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543 Cards in this Set
- Front
- Back
What is inflammation?
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reaction of vascularized living tissue to local injury
|
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what is the point of inflammation?
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to eliminate the inciting stimulus and repair the damage
|
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Four cardinal signs of inflammation...and the fifth?
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1. calor
2. dolor 3. rubor 4. tumor 5. loss of function |
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Does inflammation continue after death?
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-no it is complex and can only occur in a living creature. it ceases after death
|
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What does inflammation have to have to occur?
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an evoking stimulus, it has to evoked to respond
|
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which type of necrosis is a frequent and potent elicitor of an inflammatory response?
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-oncotic necrosis
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what are the two outcomes of inflammation?
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1. repair by regeneration
2. repair by scarring |
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What are neutrophil enzymes released from?
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-from lysozymes
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what kind of inflammatory response does mycobacterium produce?
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-granulomatious
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what kind of inflammatory response do strep, corynebacterium and pasteurella produce?
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-pyogenic response
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What are the three complement pathways to cope with injury?
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1. classical pathway
2. alternative pathway 3. mannose binding pathway |
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what do each of the following classically attack:
1. neutrophils 2. eosinophils 3. macrophages |
1. neutrophils=bacteria
2. eosinophils=parasites 3. macrophages=fungi, protozoa (clean up cell debris) |
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The inflammatory system is linked to what system intimately?
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-the blood vascular system
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what is absolutely essential to the development of a lesion?
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-response to an inflammatory stimulus
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Immediately following an injurious stimulus what happens?
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-vasoconstriction
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Immediately after an injurious stimulus there is vasoconstriction, and then what happens?
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arteriolar dilation
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What causes the endothelial cells to "round up" and leads to large macromolecules and leukocytes squeezing through?
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1. direct injury
2. mediators of inflammation |
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Increased blood flow and endothelial leakiness is a process called?
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-exudation
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what is it called when RBCs stack up into rows or columns?
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-rouleaux
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what is an absolute hallmark of inflammation?
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formation of exudate
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If an inflammatory response is acute or bacterial, what type of cell(s) will you see in histopath?
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-neutrophils
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If an inflammatory response is less acute what kind of cell(s) will you see in histopath?
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-neutrophils and macrophages
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If an inflammatory response is chronic or granulomatous, what type of cell(s) would you expect to see on histopath?
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-macrophages
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Difference between transudate and exudate?
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transudate: low specific gravity, low cellularity
exudate: high specific gravity, lots of cells |
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what are the first agents released after tissue injury occurs?
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-chemical mediators of inflammation
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what form to inflammatory mediators exist in?
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-inactive forms in plasma or in intracellular storage pools
-they are only synthesized, released or activated at the site of injury |
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what is the term to describe more than one target or acting on more than one target?
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pleiotropy
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What is the term to mean, "similar effects on other mediators"
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-redundancy
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what is the term to describe inflammatory mediators working together?
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-synergy
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What is the term meaning that production of one inflammatory stimulus my cause production of another mediator?
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-cascade effect
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what is the term to describe the fact that inflammatory mediators are not antigen specific?
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-stereotypic response
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Act on the cell which made the mediator?
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-autocrine
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acts on nearby cells?
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-paracrine
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acts on distant cells?
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-endocrine
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what are the two major functions in general that inflammatory cells perform? and how is each accomplished?
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1. produce vascular changes to intiate, promote and maintain the inflammatory response
-this is accomplished by altering hemodynamics and enhancing vascular permeability 2. activate, attract, and maintain the "soldiers" of the inflammatory response until the injurious stimulus is eliminated, neutralized or controlled -this is done through recruiters, mediators, activation of inflam cells, maintenance and regulation |
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What are the 5 vasoactive amines?
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1. histamine
2. serotonin 3. NO 4. heparin 5. kinins |
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Histamine is a derivative of what amino acid?
|
-histidine
|
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what/where is histamine stored and released from?
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-mast cells, platelets, and basophils
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which vasoactive amine is important for the first phase of the inflammatory reaction?
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-histamine
|
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what does histamine do to precapillary sphincters?
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-dilates them
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what are the two things that histamine does to endothelium?
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1. makes the cells "round up"
2. makes the endothelium express adhesion molecules so they will be "sticky" to neutrophils and macrophages |
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How long is histamine around?
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-short lived (15 to 20 min)
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which is more important in acute hypersensitivity reactions in the bovine: dopamine or histamine?
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-dopamine
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Serotonin is a derivative of what amino acid?
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-tryptophan
|
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Serotonin is stored and secreted from what cells?
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-mast cells, platelets, and basophils
|
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What is unique about serotonin?
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-it is rapidly inactivated
|
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what does serotonin do to smooth muscle and pain?
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causes contraction of smooth muscle and pain
|
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what is the major vasoactive amine in the cow with mast cell granules?
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-serotonin
|
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Is NO considered a vasoactive amine?
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technically it is not a vasoactive amine
|
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NO is derived from what amino acid?
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-arginine
|
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NO is a neurotransmitter that causes smooth muscles to: contract or relax?
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-relax
|
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What is the ultimate mediator of vascular tone?
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-NO
|
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NO in large quantities can be produced by?
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-activated macrophages
-hypoxic or damaged endothelium -damaged tissue cells (iNOS) |
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Under inflammatory conditions, NO is a potent: vasoconstrictor or dilator?
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-vasodilator
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What vasoactive amine causes neovascularization?
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-NO
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What vasoactive amine is a polysaccharide polymer?
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-heparin
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Heparin activates?
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-antithromibin 3 to inhibit the intrinsic pathway
|
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where is heparin stored?
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-stored in mast cells and basophil granules
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what vasoactive amine gives mast cells and basophils their intinsely basophilic (blue) staining?
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-heparin
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These are polypeptides derived from plasma protein precursors.
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kinins
|
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This is prototype short chain peptide
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-bradykinin
|
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activated hageman factor (factor XII) activated?
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-pre-kallikreins
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what do pre-kallikreins eventually cause the release of?
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bradykinin
|
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plasma prekallikrein is bound to hat precursor?
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-bound to the precursor of bradykinin called HMW-kinogen
|
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where are tissue kallikreins produced?
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-within neutrophils, parynchemal cells such as kidney, pancreas, GI tract, salivary gland, prostate, and the brain
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lysis of tissue leads to release of tissue kallikreins into the stroma and these can cleave?
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-cleave LMW-kininogen primarily
|
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Lysis of RBCs leads to the release of?
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kallikreins, which cleave precursor molecules to release kinin
|
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What are kinins?
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-potent, slow-acting vasodilators, increase capillary permeability, and are mediators of pain
|
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what vasoactive substances produce the dolor, rubor and calor associated with inflammation?
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-kinins
|
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What tissue rapidly inactivate kinins?
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-tissues, plasma and esp the lungs
|
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Kinins can stimulate the release of what compounds to form LT's and PG's?
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-stimulate the release of histamine and activate the eicosanoid cascade to from LT's and PG's
|
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Eicosanoids are derivatives of?
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-arachidonic acid
|
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when is arachidonic acid released from phospholipid membranes?
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-when phospholipids are broken down during cell membrane metabolism, injury or death. Phospholipase in the cell membrane begins the process
|
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Corticosteroids inhibit inflammation primarily through?
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-lipocortins, inhibitors of PLA2
|
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These are important regulators of normal cell processes and important modulators of inflammation when cell membranes are damaged by an agent and AA is released.
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-eicosanoids
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What are the two types of eicosanoids produced?
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1. leukotrienes
2. lipoxins |
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why are leukotrienes important
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they are responsible for the egress of WBC's out of blood vessels toward the inflammatory stimulus
|
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what cells produce leukotrienes?
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cells of the myelomonocytic lineage:
neutrophils, eosinophils, basophils, macrophages, mast cells |
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Neutrophils produce large numbers of the precursor form?
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-LTA4
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Myeloid cells, like neutrophils, can produce?
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-LTB as well as LTC4, LTD4, LTE4
|
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Non-myeloid cells such as platelets, endothelial cells, platelets, kupfer cells and hepatocytes can only synthesize?
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LTC4, LTD4, and LTE4
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what cells initially release LT, LT4, for cells like platelets and endothelial cells to convert to other forms?
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-neutrophils
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What cells can convert their own LTA4 to LTB4?
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-neutrophils
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what initiates the LT cascade and is activated when cytosolic calcium levels are elevated?
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-lipoxygenase
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Are LT's more or less potent than histamine?
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-way more potent
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LTB4 is extremely chemotactic, especially for?
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-neutrophils
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What leukotriene makes neutrophils more sticky and more adherent to endothelium?
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LTB4
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What leukotriene can promote the respiratory burst and stimulates the release of enzymes by neutrophils?
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LTB4
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what three LT's increase capillary permeability and act synergistically with LTB4?
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1. LTC4
2. LTD4 3. LTE4 |
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What three LT's act synergistically with LTB4?
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1. LTC4
2. LTD4 3. LTE4 |
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what is the target for LTC4, LTD4, and LTE4?
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-the endothelium, which "rounds up"
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At low concentrations LTC4, LTD4 and LTE4 are chemotactic for?
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-low concentrations=neutrophils
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At high concentrations LTC4, LTD4 and LTE4 are chemotactic for?
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-high concentrations=production of O metabolites and release of enzymes by WBC's
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What is a potent stimulator of LT?
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-endotoxin from gram negative bacteria
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why do LT's stimulate phospholipases?
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-so they can enhance their own synthesis
|
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what is SRS-A?
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-slow reacting substance of analphylaxis
-now called LT's |
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what are the two lipoxins?
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1. LXA4
2. LXB4 |
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when are lipoxins produced and by what?
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-produced later in the inflammatory response through the action of 15-lipoxygenase
|
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What do lipoxins do?
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-have antiinflammatory properties (reduce PMN recruitment)
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When and why are lipoxins important?
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-important in induction of the resolution phase of inflammation (clean up apoptotic PMN) and promotion of repair
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How are prostaglandins produced?
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-by the actions of cyclooxygenase
|
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Which cox is esp active in inflammation?
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COX-2
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what does COX-1 normally do?
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-normal regulation of blood flow ion transport and anti-coagulant properties of endothelium
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What are the important prostaglandins?
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-PGF2alpha, PGE2, PGD2
|
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PGE's in the case of inflammation are produced by?
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-macrophages and some platelets
|
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What is the role of PGE in inflammation?
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-not really know. Pain for sure though.
|
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What prostaglandins have an efffect on circulating WBCs similar to that of adrenal corticoids?
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prostaglandins of the E series
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what do prostaglandins of the E series do?
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-induce release neutrophils into circulation from the bone marrow and peripheral storage pools
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This is a lipid breakdown product produced by WBC's, platelets, and vascular endothelium
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platelet activating factor
|
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The production of platelet activating factor is through what mediator primarily?
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-C prime fragments
|
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why is PAF synthesis and LT/PG synthesis closely linked?
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1. same enzyme phosopholipase A2 triggers both synthesis pathways
2. arachidonic acid fragments go to CT and PG synthesis and the remainder of the molecule is processed to produce PAF |
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what does platelet activating factor do?
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-causes platelets and WBC's to aggregate, adhere to vascular endothelium
|
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platelet activating factor causes WBC's to release?
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-enzymes and free radicals
|
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What does platelet activating factor do to vascular permeability?
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-increases vascular permeability
|
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What are acute phase proteins?
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-proteins not normally found at detectable levels in plasma, but which become detectable when acute injury and inflammation have occured somewhere in the body
|
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where are acute phase proteins produced?
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-liver
|
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what stimulates the synthesis of acute phase proteins?
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-IL-1
-IL-6 -TNF-alpha |
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Where is fibrinogen synthesized and released?
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-hepatocytes
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What is the point of fibrinogen?
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-to wall off the bacterial agent and form a meshwork or scaffolding for the healing process to begin
|
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How does fibronogen lead to an increased sedimentation rate?
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-cuases increased RBC aggregation which leads to increase sedimentation
|
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In which species is fibrinogen esp high during prolonged inflammation?
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-cow
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These are a set of proteins that when activated by proper stimulus, become activated sequentially.
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complement proteins
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Where are complement proteins made?
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mostly in the liver, some part made in macrophages
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How does complement have its action on foreign material?
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organize into a lytic complex and poke holes in the target cells
|
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Activation of complement can occur by what three pathways?
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1. classical pathway
2. alternate pathway 3. MBL pathway (mannose binding lectin) |
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How does the classical pathway of complement work?
|
Ag-Ab binding to membrane of the infectious agent and interacts with and activates C1. Activation of C1 leads to sequential activation of other C proteins in the cascade. This makes a donut-shaped attack complex (c6-c9) thta can insert itself into a cell membrane and literally form a stable "hole" or channel out of which cell can leak contents
|
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How does the alternative pathway of complement work?
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-activates the sequence later without involving early C proteins and antibody
|
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what is the purpose of the alternative pathway of complement?
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-to protect the host during the early phases of microbial invasion when sufficient antibody have not yet been produced
|
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What activates the MBL pathway?
|
the pathogen itself
|
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What does MBL activate?
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-C4 and C2 just like C1 would activate them
|
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What are the functions of complement?
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1. coat bacteria so they will clump and also be more attractive to neutrophils for ingestion
2. enhance the inflammatory response |
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How does complement enhance the inflammatory response?
|
1. fragments produced by them are chemotactic for neutrophils and other WBC's
2. increase vascular permeability 3. lysis of cells (can be bacterial or host cells though) 4. C3a, C3b, and C5a |
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What do C3a and C5a do?
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-mediate the release of histamine from mast cells (esp. c5a)--anaphylatoxins
|
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what does C3b do?
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act as an "opsonin" to coat bacteria and make them more prone to phagocytosis by neutrophils
|
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What does C5a do?
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-powerful chemoattractant for neutrophils and increases the "respiratory burst"
-can stimulate the release of lysosomal content from neutrophils |
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what do C3 fragments do to bone marrow?
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-mobilize cells from the bone marrow
|
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what is the oldest inflammatory mediator in the world?
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-C3
|
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what inflammatory cells have receptors for C fragments?
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-neutrophils and macrophages
|
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which complement protein is pivotal for in the whole process of chemoattraction and phagocytosis?
|
C3
|
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Neutrophils and macrophages are resistant to what attack complex?
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C6-C9 attack complex-they ingest it before it can poke holes in the membrane
|
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People lacking C3 because of inherited reasons are prone to what types of infections?
|
-pyogenic bacterial infections
|
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why is salmonella so virulent?
|
-it can escape opsonization by C3
|
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Where is C reactive protein made?
|
-liver
|
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Why does C reactive protein do?
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-enhances the activity of complement and serves to speed up its formation
|
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What the oldest complement pathways found in vertebrates?
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-MBL and alternative pathways
|
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What is a vital nutrient for many bacteria?
|
-iron (Fe)
|
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In severe cases of inflammation what happens to plasma Fe and Fe-transferrin, and why?
|
-they decrease as a mechanism to fight off bacteria bc bacteria need iron to live
|
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Neutrophils release what compound which removes Fe from Fe-transferrin in tissue fluids?
|
-lactoferrin
|
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What cells commonly take up Fe-lactoferrin complexes to produce ferritin for storage?
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-macrophages
|
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what is a recently discovered mediator that turns out to be a major player in the "anemia of chronic disease"?
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-hepcidin
|
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what produces hepcidin?
|
liver
|
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How does hepcidin contribute to anemia of chronic disease?
|
-it binds to iron uptake proteins of intestinal cells to prevent iron uptake from the gut
|
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where is fibronectin in its soluble form?
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-plasma
|
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Where is fibronectin in its insoluble form?
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-tissue
|
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What is the point of fibronectin?
|
-serves a linker between fibrin and leukocytes or between fibrin and platelets
|
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What does the insoluble form of fibronectin do?
|
-insoluble form=tissue
-link cells to extracellular matrix, maintain cell shape and promote fibroblast growth |
|
what does the soluble form of fibronectin do?
|
-soluble form=plasma
-acts as a coating agent (opsonin) to decrease bacterial adherence to tissues -stimulates phagocytosis -causes bacteria to stick to themselves -ACTIVATES MACROPHAGES -CAUSE MACROPHAGES TO EXPRESS FC AND C RECEPTORS |
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During acute phase inflammation would you expect to see a high, low, steady concentration of fibronectin in plasma?
|
-low concentration of fibronectin in the plasma because it is leaving the plasma and going out to tissues
|
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these are small proteins produced by all types of nucleated cells, especially leukocytes.
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-cytokines
|
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What is a lymphokine?
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-special cytokine from lymphocytes
|
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What is a chemokine?
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-cytokine from chemotactic activity
|
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what is interleukin?
|
-produced by one leukocyte, acts on another
|
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what are the three types of interleukin?
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1. alpha
2. beta 3. gamma |
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Viruses are the most important stimulators of what type of granulocytes?
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IFN alpha and IFN beta (endotoxin and IL-1 are also good activators)
|
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What cells produce IFN gamma?
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-TH1 type helper T cells and NK cells
|
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where do IFN alpha and beta generally act?
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-act locally
|
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What is the job of IFN alpha and beta?
|
-slow the spread of a virus
-inhibit protein synthesis in adjacent cells |
|
What cells produce IFN gamma?
|
-TH1 type helper T cells and activate NK cells
|
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What does IFN gamma do to other inflammatory cells?
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-causes them to express Fc and C3b receptors
|
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What is the most important mediator for activating macrophages?
|
-IFN gamma
|
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what are the "master cytokines"?
|
-interleukins
|
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Interleukins are primarily produced by?
|
-leukocytes
|
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What is the point of an interleukin?
|
-serves as messengers between all the various participants in both the inflammatory and immunologic responses
|
|
IL-1 is primarily produced by?
|
-endothelium and macrophages
|
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what are the two forms of IL-1?
|
-IL-1 alpha
-IL-1 beta |
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The production of IL-1 alpha and beta can be stimulated by?
|
-LPS
|
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What are the actions of IL-1
|
1. stimulates synthesis of acute phase proteins
2. causes the endothelium to expression adhesion molecules and become "sticky" 3. potent stimulator of neutrophil migration 4. macrophage secretion of IL-1 which is very important in immunological reactions |
|
In plasma, IL-1 affects?
|
-the hypothalamus
-stimulates the release of ACTH -stimulates prostaglandin production and the "respiratory burst" |
|
IL-1 acts synergistically with?
|
-IFN-gamma and IL-2
|
|
Which IL has an important role in granuloma formation?
|
-IL-1
|
|
Which IL has an important role in resorption of bone and cartilage?
|
-IL-1
|
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where does the antagonist for IL-1 come from?
|
-produced by activated macrophages
|
|
How does the antagonist for IL-1 work?
|
-it competes with the IL-1 for receptors
|
|
where are IL-2 and 15 produced?
|
-produced by antigen stimulated TH1 helper T cells
|
|
IL-2 and IL-15 enhance the activity of?
|
-cytotoxic T cells and NK cells
|
|
where is interleukin 3 made?
|
-produced by helper T cells
|
|
which interleukin is a potent hematopoietin?
|
-IL-3
|
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which interleukin stimulates mature mast cells and macorphages to divide and prevents them from dying prematurely which is very important in short term local recruitment?
|
-IL-3
|
|
which IL act with IL-10 to suppress inflammation but enhance immunity?
|
IL-4 and 13
|
|
which IL's suppress inflammation but enhance immunity?
|
IL-4 and 13
|
|
What cells produce IL-4 and 13?
|
-both are produced by TH2 helper T cells to which antigen has been bound
|
|
What do IL-4 and 13 do to B cells?
|
-stimulates them to produce antibody
|
|
Which IL stimulates eosinophils?
|
IL-5
|
|
Which interleukin would you predict to see in abundance in a parastitic infection?
|
IL-5 because it stimulates eosionophils
|
|
IL-5 acts synergistically with?
|
-eotaxin
|
|
what is the most important IL in stimulating hepatocytes?
|
IL-6 and thus increases the production of acute phase proteins
|
|
what substance enhances the response of the hepatocyte to IL-6?
|
-corticosteroids
|
|
Which IL stimulates IgA?
|
IL-6
|
|
Persistance IL-6 will have what affect on the bone marrow?
|
-causes it to shift from making neutrophils to macrophages
|
|
What is the major inhibitory IL of inflammation?
|
IL-10
|
|
What cells produce IL-10?
|
-mainly TH2 helper T cells
|
|
IL-10 works with what other two IL to keep macrophages and neutrophils from getting out of control?
|
IL-4 and IL-13
|
|
If IL-10 is deficient or lacking, what will you see in inflammation?
|
-chronic inflammatory disease
|
|
IL-10 stimulates __________ and inhibits ____________.
|
IL-10 is stimulatory to T cells and B cells but inhibitory to macrophages
|
|
Which IL is key in developing cell mediated immunity and thus is essential for elimination of an agent?
|
IL-12
|
|
What cells produce IL-12?
|
-macrophages, neutrophils, and B cells
|
|
IL-12 stimulates?
|
-Th1 helper T cells
-this is accompanied by large scale release of IFN gamma from helper T cells that are activated by IL-12 |
|
TNF alpha is mainly produced by?
|
-activated macrophages, neutrophils, lymphocytes, NK cells and endothelial cells
|
|
TNF beta is only produced by?
|
-lymphocytes
|
|
which TNF is responsible for the formation of scar tissue?
|
TNF alpha
|
|
which TNF acts synergistically with IL-1 to produce fever?
|
TNF alpha
|
|
What is another name for TNF alpha?
|
-cachexin, bc it causes wasting effects
|
|
What is another name for TNF beta?
|
-lymphotoxin
|
|
where is TNF beta produced?
|
-produced by cytotoxic T cells for killing infected cells
|
|
If you are looking at an animal and you notice it has no peripheral lymph nodes, what has gone on?
|
-it is lacking TNF beta for whatever reason...animals without TNF beta have no peripheral lymph nodes
|
|
What cells produce IL-8?
|
-macrohpages
-fibroblasts -endothelium |
|
What is the most important and certainly the most potent stimulator of neutrophil migration into the site of inflammation?
|
IL-8
|
|
What are MIPs?
|
Macrophage Inflammatory Peptides
|
|
What is the purpose of MIPs?
|
-to stimulate the lymphocytes and macrophages as well as activate fibroblasts-so they have a role in healing and repair
|
|
MIPs are mainly produced by?
|
-activated macrophages
|
|
What is MCP-1?
|
-monocyte chemoattractant protein-1
|
|
What does MCP-1 do?
|
attracts macrophages
|
|
What is another name for CCL5?
|
-Eotaxin
|
|
What induces eotaxin?
|
-IL-4/IL-13
|
|
what is eotaxin important for?
|
-for maintaining eosinophils in the gut so they are ready for parasites
|
|
What are the four types of growth factors?
|
1. transforming growth factor beta (TGF beta)
2. vascular endothelial growth factor (VEGF) 3. Platelet derived growth factor (PDGF) 4. Epidermal growth factor (EGF) and Fibroblast Growth Factor (FGF) |
|
What is the major GH involved as a major factor in angiogenesis needed for wound healing?
|
VEGF
|
|
Does VGEF increase, decrease, or not change vascular permeability?
|
-increases vascular permeability
|
|
what are the two basic types of inflammatory cells?
|
1. PMNs
2. mononuclear leukocytes |
|
What is another name for PMNs?
|
-granulocytes
|
|
Describe what the nucleus of a PMN looks like? And its granules?
|
-lobed or segmented nuclei and cytoplasmic granules
|
|
What are three granulocytes that are mediators of inflammation?
|
1. neutrophils
2. eosinophils 3. basophils |
|
What is unique about all granulocytes?
|
-they are non-dividing cells. they are actually stalled in an early phase of apoptosis
|
|
Where would you find granulocytes?
|
blood and tissue both
|
|
What is the most abundant to the least abundant granulocytes?
|
"Never let monkeys eat bananas"
-Neutrophils -eosinophils -basophils |
|
Which types of inflammatory cells would you expect to see in shorter term and long term inflammatory responses?
|
1. short term: PMNs
2. Long term: mononuclear leukocytes |
|
How can you tell a PMN from a mononuclear leukocyte simply by looking at the nucleus?
|
PMN: segmented or lobed nucleus
Mononuclear leukocyte: do not have multilobed nuclei |
|
That are the two forms of mononuclear leukocytes?
|
1. in blood: monocytes
2. in tissue: macrophages, lymphocytes, and plasma cells |
|
where are mast cells found and what type of inflammatory cell are they?
|
mononuclear leukocyte, only found in tissue, not in blood
|
|
What PMN is a key actor in acute phase inflammation?
|
-neutrophils
|
|
first type of cell to enter an area after injury?
|
-neutrophils
|
|
How do neutrophils move?
|
-rapidly by ameboid motion
|
|
Are neutrophils intensely, moderately or not at all phagocytic?
|
- neutrophils are intensely phagocytic
|
|
Are neutrophils stable in circulation?
|
-no. they are a little more stable in tissues, but they still don't last very long bc they use so much ATP in their ameboid motion to move to the insiting stimulus
|
|
If a PMN in circulation isn't called to an area of injury, how long will it hang around? then what happens to it?
|
-they will last in circulation for about 6 hours and then die by APOPTOTIC NECROSIS
|
|
If a PMN gets activated in circulation to travel to a site of injury, how long will it live?
|
1-2 days
|
|
Describe a neutrophil nucleus.
|
-highly segmented and that looks fragmented in H and E
|
|
which PMN contains two types of granules?
|
-neutrophils
|
|
what are the two types of granules that neutrophils possess?
|
1. ones apparent in blood smears and will appear uniformly pink in section-these granules are too small to be well defined
2. the second type are basically lysosomes-they contain specific combos of enzymes and non-enzymatic compounds that contribute to killing and degradation of ingested organisms |
|
What are the two specific types of lysozyme granules that neutrophils contain?
|
1. azurophils granules
2. specific granules |
|
What do azurophil granules contain?
|
-degradative enzymes + myeloperoxidase + phospholipases + cytochrome B
|
|
What do specific granules contain?
|
-most of the stromal degradative enzymes (called matrix metalloporteinases, MMPs) +lactoferrin + cationic proteins +adhesion molecules
|
|
Describe the "respiratory burst".
|
-this occurs after you have phagocytized the bacteria and you have to get rid of it
-it takes lots of oxygen to do this -it is essential to kill bacteria -Involves: NADPH oxidase complex 1. takes O2 and converts it to superoxide anion (H+ is important here because it reacts with OH to make H2o2 here) 2. requires lactoferrin : Ferric iron + OH=ferrous iron and Free O2 3. Fenton reaction: O2 (with a free radical) and peroxide (H2O2)=OH minus + OH (with a free radical_ and free oxygen 4. Myeloperoxidase: H2O2 + Cl- =OCl- + H2O (this is essentially bleach and water) |
|
What are tertiary granules?
|
-three other types of granules in neutrophils that contain gelatinase
|
|
What is the function of neutrophils?
|
1. rapidly respond to chemoattractants
2. migrate to bloodstream 3. first inflammatory cells to a site of injury |
|
What the two types of adherence of neutrophils?
|
1. reversible
2. irreversible |
|
What is reversible adherence usually called?
|
-margination
|
|
What is margination (reversible adherence)?
|
-normally WBC's circulate with RBCs in a central column moving down a vessel, with plasma on the outside, in contact with the endothelium
-when blood flow through tissue is slowed it allows for interaction between WBCs and the endothelium -there is then temporary adherence to the endothelium |
|
what does endothelium express in response to histamine, thrombin and PAF?
|
-P selectin
|
|
After endothelium has expressed P selectin after 1-2 hours is expresses E-selectin in response to?
|
IL-1 and TNF
|
|
Leukocytes have ligands, a carbohydrate moiety called?
|
-sialyl-Lewisx
|
|
What is the glycoprotein being sialyl-lewisx called?
|
P-selectin glycoprotien Ligand 1 (PSGL-1)
|
|
Interaction between what two complexes causes "rolling" to occur?
|
-PSGL-1 and P-selectin binding
|
|
The sialyl-Lewisx-E-selectin interaction causes?
|
-causes slow rolling to occur
|
|
What do leukocytes recognize on high endothelial venules of the gut?
|
-MadCAM (mucosal addresin cell adhesion molecule)
|
|
what do leukocytes recognize in lymph nodes, mammary glands, uterus and lungs?
|
-glyCAM
|
|
What is pavementing?
|
-if there are chemical mediators present in tissue or the are of injury, WBC's will stick to the endothelium by an irreversible process called pavementing
|
|
what are two mediators that are very good at stimulating pavementing?
|
IL-1 and TNF-alpha
|
|
What is needed for beta-2 integrins and ICAM-1 to stick together?
|
Calcium
|
|
Histologically, what does pavementing look like?
|
-flattening of the leukocyte onto the top of the endothelial cells
|
|
Neutrophils exit the vessel via a process called?
|
diapedesis
|
|
How does the process of diapedesis and thus neutrophils exiting vessels work?
|
1. PECAM-1 (CD31) is expressed at endothelial junctions
2. WBCs squeeze through the endothelial cells |
|
Neutrophils will rapidly migrate down a concentration gradient in a coordinated response to a_______ and this process is called_________?
|
-chemoattractant-"chemotaxis"
|
|
Neutrophils generally migrate though________ via chemotaxis.
|
-migrate through post-capillary venules and sometimes capillaries
|
|
How quickly can neutrophils flood an area of injury?
|
-within 30 minutes
|
|
The migration of monocytes/macrophages seems to depend on the migration of what cells?
|
-neutrophils
|
|
What does the underlying mechanism of chemotaxis involve?
|
1. activation of a biochemical cascade started when a chemoattractant binds to a receptor on the membrane
2. this is followed by changes in membrane fluidity so the cell can send out long pseudopodia (involves actin and myosin filaments) 3. it all coordinates together to look like a balloon being squeezed at one end to push it forward over and over again |
|
What are the long range mediators chemotactic for neutrophils?
|
Long range:
IL-8 LTB4 PAF |
|
What are the short range chemotactics for neutrophils?
|
short range:
C5a C3a Formyl peptides |
|
How does a neutrophil phagocytose an insiting stimulus?
|
-it sends out processes that surround and enclose the offending particle in a vacuole
|
|
Antibody-antigen complexes, complement proteins and fibronectin on the surface of particles are particular attractive to what type of cells?
|
-neutrophils
|
|
where do neutrophils bind to antibody?
|
at the Fc region
|
|
If a neutrophil cannot ingest a particle, what will happen?
|
-it will dump its lysosomal enzymes out onto the surface of the particle which can have serious consequences for the surrounding tissues
|
|
What process is essential for normal neutrophil function?
|
-the respiratory burst
|
|
With a dramatic increase in respiratory activity there is also a dramatic increase in?
|
O2 consumption
|
|
What molecule serves as a source of iron for the respiratory burst?
|
-lactoferrin
(know the steps in the respiratory burst well!) |
|
therapeutic intervention in cases of ischemic tissues has been focused on neutralizing what system?
|
-the myeloperoxidase system
|
|
which granules from neutrophils are emptied first?
|
-specific granules
|
|
What do specific granules do?
|
-serve to acidify the phagocytosed material to allow the myeloperoxidase system to generate the free radicals and other compounds to kill the agent
|
|
which neutrophilic granule contains BPI?
|
specific granules contain bacteriocidal protein (BPI)
|
|
what neutrophilic granules would you expect to see in gram negative bacterial infections?
|
-specific makes BPI that binds to endotoxin and pokes holes in gram negative bacteria
|
|
What are MMP's?
|
-coallagenases and gelatinases
-MMPs=matrix metalloproteinases |
|
MMPs contain what metal?
|
zinc or similar metals
|
|
Why are MMPs especially damaging?
|
-they destroy the stromal framework which supports the tissue parenchyma.
|
|
What are NETs? And how do they work?
|
-Neutrophil Extracellular Traps
-appear to be a form of programmed cell death -neutrophils contract and rupture -form a fibril matrix which entraps bacteria, yeast, and other pathogens -effective at killing bacteria -also contain released granule constituents to prevent tissue damage |
|
What are five ways that neutrophils can do to further the scope of the inflammatory response?
|
1. kinins
2. PGs, LTs, and PAF 3. cleave complement to generate more active fragments 4. elaborate substances chemotactic for macrophages 5. activate mast cells and platelets to release histamine and endogenous pyogenes |
|
What do rabbits have instead of neutrophils?
|
-heterophils
|
|
What is the about the only organism to cause an obvious heterophil response in birds?
|
-staph
|
|
Eosinophils are involved in what kind of reactions?
|
-immune mediated and parasitic
|
|
Are eosinophils ameboid and phagocytic?
|
-yes but not as good at it as neutrophils
|
|
Are eosinophils very responsive to complement?
|
-no
|
|
Which is more efficient at digestion: neutrophils or eosinophils?
|
-neutrophils
|
|
Which can reside in tissues longer: neutrophils or eosinophils?
|
-eosinophils
|
|
Where are eosinophils most abundant?
|
-GI tract
|
|
what is the difference between a neutrophil nucleus and an eosinophil nucleus?
|
-neutrophil is more segmented than eosinophil
|
|
What is the major component of an eosinophil granule?
|
-eosinophil basic protein. this protein kills parasites quite effectively
|
|
What does EBP do to heparin?
|
-eosinophil basic protein
-neutralized heparin secreted by mast cells |
|
How do eosinophils kill parasites?
|
Dump out EBP, eosinophilic cationic protein and peroxidases onto the cuticle of a parasite, which causes the cuticle to separate from the body wall of the parasite
|
|
T/F. Eosinophils are not only good at killing parasites, but they are good at killing bacteria too since bacteria often have the same effects on the body as parasites.
|
False. Eosinophils are not very good at killing bacteria
|
|
Eosinophils have enzymes to specifically degrade?
|
-histamine, heparin, leukotrienes and platelet activating factor
|
|
what is similar about the morphology of mast cells and basophils?
|
-both have intensely basophilic granules
-granules are metachromatic |
|
What are some differences between the morphology of mast cells and basophils?
|
-basophil: has segmented nucleus
-mast cell: has large, oval nucleus, large in size, lots more cytoplasm |
|
which cells tend to be associated with type I hypersensitivity reactions?
|
-mast cells and basophils
|
|
What immunoglobulin do mast cells and basophils both have on their surfaces?
|
IgE
|
|
Mast cells have a regulatory role on what cells?
|
eosinophils
|
|
Are mast cells and basophils killed when they degranulate?
|
-no, neither cell is killed when it degranulates
-basophils are not able to make new granules though (like neutrophils and eosinophils) |
|
Both mast cells and basophils can synthesize ___________ and _________to attract PMN's and macrophages?
|
-PG's, LT's to attract PMNs and macrophages
|
|
Where do basophils come from?
|
-bone marrow derived
|
|
Where do mast cells come from?
|
-they are bone marrow derived like basophils, and travel through the blood indistinguishable from a monocyte until it gets into connective tissue, where it differentiates into typical granulated cells where it accumulates around blood vessels or under epithelium in tissues that are in contact with the external environment
|
|
As far as time goes, which is more associated with more chronic responses and which is associated with more acute inflammatory resonses (of mast cells and basophils).
|
mast cells-more acute
basophils-more chronic |
|
where do monocytes/macrophages originate?
|
-in the bone marrow and circulate in the blood as monocytes
|
|
what are the two things monocytes/macrophages do after they become histiocytic upon entering the tissue?
|
1. if no over inflammatory stimulus: monocytes will differentiate into fixed type histiocytic macrophages that align themselves beneath or between endothelial cells
2. if there is inflammation present: it differentiates into an active inflammatory macrophage and becomes a true inflammatory cell |
|
The histiocytic macrophage is more of an _________ cell than a true inflammatory cell.
|
-more of an immunologic cell than an inflammatory cell
|
|
What mediators activate histiocytes to become typical inflammatory macrophages?
|
-IL-12, helper T cells and IFN gamma
|
|
what inflam mediators cause the macrophage to differentiate into the histiocytic macrophage that is the classic antigen processing cell stimulating the immune response?
|
IL-4 and IL-13
|
|
which are faster? macrophages or granulocytes?
|
-granulocytes are faster (macrophages are larger and more sluggish)
|
|
What kind of cells can form a resident population of macrophages?
|
-monocyte/macrophages
|
|
T/F. Macrophages can be multinucleated and quite enormous in size.
|
True. they are "giant" cells
|
|
What IL stimulate the formation of "giant cells"?
|
-IL-4 and 13
|
|
When to giant cells occur?
|
-when large, hard to digest foreign bodies are encountered or when there is chronic infection by an intracellular microbe
|
|
What are the two types of giant cells?
|
1. langhan's type cell-nuclei in a C shape
2. Touton giant cell-nuclei are still C shaped, but peirphipherally is vacuolated and foamy, presumably due to lipid accumulation |
|
T/F. Macrophages have myeloperoxidase.
|
True. they just don't have much of it and they still undergo a respiratory burst just like granulocytes
|
|
How to macrophages kill?
|
-generate OH radicals via NO
|
|
What molecule is extremely good at generating a respiratory burst from macrophages?
|
-IFN gamma
|
|
T/F. Neutrophils are useless for wound healing unless the wound is infected.
|
true.
|
|
What are some of the self activating factors that neutrophils can produce?
|
-IL-1, IL-6, IL-12
|
|
What are three main functions of lymphocytes and plasma cells?
|
1. immune response
2. hypersensitivity reactions 3. chronic inflammatory lesions where an immune response has been mounted; in certain viral infections they can be the predominate cell |
|
What cells have a characteristic pale pink "halo" near one side of the nucleus.
|
-lymphocytes/plasma cells
|
|
What kind of receptors do platelets have?
|
-Fc and C3 receptors and are also activated by collagen
|
|
Platelets interact exclusively with neutrophils especially with regards to generating?
|
-LT's
|
|
where do platelets perform their functions vs. where neutrophils perform their actions?
|
-platelets-intravascularly
-neutrophils-extravascular |
|
What are PAMPs?
|
Pathogen Associated Molecular Patterns
-differentiate self from nonself |
|
What are DAMPs?
|
-Danger Associated Molecular Patterns
-differentiate healthy self from damaged self |
|
T/F. Without macrophages, healing will not occur.
|
true
|
|
What separate an elevation in temp with fever from things like execise, excitement, and hyperthemia?
|
-the presence of inflammation
|
|
What is the definition of fever, basically?
|
basically an adaptation in the normal thermoregulation of the body such that the body's "thermostat" is set at a higher temp
|
|
Why would the body want to heat itself up with fever?
|
1. causes biochemical processes to happen faster (heat is catalyst)
2. increased temp is unfavorable for growth of infectious bacteria |
|
what are some detrimental effects of fever?
|
-brain function can be decreased or lost
-net energy loss (that is part of the reason why you just want to sleep) -dehydration can occur quickly |
|
what is the pathogenesis of fever?
|
IL-1 and TNF alpha and IFN gamma kick in to cause increased prostaglandin E2. IL1 activates the sleep center and TNF alpha increases prostaglandins
|
|
What does the leukocyte response to inflammation usually manifest itself as?
|
leukocytosis (elevated WBCs in the blood), usually a neutrophilic (lots of neutrophils)
|
|
what the two "pools" for WBCs and where are they found?
|
-marginated pool in the blood
-storage pool in the bone marrow |
|
What is/are glucocorticoids role in inflammation?
|
cause mature marginated neutrophils to round up and enter the blood stream, this causes release of mature neutrophils in the storage pool (bone marrow) to be released, immature neutrophils do not come out of the bone marrow in response to glucocorticoids (thus you won't see bands because of glucocorticoids)
-cause decreased lymphocytes in the blood (lymphopenia) -eiosinopenia (eosinophils stay in the bone marrow or tissues) |
|
How can prolonged glucocorticoids in inflammation have a detrimental effect?
|
1. stabilize membranes. this makes it harder for neutrophils to squeeze through endothelium and get out to tissues or site of injury
2. suppress IL-1 and TNF alpha 3. can inhibit migration 4.suppress the immune response |
|
A sustained inflammation will lead to an increased number of?
|
-mature neutrophils and correlating monocytes
|
|
If a stimulus is very acutely intense and the bone marrow has no chance to respond what will occur?
|
-neutropenia (decreased number of neutrophils)
|
|
If a response to a stimulus is slightly less intense, but still severe, what will cause the bone marrow to dump out immature cells?
|
IL-1 and TNF alpha will cause bone marrow to dump out immature neutrophils earlier than they should=left shift=see bands
|
|
What is a left shift?
|
IL-1 and TNF alpha will cause bone marrow to dump out immature neutrophils earlier than they should=left shift=see bands
|
|
If the marrow is not overwhelmed and is "only a little behind" in meeting the increase demand for neutrophils what kind of shift occurs?
|
-regenerative left shift
|
|
What is a regenerative left shift?
|
If the marrow is not overwhelmed and is "only a little behind" in meeting the increase demand for neutrophils
|
|
If bone marrow is overwhelmed and cant keep up what kind of shift occurs?
|
-degenerative left shift, immature forms are outnumbering mature forms
|
|
what is a degenerative left shift?
|
If bone marrow is overwhelmed and cant keep up
|
|
An animal undergoing chronic inflammation tend s to be anemic, called?
|
-anemia of chronic disease
|
|
What inhibits iron uptake from the GI tract and contributes to anemia of chronic disease?
|
-hepcidin
|
|
What is sequestered that makes iron less available to RBCs during anemia of chronic disease?
|
-ferritin
|
|
As the lymph node gears up for this task of filtering garbage, it swells and becomes large and juicy, this is called?
|
-reactive lymphadenopathy
|
|
With reactive lymphadenopathy, what word can be used to describe the lymph node?
|
-lymphadenomegaly
|
|
when large, swollen, activated macrophages become very prominent and fill the sinuses of the lymph node, what is this called?
|
-sinus histiocytosis
|
|
term for inflammed lymph node?
|
-lymphadenitis
|
|
What agent can cause the spleen to be more meating and not bleed when cut?
|
-salmonella or erysipelothrix
|
|
Define cachexia and how it is different than starving.
|
cachexia: loss of fat and muscle and tissue
starving: loss of fat |
|
Cachetic effects are primarily due to what one factor?
|
-TNF alpha
|
|
why does TNF alpha lead to cachexia?
|
-prevents adipocyte differentiation (you can't make more fat)
-impairs uptake and utilization of triglycerides, by inhibiting lipoprotein lipase in non-adipose tissues |
|
Protein synthesis is inhibited and proteolysis is stimulated by what in the case of cachexia?
|
-probably by NO
|
|
Why do you see osteoporosis in conjunction with cachexia?
|
-osteoclasts are being stimulated by cytokines
|
|
glossa
|
tongue
glossitis |
|
arthrosis
|
joint
arthritis |
|
gaster
|
stomach
gastritis |
|
metra
|
uterus
metritis |
|
hepar
|
liver
hepatitis |
|
hepar
|
liver
hepatitis |
|
salpingo
|
fallopian tube
salpingitis |
|
enteron
|
intestine
enteritis |
|
oophor
|
ovary
oophoritis |
|
lamina(thin leaf or plate)
|
lamina of hoof
laminitis ("founder" of horses) |
|
myos
|
muscle
myositis |
|
nephros
|
kidney
nephritis |
|
typhlon
|
cecum
typhlitis |
|
enkephalos
|
brain
encephalitis |
|
balano
|
glans penis
balanitis |
|
orchio
|
testis
orchitis |
|
cheilo
|
lip
cheilitis |
|
phlebo
|
vein
phlebitis |
|
blepharo
|
eyelid
blepharitis |
|
osteo
|
bone
osteitis |
|
myelos
|
marrow
osteomyelitis (inflammation of bone marrow) |
|
sialo
|
saliva, salivary gland
|
|
mast
|
breat, mammary gland
mastitis |
|
chole
|
bile
gall bladder - cholecytis |
|
uro
|
urine
urinary bladder - urocystits |
|
cyst
|
sac, bladder
bile ducts - cholangitis |
|
angio
|
vessel or vessel-like ducts
lymph vessel - lymphangitis |
|
adeno
|
gland
lymph node - lymphadenitis |
|
Six virulence factors of bacteria?
|
1. kill phagocytes
2. inhibit chemotaxis 3. prevent engulfment 4. survive within the host inflammatory cell 5. sequester essential nutrients for growth 6. escape or avoid the immune response |
|
A polysaccharide coat such as that of salmonella can prevent attachment of what molecule?
|
C3
|
|
How can a pathogen survive within a hosts inflammatory cell?
|
-prevent fusion of phagosome and lysosome
|
|
What is one nutrient that bacteria use for growth and to evade the hosts immune system?
|
-use siderophores
-remove iron from iron-binding proteins in the body |
|
How might bacteria escape the immune response?
|
-coat themselves with host Ag, then shed their Ag and modify their Ag to mask their Ag's (mycoplasma's do this)
|
|
What is unique about E. coli and how it can stimulate its own growth?
|
-E. coli can make IL-1 like substance that when it sees hosts IL-1 will cause E. coli to increase its own growth
|
|
Five inherited defects in inflammatory cells themselves?
|
1. Chediak-Higashi syndrome
2. SCID 3. Gray collie syndrome 4. Ulcerative Histocytic Colitis 5. Canine granulocytopathy syndrome |
|
This condition is a defect in microtubules and cytoskeleton structure and function. Neutrophils cannot move normally and cannot release their lysosomal contents. Neutrophil granules are abnormally large because of abnormal fusion of azurophil and specific granules and decrease in number of neutrophils.
|
-chediak-Higashi syndrome
|
|
What should you worry about in an animal with chediak-higashi syndrome?
|
-susceptible to bacterial infection
|
|
This is a condition in which WBCs cannot generate the respiratory burst and cannot kill bacteria. There is normal phagocytosis, but intracellular killing is impaired.
|
-canine granulocytopathy syndrome
|
|
This condition is associated with cyclic fluctuations in the production of WBCs with neutrophils the most severely affected.
|
Gray Collie Syndrome
|
|
How to do dogs get Gray Collie Syndrome?
|
-inherited autosomal recessive disease
|
|
Animals that survive Gray Collie Syndrome often develop?
|
-amyloidosis
|
|
This condition is marked by neutrophilia and inability to form pus. There is an inability to form a whole family of membrane bound molecules, ie integrins and complement receptor. Pavementing cannot occur.
|
-Leukocyte Adhesion Deficiency
(CLAD in dogs, BLAD in bovine) |
|
This is an autosomal recessive defect in arabian foals.
|
Severe combined immunodeficiency (SCID)
|
|
SCID is assoc with a defect in?
|
-T and B cells production
|
|
Is there any cell mediated or antibody response associated with SCID?
|
-no
|
|
Where does IgA function?
|
-mucosa sites (upper resp tract and lower urogenital tract)
|
|
Airedales that have a defect in IgA are prone to?
|
discospondylosis
|
|
What is the most abundant Ig produced by the body on a daily basis?
|
-IgA
|
|
This is assoc with Boxers and results in E. coli accumulating in macrophages in the lamina propria.
|
-Ulcerative Histocytic Colitis
|
|
what cells distinguish "self" from "nonself"?
|
PAMPs
|
|
What type of cells distinguish "damaged self" from "healthy self"?
|
Danger associated Molecular patterns (DAMPs)
|
|
What is one of mildest exudates?
|
serous exudate
|
|
What proteins are associated with serous exudates?
|
presence of fluid with LOW MOLECULAR WEIGHT PROTEINS (mostly albumin)
|
|
what type of exudate would you expect to see form the GI tract or respiratory tract?
|
catarrhal exudate
|
|
what exudate: globlet cells release large amounts of mucopolysaccharide and glycoproteins when irritated.
|
catarrhal exudate
|
|
What immunoglobulin is associated with catarrhal exudate?
|
IgA
|
|
Which exudate leads to goblet cell hyperplasia?
|
catarrhal exudate
|
|
Which exudate is associated with enough damage to endothelium and basement membrane to allow large scale leakage of clotting factors into tissue?
|
fibrinous exudate
|
|
what is a key feature of fibrinous exudate?
|
-you can break it, it's friable (fragments)
|
|
what kind of exudate will you see with hardware disease in cattle?
|
-fibrinous exudate
|
|
What kind of exudate will you see with blisters associated with burns?
|
serous exudates
|
|
This exudate is associated with an influx of neutrophils.
|
suppurative exudate
|
|
what is pus?
|
-accumulation of viable and dead neutrophils, mixed with dead tissue cells and plasma fluid that has leaked out of vessels is grossly evident as pus
|
|
what is a term used to describe an accumulation of viable and dead neutrophils and tissue debris into a localized area within a tissue or organ
|
abscess
|
|
What staining characteristic will the content of an abscess be?
|
eosinophilic staining characteristic (the neutrophils are dead)
|
|
What is the a term used to describe grossly evident amounts of fibrin present associated with pus?
|
fibrinopurulent
|
|
What is a term used to describe large amounts of mucus mixed with neutrophils?
|
mucopurulent
|
|
Exudate associated with parasitic or immune mediated infections and has a very characteristic greenish tint to the tissue?
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eosinophilic exudate
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This exudate is usually a microscopic diagnosis, lymphocytes will predominate...
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lymphocytic exudate
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This term is reserved for certain inflammatory responses of the CNS, especially viral infections
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non-suppurative (no neutrophils present)
|
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This is not an exudate, it is a type of inflammation
-death of a lot of tissue without much of a leukocytic response, but lots of necrosis |
necrotizing inflammation
"necrohemorrhagic enteritis" |
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Term used to describe a mixture of debris and fibrin
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pseudomembrane or diphtheritic membrane
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This is a term used to describe a pseudomembrane or diphtheritic membrane subsequently infiltrated by a large number of neutrophils.
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necropurulent
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if a major blood vessel becomes involved in the necrotizing process what kind of inflammation results?
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-hemorrhagic or necrohemorrhagic
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this is a term used to describe the necrosis and loss of mucosal lining or surface in tissue or organs such as GI tract, skin, upper respiratory tract or urinary bladder. In skin, this type of inflmmation is associated with loss of epidermis and extension into underlying dermis.
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-ulcerative
|
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term used to describe a response of surviving epithelium in an inflammatory process in certain types of infections
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-proliferative
|
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the predominant cell type is a macrophage, usually arranged in a cluster or nodule, often with the causative agent in the middle, has epithelioid macs, multinucleated giant cells, surrounded by dense fibrous tissue...what kind of exudate?
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granulomatous exudate (forms granulomas)
|
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Two types of histologic granulomas?
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1. DTH
2. Foreign body driven |
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What stains for tuberculosis?
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Ziehl-Nielsen
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How does TB in birds differ from TB in other animals?
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-Bird: more necrotizing than granulomatous
-amyloidosis is the sequelae |
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What kind of inflammatory response does Johne's have assoc with it?
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-diffuse granulomatous response tends to be in ileum and ileocecal colon region
|
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Gram stain of M. paratuberculosis?
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weakly gram positive
|
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S. aureus, R. Equi both cause what kind of response?
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bacterial granulomas
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What causes "wooden tongue" in cows?
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actinobacillus
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What causes "lumpy jaw"?
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-actinomyces
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T/F. Actinomyces and Actinobacillus are not only confusing because they are named so similarly, but they are hard to distinguish in diagnosis because they are both acid fast.
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-false! Neither are acid fast!!! (that is only CMN!)
|
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If a dog gets a grass awn in its paw, what kind of response will ensue?
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granulomatous
|
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How does a granuloma form?
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IL 12-->TH1-->make things that amplify (ie IFN gamma) and makes everything more phagocytic thus producing iNOS. This increases NRAMP in the phagosome wall
TH1: TNF, IL-1, IFN gamma and chemokines-MIT-1 or MCP-1 which bring monocytes and macrophages in |
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Four dimorphic fungi?
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1. blastomyces dermatitidis
2. histoplasma capsulatum 3. cryptococcus 4. coccidiodes |
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If you see a multifocal collescing lung and BB pattern granulomas with caused it?
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-blastomyces dermatitidis
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If you are looking at skin from a blasto animal how should you describe it?
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pyogranulomatous response with draining tracts
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this can be responsible for diffuse granulomatous enteritis and has a capsule
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histoplasma capsulatum
|
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What stains can you use for histo or blasto?
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-PAS, Silver stains, musca carmine stain?
|
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Associated with sinusitis in cats, has a capsule...
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cryptococcus
|
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If you see a multifocal collescing lung and BB pattern granulomas with caused it?
|
-blastomyces dermatitidis
|
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If you are looking at skin from a blasto animal how should you describe it?
|
pyogranulomatous response with draining tracts
|
|
this can be responsible for diffuse granulomatous enteritis and has a capsule
|
histoplasma capsulatum
|
|
What stains can you use for histo or blasto?
|
-PAS, Silver stains, musca carmine stain?
|
|
Associated with sinusitis in cats, has a capsule...
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cryptococcus
|
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this causes granulomas in the lung then disseminates into the bone marrow and you see lame dog in your office
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coccidioides
|
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This can get into guttural pouches and lead to fibrinonectrotic inflammation r a diphtheriod membrane
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Aspergillus fumigatus
|
|
this can cause acidosis in cattle and damage rumen epithelium, then fungus can get in
|
mucor corymbifer
|
|
this causes a protozoal granuloma, cats are definitive hosts...
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toxoplasma
|
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How are Inflammation and Repair linked?
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Functionally, mechanistically, and temporally
|
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What is the "time frame" of healing and repair (i.e. when does it start/when does it end)?
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Healing and repair begin very soon after injury has taken place and generally extends out past the end of the inflammatory response
|
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T/F: Healing and repair involves (some of) the same mediators, factors, and cells involved in inflammation?
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True: ex. IL-1 and Macrophages
|
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Name the two methods by which healing can take place.
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Healing By:
1.) Parenchymal regeneration 2.) Scarring/fibrosis |
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Healing by Parenchymal Regeneration
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Allows complete restoration of function
|
|
Healing by Scarring/Fibrosis
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Permanent loss of function (either partial or comoplete)
|
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In healing by parenchymal regeneration, what are the 3 cell types possibly affected by the injury or inflammatory response?
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Labile cell, Stable cell, Permanent cell
|
|
Labile Cells
|
1) continually multiply under physiologic conditions
2) have a high turnover rate 3) retain the capacity to divide throughout the life of the organism 4) includes hematopoietic bone marrow cells, lymphoid cells, epithelium (skin, lower urinary tract, oral cavity, and genital tract 5) can replace themselves quite readily |
|
Stable Cells
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1) regenerate (not as readily as labile cells)
2) low turnover during adult life, but can rapidly divide under proper stimulus 3) includes glandular tissue (pancreatic acinar cells, renal tubular epithelium, hepatocytes, and salivary epithelium) 4) also includes osteoblasts, fibroblasts, vascular endothelium, chondroblasts, smooth and skeletal muscle (to a certain degree) |
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Permanent cell
|
1) mitotic potential is absent or almost absent in the adult animal
2) Loss of cell population results in permanent loss of function (replaced by non functional tissue) 3) includes: neurons, cardiac muscle, sertoli cells, and retinal rods |
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Aside from cell type, what other factors affect the tissues ability to undergo healing by parenchymal regeneration?
|
1) Vascular supply to damaged tissue (must be relatively in tact)
2) Supporting stroma (including basement membrane; must be relatively in tact) 3) degree of inflammation present |
|
Supporting stroma
(healing by parenchymal regeneration) |
- serves as scaffolding to support functional tissue, and maintains structures in proper orientation
- if lost, will be filled, but not in same organization |
|
Basement Membrane (Fxn in healing by parenchymal regeneration)
|
- provides support for tissue/governs interaction of tissue w/ underlying stroma
- if basement membrane is damaged, it must be resynthesized from parenchyma before healing can take place - if parenchyma is damaged, it must be repaired, heal basement membrane, then healing can take place |
|
Degree of inflammation and its affects on healing by parenchymal regeneration
|
-chronic inflammatory exudate can cause a connective tissue response
- probably mediated by activated inflam. macrophages producing fibroblast growth factor in response to MCP-1 |
|
Healing by connective tissue replacement is a.k.a.?
|
Healing by fibrosis or scarring
|
|
Benefits of scarring
|
-encapsulation of an offending agent
-bolstering/strengthening of damaged tissue -resolution of undesirable events (i.e. blood clot) |
|
Undesirable effects of Scarring
|
-Reduce distensibility of organ or tissue
-Fibrous/CT formed during healing tends to shrink over time -only has 70% tensile strength of original tissue |
|
Scar distensibility
|
-reduced from normal tissue
-loss of elasticity |
|
Scar tissue shrinkage
|
-can result in stricture when surrounding a hollow organ
-can form adhesion if it bridges a gap between two organs -can pull surrounding "normal" tissue out of allignment -can become sclerotic (hard) |
|
Granulation tissue
|
soft red or pink "granular" looking tissue, often found on the surface or surrounding edges of a lesion or injury
|
|
Is granulation tissue related to the terms granuloma or granulomatous?
|
No: Granuloma/Granulomatous describe a part of the inflammatory response, GRANULATION TISSUE refers to part of the healing process
|
|
Morphology of granulation tissue (i.e. zones)
|
-Zone of mature CT
-Zone of capillary proliferation -Zone of capillary sprouts and arches -Zone of necrotic debris |
|
Zone of mature connective tissue
|
-deepest edges of lesion
-oldest part of the healing lesion -healing process almost complete -well vascularized (primarily to supply blood to more superficial zones) -once completely healed, blood vessels regress |
|
Zone of capillary proliferation
|
-capillaries bud off from deeper vessels
-branch perpendicular to lesion (Forming a gridiron pattern) -proliferating Fibroblasts found between capillaries |
|
Proliferating fibroblasts
(zone of capillary proliferation) |
-fibroblasts align parallel to wound surface
-responding to fibronectin and fibroblast growth factor (from Macrophages) |
|
Fibroblasts and extracellular matrix
|
-In zone of capillary prolif. fibroblasts lay down a new extracellular matrix
-ground substance matrix containing hyaluronic acid is layed down first (promotes cell division) -collagen is primary end product -few elastic fibers |
|
Wound fibroblasts vs. Normal tissue fibroblasts
|
-in damaged tissue, wound fibroblasts take on many characteristics of smooth muscle and become very contractile (sometimes called myofibroblasts)
-wound fibroblasts result in wound contraction |
|
Zone of capillary sprouts and arches
|
-boundry between necrotic debris and viable granulation tissue below
-capillaries are initially solid, and then hollow out to become patent -initially new capillaries are very leaky and plasma can flow out to "bathe" the tissue in nutrient medium |
|
Leaky capillaries (zone of capillary sprouts and arches)
|
-bathes area in nutrient rich medium
-protein rich media provides nutrients for incoming fibroblasts and for tissue macrophages -causes edemetous appearance of damaged tissue |
|
When do capillaries bud into a wound
|
ONLY when macrophages are present due to presence of factors (produced by macrophages) stimulate growth and turn of inflammatory response (called histeocytic macrophages)
|
|
Zone of necrotic debris
|
Most superficial zone of healing
|
|
Characteristics of Zone of necrotic debris
|
-usually covered by a scab
-contains: necrotic tissue, coagulated plasma, lots of neutrophils, some macrophages (deeper) |
|
Fxn of Neutrophils in Zone of necrotic debris
|
-destroy contaminating bacteria
-steralize surface of the wound -initiate healing by elaborating ENF and IL-1 to stimulate influx of macrophages and cause proliferation of epithelium around the wound |
|
Fxn of Macrophages in Zone of necrotic debris
|
-debride the tissue (removes tissue that might interfere w/ new scaffolding of CT; removes factors that would inhibit fibroblast proliferation)
-removes old neutrophils (IDed via expression of phosphatidyl serine) |
|
Edges of the Zone of necrotic debris
|
-often become thickened/hyperplastic while trying to replace original covering
-epithelium will grow DOWN under scab |
|
Proud Flesh
|
condition in horses where new tissue formation becomes "overexuberant" forming a lumpy, nodular, oozing mass that protrudes above epithelial surface and epithelium cant cover it.
|
|
Healing by primary intention (characteristics)
|
-clean wound
-minimal bleeding -easily opposed edges |
|
Whats an example of healing by primary intention?
|
Surgery
|
|
Stages of Healing by primary intention
|
-Formation of blood clot
-Inflammatory reaction -neovascularization (48h) -Fibroblast prolif/collagen deposition (1 week-1 year) -Devascularization -Scar (unpigmented, no adnexal structures - hair/sweat glands, poor tensile strengths) |
|
Healing by secondary intention
|
-poor aposition
-contamination -extensive loss of tissue |
|
infectious agents that kill phagocytes by elaborating toxins are typically of what origin? (viral, bacterial, fungal, etc)
|
bacterial
|
|
these produce superantigens...
|
staph and strep
|
|
toxins released from bacteria will cause neutrophils to do what?
|
dump lysosomal content into cytoplasm instead of into the phagosome
|
|
_____ species can inhibit chemotaxic, thereby preventing leukocytes form reaching the site of infection.
|
Streptococcus
|
|
microbes can prevent being phagocytosed by:
|
being encapsulated with a polysaccharide or protein-polysaccharide coating
|
|
these microbes are capable of inhibiting phagocytosis:
|
E. coli, Strep, Pasteurella multocida, B. anthracis, and Cryptococcus neoformans
|
|
This is used by the host to prevent the microbial inhibition of phagocytosis
|
opsonization
|
|
what are the general means by which microbes can escape/neutralize the inflammatory response
|
1. kill phagocytes by elaborating toxins
2. inhibit chemotaxis 3. prevent phagocytosis 4. survive (even grow) in the host inflammatory cell 5. sequester essential nutrients for growth 6. escape/avoid immune response 7. trigger host cells to take them in and shelter them from the immune response. |
|
these microbes prevent the fusion of the phagosome with the lysosome:
|
Toxoplasma gondii and Mycobacterium
|
|
what are 'siderophores'?
|
ways that microbes use to remove iron from iron-binding proteins in the body, which therefore assures that the microbe can have a continuous supply of a vital nutrient.
|
|
these microbes escape from the lysosome and live free in the cytoplasm
|
Rickettsiae, Listeria, and the Trypanasomes
|
|
what are some ways that microbes can escape/avoid the immune response?
|
1. cost themselves with host Ag
2. shed their Ag 3. modify their Ag 4. mask their Ag 5. kill immune cells |
|
what is Chediak-Higashi syndrome?
|
it involves defects in microtubules and cytoskeleton structure and function so that neutrophils can't more normally and can't release their lysosomal contents in teh proper manner
|
|
what two things are remarkable about the neutrophils of animals affected with Chediak-Higashi syndrome?
|
1. neutrophil granule are abnormally large due to an abnormal fusion of azurophil and specific granules
2. decreased in number |
|
what is wrong with animals affected with canine granulocytopathy syndrome?
|
they have normal phagocytosis, but intracellular killing impaired. this is because WBCs cannot generate a respiratory burst, and therefore cannot kill bacteria
|
|
what is another name for cyclic hematopoiesis
|
'gray collie syndrome'
|
|
what is wrong with animlas who have gray collie syndrome (cyclic hematopoiesis)
|
affect dogs have cyclic fluctuations in the production of all WBC types, with neutrophils the most severely affected. Every 10-11 days, their neutrophil counts in blood drop to zero.
|
|
which WBCs are the most affected by gray collie syndrome (cyclic hematopoiesis)
|
neutrophils
|
|
animals with gray collie syndrome (cyclic hematopoiesis) also tend to develop this:
|
amyloidosis (associated with chronic inflammation)
|
|
An animal is unable to form a whole family of membrane-bound molecules, including integrins and complement receptor by the neutrophil, macrophage, and lymphocyte... what inherited defect does the animal have?
|
Leukocyte Adhesion Deficiency
|
|
Leukocyte Adhesion Deficiency (LAD) has been identified in these creatures:
|
holstein calves and irish setter dogs (humans too)
|
|
Animals with Luekocyte Adhesion Deficiency (LAD) have these clinical signs:
|
1. impaired wound healing
2. recurrent bacterial infections without pus formation (often involving skin & gingiva) 3. marked neutrophilia and bone marrow hyperplasia |
|
Combined immunodeficiency CID is associated in a defect in ___ and ____
|
T Cells and B cells
|
|
animals with combined immnodeficiency are prone to respiratory disease, especially ___ and ____
|
pneumocystis
adenovirus infections |
|
Airedale terriers can have the immunodeficiency where they have a defect in ___ production, adn are therefore prone to discospondylitis
|
IgA
|
|
What immunodeficiency is seen in Gemrany shepard dogs, and what does it make the animal prone to?
|
decreased gastrointestinal IgA
makes them prone to bacterial overgrowth |