Autoimmunity refers to a condition where the body’s immune system fails to recognize its own tissues and starts attacking them. This happens because the immune system loses the ability to differentiate between self and non-self. As a result, the body forms autoantibodies or autoreactive lymphocytes that damage its own cells.
Immune Tolerance
Immune tolerance is the normal ability of the immune system to recognize and protect the body’s own tissues. It begins in fetal life.
The immune system distinguishes self from non-self through three major mechanisms:
- Clonal elimination: Self-reactive T cells are removed (via apoptosis) during development in the thymus.
- Clonal anergy: Self-reactive T cells are not destroyed but become inactive.
- Suppressor (regulatory) T cells: These cells prevent activation of harmful immune responses.
Criteria for Autoimmunity (Witebsky’s Postulates)
- Presence of autoantibodies or autoreactive lymphocytes with tissue damage.
- Ability to reproduce the disease in experimental animals.
- Experimental disease must resemble the human disease.
- Ability to transfer the disease to another host using autoantibodies or lymphocytes.
Classification of Autoimmune Diseases
1. Organ-Specific Autoimmune Diseases
Autoantibodies target one specific organ, causing chronic inflammation and destruction.
Examples: Thyroid disorders, type 1 diabetes, Addison’s disease, pernicious anemia.
2. Systemic Autoimmune Diseases (Organ Non-Specific)
Autoantibodies attack multiple tissues and organs.
Examples: Systemic lupus erythematosus, rheumatoid arthritis.
Mechanisms of Autoimmunity
Autoimmunity can develop due to immunological, genetic, or microbial factors.
1. Immunological Factors
- Polyclonal B cell activation: Infections may activate B cells nonspecifically, bypassing T cell control.
- Self-reactive B cell clones: Abnormal activation leads to autoantibody production.
- Imbalance of T cells: Reduced regulatory T cells and increased helper T cells enhance autoantibody formation.
- Anti-idiotype network disturbances: Loss of regulatory antibody interactions.
- Release of sequestered antigens: Trauma to immune-privileged sites (testis, lens) exposes hidden antigens and induces autoantibody formation.
2. Genetic Factors
- Strong association with certain HLA alleles (e.g., HLA-B27).
- Higher incidence in families.
- Increased expression of Class II MHC molecules in affected organs.
3. Microbial Factors
- Viruses (e.g., EBV), bacteria (streptococci), and mycoplasma may trigger autoimmunity.
- Molecular mimicry: microbes resemble self-antigens, causing cross-reactions.
Immunologic Tolerance
Lymphocytes respond to antigens in two ways:
- Activation → immune response
- Inactivation or elimination → tolerance
Factors favoring tolerance:
- High antigen dose
- Long-term antigen exposure
- IV or oral administration
- Absence of adjuvants
- Low co-stimulation
- Antigen presentation by immature APCs
Types of Immunologic Tolerance
1. Central Tolerance
Occurs in primary lymphoid organs:
- B cells: Bone marrow
- T cells: Thymus
Self-reactive cells undergo:
- Deletion (apoptosis)
- Receptor editing (B cells)
- Development into regulatory cells (T cells)
2. Peripheral Tolerance
Occurs after lymphocytes leave primary organs and encounter self-antigens in tissues.
Mechanisms include:
- Clonal anergy (cells become inactive)
- Clonal deletion (cell death)
- Suppression by regulatory T cells
Antigen Sequestration
Certain body sites (e.g., eye, CNS, testis) contain antigens that are normally hidden from immune cells. If these areas are damaged, the sudden exposure causes autoimmunity.
Example: Trauma to one eye may induce inflammation in both eyes due to immune activation.
Transplantation and Autoimmunity
The immune system also plays a major role in transplant rejection. The graft may be recognized as foreign due to mismatched HLA antigens.
Types of Grafts
- Autograft: Same person
- Isograft: Genetically identical individuals
- Allograft: Different individuals of same species
- Xenograft: Different species
- Stem cell transplant
Types of Rejection
- Hyperacute: Minutes–hours; pre-existing antibodies
- Acute: Weeks–months; T cell and antibody-mediated
- Chronic: Months–years; fibrosis and scarring
Detailed Notes:
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