Immunodeficiency: Definition, Types, Causes, Symptoms, Treatment and Prognosis

It is a state in which the immune system’s ability to fight infectious diseases and cancer is compromised or completely absent.

Most cases of immunodeficiency are acquired due to extrinsic factors that affect the immune system of the patient. Examples of these extrinsic factors include HIV infection, extremes of age, and environmental factors such as nutrition.

In the clinical setting, immunosuppression of some medications, such as steroids, may be an adverse effect on the intended purpose of treatment.

Examples of such use are found in organ transplant surgery as an anti- rejection measure and in patients suffering from an overactive immune system, such as autoimmune diseases.

Some people are born with intrinsic defects in their immune system or primary immunodeficiency. A person who has an immunodeficiency of any kind is said to be immunocompromised.

An immunocompromised person can be particularly vulnerable to opportunistic infections, in addition to the normal infections that could affect everyone. Immunodeficiency also decreases immunosurveillance of cancer, in which the immune system scans the body’s cells and kills neoplastic cells.


By affected component

  • Humoral immunodeficiency: with signs or symptoms depending on the cause, but generally including signs of hypogammaglobulinemia with presentations that include repeated mild respiratory infections and / or agammaglobulinemia resulting in frequent and often fatal severe infections.
  • T cell deficiency: often causes secondary disorders such as acquired immunodeficiency syndrome (AIDS).
  • Granulocyte deficiency: which includes a decrease in the number of granulocytes such as neutrophil granulocytes. Granulocyte deficiencies also include decreased function of individual granulocytes, as in chronic granulomatous disease.
  • Asplenia: where there is no function of the spleen.
  • Complement deficiency is when the function of the complement system is poor.

In reality, immunodeficiency often affects multiple components, with notable examples including severe combined immunodeficiency (which is primary) and acquired immunodeficiency syndrome (which is secondary).

Immunodeficiencies by affected component

Humoral Immunodeficiency
Components affected

B cells, plasma cells, or antibodies

Main causes
  • Humoral primario.
  • Multiple myeloma.
  • Chronic lymphoid leukemia.
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Main pathogens of resulting infections.
  • Steotococci pneumonia.
  • Hemophilus influenzae.
  • Pneumocystis jirovecii.
  • Giardia intestinalis.
  • Cryptosporidium parvum.
T cell deficiency
Components affected

Células T.

Main causes
  • Marrow and other transplants.
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  • Cancer chemotherapy.
  • Lymphoma
  • Glucocorticoid therapy.
Main pathogens of resulting infections
  • Intracellular pathogens, including Herpes simplex virus.
  • Mycobacteriu.
  • Listeriam.
  • Intracellular fungal infections.
Components affected

Neutrophilic granulocytes.

Main causes
  • Chemotherapy.
  • Bone marrow transplant.
  • Dysfunction, such as chronic granulomatous disease.
Main pathogens of resulting infections
  • Enterobacteriaceae.
  • Oral streptococci.
  • Pseudomonas aeruginosa.
  • Enterococcus species.
  • Candida species.
  • Aspergillus species.
Components affected


Main causes
  • Splenectomy
  • Trauma.
  • Sickle cell anemia.
Main pathogens of resulting infections

Polysaccharide encapsulated bacteria, particularly:

  • Streptococcus pneumoniae.
  • Haemophilus influenzae.
  • Neisseria meningitidis.
  • Plasmodium species.
  • Babesia species.
Complement deficiency
Components affected

Complementary system.

Main causes

Congenital deficiencies.

Main pathogens of resulting infections
  • Neisseria species.
  • Steotococcus neumonia.

Primary or secondary immunodeficiency

The distinction between primary versus secondary immunodeficiencies is based on, respectively, whether the cause originates in the immune system itself or is, in turn, due to the insufficiency of a supporting component of the same or a factor of the decrease. external of it.

Primary immunodeficiency

Several rare diseases are more susceptible to infection from infancy onward. Primary immunodeficiency is also known as congenital immunodeficiencies.

Many of these disorders are inherited and are autosomal recessive or X-linked.

There are more than 80 recognized primary immunodeficiency syndromes; They are generally grouped by the part of the immune system that is malfunctioning, such as lymphocytes or granulocytes.

Treatment of primary immunodeficiencies depends on the nature of the defect and may include antibody infusions, long-term antibiotics, and (in some cases) stem cell transplantation.

Characteristics of missing and / or altered antibody functions may be related to diseases such as X-linked Agammaglobulinemia and common variable immunodeficiency.

Secondary immunodeficiencies

Secondary immunodeficiencies, also known as acquired immunodeficiencies, can result from various immunosuppressive agents, for example malnutrition, aging, particular medications, and environmental toxins such as mercury and other heavy metals, pesticides, and petrochemicals such as styrene, dichlorobenzene, xylene, and ethylphenol.

For medications, the term immunosuppression generally refers to the beneficial and potential adverse effects of decreased immune system function, while the term immunodeficiency generally refers only to the adverse effect of increased risk of infection.

Many specific diseases cause immunosuppression directly or indirectly. This includes many types of cancer, particularly those of the bone marrow and blood cells (leukemia, lymphoma, multiple myeloma) and certain chronic infections.

Immunodeficiency is also the hallmark of acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus. HIV directly infects a small number of helper T cells, and it also indirectly damages other immune system responses.

Various hormonal and metabolic disorders can also lead to an immune deficiency including anemia, hypothyroidism , diabetes, and hypoglycemia.

Smoking, alcoholism, and drug abuse also lower the immune response.

Immunodeficiency and autoimmunity

There are a large number of immunodeficiency syndromes that exhibit clinical and laboratory features of autoimmunity.

The reduced ability of the immune system to clear infections in these patients may be responsible for causing autoimmunity through perpetual activation of the immune system.

An example is common variable immunodeficiency (CVID) in which multiple autoimmune diseases are seen, for example inflammatory bowel disease, autoimmune thrombocytopenia, and autoimmune thyroid disease.

Familial hemophagocytic lymphohistiocytosis, an autosomal recessive primary immunodeficiency, is another example.

Pancytopenia, skin rashes, lymphadenopathy, and hepatosplenomegaly are frequently seen in these patients. The presence of multiple unclear viral infections due to lack of perforin is believed to be responsible.

In addition to chronic and / or recurrent infections, many autoimmune diseases such as arthritis, autoimmune hemolytic anemia, scleroderma, and type 1 diabetes are also seen in X-linked agammaglobulinemia.

Recurrent bacterial and fungal infections and chronic inflammation of the intestine and lungs are also seen in chronic granulomatous disease (CGD).

CGD is caused by decreased production of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by neutrophils.

Hypomorphic RAG mutations are seen in patients with midline granulomatous disease; an autoimmune disorder commonly seen in patients with granulomatosis with polyangiitis (Wegner’s disease) and NK / T cell lymphomas.

Patients with Wiskott-Aldrich syndrome (WAS) also have eczema, autoimmune manifestations, recurrent bacterial infections, and lymphoma.

Autoimmunity and infections also coexist in autoimmune poliendocrinopathy-candidiasis-ectodermal dystrophy (APECED): organ-specific autoimmune manifestations (eg, hypoparathyroidism and adrenocortical failure) and chronic mucocutaneous candidiasis.

Finally, IgA deficiency is also sometimes associated with the development of autoimmune and atopic phenomena.


The cause of immunodeficiency varies depending on the nature of the disorder. The cause can be genetic or acquired by malnutrition and poor sanitary conditions. Only for some genetic causes, the exact genes are known.

Although there is no true discrimination as to who is affected by this disease, genes are passed from mother to child, and sometimes from father to child.

Women tend not to show symptoms because their second X chromosome does not have the mutation while men are symptomatic because they have an X chromosome.


One of the most common signs of immunodeficiency is an increased susceptibility to infections.

Signs and symptoms vary depending on the type of primary immunodeficiency disorder, and vary from person to person and may include:

  • Frequent and recurring pneumonia , bronchitis, sinus infections, ear infections, meningitis, or skin infections.
  • Inflammation and infection of internal organs.
  • Blood disorders, such as low platelet counts or anemia.
  • Cramps
  • Loss of appetite
  • Nausea and diarrhea.
  • Delayed growth and development.
  • Autoimmune disorders, such as lupus , rheumatoid arthritis, or type 1 diabetes.


The available treatment is divided into two modalities: treatment of infections and boost of the immune system.

Prevention of Pneumocystis pneumonia with trimethoprim / sulfamethoxazole is useful in immunocompromised patients.

In the early 1950s, immunoglobulin (Ig) was used by physicians to treat patients with primary immunodeficiency by intramuscular injection.

Ig replacement therapy are infusions that can be administered subcutaneously or intravenously, resulting in higher Ig levels for approximately three to four weeks, although this varies with each patient.


The prognosis largely depends on the nature and severity of the disease.

Some deficiencies cause early mortality (before the first year of age), others with or even without treatment are lifelong conditions that cause little mortality or morbidity.

New stem cell transplantation technologies can lead to gene-based treatments of debilitating and fatal genetic immune deficiencies.

The prognosis of acquired immune deficiencies depends on avoiding or treating the causative agent or condition (such as AIDS).