1. Chapter 28
Autoimmune Disorders

2. 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

3. 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

4. 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

5. 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.

6. 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.

7. 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

8. 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 years peak age
Exogenous Factors- drugs, ultraviolet radiation, chronic infectious disease

9. 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.

10. 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

11. 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

12. 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.

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. Review Questions
1-4