Immunodeficiency is a condition in which one or more components of the immune system are absent, reduced, or functionally impaired, weakening protection against infectious diseases. It comprises many disorders rather than a single disease. Immunodeficiencies are broadly classified as primary, usually arising from genetic abnormalities, or secondary, resulting from another condition or its treatment. The consequences depend on which immune mechanisms are affected and how severely their function is impaired. (cdc.gov)
Classification and causes
Primary immunodeficiencies belong to the broader group called inborn errors of immunity. This terminology recognizes that genetic immune disorders can cause not only inadequate defense against infection but also abnormal immune regulation, excessive inflammation, or other manifestations. Classification includes combined cellular and antibody deficiencies, predominantly antibody deficiencies, phagocyte defects, complement deficiencies, and several other groups. Not every inborn error of immunity presents primarily as recurrent infection. (aaaai.org)
An underlying abnormality may affect a gene required for immune-cell development, signaling, or antimicrobial activity. Primary disorders can run in families, but the absence of a known family history does not exclude them. Although severe forms often become apparent in infancy, milder disorders may first be recognized in adolescence or adulthood. Thus, “primary” describes the origin of the disorder, not necessarily the age at diagnosis. (data.niaid.nih.gov)
Secondary immunodeficiency can occur with malnutrition, diabetes mellitus, blood malignancies, certain infections, or treatments that suppress immune activity. These treatments include cytotoxic chemotherapy, radiation therapy, and immunosuppressive medicines used after organ transplantation or for inflammatory disorders. Its severity may depend on the underlying disease, drug, dose, and duration of exposure. Loss of immune cells or immunoglobulins through certain intestinal or lymphatic disorders can also impair immunity. (cdc.gov)
Human immunodeficiency virus infection is an important acquired cause. HIV infects and destroys CD4 T lymphocytes, reducing immune protection. Acquired immunodeficiency syndrome, or AIDS, is the most advanced stage of HIV infection, not a synonym for immunodeficiency in general. Antiretroviral treatment suppresses viral replication and can allow immune function to recover. (hivinfo.nih.gov)
Affected immune mechanisms
Immunodeficiency can involve innate immunity, adaptive immunity, or both. The pattern of susceptibility often reflects the affected component, although considerable overlap exists between disorders. (aaaai.org)
- Antibody deficiencies: Abnormal development or function of B cells can impair production of antibodies. Examples include X-linked agammaglobulinemia and common variable immunodeficiency. Recurrent respiratory infections are a common presentation.
- Cellular and combined deficiencies: Defects involving T cells can compromise cellular defense and antibody responses. Severe combined immunodeficiency comprises disorders with profound T-cell impairment and additional defects of immune function.
- Phagocyte defects: Abnormal numbers or function of neutrophils and other phagocytes can reduce microbial killing. Chronic granulomatous disease is a characteristic example.
- Complement deficiencies: Defects in the complement system impair particular antimicrobial functions; some are associated with recurrent infections caused by Neisseria species. (aaaai.org)
These categories describe mechanisms rather than rigid boundaries. A single disorder may disrupt several interacting immune pathways. (cdc.gov)
Clinical manifestations
Common manifestations include infections that are unusually frequent, prolonged, severe, or difficult to treat. Respiratory infections, skin infections, abscesses, persistent thrush, and chronic diarrhea may occur. In infants, severe immune defects may be associated with poor growth. Opportunistic infections arise when organisms that rarely cause serious illness in people with intact defenses produce disease in an immunocompromised host. (cdc.gov)
Infection susceptibility does not necessarily imply uniformly reduced immune activity. Some primary disorders also involve autoimmunity, abnormal inflammation, or increased risk of particular forms of cancer. These manifestations reflect disturbances in immune regulation as well as protective function. Their occurrence and severity vary substantially among disorders. (cdc.gov)
Repeated infections alone do not establish immunodeficiency. Frequent exposure to pathogens, anatomical abnormalities, resistant organisms, and other diseases can produce similar histories. The type of infection, its severity, and associated clinical findings are therefore important to interpretation. (merckmanuals.com)
Diagnosis
Diagnosis combines clinical history, examination, and laboratory assessment. Evaluation considers infection patterns, age at onset, family history, medication exposure, and possible secondary causes. Initial investigations commonly include a complete blood count with differential, quantitative immunoglobulin concentrations, and measurements of antibody responses. (merckmanuals.com)
Further testing is directed toward the suspected defect. Flow cytometry can measure lymphocyte populations, while specialized assays assess cellular responses, phagocyte function, or complement activity. Genetic testing can identify the molecular basis of some primary disorders. No single test measures every aspect of immune competence, and results require interpretation alongside the clinical findings. (merckmanuals.com)
Treatment and vaccination
Treatment is disorder-specific and may include antimicrobial therapy, infection prophylaxis, or replacement of deficient immune components. Immunoglobulin replacement supplies antibodies to people with selected antibody deficiencies. Hematopoietic stem cell transplantation can restore immune function in certain severe disorders. Treatment of secondary immunodeficiency also addresses its underlying cause where possible. (aaaai.org)
The safety and effectiveness of vaccines depend on the immune defect. Non-live vaccines are generally safe in immunocompromised people, but responses may be reduced. Live-attenuated vaccines can cause serious complications in some forms of immunodeficiency, particularly severe cellular deficiencies. Restrictions are not identical for all disorders: isolated complement deficiencies and some phagocyte defects have different vaccination considerations from profound T-cell deficiencies. (cdc.gov)