Immunodeficiency Diseases Overview

Introduction to Immunodeficiency Diseases
  • Disorders caused by defective immunity are known as immunodeficiency diseases.
  • Congenital (primary) immunodeficiencies arise from genetic abnormalities in the immune system's components.
  • Two main types of immune systems:
    • Innate Immunity: First line of defense; failures can lead to acute infections.
    • Adaptive Immunity: Slower to develop infections; identified and treated differently based on type of infection.
  • Indicators of Defects:
    • Bacterial infections usually indicate humoral (antibody and/or complement) defects.
    • Viral or fungal infections suggest T-cell defects.
Types of Immunodeficiencies

  • B-cell Deficiencies:

    • Often absent or reduced follicles and germinal centers in lymphoid tissues.
    • Associated with reduced serum immunoglobulin (lg) levels.

  • T-cell Deficiencies:

    • Usually indicated by reduced T cell zones in lymphoid organs.

  • Innate Immune Deficiencies:

    • Vary according to the defective component; characterized by reduced delayed-type hypersensitivity (DTH) reactions and defective T cell responses.
Common Infectious Complications
  • B cells (antibody): Risk for respiratory tract sepsis, gastrointestinal (GI) tract sepsis.
  • T cells (cellular immunity): Susceptibility to viral infections.
  • Phagocytes (non-specific immunity): Increased risk of lymphadenitis, skin infections, and abscesses.
  • Complement Deficiencies: Associated with systemic bacterial infections, autoimmune diseases, and infections from pyogenic bacteria.
Infections by Common Microorganisms
  • Bacteria: Staphylococci, Streptococci, Haemophilus, and specific intracellular organisms like cytomegalovirus and adenovirus.
  • Fungi: Candida, Aspergillus, and Pneumocystis jirovecii.
  • Protozoa: Cryptosporidium defects are noted due to particular immune insufficiencies.
Histopathological and Laboratory Findings
  • B cell Deficiencies: Characterized by absence of mature B cells and low/impaired immunoglobulin levels.
  • T cell Deficiencies: Indicated by low/absent T cell zones.
  • Innate Deficiencies: Laboratory tests will show variable results depending on which components are defective.
Chronic Granulomatous Disease (CGD)
  • Etiology: Caused by mutations affecting NADPH oxidase composition, impeding reactive oxygen species production in phagocytes.
  • Infections: Patients often suffer from infections by catalase-positive organisms and suffer from granuloma formation.
  • Diagnosis: Nitroblue tetrazolium test (NBT) assesses superoxide radical generation in neutrophils.
  • Management: Includes prophylactic antibiotics and antifungal agents, and potential bone marrow transplantation.
Neutropenia and Related Conditions
  • Can result from genetic or secondary causes such as drug reactions or infections. Chronic benign forms often managed with granulocyte-colony stimulating factor (G-CSF).
Defects in Innate Immunity
  • Leukocyte Adhesion Deficiency: Impaired recruitment of leukocytes to infection sites due to integrin mutations.
  • Hyper-IgE Syndrome (HIES): Linked to mutations in STAT3 affecting multiple inflammatory pathways leading to organ abnormalities and susceptibility to infections.
Treatment Options
  • Replacement therapies or immunoglobulin infusions are often effective for various deficiencies, with specific treatments like gene therapy being practical for certain genetic immunodeficiencies.
Management Strategies for Immunodeficiencies
  • Prophylactic measures, IVIG therapy, and potential for long-term stem cell donations are vital for patient outcomes.
  • Regular monitoring for complications, including cancer placements due to immune dysregulation, is necessary for comprehensive care.