the difference between an abscess and an empyema? |
an empyema is a collection of pus that forms in a preexisting cavity instead of one that is newly walled off. |
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how does hageman factor cause DIC? what conditions cause this? |
when it is activated, it causes a lot of coagulation.
gram negative sepsis like neisseria meningitidis in waterhouse friedrichson |
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how long is an acute inflammation? |
can be as long as macrophages make it |
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how do macrophages create continued acute inflammation? |
keep ecreting il-8 |
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how can macrophages create chronic inflammation? |
acting as APC's to induce T helper cells |
