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Immunodeficiencies

Immunodeficientia

For medical students2 min readUpdated 2026-10-10

Immunodeficiencies are pathological conditions characterized by impaired immune reactivity. They develop due to the failure or critical defect of one or more components of the immune system, making adequate defense against infections impossible.

Primary formsCaused by genetic mutations and hereditary factors

Secondary formsDevelop in the postnatal period due to external factors

Main syndromeSevere, recurrent infections (pneumonia, meningitis, sepsis)

Registry dataNational patient registries are maintained continuously to track epidemiological data

Role in Immune Pathology

The spectrum of immunological disorders is broad and divided into several groups based on mechanisms of development and clinical presentation. There are four main categories:

Immunodeficiencies — conditions characterized by insufficient protective functions.
Allergic diseases and hypersensitivity — excessive, exaggerated reactions to antigens.
Autoimmune diseases — pathological aggression of the system against the body's own tissues.
Diseases with immune-mediated inflammation.

Thus, immunodeficiency represents a malfunction where the immune system fails to perform its primary function due to the absence or dysfunction of specific defensive elements.

Etiology and Basic Classification

Globally, all immunodeficiencies are divided into two broad groups, with the key difference lying in their mechanisms of origin. Understanding this distinction is critical for differential diagnosis.

Primary immunodeficiencies (PIDs) have a strictly genetic origin. Their development is triggered by gene mutations that lead to defective protein products. As a result, the immune response cascade is blocked or functions improperly.

Secondary (acquired) immunodeficiencies arise in the postnatal period against the background of initially normal genetics. Their development is provoked by external factors:

Infectious agents (herpesviruses and HIV are especially dangerous).
Iatrogenic factors (e.g., targeted immunosuppressive therapy in the treatment of other diseases).
Physical factors (radiation exposure).
Chemical agents (various toxins and poisons).

Clinical Presentation of Genetic Defects

Patients with primary immunodeficiencies have a specific clinical profile centered around a pronounced infection syndrome. Infections in these patients are extremely severe, frequently recurrent, and resistant to standard conservative therapy.

Typical manifestations include sepsis, otitis media, pneumonia, and meningitis. Additionally, comorbid conditions often manifest due to reduced immune surveillance, including malignancies, various allergic reactions, and autoimmune disorders.

History of Study and Management

Active study of primary immunodeficiencies began in the early 1950s. The first described condition was X-linked agammaglobulinemia (a disease associated with a mutation on the X chromosome). To date, scientists have identified over 100 different gene mutations responsible for encoding immune response proteins. The classification of these conditions is based on the affected component of the immune system and clinical-genetic features.

When PID is suspected, the diagnostic algorithm necessarily includes a detailed family history to identify a genetic trail among blood relatives. The combination of a positive family history and recurrent infections is a direct indication for a detailed evaluation of the patient's immune status. Therapeutic management in such cases involves prolonged courses of antibiotic therapy using the latest generation of drugs to control the infectious process.

Mnemonic

To quickly remember the causes of secondary immunodeficiencies, use the "four I's" rule: Infections (HIV, herpes), Irradiation (radiation), Immunosuppression (iatrogenic), and Intoxication (toxins/poisons).

Frequently asked questions

Which components of the immune system can be affected in primary immunodeficiencies?

Both specific (adaptive) and nonspecific (innate) immunity can be affected in primary immunodeficiencies. The following levels of impairment are distinguished:

Humoral immunity — B-lymphocyte defects (predominantly antibody deficiencies).
Cellular immunity — T-lymphocyte defects.
Combined defects — simultaneous impairment of T- and B-cell arms.
Innate immunity — defects in phagocytes, the complement system, or receptor apparatus and effector molecules.

Which specific nosological forms belong to primary immunodeficiencies with a humoral defect?

Primary immunodeficiencies with a predominant humoral defect (antibody deficiency) include:

Agammaglobulinemia — including X-linked agammaglobulinemia (Bruton disease).
Hypogammaglobulinemia — decreased antibody levels.
Selective IgG deficiency — impaired switching to IgG synthesis.
Selective IgA, IgE, IgD deficiency — isolated impairments in synthesizing corresponding immunoglobulin classes.
Common variable immunodeficiency (CVID).

What laboratory diagnostic methods are used for an advanced evaluation of immune status?

A complex of laboratory methods forming an immunogram is used for an advanced evaluation of immune status. The main methods include:

Flow cytometry — a key method for quantitative analysis of lymphocyte subpopulations, cytokine levels, and cellular functional activity (phagocytosis, NK-cell activity).
Determination of specific immunoglobulin levels — to assess the humoral response.
TUNEL assay — detection of apoptotic bodies to assess the completion of the immune response.
Caspase activity assay — analysis of cell death processes.

What pathogenetic therapies are used for primary immunodeficiencies besides antibiotics?

In addition to antibacterial therapy, treatments for primary immunodeficiencies include:

Replacement immunotherapy with immunoglobulin preparations.
Bone marrow transplantation — a radical method used as a last resort, including for severe combined immunodeficiency (SCID).
Gene therapy for immunodeficient states as a method to correct genetic defects.

What is the main difference between primary and secondary immunodeficiencies?

Primary immunodeficiencies are always caused by genetic mutations and are inherited. Secondary immunodeficiencies develop after birth due to external factors (viruses, radiation, toxins) in the absence of initial genetic defects.

What clinical signs point toward a primary immunodeficiency?

The primary markers are severe infections (meningitis, pneumonia, sepsis) that constantly recur and fail to respond to standard conservative treatment regimens.

What is a direct indication for an advanced evaluation of immune status?

The presence of a treatment-resistant infection syndrome in combination with a burdened family history (similar problems in blood relatives).

Go deeper

Detailed classification of primary immunodeficiencies by the affected immune component
Mechanisms of autoimmune disease development secondary to immunodeficiency
Impact of specific viruses (HIV, herpes) on the development of secondary immunodeficiencies
Methods and laboratory tests for comprehensive immune status evaluation