Immunodeficiency

Overview of Immunodeficiency

• Immunodeficiency refers to a state of increased susceptibility to infections due to deficiencies or defects in one or more components of the immune system.

• It can affect specific immune responses (e.g., IgA deficiency) or have a more generalized impact (e.g., severe combined immunodeficiency disorder, SCID).

• Immunodeficiency can be transient or permanent, leading to individuals being classified as immunocompromised or immunodeficient.

Types of Immunodeficiency

• Primary Immunodeficiency (PI) (< 10% of cases):

  • Intrinsic defects, either congenital or acquired, typically manifesting at an early age.

  • Not caused by other diseases or medications and is non-contagious.

  • Can involve genetic abnormalities leading to missing enzymes, cell types, or non-functioning components.

• Secondary Immunodeficiency (> 90% of cases):

  • Acquired due to underlying diseases or medications, occurring at any age.

  • Common causes include lymphoid malignancies, infections (e.g., HIV), malnutrition, and immunosuppressive drugs.

Warning Signs of Immunodeficiency

• 8 or more new ear infections in a year.

• 2 or more serious sinus infections in a year.

• Antibiotics for 2 months without effect.

• 2 or more episodes of pneumonia in a year.

• Recurrent, deep skin or organ abscesses.

• 2 or more deep-seated infections (e.g., osteomyelitis, cellulitis, sepsis).

• Surgical intervention for chronic infections.

• Persistent thrush after age 1 year.

• Failure to thrive.

• Family history of primary immunodeficiency.

Types of Primary Immunodeficiency

• Bruton’s Disease (X-linked Agammaglobulinemia):

  • Characterized by hypogammaglobulinemia due to mutations in the Bruton tyrosine kinase (BtK).

  • B cells fail to mature, leading to a lack of antibodies after maternal IgG is depleted.

  • Patients present with bacterial infections after 3 months of age.

  • Treatment involves immunoglobulin replacement (IVIg).

• IgA Deficiency:

  • Most common primary immunodeficiency with a prevalence of 1:600.

  • Characterized by serum IgA levels < 0.05 g/L.

  • 50% of patients experience respiratory tract infections.

  • Increased risk of allergies, autoimmunity, and malignancy; many remain asymptomatic.

• Common Variable Immunodeficiency (CVID):

  • Low serum IgG levels (<5 g/L) with variable IgA and IgM levels.

  • Impaired B cell maturation due to T cell help issues.

  • Prevalence is 4:100,000; can develop at any age, often in young adults.

  • Increased incidence of autoimmunity; immunoglobulin replacement is essential.

• Hyper IgM Syndrome:

  • X-linked condition due to lack of CD40L expression on T cells.

  • Results in high IgM levels but low IgG, IgA, and IgE levels.

  • Patients may have low neutrophil and platelet counts.

• IgG Subclass Deficiencies:

  • IgG2 subclass deficiency leads to respiratory tract infections.

  • Specific antibody deficiency may prevent antibody production against bacterial capsular polysaccharides.

T Cell Deficiencies

• DiGeorge Syndrome:

  • Characterized by the absence of the thymus, leading to a lack of mature T cells.

  • Patients often present with congenital heart defects and convulsions due to low calcium levels.

  • Facial abnormalities may also be present.

Combined B and T Cell Deficiencies

• Severe Combined Immunodeficiency (SCID):

  • Caused by defects in lymphocyte lineage affecting both T and B cell functions.

  • Genetic defects can be autosomal recessive or X-linked.

  • Commonly presents in the first 3 months with severe infections.

  • Bone marrow transplantation is often necessary for treatment.

Neutrophil Deficiencies

• Neutropenia: Can be persistent or cyclical.

• Chronic Granulomatous Disease (CGD):

  • Failure of respiratory burst; patients cannot kill phagocytosed bacteria.

• Leukocyte Adhesion Deficiency (LAD):

  • Defects in adhesion molecules prevent neutrophils from adhering to endothelium.

  • Results in poor pus formation and wound healing.

  • Two types: LAD I (integrin expression defects) and LAD II (selectin ligand expression defects).

Complement Deficiencies

• Classical Pathway Deficiencies (C1, C4, C2):

  • Increased susceptibility to infections with encapsulated bacteria.

  • Associated with immune complex-mediated diseases (e.g., SLE).

• C3 Deficiencies: Similar consequences as classical pathway deficiencies.

• CFP Deficiencies (B, D, properdin, H, I):

  • Increased susceptibility to Neisserial infections.

• C1 Esterase Inhibitor Deficiency:

  • Causes hereditary angioedema, leading to tissue and mucosal swelling.

  • Can be life-threatening if laryngeal edema occurs; treated with C1 esterase inhibitor infusions.

Diagnosis of Primary Immunodeficiency

• Quantification of blood cells, including T lymphocytes (CD4, CD8, CD3), B lymphocytes (CD19, CD20, CD21), NK cells, and monocytes.

• Tests for T cell function (skin tests, cytokine production) and B cell function (antibody levels).

• Phagocyte function tests (NBT reduction, chemotaxis, bactericidal activity).

• Complement testing (CH50, individual components).

Treatment of Primary Immunodeficiency

• Passive supplementation of deficient components (e.g., immunoglobulins, cytokines, enzymes).

• Bone marrow transplantation.

• Genetic engineering to replace defective cells with repaired ones.

Secondary Immunodeficiency

• Causes include environmental factors such as infections (HIV/AIDS, malaria), medications (corticosteroids, anti-cancer drugs), malnutrition, and aging.

• Other contributing factors include malignancies, systemic diseases (e.g., diabetes), splenectomy, and severe burns.

Immunology of HIV Infection and AIDS

• HIV specifically infects cells expressing CD4 receptors, including T helper cells, monocytes, macrophages, and dendritic cells.

• HIV can evade the immune system by using infected immune cells to spread throughout the body.

Rules for Managing Immunodeficiency

• Early suspicion and diagnosis are crucial.

• Avoid live vaccines in immunocompromised patients.

• Blood transfusions should be irradiated and CMV negative.

• Consult a professional immunologist early for guidance.This proactive approach helps to prevent complications and ensures tailored treatment plans that consider the unique needs of these patients.