Table of Contents
What Are Autoimmune Diseases?
Autoimmune diseases arise when the specific immune system mistakenly attacks the body’s own cells, tissues, or molecules. In other words, structures that should be recognized as “self” are treated as if they were foreign pathogens.
Normally, immune tolerance mechanisms ensure that lymphocytes reacting strongly against self-components are eliminated, inactivated, or controlled. In autoimmune diseases, these tolerance mechanisms fail in some way, so that self-reactive T or B lymphocytes become active and cause damage.
Important features:
- The immune response is directed against self-antigens (autoantigens).
- Autoantibodies and/or self-reactive T cells are often detectable.
- The disease process is usually chronic and can flare up in episodes.
- Many autoimmune diseases involve inflammation and tissue destruction.
Autoimmune diseases are not infections; they are misdirected immune responses.
Forms and Targets of Autoimmune Reactions
Autoimmune diseases can be grouped according to the main site or type of target:
Organ-Specific Autoimmune Diseases
In organ-specific autoimmune diseases, the immune attack is mainly directed against a particular organ or cell type. Examples (for orientation):
- Thyroid gland (e.g., autoimmune thyroiditis)
- Pancreatic β‑cells (type 1 diabetes mellitus)
- Melanocytes in the skin (vitiligo)
Typical features:
- Autoantigens are largely restricted to one organ.
- Symptoms are mainly found in that organ.
- Function can be either reduced (e.g., cell destruction) or excessively stimulated (e.g., autoantibodies mimicking hormones).
Systemic Autoimmune Diseases
Systemic autoimmune diseases involve autoantigens that are present in many tissues (e.g., nuclear components, connective tissue). This leads to widespread involvement of several organs.
Examples of targets (not full disease descriptions):
- Components of connective tissue
- Nuclear components (DNA, histones, nuclear proteins)
- Blood vessel walls
Typical features:
- Multiple organs are affected (e.g., skin, joints, kidneys, blood vessels).
- General symptoms like fatigue, fever, and weight loss are common.
- Clinical course often shows phases of remission and exacerbation (flares).
Mechanisms Leading to Autoimmunity
Autoimmune diseases do not have a single cause. Rather, several factors usually interact.
Breakdown of Immune Tolerance
The immune system normally develops tolerance to self:
- Central tolerance: occurs during the development of T and B lymphocytes in primary lymphoid organs (e.g., thymus, bone marrow). Self-reactive cells are deleted or altered here.
- Peripheral tolerance: additional control mechanisms in the rest of the body (e.g., regulatory T cells, anergy, deletion).
Possible disturbances:
- Incomplete deletion of self-reactive cells.
- Failure or reduction of regulatory T cell function.
- Inappropriate activation signals that overcome tolerance (e.g., strong inflammation).
Role of Genetic Factors
A genetic predisposition increases the risk of autoimmune disease but does not guarantee it will occur.
Important aspects:
- Certain variants of genes in the MHC (HLA) region influence which peptides are presented to T cells and can predispose to autoimmunity.
- Other genes involved in immune regulation, cell signaling, or apoptosis can contribute.
- Autoimmune diseases often cluster in families, but different family members may develop different autoimmune conditions.
Environmental and Triggering Factors
External factors often act as triggers in genetically predisposed individuals:
- Infections
Some pathogens may initiate autoimmunity or trigger flares, e.g. by: - Molecular mimicry: pathogen antigens resemble self-structures; antibodies or T cells generated against the pathogen cross-react with self.
- Bystander activation: strong inflammation activates previously silent self-reactive lymphocytes in the neighborhood.
- Physical and chemical influences
Radiation, certain chemicals, or drugs can alter self-structures or promote cell damage, exposing hidden antigens. - Hormonal influences
Many autoimmune diseases are more common in women, suggesting a role for sex hormones and other hormonal factors.
Role of Autoantibodies and Self-Reactive T Cells
Autoimmune reactions can be mediated by:
- Autoantibodies:
Antibodies directed against self-antigens. They can: - Bind to receptors and block or mimic normal ligands.
- Mark cells for destruction by other immune cells.
- Form immune complexes with soluble antigens that deposit in tissues and cause inflammation.
- Self-reactive T cells:
T helper and cytotoxic T cells recognizing self-peptides can: - Directly attack and kill target cells.
- Activate macrophages and B cells, thereby amplifying inflammation and autoantibody production.
Often, both arms (antibodies and T cells) interact and sustain the disease process.
Consequences for Tissues and Organs
The chronic autoimmune attack leads to typical changes:
- Chronic inflammation:
Persistent presence of immune cells and inflammatory mediators in the affected tissue. - Tissue destruction and functional loss:
For example, loss of hormone-producing cells, nerve cells, or joint cartilage. - Fibrosis and scarring:
Damaged tissues may be replaced by connective tissue, which usually has reduced function. - Altered organ function:
Depending on whether cells are destroyed, blocked, or overstimulated, the organ can underperform or become overactive.
Symptoms arise from:
- The direct loss or alteration of organ function.
- Inflammatory reactions (pain, swelling, redness).
- General effects of chronic inflammation (fatigue, mildly elevated body temperature, malaise).
Examples of Autoimmune Disease Patterns
Without going into full disease descriptions (which would belong in more specialized chapters), some typical patterns can be highlighted:
- Endocrine autoimmune diseases
Target hormone-producing organs. Consequences: - Hormone deficiency when cells are destroyed.
- Possibly hormone excess when receptors are activated by autoantibodies.
- Autoimmune diseases of the nervous system
Target nerve cells or myelin sheaths. - Disturbance of signal conduction.
- Motor and sensory failures, depending on which structures are affected.
- Autoimmune connective tissue and joint diseases
Target joint structures or connective tissue components. - Chronic joint inflammation.
- Deformation and restriction of movement.
- Possible involvement of internal organs if the disease is systemic.
These patterns illustrate that virtually any organ system can become the target of an autoimmune response.
Diagnosis of Autoimmune Diseases
Typical components of diagnostic workup (principles only):
- Clinical picture and history
- Symptoms, course (chronicity, flares), and family history.
- Laboratory tests
- Detection of characteristic autoantibodies in blood.
- Inflammatory markers.
- Organ-specific parameters (e.g., hormone levels, kidney function).
- Imaging and functional tests
- To evaluate structural changes and organ performance.
- Tissue biopsy (in selected cases)
- Microscopic signs of immune-mediated inflammation.
- Deposition of antibodies or immune complexes.
The combination of specific autoantibodies and typical organ involvement is often decisive for diagnosis.
Principles of Treatment and Management
There is no single “cure” that removes a fundamental tendency to autoimmunity, but many autoimmune diseases can be successfully managed.
Main goals:
- Reduce excessive or misdirected immune activity.
- Limit tissue damage.
- Preserve or restore organ function.
- Improve quality of life.
Basic strategies:
- Immunosuppression and immunomodulation
- Drugs that dampen the immune response globally or selectively.
- Targeted agents that interfere with specific cytokines or cell types.
- Symptomatic treatment
- Pain control, anti-inflammatory medications.
- Support of affected organs (e.g., cardiovascular support if needed).
- Replacement of missing substances
- Hormone replacement.
- Enzyme replacement.
- Other supportive therapies to compensate for functional loss.
- Lifestyle and monitoring
- Regular medical follow-up, since disease activity can change.
- Vaccination considerations and infection prevention (especially under immunosuppression).
- Individual adaptation of physical activity, stress management, and nutrition as supportive measures.
Autoimmunity as a Balance Problem
Autoimmune diseases illustrate a fundamental trade-off in immunobiology:
- A strong, flexible immune system is needed to combat a wide range of pathogens.
- This same flexibility risks recognizing self as foreign if tolerance fails.
Thus, health requires a finely tuned balance between immune defense and immune tolerance. Autoimmune diseases are conditions in which this balance is permanently disturbed in favor of harmful self-directed reactions.