1. AUTOIMMUNE DISEASES

2. AUTOIMMUNITY
Autoimmune disease occurs when a specific adaptive immune response is reacted against self antigens.
 In humans, autoimmunity usually arises spontaneously; that is, we do not know what events initiate the immune response to self that leads to the autoimmune disease.

3. Immune tolerance
Immune tolerance or immunological tolerance, or immunotolerance, describes a state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response.

4. Tolerance
Central tolerance – deleting T or B clones before maturity if they have receptors that recognize self- antigens with great affinity
Peripheral tolerance – kills lymphocytes in secondary lymphoid tissue
Also, life span of lymphocytes regulated by apoptosis

7. Development of Autoimmune Disease
Autoimmune disease occurs as a result of breakdown in tolerance to self
Autoimmune disease is characterized by immune system “attack” against self antigens that lead to tissue damage
The attack can be either humoral (by auto- antibodies) or cellular (by auto-reactive T cells).
The attack can be directed either against a very specific tissue, or to a large number of tissues (systemic autoimmune disease), depending on the self-antigen which is attacked.

8. Molecular Mechanisms of Autoimmunity
Cross-reactivity (Molecular and Viral Mimicry)
Viral and nonviral peptides can mimic self-peptides and induce autoimmunity
Example: papilloma virus (HPV) and insulin receptor

9. Cross-Reactivity

10. Molecular Mechanisms of Autoimmunity
Release of Sequestered Antigen
Antibodies in blood can attack Myelin Basic Protein if Blood- Brain barrier is breached.

11. Molecular Mechanisms of Autoimmunity
Inappropriate MHC expression
Type I Diabetes: Pancreatic β cells express abnormally high levels of MHC I and MHC II (?)
MHC II – APC only! This may hypersensitize TH cells to β cell peptides.

12. Molecular Mechanisms of Autoimmunity
Polyclonal B Cell Activation by Viruses and Bacteria
If B cells reactive to self-peptides are activated, autoimmunity can occur.
Example: Epstein-Barr Virus, which is the cause of infectious mononucleosis.

13. Autoimmune diseases Specific:
Juvenile diabetes (attacks insulin-producing cells)
Multiple sclerosis (attacks myelin coating of nerve axons)
Myasthenia gravis (attacks nerve-muscle junction)
Thyroiditis (attacks the thyroid) …
Systemic: Immune complexes accumulate in many tissues and cause inflammation and damage.
Systemic Lupus Erythematosus (anti-nuclear antibodies): harms kidneys, heart, brain, lungs, skin…
Rheumatoid Arthritis (anti-IgG antibodies): joints, hearts, lungs, nervous system…
Rheumatic fever: cross-reaction between antibodies to streptococcus and auto-antibodies.

14. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Chronic systemic autoimmune disease
Cause unknown
Affects almost any organ(s)
Characterized by chronic inflammation

15. SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
Auto-antibodies formed against variety of self antigens
Anti-double stranded DNA,RNA and histones
Antibodies against cell surface antigens on RBC’s and/or platelets
Tissue damage caused by Type III hypersensitivity reactions
Immune circulating complexes formed against self deposit on tissues
Vasculitis, synovitis, glomerulonephritis

16. Systemic lupus erythematosis is the most commonly known autoimmune disorder. This characteristic “butterfly” rash is made worse by exposure to sunlight. Lupus is a potentially fatal autoimmune disease that
strikes 1 in 2,000 Americans and 10 times as many women as men.

17. Rheumatoid Arthritis Systemic autoimmune disease
Genetic factors (HLA-DR1, HLA- DR4)
Autoreactive B-cells synthesize auto antibody
against Fc portion of IgG
Rheumatoid factor (RF)
Chronic inflammation of synovial joints
Proliferation of synovial lining cells
Erosion of articular cartilage and adjacent bone

18. Rheumatoid arthritis (RA) affects peripheral joints and may cause destruction of both cartilage and bone. The disease affects mainly individuals carrying the DR4 variant of MHC genes.
This fact can lead to better prognoses and in aiding efforts to change immune reactions that involve the DR4 variant while leaving other reactions intact.

19. Hemolytic Anemia
- results from monoclonal antibodies to normal RBC constituents
- antibodies coat the erythrocytes, causing clumping, lysis, and premature clearance by the spleen
- can be induced by an “offending” agent (parasite, drug, or toxin) that adheres to the RBC
- Drug-induced Hemolytic Anemia- drug binds to RBC’s and causes them to become antigenic
- antibodies that develop from the drug recognize these cells and they are lysed