Chapter 28 Autoimmune Disorders
Behavioral Objectives At the end of this lecture, the MLS and MLT student will be able to: Define tolerance Describe mechanisms for autoimmunity MLS MLT Describe Proposed mechanisms of autoimmunity (Level 1) Describe proposed mechanisms of autoimmunity (Level 1) 1. Release of sequestered antigens - 2. Escape of tolerance at the T cell level
The MLS and MLT students will be able to: Describe the clinical symptoms and lab findings of classic autoimmune diseases: Systemic Lupus erythematosus Graves Disease Rheumatoid arthitis Addison’s Disease Diabetes mellitus
What is Autoimmunity? The breakdown of the immune system’s ability to discriminate between self and non-self; the body’s immune system therefore mounts immune reaction (i.e. produce antibodies) against self antigens with harmful effects to the individual
Self-Recognition (Tolerance) Tolerance- or self-recognition- is the lack of immune response to self antigens and is initiated during fetal development. This is our normal state of being- our immune system tolerates proteins and antigens that belong to us (self). Central tolerance- develops in thymus during fetal life- Peripheral tolerance- a process involving mature lymphocytes and occurs in circulation.
Auto-antibodies and Role Not all autoantibodies are bad or cause disease Normal function of Autoab- binds with certain antigen to rid of dead cells and defective self-antigens; form complexes which are then rid of from the body For autoimmune disorder to occur, autoantibodies must be present and damage to organ/s.
Spectrum of Autoimmune Disorders Over 80 serious chronic diseases All characterized by the immune system that has gone awry or misdirected. The immune system is always being activated Unable to recognize the self that it was supposed to protect- instead it attacks it. Autoantibody- immunoglobulins in autoimmune disorders Autoantigens- specific antigens being attacked
Factors Influencing Development of Autoimmunity Genetic Factors- not well established, but certain genetic predisposition in some cases- Autoimmune disorders more likely in women than men Presence of certain HLA Patient Age- 60-70 years peak age Exogenous Factors- drugs, ultraviolet radiation, chronic infectious disease
Immunopathogenic Mechanisms 1. Sequestered antigen or Hidden antigen theory Certain antigen are hidden within the organ, escapes the detection by the immune system during fetal development- (lack of contact with monophagocyte system, :. No tolerance was developed for it. However, when the antigen escapes to the circulation (e.g due to trauma), the immune system now detects this and sees it as foreign.
Mechanisms for Autoimmunity, con’t: 2. Altered antigens- that arise from biological, chemical or physical processes 3. A foreign antigen- shared or cross-reactive with self antigens or tissue components Mutation Loss of the immunoregulatory function by the T lymphs subsets
Systemic Lupus Erythematosus (SLE) - antibodies directed against T lymphs Grave’s disease- antibodies against thyroid Rheumatoid Arthritis (RA)- antibodies against joints Addison’s disease- antibodies against cortical elements Diabetes mellitus- (IDDM)- antibodies against pancreatic Beta cells
Select Autoimmune Disorders we will study Organ Specific Disorders Thyroid- Hashimoto’s; Graves disease Stomach – Pernicious anemia Adrenal- Addison’s disease Pancreas- Juvenile diabetes Organ-Non-Specific Disorders Kidney- Systemic Lupus erythematosus Joints- Rheumatoid arthritis Organ-specific – lesions and autoantibodies are directed against one target organ (e.g. Thyroid) Midsprectrum– characterized by localized lesion in a single organ and by organ non-specific autoantibodies Some overlap occur between clinical and serologic occur.
Hashimoto’s Disease Symptoms Lab Findings Autoimmune disease of the thyroid gland Damage to the thyroid is mediated b y producing autoantibodies against the thyroid proteins –notably the thryroglobulins and thyroperoxidase Hypothryoidism- dry skin, intolerance to cold temp. fatigue, weight gain. Hypothyroidism with bouts of hyperthryoidism Testing for thyroid-stimulating hormone (TSH) Free T3, Free T4, Antibodies against: a. thyroglobulin anti-Tg) thyroid peroxidase(anti-TPO) microsomal antibodies
Grave’s Disease Symptoms Clinical Findings Too much thyroid hormone Hyperthryroidism When TSH receptor antibody occupies the receptor sites , there is no negative feedback resulting in increased levels of T3 and T4 Antigens implicated: Thyrothropin receptor; Thyroid peroxidase; Thyroglobulin Due to autoantibodies that mimic TSH
Addison’s Disease Clinical Findings Symptoms Clinical Findings Also called chronic adrenal insufficiency; hypocorticolism, hypoadrenalism Adrenal atrophy- idiopathic autoimmune process Women- 2x more affected than men HLA class II antigens DR3 and DR4 against cortical elements Antibodies against adrenal cells Low serum Cortisol with elevated corticotropin Antibodies
Diabetes mellitus Symptoms – High blood sugar Clinical Findings Type 1; Insulin-dependent diabetes mellitus (IDDM); juvenile onset diabetes; diabetes before 30- IDDM Immune destruction of B cells in pancreas Congenital Rubella infection Associated with HLA-DR3, DR4, DQ2, DQ8 antigens Exogenous insulin injections- to maintain normal blood sugar level Antibodies: anti-insulin, anti-islet cell antigen 2
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) symptoms Lab findings Tests used to diagnose SLE: �Antibody tests, including: �Antinuclear antibody (ANA) panel �Anti-double strand (ds) DNA �Antiphospholipid antibodies �Anti-Smith antibodies SLE - chronic autoimmune disorder that may affect the skin, and other organs Inflammation and B cell activation. Characteristic “butterfly rash” of the face Joint pain and swelling
Rheumatoid Arthritis (RA) symptoms Clinical findings Chronic Inflammation of the peripheral joints- Lab testing- ESR RF - IgM marker ANA- antinuclear antibodies - TITERS OF > 1:160 is indicative of autoimmune disease
Review Questions 1-4