Understanding Autoimmune Diseases

• Autoimmune diseases arise when the body's immune system mistakenly recognizes its own healthy cells as foreign invaders, leading to destructive responses against these self-cells.

General Information

• There are over 100 autoimmune diseases, including Type 1 Diabetes, which attacks insulin-producing cells, and Lupus, affecting various systems. Women represent about 80% of diagnoses, potentially due to hormonal or genetic factors. These disorders affect 5-10% of the global population, indicating their public health significance.

Symptoms and Diagnosis

• Symptoms of autoimmune diseases vary; rheumatoid arthritis includes fatigue, joint stiffness, pain, and swelling, while multiple sclerosis causes fatigue, vision loss, and balance issues. Diagnosis includes symptom assessment, blood tests, and autoantibody detection, with environmental and genetic triggers largely unknown.

Autoimmunity and Immune Tolerance

• Autoimmunity involves autoantibodies and T-cells. A healthy immune system maintains tolerance and has checkpoints to eliminate self-reactive components; failure leads to autoimmunity.

Development of Autoantibodies and Self-T-Cells

• Antibodies neutralize pathogens or mark them for elimination. B-cells, which produce antibodies, start in the bone marrow, where they are tested for autoreactivity—reactive B-cells are eliminated, while non-reactive ones move to the spleen. There, immature B-cells face further self-antigen exposure and die if reactive. This tolerance process also applies to T-cells, which kill infected cells and help B-cells. T-cells mature in the thymus, eliminating self-reactive types.

Activation Mechanisms

• Molecular mimicry: Viral or bacterial peptides resemble self-peptides, activating self-B and T-cells to attack both the virus and normal cells.
• Before B and T-cells activate there must also be inflamation
• Dendritic cells detect infections via pattern recognition receptors, triggering B and T-cells

Bystander Activation

• Tissue damage leads to dendritic cells taking up self-antigens.
• Activated dendritic cells can trigger autoimmune and viral B and T-cells.
• B-cell receptors can bind and process protein complexes, presenting them to T-cells.
• A T-cell activated by molecular mimicry can activate B-cells producing other antibodies, if the original peptide is present

Epitope Spreading

• Autoantibodies targeting one part of a protein can lead to autoreactive T-cells targeting other parts of the same protein
• B-cells can take in whole receptors during tissue damage and present peptides to T-cells.
• Autoreactive T-cells targeting different parts of the receptor can activate B-cells reactive to many other sites on the receptor.
• Epitope spread is the name given to this process
• Epitope spreading contributes to more inflammation and disease progression

Viral Persistence

• Viral persistence, where viruses remain in cells and cannot be eliminated, can contribute as well.
• Constant immune system activation increases chances of activating auto-reactive T or B-cells.
• The target and distribution of autoreactive T-cells or autoantibodies determine the symptoms.
• Targets in a single organ (e.g., pancreas in type 1 diabetes) cause localized damage.
• Targets present in many organs (e.g., lupus, targeting proteins in the cell's nucleus) cause widespread damage.

Current Treatments

• There is no cure
• Treatments focus on reducing symptoms and inflammation.
• Treatments: immunosuppressants, steroids, and NSAIDs.
• Further research is needed to understand the causes and develop targeted therapies.