class notes 10 - flashcards

Flashcards about Inflammation

What is inflammation?

A coordinated response at the level of tissues or the body as a whole, not an individual cell's response.

Is inflammation the same as immunity?

Immunity is not the same thing as inflammation, and inflammation is not the same thing as an immune response.

What is the purpose of inflammation?

To destroy, dilute, or sequester the injurious agent and injured tissue, and to incite healing.

What is healing?

Repair of damaged tissue by regeneration (hyperplasia) or fibrosis.

What are the categories of stimuli that incite inflammation?

Physical injury, necrosis, infection, and errors of the immune system.

What are allergies?

Immune response to otherwise harmless environmental substances.

What is autoimmunity?

Immune response to self antigens.

What are the most effective treatments for inflammation associated with errors of the immune system?

To suppress the immune response or ameliorate the secondary inflammatory response.

What are adjuvants?

Compounds added to killed vaccines and toxoids to nonspecifically increase the body's immune response.

When are adjuvants seldom used and why?

Rarely used in live vaccines because living organisms tend to express a range of antigens for a sustained period.

What are selectins and sialylated Lewis X receptors?

Selectin adhesion molecules bind complementary receptor proteins on leukocytes that contain a complex sugar called “Lewis X” and a sialic acid moiety.

What are two examples of selectins?

P-selectin on platelets and E-selectin on endothelium.

What happens when sialyl Lewis X receptors on leukocytes contact selectin adhesion molecules on endothelium?

They slow leukocyte travel and initiate rolling.

What does P-selectin do?

It temporarily binds neutrophils to platelets, which permits transcellular metabolism to form lipoxins.

What do lipoxins do?

They inhibit leukocyte recruitment.

What inflammatory mediators stimulate the rapid expression of selectin molecules?

Histamine, thrombin, and Platelet Activating Factor (PAF).

What are CAMs?

Proteins which bind complementary receptors on leukocytes that are integrins.

What are integrins?

Protein dimers that are receptors for CAMs.

What are examples of CAMs?

Intercellular CAM (ICAM) and Vascular CAM (VCAM).

Give examples of CAM - integrin binding

ICAM on endothelium binds CD11/CD18 integrin on leukocytes and VCAM on endothelium binds á4â1 integrin on leukocytes.

How is the binding activity of Integrins and Cell Adhesion Molecules regulated?

Increased synthesis of CAMs after stimulation by the major inflammatory cytokines (TNF and IL-1) and conformational change of integrins on leukocytes in response to activation by chemokines.

Why is firm adhesion created by binding between integrins and CAMs important?

It is necessary for leukocyte emigration.

What do Leukocyte adhesion deficiencies result in?

Fewer leukocytes exiting blood vessels during an inflammatory response, and a corresponding increase in the frequency and severity of bacterial infections.

What are examples of Leukocyte Adhesion Deficiency?

Bovine Leukocyte Adhesion Deficiency (BLAD) in Holstein cattle and Canine Leukocyte Adhesion Deficiency (CLAD) in Irish Setters.

What are the sequence of events in inflammation?

Pain, vasodilation, vascular leakage, haemoconcentration and stasis, endothelial expression of sialyl-Lewis X (selectin) adhesion molecules, leukocyte margination, emigration of leukocytes, and secretion of chemokines.

What mediates rapid pain in inflammation?

Histamine and bradykinin.

What is responsible for sustained pain in inflammation?

Prostaglandins.

What causes rapid vasodilation?

Histamine and bradykinin.

What causes sustained vasodilation?

Prostaglandins and NO.

What mediates rapid vascular leakage?

Histamine and bradykinin.

What is the cause of sustained vascular leakage?

Complement C3a and C5a, PAF, leukotrienes, and leukocyte-induced endothelial damage.

What is haemoconcentration and stasis?

Fluid leakage from capillaries concentrates the erythrocytes and increases blood viscosity.

What does endothelial expression of sialyl-Lewis X adhesion molecules create?

Weak attachments between leukocytes and endothelium.

What results in leukocyte margination and pavementing?

Conformational change in leukocyte integrins and expression of complementary endothelial CAMs.

What are the steps of emigration of leukocytes out of the venules?

Extension of leukocyte pseupodia, attachment to PECAM integrins, digestion of basement membrane components, and migration towards chemotactic gradient.

What do secreted chemokines do?

Activate and attract specific types of leukocytes.

Regarding secreted chemokines, what is IL-8?

IL-8 is a chemokine for neutrophils that is secreted by endothelium and macrophages in response to IL-1 and TNF-á.

What does the first term in the morphological diagnosis of inflammation usually indicate?

Indicates the approximate duration of the process: acute, chronic, or subacute.

What does the second term in the morphological diagnosis of inflammation refer to?

Indicates the distribution of the lesion: focal, multifocal, or diffuse.

What does the third term in the morphological diagnosis usually indicate?

Indicates the character of the inflammatory exudate, such as suppurative, lymphocytic, plasmacytic, or granulomatous.

What does the fourth term in the morphological diagnosis combine?

Combines the location (organ) with an “-itis” suffix, indicating the presence of inflammation.

What is an example of a morphologic diagnosis of inflammation?

Acute diffuse suppurative enteritis.

Which types of leukocytes are generally the first to respond in acute (non-viral) inflammation or to necrosis?

Neutrophils.

Which cells are usually the first to respond to viral infections or autoimmune diseases?

Lymphocytes.

Which cells begin to appear a few days after the onset of inflammation from almost any cause?

Macrophages.

What are the two types of activated macrophages?

Epithelioid macrophages and giant cells.

Eosinophilic inflammation is highly suggestive of what type of response?

Helminths, arthropods, or allergens.

What do chemotactic factors do?

Stimulate leukocytes to migrate towards an increasing chemotactic gradient.

What do chemotactic factors include?

Foreign substances, chemical mediators, and chemokines.

What is neutrophil activation stimulated by?

Chemokines (IL-8) and chemical mediators (LTB4).

What does activation of nuetrophils result in?

Conformational change of integrin cell adhesion molecule, activation of Arachidonic Acid metabolic cascades, activation of the oxidative burst, and secretion of lysosomal enzymes.

What are the steps of phagocytosis?

Recognition and attachment, engulfment, and killing.

What does recognition and attachment usually require?

Usually requires opsonization (labelling an organism for removal).

What are the types of opsonins?

Collectins, complement component C3b, and IgG antibodies.

What occurs during engulfment?

Entrapment of organisms by pseudopodia and surrounding it within a primary phagocytic vacuole.

What occurs after the entrapment of an organism with pseudopodia?

Fusion of the primary phagocytic vacuole with lysosomes, called a secondary phagocytic vacuole or a phagolysosome.

What is the Chédiak-Higashi Syndrome?

An inherited defect in a gene that affects production and fusion of lysosomes with other membranes.

What are the two types of killing in phagocytosis?

Oxygen dependent and oxygen independent killing.

What causes the digestion of basement membranes during transmigration of phagocytes?

Elastase and metalloproteinases.

What does lysosomal leakage during phagocytosis cause?

Leaks acid hydrolases, free radicals, and hypochlorous acid.

What is preferable to necrosis in situ?

The drainage of exhausted leukocytes to lymph nodes followed by apoptosis.

How is nitric oxide (NO) produced by macrophages?

Action of inducible nitric oxide synthase (iNOS).

What are the initiating factors for hemostasis?

Collagen “contact activation” in intrinsic; tissue factor in extrinsic; Virchow's triad is damage to endothelium, altered flow (stasis or turbulence), & hypercoagulability.

What are the inhibiting factors in hemostasis?

AT-III, thrombomodulin, proteins S & C, PGI2, adenosine diphosphatase, and FDP's.

How is hemostasis degraded?

Plasmin chops fibrin.

Where do systems converge in hemostasis?

Intrinsic and extrinsic systems join at factor Xa. Hageman factor interacts with haemostatic, kinin, fibrinolytic, and complement systems.

Which cascades have linked reactions, each is stimulated under similar conditions and contributes to inflammation?

Haemostatic, kinin, fibrinolytic, and complement systems.

Which factor begins the intrinsic system of coagulation?

Factor XIIa (Hageman factor).

What is an inactive precursor in the plasma involved in inflammation?

High Molecular Weight Kininogen (HMWK).

What are the complement products important in inflammation and innate immunity?

C3a, C5a, C3b, and C5-9.

What are the initiating factors for Complement?

Classic pathway, alternate pathway and mannose-binding pathways

What are the necessary cofactors for Complement?

The alternative path needs properdin and factors B and D

Where is the site of convergence of classic and alternate paths in complement?

Forming C3a and C3b by splitting C3

How is Arachidonic acid created?

Membrane phospholipids are metabolized to arachidonic acid by phospholipases

Which is a potent anti-inflammatory drugs, in part because they block AA production?

Corticosteroids

Which can inhibit 5-Lipoxygenase (5-LO) and reduce LTB4 production?

Celecoxib

What are the two prostaglandins produced by the cyclooxygenase pathway that have opposing effects on platelets?

Prostacyclin (PGI2) and thromboxane (TXA2).

How do Nonsteroidal Anti-inflammatory Drugs (NSAIDS) inhibit COX enzymes?

Aspirin inhibits thrombosis because it reduces production of TXA2, NSAIDs relieve pain by reducing the synthesis of PGs and the associated pain and vasodilation

Systemic effects of infection include a what?

Series of responses called an acute phase reaction

Which chemicals mediate fever, together with inappetence and sleepiness?

IL-1, TNF, IL-6, and PGE2

What is a stress leukogram?

Neutrophilia and lymphopaenia

What are the increased plasma concentrations of acute phase proteins produced by the liver?

C-reactive protein (CRP), serum amyloid A (SAA) and serum amyloid P (SAP)

What can the outcome of inflammation include?

healing and granulation, stem cells and regenerative hyperplasia, specialised healing responses, and factors in wound healing.

Coordinated proliferation of fibroblasts with a rich bed of capillaries is called what?

Granulation

What growth factors promote fibroplasia and angiogenesis?

Fibroblast Growth Factors, Epidermal Growth Factor, Transforming Growth Factors, Platelet Derived Growth Factor, and Vascular Endothelial Growth Factors

What types of stem cells may facilitate regenerative hyperplasia?

Adult stem cells and embryonic stem cells.

What does an intact sarcolemmal tube provide?

A framework for the muscle’s satellite cells to enter the tube, proliferate, and form myofibrils.

What affects the rate and outcome of healing?

Nutritional status, movement of the wound, and overall health

What is healing by 1st intention?

Healing that occurs when wind edges are held together

What is healing by 2nd intention?

Healing that occurs in larger defects in which the wound cannot be closed with sutures

What issue arises in Horses when healing open wounds in distal limbs?

The exuberant healing response may create a raised protruding mass of red granulation tissue

Distinguish granuloma from granulation tissue.

A granuloma is a discrete area of granulomatous inflammation, not an area of granulation tissue

What is chronic inflammation caused by?

Persistent infection, failing immune system, sequested material, allergies, irritating exogenous compounds and autoimmune diseases.