Immunodeficiency refers to a condition in which the immune system cannot mount an adequate response to pathogens, leading to increased susceptibility to infections.
Explanation
Immunodeficiency is a state of impaired immune function that reduces the body’s ability to defend against infections and malignancies. It can be classified as primary or secondary. Primary immunodeficiencies are genetic disorders that affect the development or function of immune cells. They include defects in B cells, such as X‑linked agammaglobulinemia and selective IgA deficiency, T cell disorders like DiGeorge syndrome, combined immunodeficiencies exemplified by severe combined immunodeficiency, phagocytic defects such as chronic granulomatous disease, and complement deficiencies. Secondary immunodeficiencies arise from external factors such as HIV infection, malnutrition, metabolic disease, aging, cancer, or immunosuppressive treatments. The degree of immunodeficiency depends on which components of the immune system are compromised and may range from mild to profound.
Individuals with immunodeficiency often experience recurrent or persistent infections with common pathogens and are vulnerable to opportunistic organisms. They may also develop autoimmune diseases or malignancies because immune regulation is disrupted. Diagnosis involves clinical assessment, measurement of immunoglobulin levels, enumeration of lymphocyte subsets, evaluation of complement activity and, for inherited disorders, genetic testing. Management strategies are tailored to the specific condition and may include immunoglobulin replacement therapy, prophylactic antimicrobial agents, hematopoietic stem cell transplantation, gene therapy or avoidance of live vaccines. For secondary immunodeficiency, treatment focuses on addressing the underlying cause and mitigating immunosuppressive exposures. Early recognition and appropriate management are critical for preventing complications and improving survival.
Illustrative cases
Severe combined immunodeficiency is a primary immunodeficiency marked by the absence of functional T and B cells; affected infants present with failure to thrive and recurrent infections and require hematopoietic stem cell transplantation. Chronic granulomatous disease results from defects in the NADPH oxidase complex in phagocytes, leading to recurrent bacterial and fungal infections and granuloma formation. Deficiencies in complement components C5 through C9 predispose individuals to recurrent infections with Neisseria species. Secondary immunodeficiency due to HIV infection leads to progressive loss of CD4+ T lymphocytes and susceptibility to opportunistic infections such as Kaposi’s sarcoma, Pneumocystis pneumonia and candidiasis. Patients receiving chemotherapy or corticosteroids may become neutropenic and need prophylactic antibiotics and growth factor support.
Immunodeficiency highlights the importance of a fully functional immune system in maintaining health. Differentiating between primary and secondary forms guides diagnostic workup and therapy. Advances in genetics and transplantation offer hope for curative treatments for many inherited immunodeficiencies.
Related Terms: Primary immunodeficiency, secondary immunodeficiency, immunocompromised, HIV, antibodies