chapter 28 autoimmune disorders. behavioral objectives at the end of this lecture, the mls and mlt...
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Chapter 28
Autoimmune Disorders
Behavioral ObjectivesAt the end of this lecture, the MLS and MLT
student will be able to:Define toleranceDescribe mechanisms for autoimmunity
MLS MLT
Describe Proposed mechanisms of autoimmunity (Level 1)
Describe proposed mechanisms of autoimmunity (Level 1)
1. Release of sequestered antigens
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2. Escape of tolerance at the T cell level
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The MLS and MLT students will be able to:Describe the clinical symptoms and lab
findings of classic autoimmune diseases:Systemic Lupus erythematosusGraves DiseaseRheumatoid arthitisAddison’s DiseaseDiabetes 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 RoleNot all autoantibodies are bad or cause
diseaseNormal 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
activatedUnable to recognize the self that it was
supposed to protect- instead it attacks it.Autoantibody- immunoglobulins in
autoimmune disordersAutoantigens- 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 HLAPatient Age- 60-70 years peak ageExogenous Factors- drugs, ultraviolet
radiation, chronic infectious disease
Immunopathogenic Mechanisms
1. Sequestered antigen or Hidden antigen theoryCertain 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 processes3. A foreign antigen- shared or cross-
reactive with self antigens or tissue components
MutationLoss of the immunoregulatory function
by the T lymphs subsets
Systemic Lupus Erythematosus (SLE) - antibodies directed against T lymphs
Grave’s disease- antibodies against thyroidRheumatoid Arthritis (RA)- antibodies
against jointsAddison’s disease- antibodies against
cortical elementsDiabetes mellitus- (IDDM)- antibodies
against pancreatic Beta cells
Select Autoimmune Disorders we will study
Organ Specific DisordersThyroid-
Hashimoto’s; Graves diseaseStomach –
Pernicious anemia
Adrenal- Addison’s disease
Pancreas- Juvenile diabetes
Organ-Non-Specific DisordersKidney- Systemic
Lupus erythematosus
Joints- Rheumatoid arthritis
Hashimoto’s DiseaseSymptoms 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 DiseaseSymptoms Clinical Findings
Too much thyroid hormoneHyperthryroidism
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 DiseaseSymptoms 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 DR4against cortical elementsAntibodies against adrenal
cells
Low serum Cortisol with elevated corticotropin
Antibodies
Diabetes mellitusSymptoms – High blood sugar
Clinical Findings
Type 1; Insulin-dependent diabetes mellitus (IDDM); juvenile onset diabetes;
diabetes before 30- IDDMImmune destruction of B
cells in pancreasCongenital Rubella
infectionAssociated 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
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
Tests used to diagnose SLE:�Antibody tests,
including:�
Antinuclear antibody (ANA) panel
�Anti-double strand (ds) DNA
�Antiphospholipid antibodies
�Anti-Smith antibodies
Rheumatoid Arthritis (RA)
symptoms Clinical findings
Chronic Inflammation of the peripheral joints-
Lab testing-ESRRF - IgM markerANA- antinuclear
antibodies - TITERS OF > 1:160 is
indicative of autoimmune disease
Review Questions1-4