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08 Pa Tho Physiology of Imunity
08 Pa Tho Physiology of Imunity
08 Pa Tho Physiology of Imunity
Hyposensitivity
1) Activity insufficient for protection of the body (immune deficiency)
Types of hypersensitivity
are differentiated by the sorce of the antigens against which the hypersensitivity is directed
A) Allergy
it has two facets: a) immune response which is benefitial b) hypersensitivity which is harmful
Definition: Deleterious effects of hypersensitive reactions to environmental (aerogenous) antigens expressed by disease
B) Autoimmunity
disturbance in the immunologic tolerance of self-antigens immune system reacts against self antigens by creating autoantibodies- autoimmune diseases
Autoimmune disease
With main manifestation in: Endocrine system
hyperthyroidism (Grave s disease) autoimmune thyroiditis primary myxedema (hypothyroidism)
diabetes mellitus-type 1 Addison disease male and female infertility idiopathic hypoparathyroidism partial pituitary deficiency
Skin
Neuromuscular tissues
dermatomyositis multiple sclerosis myasthenia gravis postvaccinal or postinfection encephalitis polyneuritis rheumatic fever (heart effects) cardiomyopathy
Gastrointestinal system
celiac disease (gluten-sensitive enteropathy) ulcerative colitis Crohn s disease atrophic gastritis primary biiary cirhosis antibodies against intrinsic factor
Connective tissue
ankylosing spondylitis rheumatic arthritis systemic lupus erythematosus polyarteritis nodosa (necrotising vasculitis) scleroderma (progressive systemic sclerosis)
Eye
Sjgren s syndrome Sj uveitis
Kidney
immune complex glomerulonephritis Goodpasture s syndrome (basement membrane of glomerulus)
Hematopoietic system
idiopathic neutropenia, lymphopenia autoimmune haemolytic anemia autoimmune thrombocytopenic purpura pernicious anemia
Respiratory system
Goodpasture s disease (interalveolar septas) Autoantibodies are also produced by healthy individuals, particularly by the elderly. This is one of the mechanisms responsible for the ageing process (due to a deterioration of tolerance to self-antigens) Yonger healthy individuals may produce autoantibodies without the development of overt autoimmune disease (reaction is weak)
Isoimmune disease
immune system of one individual produces an immune reaction against tissues of another individual, e.g. against transfused Er, grafted tissue, fetus during its intauterine life
Pathogenesis of hypersensitivity
it is not completly understood
Most diseases related to hypersensitivity evolve because of interaction of at least 3 variables: a) an original insult which alters immunologic homeostasis b) the individual s genetic makeup which determins susceptibility to the effects of the insult c) immunologic process that amplyfies the insult
Type II: Tissue specific reactions Type III: Immune-complexes mediated reactions Type IV: Cell-mediated reactions
Time corse of hypersensitivity reactions Immediate hypersensitivity reactions Delayed hypersensitivity reactions
within minutes
within sevral hours and days from the time of exposure to antigen
Type I hypersensitivity
1) Anaphylaxis
rapid and severe reaction developed within minutes
a) systemic (generalised):
itching, erithema, womiting, abdominal cramps, diarhea, breathing difficulties, laryngeal edema, angioedema, vascular collapse, shock, death
b) cutaneous (localised):
signes of local inflammation
3) Atopy Characteristics:
- it expresses the proneness to allergy - the atopic persons produce more than normal IgE and have more Fc receptors on their mast cells - subtle defect in T-Ly function (e.g. deficiency in IgE-specific supressor cells) may account for hightened IgE production
Type II hypersensitivity
Characteristics:
- destruction of target cells through the action of antibodies against an antigen on the surface of cell membrane
Explanation:
- in addition to HLA system most tissue have tissue specific antigens (TSA) = expressed only on the plasma membrane of certain type of cells - because of limited distribution of TSA, type II disease are limited to those tissue and organs that expresse the particular antigen
3)
Atb is bind to TSA Fc receptors on cytotoxic cells are able to recognize the antigen on the target cells p p binding of cytotoxic cells on target cells p p cytotoxic cells release of toxic substances p p lysis of target cells
4)
Atb is bind to TSA Atb occupy and alters receptors on target cellsp p blockade of normal ligands for these receptors p p changes in cellular functions - e.g. Grave s disease
ANt-Atb- harmful effect of ANt-Atb-C is caused by activation of complement and by attempt of NE-Le to ingest NEthese complexes p releasing of lysosomal enzymes p p tissue damage
Diseases caused by type III hypersensitivity Serum sickness (called according the foreign serum
used and symptoms and signs development) - general deposition of immune-complexes in blood vessels, joints, kydney - symptoms and signs: fever, enlarged lymphonodes, rash, pain
Rayanaud s phenomenon:
- temperature-dependent deposition of immune complexes in peripheral vessel (cryoglobulins)
Arthus phenomenon:
- example of localised immune-complexes-mediated inflammatory response. It developes due to repeated local exposure to exogenous antigen which reacts with preformed antibodies in the vessel wall
Type IV hypersensitivity
Characteristics:
- it is mediated by specifically sensitised T-Ly T- it does not involve antibodies - types of sensitised Ly ivolved in reaction: - cytotoxic T-Ly T- lymphokine-producing T-cells lymphokineT-
Pathologic processes induced by type IV hypersensitivity - graft rejection - tuberculin reaction - tumor rejection - reaction to contact with e.g. metals or ivy
Pathogenesis of hyposensitivity
This disorder results from deficiciences in immunity and leads to development of different clinical manifestations. These manifestations are the result of impaired function of one or more components of the immune system e.g. B-cells,T-cells, phagocytic cells, complement
Classification:
1) Congenital (primary) immune deficiency - due to genetic disorders 2) Acquired (secondary) immune deficiency - due to another illness-e.g. cancer, viral infection illness- due to physiologic changes- e.g. ageing changes-