Autoimmunity

 

Autoimmunity

 Definition

Autoimmunity refers to an immune response in which the body's immune system mistakenly targets its own cells, tissues, or organs, leading to self-reactivity (loss of tolerance to self-antigens). This can result in autoimmune diseases, which may be organ-specific (targeting a single organ) or systemic (affecting multiple systems).

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Causes of Autoimmunity (All Dimensions)

1. Genetic Factors

• HLA (Human Leukocyte Antigen) Association – Certain HLA genes predispose individuals to autoimmunity (e.g., HLA-DR3/DR4 in Type 1 Diabetes).
• Gene Mutations & Polymorphisms – Variants in genes regulating immune tolerance (e.g., CTLA-4, PTPN22) can trigger self-reactivity.
• Familial Clustering – Autoimmune diseases often run in families due to shared genetic risk factors.

2. Environmental Triggers

• Infections – Molecular mimicry (microbial antigens resemble self-antigens, e.g., Streptococcus infection in Rheumatic fever).
• Toxins & Drugs – Exposure to chemicals (e.g., Procainamide-induced lupus, mercury exposure) can break self-tolerance.
• Dietary Factors – Gluten in genetically predisposed individuals (Celiac Disease).
• Radiation & UV Exposure – DNA damage leading to lupus flares in Systemic Lupus Erythematosus (SLE).

3. Immunological Factors

• Defective Central Tolerance – Failure in thymic deletion of autoreactive T-cells (e.g., Autoimmune Polyendocrine Syndrome Type 1 - AIRE gene mutation).
• Defective Peripheral Tolerance – Dysfunction in regulatory T-cells (Tregs), leading to uncontrolled immune activation.
• Bystander Activation – Non-specific activation of immune cells (e.g., viral infections leading to Multiple Sclerosis).
• Epitope Spreading – Immune response against an antigen expands to attack self-tissues (e.g., epitope spreading in Pemphigus vulgaris).

4. Hormonal Influence

• Female Predominance – Estrogen enhances immune response (SLE is more common in women).
• Pregnancy & Postpartum Changes – Immune shifts during pregnancy can either worsen or improve autoimmune conditions (e.g., RA improves in pregnancy but flares postpartum).

5. Psychological & Neurological Influence

• Chronic Stress – Elevation of cortisol can dysregulate immune responses, promoting inflammation in conditions like Multiple Sclerosis.
• Neuroimmune Interaction – Dysregulation of the gut-brain axis (e.g., Microbiome shifts in autoimmune diseases).

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Mechanisms of Autoimmunity

1. Loss of Immune Tolerance

• Central Tolerance Failure (Thymus/Bone Marrow) – Ineffective deletion of self-reactive T/B cells.
• Peripheral Tolerance Failure – Regulatory T-cells (Tregs) fail to suppress autoimmunity.

2. Molecular Mimicry

• Example – Streptococcal M-protein resembles heart tissue, leading to Rheumatic Heart Disease.

3. Bystander Activation

• Example – Hepatitis C infection triggering immune-mediated vasculitis (Cryoglobulinemia).

4. Epitope Spreading

• Example – Autoimmune destruction spreads in Myasthenia Gravis, affecting multiple neuromuscular junction sites.

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Examples of Autoimmune Diseases

Organ-Specific Autoimmune Diseases

• Type 1 Diabetes Mellitus – Autoimmune attack on pancreatic β-cells (Insulin-producing cells).
• Graves' Disease – Autoantibodies stimulating TSH receptors (thyroid hormone overproduction).
• Hashimoto’s Thyroiditis – Lymphocytic destruction of the thyroid gland.
• Addison’s Disease – Autoimmune destruction of the adrenal cortex.
• Pernicious Anemia – Autoimmune attack on parietal cells (intrinsic factor deficiency → B12 malabsorption).

Systemic Autoimmune Diseases

• Systemic Lupus Erythematosus (SLE) – Immune complexes deposit in multiple organs (skin, kidneys, joints).
• Rheumatoid Arthritis (RA) – Chronic inflammation of the synovium (joint lining).
• Sjogren’s Syndrome – Autoimmune destruction of salivary and lacrimal glands (dry eyes, dry mouth).
• Systemic Sclerosis (Scleroderma) – Fibrosis and autoimmunity affecting skin, lungs, kidneys.

Neurological Autoimmune Diseases

• Multiple Sclerosis (MS) – Demyelination of CNS neurons by autoreactive T-cells.
• Myasthenia Gravis – Autoantibodies blocking acetylcholine receptors at the neuromuscular junction.

Autoimmune Hematological Disorders

• Autoimmune Hemolytic Anemia – Destruction of RBCs by autoantibodies.
• Idiopathic Thrombocytopenic Purpura (ITP) – Autoantibodies against platelets.

Gastrointestinal Autoimmune Diseases

• Celiac Disease – Autoimmune response against gluten (HLA-DQ2/DQ8 association).
• Inflammatory Bowel Disease (IBD) – Crohn’s Disease, Ulcerative Colitis (chronic intestinal inflammation).

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Diagnostic Markers in Autoimmune Diseases

• Antinuclear Antibody (ANA) – SLE, Scleroderma, Sjogren’s Syndrome.
• Rheumatoid Factor (RF), Anti-CCP – Rheumatoid Arthritis.
• Anti-dsDNA, Anti-Smith – SLE.
• Anti-TPO, Anti-TG – Hashimoto’s Thyroiditis.
• HLA Typing – Genetic predisposition in various diseases.

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Treatment Approaches

1. Immunosuppressive Therapy

2. Symptomatic Management

3. Lifestyle & Complementary Approaches

• Dietary Modifications – Gluten-free diet in Celiac Disease.
• Gut Microbiome Modulation – Probiotics, fiber-rich diet for IBD.
• Stress Reduction – Yoga, meditation for chronic autoimmune conditions.

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Conclusion

Autoimmunity results from a complex interplay of genetic, environmental, hormonal, and immunological factors. Understanding the diverse mechanisms helps in early diagnosis, personalized treatment, and improved management of autoimmune diseases.