5 Inflammation and Repair Part 2 Flashcards
What are the 2 major sources of chemical mediators?
- Cells (produced locally)
- plasma (Produced elsewhere)
What are the 2 types of chemical mediators that are produced by cells?
- Preformed (vasoactive amines)
- Newly synthesized (Prostaglandins and cytokines)
What are the chemical mediators within plasma (3)?
Complement, kinins and coagulation system
Where are many of the plasma chemical mediator produced? Where are they activated?
- Many produced in the liver
- Activated at the site of injury
What is the major preformed vasoactive amine? What cells secrete it? Where is it found?
- Histamine Secreted by mast cells
- Found in most tissues
What are the 3 major functions of histamine?
- Causes vasodilatation of arterioles
- increased venule permeability
- Prominent in allergic response, edema
What is a vasoactive amine found in platelets? What is its major function?
Serotonin Induces vasoconstriction during clotting
Arachidonic acid is considered a cell derived mediator. Where is it found in the cell? What activates it?
- Found in the cell membrane
- Activated by phospholipases
Regarding the arachidonic acid metabolites pathway, which enzyme is inhibited by steroids? Which is inhibited by NSAIDs?
- Phospholipases inhibited by steroids
- Cycloxygenase inhibited by NSAIDs
Regarding the cyclooxygenase pathway, what are the 2 major bioactive downstream products? What are their functions?
- Prostacyclin - vasodilation, platelet inhibition
- Thromboxane - vasoconstriction, platelet activation
What are the 2 major bioactive products of the lipoxygenase component of the arachidonic acid pathway? What are their functions?
Leukotrienes - Bronchospasm and increased vascular permeability
Lipoxins - Inhibit neutrophil adhesions and chemotaxis
What are the 4 mediators that are important for vasodilation?
PGI2, PGE1, PGE2 and PGD
What ae the 4 mediators that are important for vasoconstriction?
TXA2, Leukotrienes C4, D4 and E4
What are the cell derived mediators that increase vascular permeability?
Leukotrienes C4, D4 and E4
What are the cell derived mediators that promote chemotaxis and leukocyte adhesion?
Leukotriene B4 and HETE
What are the 4 major cytokines that are important for acute inflammation?
TNFIL-1IL-6 Chemokines
What are the 2 cytokines that are important for chronic inflammation?
Interferon gamma IL-12
TNF and IL1 are produced by what 3 types of cells?
- Activated macrophages
- Endothelial cells
- Mast cells
What is the major role of TNF and IL1?
Endothelial activation leading to increased permeability and expression of adhesion molecules
What are the 2 major functions of nitric oxide?
- Vasodilation
- Macrophage cytotoxicity
What are the sources of nitric oxide (2)?
- Endothelial cells (chronic low levels)
- Macrophages (inducible, plays a role in killing of microorganisms)
What are the 2 antiinflammatory roles of nitric oxide?
- Reduces leukocyte activity
- Reduces platelet adhesion
Nitric oxide is short lived or long lived?
Short lived, made as needed
True or false, nitric oxide is both proinflammatory and anti-inflammatory?
True
What is another name for Hageman factor? Under what conditions is it activated?
- Factor 12
- Activated by exposed collagen, basement membrane or activated platelets (endothelial injury)
From the point of view of activating inflammation, what 3 cascades does Factor 12 play a role in initiating?
Initiates the complement cascade, kinin and clotting
What are the 3 ways that complement is activated?
- Antibody antigen - Classical
- Microbial surface antigen - Alternative pathway
- Mannose binding lectin - Lectin Pathway
What component of the complement cascade important in chemoattraction?
C5a
What component of the complement cascade is important for opsonization? What about for cell lysis?
- Opsonization - C3b
- Cell lysis - MAC complex
Regardining the complement system, what are the 2 components that are important for vasodilation and permeability?
C3a and C5a
Regardining the complement system, what component is an important chemotactic agent for neutrophils?
C5a
Regardining the complement system, what 2 components act as opsonins (attach to bacterial cell wall and promote phagocytosis)?
C3b and C3bi
Regardining the acute inflammtory response, what are the three chemical mediators that cause vasodilation?
- Prostaglandins
- Nitric Oxide
- Histamine
Increased vascular permeability during acute inflammation is mediated by _ (5)
- Histamine
- Serotonin
- Complement
- Bradykinin
- Leukotrienes
Leukocyte emigration is mediated by _ (5)
- Complement components
- Leukotrienes
- Bacterial products
- Cytokines
- Chemokines
What are the 3 major mechanisms by which down regulation of acute inflammation occurs?
- Cessation of proinflammatory stimuli
- Anti inflammatory mediators
- Immunoregulatory processes
What are the 3 major anti-inflammatory mediators / mechanisms as referenced in the notes?
- Lipoxin
- Nitric Oxide
- Anti inflammatory cytokines (IL10, TGF-beta)
What are the 3 steps that have to occur for resolution of acute inflammation and what are responsible (where applicable)?
- Return of vascular permeability to normal
- Drain edema (lymphatics)
- Remove debris and neutrophils (macrophages)
An inflammation that goes on for weeks to years is termed _. What are the predominant cells?
- Chronic
- Macrophages and lymphocytes
What are 3 processes that may be occuring simultaneously during chronic inflammation?
- Active inflammation
- Tissue injury
- Attempts at healing
What are 2 reasons why an acute inflammation can progress to a chronic inflammation?
- Persistence of injurious agent
- Interference with normal healing
What are 2 forms of injury that engender a chronic inflammatory response from the onset?
- Immunological reactions
- Viral Infections
What are the 2 bone marrow precursors of macrophages? What do they called when they get into the blood?
- Stem cells and monoblasts ( in the bone marrow)
- In blood, they are monocytes
Where are macrophages activated?
-Reside in tissues, activated when needed there
What are the 2 means by which macrophages can become activated?
Classical and alternative methods
What are the 2 mediators of classical macrophage activation? What occurs after this type of activation?
- Microbes and IFN-gamma activate macrophages classically
- Leads to microbicidal activity (ROS, NO, lysozyme) and proinflammatory activity (IL1, IL12, IL23 and chemokine production)
What are the 2 molecules involved in alternative activation of macrophages? What are their source? What is the net effect of alternative activation of macrophages?
- IL13 and IL4 -Produced by T cells
- Net effect is tissue repair, scar formation and anti-inflammation
How do activated T cells and Activated macrophages interact? What is the net effect?
- Both feedforward to prolong and to maintain inflammation
- Increased accumulation of macrophages and lyphocytes in the tissues
What are the 3 mechanisms by which macrophages accumulate in tissues?
- Recruitment
- Local proliferation and division
- Cytokine driven immobilization at inflammation site
What was the example disease of chronic inflammation characterized by lyphocytic inflammation and fibroblast proliferation in the lung?
Chronic interstitial pneumonia
A distinctive pattern of chronic inflammation that is characterized by epithelioid macrophages is _. What are the 2 major causes of granuloma formation? What lymphocyte cell type is very involved in this process?
- Granulomatous inflammation
- Foreign body or immune system
- CD4+ T helper cells
What are 3 types of microbes that can causes granulomatous inflammation?
- Mycobacteria
- Parasites
- Yeast forms
A central core of highly activated macrophaes surrounded by lymphocytes, with multinucleated giant cells describes _
Granulomas
Multinucleated giant cells are associated with what type of process?
Granuloma formation
What is the stain type used to identify giant cells containing mycobacterium as seen in tuberculosis?
Acid fast stain
When a patient has an acute presentation of an inflammatory disease like lupus, what kinds of cells will mediate the reaction? Why?
- Lymphocytes and macrophages
- Even if acute, these are the cells that mediate immune mediated inflammatory disease
