Autoimmune+diseases

AUTOIMMUNE DISEASES

Dr Adefuye MBChB., MS., PhD

Session Learning Objectives

  • Discuss autoimmunity and immune tolerance
  • Describe the pathogenesis and pathogenic mechanism of autoimmune disorders
  • Provide an overview of major autoimmune diseases
  • Define Rheumatoid Arthritis (RA)
  • Discuss the epidemiology and risk factors for RA
  • Discuss the pathophysiology of RA
  • Summarize the clinical features and diagnostic protocol for RA
  • Discuss the management of RA
  • Define Systemic Lupus Erythematosus (SLE)
  • Discuss the epidemiology and risk factors for SLE
  • Discuss the pathophysiology of SLE
  • Summarize the clinical features and diagnostic protocol for SLE
  • Discuss the management of SLE
  • Discuss dental considerations for patients with autoimmune disorder

INTRODUCTION

  • Autoimmunity refers to an immune reaction against the body's own cells resulting from a loss of immune tolerance.
  • Characterized by:
    • Inflammation
    • Cell injury
    • Dysfunction of tissues or organs

EPIDEMIOLOGICAL CHARACTERISTICS OF AUTOIMMUNE DISORDERS

  • Prevalence: Affects around 5%–10% of the U.S. population.
  • Gender disparity: Most autoimmune diseases are more common in women (ratio 2:1).
  • Stress factors: Pregnancy or hormonal disturbances may increase occurrence.
  • Age of onset varies by disease:
    • Sjögren’s syndrome: 40–60 years
    • SLE: 15–55 years (earlier onset correlates with severe forms)
    • Rheumatoid arthritis: Diagnosed 30–60 years
  • Diagnostic delays are common due to subtle signs and symptoms.

IMMUNE TOLERANCE

  • Immunologic tolerance: Unresponsiveness of the immune system to self-antigens to prevent harmful over-reaction.
    • Activation of lymphocytes to defend against pathogens while preserving self-tolerance.
Types of Immunologic Tolerance
  • Central tolerance
  • Peripheral tolerance
Central Tolerance
  • Occurs early in lymphoid cell development.
  • Ensures self-antigen recognition before full lymphocyte development.
Mechanisms of Central Tolerance
  • Negative selection of T cells and B cell clonal deletion: Lymphocytes with high affinity to self-antigens undergo apoptosis.
  • Development of regulatory T cells (CD4+).
  • Receptor editing in B cells modifies specificity through antibody gene recombination.
Peripheral Tolerance
  • Occurs in peripheral immune tissues after T and B cells exit primary lymphoid organs.
Mechanisms of Peripheral Tolerance
  • Anergy: Lack of immune response due to absence of costimulatory signals.
  • Deletion of autoreactive T cells through apoptosis.
  • Suppression by inducing regulatory T cells through TGF-β exposure.
  • Recognition of self-antigens triggering inhibitory receptors ultimately prevents B-cell activation.

PATHOGENESIS OF AUTOIMMUNE DISORDERS

  • Emergence involves genetic, environmental, and immunologic interactions leading to autoimmune responses.
Autoreactivity
  • Immune reaction against self-antigens or self-tissues (e.g., autoantibodies).
  • Autoantibodies present in healthy individuals, do not convey disease unless symptoms are evident.
  • Triggers for autoreactivity can include:
    • Infections by viruses such as HIV and EBV causing polyclonal B-cell activation.
    • Molecular mimicry: Shared sequences in streptococcal proteins and cardiac myosin lead to increased antibodies contributing to Rheumatic Heart Disease (RHD).
    • Modification