Acute Inflammation

Acute Inflammation

Some Terms to Understand

Acute inflammation = a stereotyped response to recent or ongoing injury. Although the process is complex, the principal features are dilatation and leaking of vessels, and involvement of circulating neutrophils.

Chronic inflammation ("late-phase inflammation") = a response to prolonged problems, orchestrated by T-helper lymphocytes. It may feature recruitment and activation of T- and B-lymphocytes, macrophages, eosinophils, and/or fibroblasts. Again, the process is complex. You will recognize lymphocytes in tissue section by their small, "blue button" nuclei.

Granulomas are seen in certain chronic inflammation situations. They are clusters of macrophages that have stuck tightly together, typically to wall something off. Such macrophages are called epithelioid cells. You will recognize granulomas in tissue sections by their characteristic appearance, or the presence of giant cells.

Fibrin is fibrinogen released from damaged vessels, and activated by the clotting cascades when blood meets tissue juices. Fibrin forms the meshwork that controls bleeding, and then becomes the framework for fibroblasts and angioblasts that will form the scar. Until the new scar is complete, the whole meshwork of immature scar is called granulation tissue. When the scar has matured, it contracts.

Inflammation Overveiw
Chemical & Cellular Mediators
Acute vs Chronic Inflammation
Causes of Inflammation
Clinical Signs
Microscopic features of inflammation
Mechanisms of - Vascular Permeability
Chemotaxis (migration along a chemical gradient)
Cellular Events
Phagocytosis
Chemical Mediators of inflammation
Vasoactive Amines
Histamine
Complement System
Kinin System, Coagulation System & Fibrinolytic System
Kinin System Activation
Coagulation (Clotting) System
Fibrinolytic System
Arachidonic Acid Metabolites
Platelet-Activating Factor
Cytokines
Cellular Mediators
Reaction to Acute Inflammation

Acute Inflammation.ppt

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Amyloid: Amyloidosis

Amyloid: Amyloidosis


Definition
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Amyloidosis is a clinical disorder caused by extracellular deposition of insoluble abnormal fibrils that injure tissue. The fibrils are formed by the aggregation of misfolded, normally soluble proteins. In humans, about 23 different unrelated proteins are known to form amyloid fibrils in vivo. All types of amyloid consist of a major fibrillar protein that defines the type of amyloid (approximately 90%) plus various minor components. Although each type of fibril may be associated with a distinct clinical picture, all share certain physical and pathologic properties, as follows:

* Amorphous eosinophilic appearance on light microscopy after hematoxylin and eosin staining
* Bright green fluorescence observed under polarized light after Congo red staining
* Regular fibrillar structure as observed by electron microscopy
* Beta pleated sheet structure as observed by x-ray diffraction
* Solubility in water and buffers of low ionic strength

* Amyloid

= insoluble fibrous protein aggregations that share specific structual traits
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* Amyloidosis

= abnormal deposition of amyloid proteins in tissues or organs ? cause disease

* Histological Definition
* extracellular proteinaceous deposits exhibiting cross-beta structure due to misfolding of unstable proteins
* stains with Congo-Red & seen under polarised light

* Biophysical Definition
* Any polypeptide which adopts a cross-beta polymerization (in vivo or in vitro)
* Some may fail congo red birefringence test
* Characterised by cross-beta quaterny structure


Recognition of Amyloid
Biochemical Nature of Amyloid
Biochemical Classification of Amyloid
Clinical Classification of Amyloidosis
Pathogenesis of Amyloid
Immunocytic Dyscrasias with Amyloid
Reactive Systemic Amyloidosis
Familial Amyloidosis
Familial Mediteranean Fever
Localised Amyloidosis

* Amyloid deposits limited to single organ or tissue.
* Deposits may produce grossly detachable nodular masses or be evident only on microscopic investigation.
* Nodular deposits of amyloid most often found in lung, larynx, skin, bladder, tongue & region around the eye.
* Frequently there are infiltrates of lymphocytes and plasma cells in the periphery of amyloid masses.
* Some cases consists of AL protein, and may therefore represent a localized form of immunocyte-derived amyloid.

Amyloid of Ageing
Clinical Effect on Spleen
Nodular Distribution
Clinical Effect on Kidney
Clinical Effect on Liver
Clinical Effect on GIT
Diagnosis & Prognosis

Amyloid: Amyloidosis.ppt

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Autoimmune Disorders

Autoimmune Disorders

Classification of Autoimmune Diseases
Local single organ
Probable:

* Hashimoto thyroidistis
* Autoimmune haemolytic anaemia
* Autoimmune atrophic gastritis (pernicious anemia)
* Autoimmune encephalomyelitis
* Autoimmune orchitis
* Goodpasture syndrome
* Autoimmune thrombocytopaenia
* Type I DM (IDDM)
* Myasthenia gravis
* Graves disease

Possible:

* Primary biliary cirrhosis
* Chronic active hepatitis
* Ulcerative colitis
* Membranous glomerulonephritis

Systemic multiple sites

Probable:

* Systemic Lupus Erythematosus
* Rheumatoid arhtritis
* Sjogren’s syndrome
* Reiter syndrome
* Inflammatory myopathy
* Systemic sclerosis (scleroderma)
* Polyarteritis nodosa

Immunological Tolerance

* State in which an individual is capable of developing an immune response against a specific antigen
* Self- tolerance specifically refers to a lack of immune responsiveness to one’s own tissue antigens
* Immunologically competent cells learn to recognize the body’s own antigens at an early stage
* Central vs peripheral tolerance

Central Tolerance
Clonal deletion
Peripheral Tolerance
Apoptosis
Peripheral suppression
Failure in Tolerance

* Failure in activation-induced cell death (apoptosis)
* Breakdown of T-cell anergy
* Bypass of B-cell requirement for T-cell help
* Failure in T-cell mediated suppression
* Polyclonal lymphocyte activation
* Release of sequestered antigens
* Exposure of cryptic self & epitope speading
* Normally maintained in isolation from immune mechanisms
* Hidden/sequestered antigens may not be recognised as self (such as intracellular substances)
* E.g spermatazoa; myelin protein; lens material



Breakdown of T-cell helper tolerace
T-cell suppressor function
Genetics
Infection
Autoimmune Disorders & Mechanisms
General Pathology
Immunological Antibodies & HLA
Rheumatoid Factor
Antinuclear Antibody
Pansma autoantibodies & Disease Association
Human Leukocyte Antigen (HLA)
HLA – B27

Autoimmune Disorders.ppt

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