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62 Cards in this Set
- Front
- Back
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What is inflammation?
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The term used to describe the events that either occur locally, following a trauma or infection and leading to redness, heat, edema and pain.
They can also occur systemically, generally following the release of chemical mediators from the local reaction. |
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Which types of infections is the accumulation of pus observed in?
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Local infections
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What causes heat and redness?
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Reflects increased blood flow (vasodilation) and red blood cell extravasation.
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What causes Edema ?
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caused by the leakage of fluid from the circulation into tissues (increased vascular permeability)
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What causes Pain?
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result of stimulation of nerve endings by bradykinin.
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What is the cause of pus?
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the accumulation of dead phagocytes and bacteria along with byproducts of tissue destruction.
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What are the classical inducers of inflammation?
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- Tissue damage
- Microbial infections - Toxic agents |
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What do the Inflammation inducers activate?
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1. The Complement System
2. Mast cell degranulation 3. The Blood Coagulation Contact System, leading indirectly to bradykinin production 4. Macrophages. |
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What causes the diapedesis of leukocytes at the site of infection?
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1. The Complement System
2. Mast cell degranulation 3. The Blood Coagulation Contact System, leading indirectly to bradykinin production 4. Macrophages. |
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What are the biological changes that culminate in the diapedesis of leukocytes?
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1. Secretion of chemokines and cytokines
2. Generation of inflammatory mediators 3. Altered expression and/ or enhanced affinity of adhesion molecules 4. Increased vascular permeability 5. Localized degradation of the basement membrane 6. Extravasation of neutrophils, monocytes and lymphocytes from the circulation. |
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What is increased blood flow to a certain area caused by?
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Vasodilatation
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Bacterial or necrotic tissue phagocytosis begins the release of cytokines and chemokines, which three things do cytokines IL-1 and TNF do to endothelial cells?
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1. Express E-selectin
2. Secrete IL-8 and MCP-1 (chemokines) 3. Up-regulate expression of ICAM-1 and VCAM-1. |
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After damage to the skin causes a wound, what is activated? What is the function?
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The contact system is activated and it generates bradykinin and C5a.
Bradykinin increases vascular permeability (also causes pain). C5a - induce degranulation of mast cells = release histamine = vasodilation |
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Which 3 mediators lead to vasodilation?
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histamine, leuktriene B4, Bradykinin
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What causes the release of histamine? What are its 2 affects?
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Released by complement activation C3a, C4a and C5a.
- Increases vascular permeability - Induces expression of P-selectin. |
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What is diapedesis?
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Transmigration of leukocytes into tissue.
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Name three functions of leukocytes that allow them to enter the tissue area of damage:
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1. Leukocyte rolling
2. Firm Adhesion 3. Diapedesis |
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What is the first responder to a primary infection?
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Macrophage
-it's already in the tissue |
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What is the function of Leukotriene B4?
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Vasodilatation
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What are the steps involved in the generation of Bradykinin?
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1. Factor XII is converted to Factor XII(a) by Kininogen.
2. Prekallikrein is converted to kallikrein by Factor XII(a). 3. Kallikrein cleaves kininogen into Bradykinin |
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What is the result of histamine’s actions of vasodilatation and contraction of the endothelial cells in capillary beds and postcapillary venules?
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This produces an increase in vascular permeability and is associated with edema.
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Where are IgEs bound to on mast cells?
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FcεR receptor.
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What happens if an antigen binds to the mast cells IgE?
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The mast cell degranulates releasing histamine, leukotrienes C4, D4 and E4 (LTC4, LTD4 and LTE4).
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What activates the Coagulation pathway contact system?
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Tissue damage.
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Name the four proteins that the contact system is composed of:
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Factor XII
Factor XI Prekallikrein Kininogen |
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Where does Factor XII bind to and become enzymatically active?
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Binds to Collagen exposed in damaged tissue.
Platelet membranes. |
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Kellikrein
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activates neutrophils
- cleaves kinnogen → bradykinin and C5 → C5a + C5b |
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C5a
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- anaphylatoxin
- binds to receptors on basophil and mast cell - induce degranulation of mast cell release |
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What is present on Neutrophils that binds to the endothelium? What is present on monocytes?
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Neutrophils – LFA-1 and Mac-1
Monocytes – VLA-4, LFA-1 and Mac-1. |
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Where is L-Selectin present? What is its function?
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Naïve lymphocytes, monocytes and neutrophils.
Regulates cell trafficking during non-inflammatory states. |
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What is the function of metalloproteinases?
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- degrade basement layer to allow migration.
- secreted by macrophages |
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What inhibits metalloproteinases?
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Tissue Inhibitors of matrix metalloproteinase
- also secreted by macrophages |
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Where are P- and E- Selectins expressed? When?
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On post-capillary venules.
During inflammatory states. Not expressed on circulating cells |
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What causes the expression of P-Selectin?
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It is translocated to the plasma from cytoplasmic stores, induced by Histamine.
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What causes the expression of E-Selectin?
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Cytokines derived from activated macrophages (TNF, IL-1) and requires de novo protein synthesis.
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What is the purpose of leukocyte rolling?
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Prolongs the duration of time to which leukocytes are exposed to chemoattractants and activators secreted into the inflammatory microenvironment
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What is the classification of integrins based on?
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The beta chain that they express.
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What is the plieotropic activity of the cytokines TNF and IL-1?
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Stimulate endothelial cells to express adhesive molecules E-Selectin and VCAM-1 as well as to secrete the chemokines IL-8 and MCP-1
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What is the function of IL-8?
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It induces the increased adhesiveness of B2 integrins, LFA-1 and Mac-1 as well as shedding of L-selectin.
chemotactic for neutrophils |
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What are MCP-1 and RANTES chemotactic for?
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Monocytes and lymphocytes.
(NOT Neutrophils) |
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What is chemotactic for neutrophils?
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IL-8
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What causes a fever?
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IL-1 and TNF acting on the hypothalamus.
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What causes the low bp in shock?
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Vasodilatation caused by IL-1 and TNF.
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How is Gelatinase B secreted? Activated?
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Secreted as a zymogen, pro-gelatinase B, and is activated following limited proteolysis with elastase or other endopeptidases.
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What does the first (primary) exposure to an antigen in secondary lymphoid tissues lead to?
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Differentiation of CD4+T cells and B cells into effector cells.
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What is the role of Type I Cytokines? What is the role of Type II Cytokines?
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Type 1 cytokines are IL-2, IFNγ and TNF. IFNγ is a potent activator of macrophages by the CD40L(Tcell)/CD40(monocyte) interaction.
Type 2 cytokines are IL-4, IL-10 and TGFβ; they dampen the development of Th1 responses. Roles include elimination of microbes, tissue healing and shedding of adhesion molecules that competitively inhibit leukocyte binding to counter-molecules on the endothelium. |
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What does IL-6 secrete?
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C Reactive Protein
- induces E-selectin, VCAM-1, ICAM-1 |
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Platelet Activating Factor (PAF)
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- in early phase of inflammation = serve as potent chemoattractant, activator of neutrophils
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What do secretin bind to?
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specific carbohydrates on glycoprotein
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Integrin
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- Firm Adhesion
- high affinity integrin - heterodimeric α & β polypeptides - β chain determines tissue specificity |
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Gelatinase B
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- zinc binding metalloproteinase
- degrades type IV collagen - secreted as pro-gelatinase, activated by cleavage to Gelatinase B |
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MMP-2/MMP-9
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MMP-2 = pro-gelatinase A
- induces secretion in inflammation MMP-9 = pro-gelatinase B - enhanced by Vasoactive Intestinal Peptide or VLA-4 |
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β1 integrins
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- expressed on monocytes of memory lymphocytes
- VLA-4 (α4β1) - Counter molecule = VCAM-1 |
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β2 Integrin
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- present in low affinity
- stimulated by IL-8, TNF, IL-1 - Expression by lymphocytes, monocytes, neutrophils - LFA-1 (αLβ2) Countermolecule = ICAM-1 and ICAM-2 - Mac-1 (αMβ2) - all the M's - Countermolecule = ICAM-1 |
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β7 Integrin
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- expression of memory T-cells
- LPAM (α4β7) - countermolecule = VCAM-1 |
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C-reactive protein
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- secreted by IL-6
- serves as an opsonin for enhanced phagocytosis of bacteria |
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What is the mortality rate for SIRS?
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50%
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Which complement pathway generates anaphylatoxins C3a C5a?
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Both classical and alternative
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What rxn does factor XII catalyze?
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Prekallikrein → Kallikrein
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What do selectins bind to?
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Carbohydrate molecules
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Which cells express L-selectins?
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Naïve lymphocytes, monocytes neutrophils
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Where are P/E selectins expressed?
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Endothelium of postcapillary venules during inflammation (not on circulating cells)
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