Your body's immune system protects you from disease and infection. But if you have an autoimmune disease, your immune system attacks healthy cells in your body by mistake. Autoimmune diseases can affect many parts of the body.
No one is sure what causes autoimmune diseases. They do tend to run in families. Women - particularly African-American, Hispanic-American, and Native-American women - have a higher risk for some autoimmune diseases.
There are more than 80 types of autoimmune diseases, and some have similar symptoms. This makes it hard for your health care provider to know if you really have one of these diseases, and if so, which one. Getting a diagnosis can be frustrating and stressful. Often, the first symptoms are fatigue, muscle aches and a low fever. The classic sign of an autoimmune disease is inflammation, which can cause redness, heat, pain and swelling.
The diseases may also have flare-ups, when they get worse, and remissions, when symptoms get better or disappear. Treatment depends on the disease, but in most cases one important goal is to reduce inflammation. Sometimes doctors prescribe corticosteroids or other drugs that reduce your immune response.
2. CONTENTS :
• Introduction
• History
• Causes of Autoimmunity
• Mechanisms of Autoimmune response
• Types of Autoimmune disorders
• Examples
• Treatment
• Summary
• Future Prospectives
3. Introduction
The Immune system : Defence
system in body.
This defence occurs through a
series of steps called the immune
response.
A defect in any arm of the
immune system can trigger
autoimmunity.
4. SELF/NON-SELF DISCRIMINATION: Failure
of an organism in recognizing its own constituent
parts as self.
More than 80 -100 human diseases are
autoimmune in origin.
5 % to 7% adult affected. LEFT handed
individuals more affected.
The majority of these diseases are far more
common in women than in men - an estimated
75 % of those living with autoimmune diseases
are female.
Autoimmunity
“INJURY TO SELF”
5. History
A term coined by the German
immunologist Paul Ehrlich (1854-1915)
to describe the body's strong dislike to
its own self.
Horror autotoxicus: Literally, means
immunity is directed against foreign
materials but not against the constituents
of one's own body, exceptions to this
concept are horror.
7. Mechanisms
Idiotype Cross reaction
Formation of
neoantigens
Cross-reactivity and
molecular mimicry
Release of sequestered/
cryptic antigens
Mechanisms Of Autoimmune Response
Super antigens
Dendritic cell apoptosis &
clearance deficiency
8. 1. Cross reactivity and Molecular mimicry:
The microorganism express antigens that are structurally similar enough to self-
antigens.
The immune response can eventually turn toward the self-peptide as a result of
cross-reactivity.
Ex: Type 1 Diabetes mellitus.
9. 2. Formation of Neoantigens :
• Neoantigens are formed by modification of self antigen by chemical binding with
reactive molecule or formed during tissue injury, cell death, oxidative stress,
metabolic pathways, etc. .
• Drugs are capable of binding to erythrocytes membrane forming neoantigen.
• Ex :Penicillin , streptomycin.
10. 3. Super antigens:
Superantigens (SAgs) are a class of antigens which cause non-specific
activation of T-cells resulting in polyclonal T cell activation and massive
cytokine release.
Produced by pathogenic microbes as a defense mechanism against the immune
system.
Life-threatening symptoms, including shock and multiple organ failure.
11. 4. Idiotype cross reaction :
Idiotypes are antigenic epitopes found in the antigen-binding portion (Fab)
of the immunoglobulin molecule.
Cross-reaction between this idiotype and antiviral antibody or with a host
cell receptor for the virus in question can induce autoimmunine response.
Self reactive T cells / B cells
12. 5. Release of sequestered/cryptic antigens:
Sequestered antigens: Some self-antigens are not normally exposed to the
immune system and said to be sequestered and these sometimes get exposed to
the immune system and become immunogenic.
Cryptic Antigens: self epitopes which appear in very low concentration on APC
are termed cryptic in the sense that they do not delete autoreactive T-cells.
6. Dendritic cell apoptosis and clearance deficiency:
Immune system cells called dendritic cells present antigens to
active lymphocytes.
Dendritic cells that are defective in apoptosis can lead to inappropriate
systemic lymphocyte activation.
Deficiency in the clearance of apoptotic or necrotic cells induce autoimmunity.
13.
14. Types of Autoimmune diseases
1. Haemolytic Autoimmune Diseases:
Distructions of blood components.
E.g. Haemolytic anaemia, Leucopenia, Thrombocytopenia, etc.
2. Localized Autoimmune Disease:
A particular organ is affected due to auto Abs . E.g.
→ Thyroiditis (attacks the thyroid)
→ Juvenile diabetes or Type I DM (attacks insulin-producing cells).
3. Systemic Autoimmune Disease:
Non organ-specific autoimmune diseases
Immune complexes accumulate in many tissues and cause inflammation and
damage. E.g.
→ Systemic Lupus Erythematosus - Harms kidneys, heart, brain, lungs, skin.
→ Rheumatoid Arthritis - Joints, heart, lungs, nervous system.
15. Hashimoto’s Thyroiditis
It was the first disease to be recognized as an
autoimmune disease.
The thyroid gland is attacked by a variety of cell-
and antibody-mediated immune processes.
This can lead to hypothyroidism.
The exact cause of Hashimoto's is not known.
Since it affects about 7 times as many women as
men, suggesting that sex hormones may play a
role.
16. Autoantibodies may be present against thyroid peroxidase , thyroglobulin and TSH
receptors.
Activation of cytotoxic T-lymphocytes (CD8+ T-cells) in response to cell-mediated
immune response affected by helper T-lymphocytes (CD4+ T-cells) may cause
thyrocyte destruction.
Tests:
Detecting elevated levels of Thyroid autoantibodies:
Antithyroid peroxidase antibody
Antithyroglobulin antibody
Treatment :
Hypothyroidism caused is treated with thyroid hormone replacement agents such
as levothyroxine, triiodothyronine .
Pathophysiology
17. Butterfly Rash appears on face.
It is a systemic disease affecting the whole body.
The plasma cells produce antibodies that are specific
for self protein and ds-DNA.
90% of all cases occur in women.
SLE is triggered by environmental factors and
genetic factors that are unknown.
Systemic Lupus Erythematosus (SLE)
18. SLE- Pathophysiology
LE cell (more of activated neutrophils) appears in blood & bone marrow.
Overactive B cells are observed.
Clearance deficiency.
Tests :
Urine analysis.
Immunoglobulin level (↑ >90%)
Immune complex deposits in the skin(60%)
Complement Test: levels of C3, C4, CH50 (Low levels indicates possible
presence of disease), FANA – Fluorescent antinuclear antibody.
Treatment:
Treated with nonsteroidal anti-inflamatory drugs such as ibuprofen or naproxen,
antimalarial drugs, and corticosteroids.
19. • Rheumatoid arthritis (RA) is a long-term disease
that leads to inflammation of the joints and
surrounding tissues. It can also affect other organs.
• RA can occur at any age, but is more common in
middle age. Women(from 40 to 60 years old) get RA
more often than men.
• RA usually affects joints on both sides of the body
equally. Wrists, fingers, knees, feet, and ankles are the
most commonly affected.
• Major symptom is the chronic inflammation
Rheumatoid arthritis
20. Many individuals with Rheumatoid Arthrtis produce group of antibodies(IgM) which
bind to normal circulating IgG,forming IgM-IgG complexes which deposits in the
joints.
These immune complexes can activate the complement cascade,resulting in a type III
hypersensitive reaction,which leads to chronic inflammation
Pathophysiology
21. Rheumatoid factor test
Anti-CCP antibody test
Other tests that may be done include:
Complete blood count
C-reactive protein
Erythrocyte sedimentation rate
Joint ultrasound or MRI
Joint x-rays
Synovial fluid analysis
TREATMENT:
RA usually requires lifelong treatment, including medications, physical therapy,
exercise, education, and possibly surgery. Early, aggressive treatment for RA can delay
joint destruction.
Celecoxib (Celebrex)
Corticosteroids etc…
TESTS
22. Myasthenia Gravis
One of the less common
autoimmune disorders.
Myasthenia Gravis is
an autoimmune neuromuscular
disease leading to fluctuating muscle
weakness and fatigue
Pathophysiology
Acetylcholine receptor antibodies
blocks the normal binding of
acetylcholine and subsequent muscle
activation.
In addition it also activates
complement which damages the end
plate.
The number acetylcholine receptor
declines as the disease progresses.
23. SYMPTOMS:
Myasthenia gravis more commonly occurs in women
under 40 years and men over 60.
First noticeable symptom is weakness of the eye muscles.
swallowing and slurred speech
Asymmetrical Ptosis
Diplopia
shortness of breath and dysarthria(impaired speech)
TESTS:
Edrophonium test
Blood tests
Single-fiber electromyography (EMG)
Imaging scans
Pulmonary function test (spirometry)
Muscle biopsy
24. Treatment
There is no cure for myasthenia gravis. However, most therapies
(treatments) are very effective in controlling symptoms.
• Cholinesterase inhibitors
• Steroids or Immunosuppressants
• Removal of the thymus gland (thymectomy)
• Plasmaphoresis and immunoglobulin therapy
25. Treatment of autoimmune diseases
Most autoimmune diseases cannot be treated completely.
Current goals of treatments :
To relieve symptoms like fever , inflammation, rashes on skin.
Minimize organ and tissue damage and preserve organ function.
Maintain the body's ability to fight disease.
Since these diseases are often chronic, they require lifelong care and
monitoring, even when the person may look or feel well.
The key to treat autoimmunity is by immunomodulation.
26. Treatments
1. Immunosuppressor Drugs: Cyclosporin, Cyclophosphamide, Methotrexate,
Azathioprine, Corticosteroids and non-steroidal anti-inflammatory drugs
(NSAIDs).
2. Immunoglobulin replacement therapy: Plasmapheresis.
3. Monoclonal Anibodies: anti-CD4 monoclonal antibodies.
4. Inflammation as a target for treatment of autoimmunity: Blockers of TNF-α.
5. Radiation Therapy of the lymph nodes.
6. Surgery: Removal of Thymus.
7. Blood transfusions: If the autoimmune disorder affects the blood.
8. Oral Antigens: More promising study in mice than in humans.
27. Summary
Self/Non-self Discrimination
• 80-100 autoimmune diseases affecting 23.5* million Americans
(estimation by The National Institutes of Health).
• Causes: Multiple—genetic, environmental, nutrition, infections.
• Mechanisms of autoimmunity: Molecular mimicry, neoantigens, cryptic
antigens, failure of suppressive mechanism.
• Autoimmune diseases are a group of disorders in which tissue injury is
caused by humoral or cell mediated immune response.
28. Future Prospective
• In stem cell therapies, attempts are being made to wipe out the old
immune cells and replace them with fresh stem cells.
• The genetic therapy approaches : Transfer of genes encoding for
immunomodulatory responses that would induce immune tolerance.
What if you could "reboot" your immune system like a laptop?