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Unit 3 Autoimmunity Part 1 Introduction. Terry Kotrla, MS, MT(ASCP)BB. Tolerance. Do not mount immune response to “self” antigens. Term “self-tolerance”. Immune system constantly challenged to discriminate between self and non-self and make the right choice.
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Unit 3 AutoimmunityPart 1 Introduction Terry Kotrla, MS, MT(ASCP)BB
Tolerance • Do not mount immune response to “self” antigens. • Term “self-tolerance”. • Immune system constantly challenged to discriminate between self and non-self and make the right choice. • Under normal circumstances immune system will not destroy self antigens.
Autoimmunity • Autoimmunity can be defined as breakdown of mechanisms responsible for self tolerance and induction of an immune response against components of the self. • Autoimmune disease occurs when the immune system attacks self-molecules as a result of a breakdown of immunologic tolerance to autoreactive immune cells.
Autoimmune Response • Antibody directed against “self”, termed auto-antibody • Considered abnormal but usually does not result in disease. • May occur in healthy individuals.
Autoimmune Disease • Disorder in which tissue injury is caused by an immunologic reaction of the host to its own tissues. • Precise mechanisms unknown. • Comprising multiple disorders and symptoms ranging from organ-specific to systemic.
Proposed Mechanisms • Many mechanisms postulated. • The following will be discussed: • Forbidden clone • Altered antigen • Sequestered Antigen • Immunologic deficiency theory • Genetic influence
Forbidden clone • Clone of changed or altered lymphocytes arise through mutation. • Lack foreign surface antigens, not destroyed. • Because of alteration may recognize host as foreign. • May be cause of increased incidence of autoimmune disease in elderly.
Altered Antigen • Surface antigens on host altered by chemical, biological or physical means. • This new antigenic determinant may be recognized as foreign by the host.
Sequestered Antigen • Some antigens in the body are hidden from cells of the immune system. • If there is damage to these organs causing exposure of these sequestered antigens an immune reaction to these antigens may occur.
Immunologic Deficiency Theory • Relates the increased frequency of auto-antibodies and increased immune system deficiency to age. • Mutation or loss of immune regulatory powers results in the condition in which self antigens behave as foreign antigens.
Genetic Influence • It is well recognized that certain immune disorders predominate in females and in families. • Determined by family studies. • Genetic links have occurred between diseases and HLA antigens
Contributing Factors • Defects in the immune system. • Influence of hormones • Environmental conditions
Classification of Autoimmune Diseases • Systemic- the auto-immunity is directed against an antigen that is present at many different sites and can include involvement of several organs • Organ specific - Organ specific means the auto-immunity is directed against a component of one particular type of organ. • Both – can get overlap • Excellent chart on classification: http://tinyurl.com/3a7oas3
Diagnosis • Symptoms • Detection of antibodies reactive against antigen of tissues and cells involved. • Tests may involve • Immunofluorescence • ELISA • RIA • Agglutination