Autoimmunity

What is Autoimmunity?

Autoimmune diseases occur when the adaptive immune system launches specific responses against self-antigens. These responses mimic normal immunity but are misdirected, leading to tissue destruction, inflammation, and chronic disease.

Autoimmune Responses:

  • Involve both autoreactive effector T-cells and autoantibodies
  • Can be organ-specific (e.g., Type 1 Diabetes, Myasthenia Gravis) or systemic (e.g., SLE, Rheumatoid Arthritis)
  • Often involve Type II, III, or IV hypersensitivity reactions
  • Are more common in females (~2/3 of cases)

How Do Autoreactive T and B Cells Arise?

During lymphocyte development:

  • Random gene rearrangement sometimes generates self-reactive lymphocytes
  • Normally, these are deleted or inactivated (a process called self-tolerance)
  • Autoimmunity = failure of self-tolerance mechanisms

Mechanisms of Immune Tolerance

1. Central (Thymic) Tolerance

  • Strongly self-reactive lymphocytes are deleted in the thymus (T-cells) or bone marrow (B-cells)
  • Involves expression of self-antigens by dendritic-like cells
  • Some autoreactive lymphocytes escape into the periphery

2. Peripheral Tolerance

  • Anergy: Without co-stimulation (signal 2), self-reactive lymphocytes become inactive
  • Regulatory T-Cells (Tregs): Suppress immune responses via inhibitory cytokines
  • Ignorance: Weakly autoreactive cells may never encounter sufficient antigen or stimulus
  • Physical Separation: Some antigens are hidden in immune-privileged sites (e.g., brain, eye)

What Triggers Autoimmunity?

A. Genetic Predisposition

  • Many autoimmune diseases run in families
  • Associated with certain HLA alleles (especially MHC-II)
  • More frequent in females due to hormonal & genetic factors

B. Environmental Factors

  • Identical twins only show ~25% concordance in some diseases (e.g. SLE)
  • Suggests strong environmental component

Pathogenic Mechanisms of Autoimmunity

1. Exposure of Hidden Epitopes

  • Trauma or disease exposes normally hidden antigens
  • Autoantibodies form → Chronic inflammation → More antigen release → Disease perpetuation
autoimmunity: Exposure of Hidden Epitopes
Source: Unattributable

2. Epitope Spreading

  • Autoreactive B-cells present multiple antigenic fragments
  • Activates multiple autoreactive T-cells
  • Results in widened autoimmune response
  • Example: SLE → Anti-DNA and Anti-Histone antibodies

Infectious Triggers of Autoimmunity

A. Promotion of Lymphocyte Activation

  • Infection causes inflammation & high levels of co-stimulation
  • May activate ignorant autoreactive lymphocytes
  • APCs may present self-antigens → Activation of autoreactive T-cells

B. Molecular Mimicry (Cross-Reactivity)

  • Pathogen antigens resemble host proteins
  • B-cell and T-cell responses cross-react with self
  • Examples:
    • Rheumatic Fever: Strep M-protein mimics cardiac tissue
    • MS: Anti-EBV antibodies cross-react with myelin

M-Protein & Rheumatic Heart Disease

Group A Streptococcus (GAS) can cause:

  • Pharyngitis, cellulitis, necrotising fasciitis, and toxic shock
  • Some strains are rheumatogenic → cause autoimmune disease

Mechanism:

  • GAS M-Protein structurally mimics cardiac myosin
  • Induces cross-reactive antibodies → Damage to:

Organ-Specific Autoimmune Diseases

Organ-Specific autoimmunity Diseases To Be Aware Of
CNX OpenStax, CC BY 4.0 https://creativecommons.org/licenses/by/4.0, via Wikimedia Commons

Summary – Autoimmunity

Autoimmunity arises from a breakdown in immune tolerance, allowing the adaptive immune system to target self-antigens. It can manifest in organ-specific or systemic forms, and is often influenced by both genetic and environmental factors. Key mechanisms include central and peripheral tolerance failure, epitope spreading, molecular mimicry, and pathogen-induced immune activation. For a broader context, see our Immune & Rheumatology Overview page.

Shopping Cart
Scroll to Top