Immune Mediated Flashcards
(16 cards)
Hypersensitivity type 1
Immediate, rapid immunologic reaction occurring in a previously sensitized individual that is triggered by the binding of an antigen to IgE antibody on the surface of mast cells.
Most immediate hypersensitivity disorders are caused by excessive TH2 responses and these cells play a central role by stimulating IgE production and promoting in am- mation. These TH2-mediated disorders show a characteris- tic sequence of events.
Hypersensitivity type 2
Antibody mediated
Antibodies that react with antigens present on cell sur- faces or in the extracellular matrix cause disease by destroying these cells, triggering in ammation, or inter- fering with normal functions. The antibodies may be speci c for normal cell or tissue antigens (autoantibodies) or for exogenous antigens, such as chemical or microbial pro- teins, that bind to a cell surface or tissue matrix.
Hypersensitivity type 3
Immune complex mediated
Antigen-antibody complexes produce tissue damage mainly by eliciting in ammation at the sites of deposi- tion. The pathologic reaction is usually initiated when antigen combines with antibody in the circulation, creating immune complexes that typically deposit in vessel walls. Less frequently, the complexes may be formed at sites where antigen has been “planted” previously (called in situ immune complexes). The antigens that form immune com- plexes may be exogenous, such as a foreign protein that is injected or produced by an infectious microbe, or endoge- nous, if the individual produces antibody against self antigens (autoimmunity).
Hypersensitivity type 3 pathology phases 3
I.c formation, deposition, inflammation and tissue injury
Hypersensitivity type 4
T cell mediated
The cell-mediated type of hypersensitivity is caused by in ammation resulting from cytokines produced by CD4+ T cells and cell killing by CD8+ T cells (Fig. 6-18). CD4+ T cell–mediated hypersensitivity induced by envi- ronmental and self antigens is the cause of many chronic in ammatory diseases, including autoimmune diseases (Table 6-5). CD8+ cells may also be involved in some of these autoimmune diseases and may be the dominant effector cells in certain reactions, especially those that follow viral infections.
Autoimmune diseases
tend to be chronic, sometimes with relapses and remissions, and the damage is often progressive
The clinical and pathologic manifestations of an auto- immune disease are determined by the nature of the underlying immune response.
SLE
autoimmune disease involving multiple organs, characterized by a vast array of autoantibodies, particu- larly antinuclear antibodies (ANAs), in which injury is caused mainly by deposition of immune complexes and binding of antibodies to various cells and tissues. The disease may be acute or insidious in its onset, and is typi- cally a chronic, remitting and relapsing, often febrile, illness. Injury to the skin, joints, kidney, and serosal mem- branes is prominent. Virtually every other organ in the body, however, may also be affected.
the disease is very heterogeneous, and any patient may present with any number of these clinical features. SLE is a fairly common disease, with a prevalence that may be as high as 1 in 2500 in certain populations. Similar to many autoimmune diseases, SLE predominantly affects women
SLE hallmark
Production of autoantibodies
ANAs- antinuclear antibodies
SLE etiology
The fundamental defect in SLE is a failure of the mecha- nisms that maintain self-tolerance. Although what causes this failure of self-tolerance remains unknown, as is true of most autoimmune diseases, both genetic and environmen- tal factors play a role.
SLE mechanism of tissue injury
Mostly type 3 hypersensitivity. Systemic lesions cause by immune complexes deposition
Systemic sclerosis
commonly called scleroderma) is char- acterized by progressive brosis involving the skin, gastro- intestinal tract, and other tissues.
Fibrosis may be the result of activation of broblasts by cytokines produced by T cells, but what triggers T-cell responses is unknown.
■ Endothelial injury and microvascular disease are com- monly present in the lesions of systemic sclerosis, perhaps causing chronic ischemia, but the pathogenesis of vascu- lar injury is not known.
Polyarteritis nodosa
Polyarteritis nodosa belongs to a group of diseases charac- terized by necrotizing in ammation of the walls of blood vessels and showing strong evidence of an immunologic pathogenetic mechanism. The general term noninfectious vasculitis differentiates these conditions from those due to direct infection of the blood vessel wall (such as occurs in the wall of an abscess) and serves to emphasize that any type of vessel may be involved—arteries, arterioles, veins, or capillaries.
The pathogenesis of this condition is not understood, and although IgG4 production in lesions is a hallmark of the disease it is not known if this antibody type contributes to the pathology. The key role of B cells is supported by initial clinical trials in which depletion of B cells by anti–B cell reagents such as rituximab provided clinical bene t. It is unclear if the disease is truly autoimmune in nature, and no target autoantigens have been identi ed.
Amyloidosis
condition associated with a number of inherited and in ammatory disorders in which extracel- lular deposits of brillar proteins are responsible for tissue damage and functional compromise. These abnormal fibrils are produced by the aggregation of misfolded proteins (which are soluble in their normal folded configuration ration). The brillar deposits bind a wide variety of pro- teoglycans and glycosaminoglycans, including heparan sulfate and dermatan sulfate, and plasma proteins, notably serum amyloid P component (SAP).
Amyloid is deposited in the extracellular space in various tissues and organs of the body in a variety of clini- cal settings.
AL amylodosis
The AL (amyloid light chain) protein is made up of complete immunoglobulin light chains, the amino- terminal fragments of light chains, or both. Most of the AL proteins analyzed are composed of λ light chains or their fragments, but κ chains are present in some cases. The amyloid bril protein of the AL type is produced from free Ig light chains secreted by a monoclonal popu- lation of plasma cells, and its deposition is associated with certain forms of plasma cell tumors
AA amyloidosis
The AA (amyloid-associated) type of amyloid bril protein is derived from a unique non-Ig protein made by the liver. It has a molecular weight of 8500 and con- sists of 76 amino acid residues. AA brils are derived by proteolysis from a larger (12,000 daltons) precursor in the serum called SAA (serum amyloid-associated) protein that is synthesized in the liver and circulates bound to high density lipoproteins. The production of SAA protein is increased in in ammatory states as part of the acute phase response; therefore, this form of amy- loidosis is associated with chronic in ammation, and is often called secondary amyloidosis.
Abeta amyloidosis
β-amyloid protein (Aβ) constitutes the core of cerebral plaques found in Alzheimer disease as well as the amyloid deposited in walls of cerebral blood vessels in individuals with this disease. The Aβ protein is a 4000- dalton peptide that is derived by proteolysis from a much larger transmembrane glycoprotein, called amyloid precursor protein. This form of amyloid is discussed in Chapter 28.
