Acquired Immunodeficiency

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  • List the causes of acquired immunodeficiency
    • Extremes of age: Neonates, Infants, and elderly
    • Surgery or trauma
    • Malignancies
    • Metabolic diseases: Diabetes, Uremia
    • Malnutrition
    • Infection: HIV, Measles
    • Immunosuppressive therapy: Chemotherapy, Radiation therapy
  • Describe the mechanism of immunodeficiency in Neonates
    • Absent IgG transfer before 32 weeks (Premature)
    • Immature secondary lymphoid tissue (MALT)
    • Decreased marginal-zone B cells and CD21 expression
    • Decreased neutrophil storage pool
    • Decreased in vitro neutrophil function (phagocytosis, oxidative burst, chemotaxis, adhesion, capacity to develop NETs)
    • Decreased NK activity
    • Decreased TLR signalling
    • Decreased cytokine production
    • Reduced complement proteins
  • Describe the mechanism of immunodeficiency in the Elderly
    • Increased breakdown pf skin and mucosal barriers
    • Slow healing associated with metabolic and endocrinologic changes
    • Decreased hemtopoietic growth factors
    • Decreased delayed type hypersensitivity skin reaction
    • Decreased lymphocyte proliferative response to mitogens
    • Limited capacity of thymus to generate naive T cells
    • Restricted B-cell diversity repertoire
    • Limited response to vaccines
  • Describe the mechanism of immunodeficiency in Malnutrition
    • Decreased antibody titres
    • Decreased immune response to vaccines
    • Micronutrient deficiency (Zinc, ascorbate)
    • Vitamin D deficiency (MTB and macrophages)
  • Describe the mechanism of immunodeficiency in Diabetes mellitus
    • Defective phagocytosis
    • Defective macrophage chemotaxis
    • T-cell anergy (Chronic Hyperglycemia)
      • Delayed hypersensitivity skin tests
      • Poor lymphoproliferative response to mitogens
  • Describe the mechanism of immunodeficiency in Uremia
    • Diminished capacity to generate memory
    • Defective chemotaxis
    • Decreased microbicidal activity
  • What drugs lead to immunodeficiency
    • Physical agents: UV light, Ionizing radiation
    • Corticosteroids
    • Calcineurin inhibitors (Cyclosporine, tacrolimus, pimecrolimus)
    • mTOR inhibitors
    • Alkylating agents, Antimetabolites, Cytotoxic antibiotics etc.
  • Describe the mechanism of immunodeficiency in Surgery and Trauma
    • Disruption of epithelial barriers
    • Cell destruction triggers inflammation
    • Non-specific cell activation leading to anergy
    • Elevated cortisol
    • Splenectomy (SHiN infections)
  • Describe the mechanism of immunodeficiency in HIV
    • Quantitative
      • Direct Killing
      • Activation induced cell death
      • Death by syncytia formation
    • Qualitative
      • Reduced antigen-induced T-cell proliferation
      • Decreased Th1 response
      • Defective intracellular signalling
      • Loss of memory CD4+ helper T cells
Jeffrey Kalei
Jeffrey Kalei
Articles: 335

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