Autoimmune Diseases and Autoantibodies

• Auto-reactive B and T cell clones can be activated despite regulatory layers, causing tumoral or cell-mediated responses against self-antigens.
• Auto-reactive B cells produce autoantibodies that damage cells, tissues, and organs in autoimmune cases.
• B cells must pass governor tolerance after positive selection; some auto-reactive B cells persist, producing autoantibodies.
• Autoimmune diseases can be organ-specific, like those affecting pancreatic beta cells or red blood cells.

Autoimmune Diseases and Autoantibodies

• Autoimmune diseases are associated with specific autoantibodies.
• Autoimmunity and similar immune disorders are examined in later learning objectives.

Tolerance Mechanisms

• Tolerance prevents auto-reactive antibodies and cells from reacting with self, preventing autoimmune diseases.
• Under tolerant conditions, cells have a high affinity for self-antigens.
• Central and peripheral tolerance removes or silences B cells that react with self-antigens in different tissues.

Central and Peripheral Tolerance

• Central tolerance limits the development of auto-reactive B and T cells in the bone marrow and thymus, respectively.
• Receptor editing can rescue B cells from deletion if their B cell receptor (BCR) does not react to self-antigens.
• Peripheral tolerance up-regulates auto-reactive cells in circulation, leading to anergy or unresponsive B cells.
• Immune checkpoints require a threshold of antigen-binding affinity to self-antigens before deletion, allowing some weakly self-reactive clones to survive.

Factors Promoting Tolerance

• High doses of antigen, persistent antigen presence, absence of adjuvants, and low levels of co-stimulatory proteins promote tolerance.
• Autoimmune diseases occur when the immune system attacks the body’s own tissues.
• B cells and T cells play a primary role in these diseases by producing antibodies that target self-tissues.
• Healthy individuals have self-reactive B cells, but these are typically harmless.

Chronic Infections and Autoimmunity

• A recent study proposes chronic bacterial infection may indirectly play a role in triggering autoimmunity.
• Stimulation of the immune system by infection can trigger immune cells to attack self-tissues, as pathogens can mimic self-antigens.
• Responding to infection, B cells might inadvertently produce antibodies against self-antigens.
• This mechanism does not seem applicable in autoimmune diseases like lupus and rheumatoid arthritis.
• Chronic infections may induce autoimmunity indirectly, causing B cells to produce new types of self-reactive antibodies.
• Mice infected with Lyme disease bacteria stimulated self-reactive B cells to express a new mutated type of self-reactive antibody.
• B cells did not release significant amounts of the antibody, possibly due to safety mechanisms.
• Autoimmunity requires high-affinity antibodies for self-antigens, which these B cells did not produce.

Why Chronic Infection Alone Doesn't Cause Autoimmunity

• Self-reacted antibody production in response to bacteria and other pathogens is uncommon in healthy individuals due to frequent human infection.
• Future research should investigate factors besides infection that may help reduce autoimmunity, such as other immune cells and genetic mutations.

Key points about Autoantibodies and B Cells

• Tolerance mechanisms prevent autoimmunity via high antigen levels, persistent antigen exposure, lack of adjuvants, and low levels of co-stimulatory proteins.
• B cells produce self-reactive antibodies (autoantibodies) that attack the body’s own tissues.
• Healthy individuals have a small number of self-reactive B cells, but they are typically harmless.
• A study suggests that chronic bacterial infections might indirectly trigger autoimmunity.
• Pathogens might mimic the body’s proteins, leading B cells to produce antibodies against self-antigens accidentally.
• Lyme disease bacteria activated self-reactive B cells to produce mutated autoantibodies.
• These B cells didn’t release large amounts of the antibody for the safety mechanisms in place.
• Even though infections are common, most people don’t develop autoimmunity because of built-in safeguards.
• Future research should focus on identifying other factors that influence autoimmunity.

Autoantibodies Induce Autoimmunity

• Autoantibodies target the body's own cells, tissues, or proteins, disrupting normal processes and causing inflammation/tissue damage.
• Autoantibodies bind to specific self-antigens, triggering inflammation or tissue destruction.
• They can activate the complement system, leading to cell lysis or inflammation.
• Autoantibodies mark cells for destruction by phagocytes.
• They can interfere with receptor function by blocking or stimulating receptor activity.
• Autoantibodies form immune complexes with soluble self-antigens, depositing in tissues and triggering inflammation.
• Autoantibodies trigger autoimmunity when pathogens mimic the body's proteins, leading B cells to produce antibodies against self-antigens accidentally.
• Mutated autoantibodies have also been studied as a potential mechanism.
• Myocardial infarction includes an example of an autoimmune disease, where autoantibodies build up in the heart.

Systemic Lupus Erythematosus (SLE)

• A 30-year-old female presents with fatigue, weight loss, arthritis of her hands, and a malar rash.
• Findings supports Systemic Lupus Erythematosus (SLE).
• Blood tests reveal decreased hemoglobin and the presence of antinuclear antibodies.
• Common systemic symptoms SLE include fatigue and weight loss.
• Non-erosive arthritis is a hallmark of SLE.
• A butterfly-shaped rash on the cheeks is very characteristic of SLE.
• Decreased hemoglobin is suggestive of anemia, often autoimmune hemolytic anemia in SLE.
• Antinuclear antibodies (ANA) are highly sensitive for SLE and present in most cases.