Immunodeficiency: Causes

Pathogenesis (disease development)

The pathogenesis of immunodeficiency (immune deficiency) is complex and depends on the type of immune system dysfunction.If a majority of immune cells (e.g., lymphocytes) are affected (i.e., cellular defenses), the condition is called cellular immunodeficiency. A humoral immunodeficiency is present when antibodies and other defensive immunoglobulins (i.e., the humoral defense) are more likely to be affected. In most cases, both systems are affected. The cause of immunodeficiency is congenital immunodeficiency (primary immunodeficiency, PID) or acquired immunodeficiency. Another cause of immunodeficiency is immune senescence, which is the cause or consequence of physiological aging of the immune system. Immune senescence affects both the innate and acquired immune systems. The following are typical changes in the aging immune system:

Cell type Definition Change
B cells = B lymphocytes; the only cells capable of producing antibodies. Together with T lymphocytes, they make up the critical component of the adaptive immune system.
  • B-cell lymphopoiesis (formation and maturation of lymphocytes) ↓
  • Immunoglobulin synthesis ↓
  • Antibodies with reduced affinity
T cells Cell group of lymphocytes (subgroup of leukocytes/white blood cells)); the “T” in T cell stands for thymus, where their differentiation takes place.
  • T-cell lymphopoiesis ↓
  • Proliferative capacity ↓
  • Poorer response of memory T cells (subpopulation of T lymphocytes) to antigens.
Macrophages Monocytes (subset of leukocytes/white blood cells)) recruited to tissues to differentiate into macrophages (phagocytes); in addition, there are resident macrophages in all organs.
  • Phagocytotic activity ↓
  • Impaired Toll-like receptor expression and function.
Dendritic cells Cells of the immune system that develop either from monocytes or from precursors of B and T cells, depending on the type.
  • Number of cells ↓
  • Ability of interleukin-12 formation ↓
Natural killer cells (NK cells; Engl. Natural killer cells). Lymphocytes with cytotoxic activity that have the ability to induce apoptosis (programmed cell death) in certain target cells.NK cells in blood are defined as CD3-CD56+.
  • Cytotoxic activity ↓
  • Cytokine formation ↓

Etiology (causes)

Biographical causes

  • Primary immunodeficiencies (PID).
    • Defects of the B-cell series such as.
      • Dysimmunoglobulinemias
      • Congenital sex-linked agammaglobulinemia.
      • Selective IgA deficiency
      • Transitory hypogammaglobulinemia in infants/toddlers.
    • Defects of the T-cell series such as.
      • Chronic mucocutaneous candidiasis (fungal disease).
      • Di-George syndrome – congenital deletion on the q11 region of chromosome 22, sporadic occurrence; recurrent infections, tetanic convulsions, congenital heart defects or malformations of blood vessels.
      • Nezelof syndrome – autosomal recessive inheritance; general susceptibility to infections.
    • Combined T- and B-cell defects such as.
      • Agammaglobulinemia (Swiss type).
      • Episodic lymphopenia with lymphocytotoxin.
      • Immune deficiency with dysproportionate dwarfism.
      • Louis Bar syndrome (synonyms: (Ataxia teleangiectatica (Ataxia teleangiectasia); Boder-Sedgwick syndrome) – autosomal recessive inheritance; first symptoms around the second to third year of life; cerebellar ataxia (gait and stance unsteadiness) with cerebellar atrophy (loss of substance); Teleangiectasia (dilatation of the small arteries) mainly on the face and conjunctiva of the eye on; T-cell defect and associated with a reduced immunocompetence; hypersalivation (salivation) and hypogonadism (gonadal hypofunction).
      • Reticular dysgenesis
      • Variable immunodeficiency diseases (unclassifiable).
      • Wiskott-Aldrich syndrome – X-linked recessive inherited disorder with insufficiency (weakness) of blood clotting and immune system; symptom triad: eczema (skin rash), thrombocytopenia (lack of platelets), and recurrent infections
    • Phagocytosis disorders – form of nonspecific defense against infection – such as.
      • Chedak-Higaski syndrome – autosomal recessive inheritance; characteristics include oculocutaneous albinism (decreased pigmentation), silvery blond hair, hepatosplenomegaly (liver and spleen enlargement), ganglionic hypertrophy, and recurrent purulent infections of the skin and respiratory tract
      • Job syndrome – autosomal dominant inheritance; characteristic are skin abscesses, recurrent infections in the face in the face, upper respiratory tract and pneumonia; already in childhood as well as infancy eczematoid dermatitis (inflammatory skin reaction).
      • Lazy Leucocyte Syndrome – unclear inheritance; recurrent infections.
      • Myeloperoxidase defect
      • Progressive septic granulomatosis
    • Complement defects – complement system = special immune defense system.
      • C1 – C9 defects
    • Severe combined immunodeficiency (SCID) – group of genetic diseases (autosomal or X-linked recessive genetic defects) characterized by a complete absence of immune defense (inhibition of the development of T lymphocytes and possibly. Absence of B-lymphocytes and NK-lymphocytes); untreated, most affected individuals die in infancy; prevalence (disease frequency) about 1:70,000.
    • Other genetic diseases
      • Sickle cell anemia (med.: drepanocytosis; also sickle cell anemia, sickle cell anemia) – genetic disorder with autosomal recessive inheritance affecting erythrocytes (red blood cells); it belongs to the group of hemoglobinopathies (disorders of hemoglobin; formation of an irregular hemoglobin called sickle cell hemoglobin, HbS).
      • Trisomy 21 (Down syndrome; mode of inheritance: mostly sporadic) – special genomic mutation in humans in which the entire 21st chromosome or parts of it are present in triplicate (trisomy). In addition to physical characteristics considered typical for this syndrome, the cognitive abilities of the affected person are usually impaired; furthermore, there is an increased risk of leukemia.
  • Delivery by caesarean section (cesarean section; risk increase for immunodeficiencies 46%).
  • Age – increasing age (= senile immunodeficiency; immunosenescence); from the age of 50, the T-cell immunity decreases.
  • Socioeconomic factors – poverty

Behavioral causes

  • Nutrition
    • Malnutrition
    • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
  • Consumption of stimulants
    • Alcohol
    • Tobacco (smoking)
  • Physical activity
    • Competitive sports
    • High workload (e.g., heavy labor).
    • Shift work
  • Psycho-social situation
    • Bullying
    • Serious life cuts
    • Mental conflicts
    • Social isolation
    • Stress
  • Sleep deprivation
  • Overweight (BMI ≥ 25; obesity) (NK cell production ↓)
  • Underweight (BMI < 18.5)

Disease-related causes

Underlying diseases

  • Asplenia – absence of the spleen; congenital or acquired by splenectomy (removal of the spleen).
  • Malignancy – e.g., leukemia (cancer of the blood; chronic lymphocytic leukemia), lymphoma (malignant neoplasm originating in the lymphatic system); malignancy not in remission (decline)
  • Sarcoidosis – inflammatory systemic disease affecting mainly the skin, lungs and lymph nodes.
  • Sickle cell anemia (med.: Drepanocytosis; also sickle cell anemia, sickle cell anemia) – genetic disease with autosomal recessive inheritance, which affects the erythrocytes (red blood cells); it belongs to the group of hemoglobinopathies (disorders of hemoglobin; formation of an irregular hemoglobin, the so-called sickle cell hemoglobin, HbS).

Congenital malformations, deformities, and chromosomal abnormalities (Q00-Q99).

  • Alcohol embryopathy

Endocrine, nutritional and metabolic diseases (E00-E90).

  • Diabetes mellitus (diabetes).
  • Malnutrition
  • Malnutrition

Infectious and parasitic diseases (A00-B99).

  • Infectious diseases of all kinds, especially infection with the
    • Human immunodeficiency virus (HIV).
    • Epstein-Barr virus (EBV)
    • Cytomegalovirus (CMV)
    • Measles

Liver, gallbladder and bile ducts – Pancreas (pancreas) (K70-K77; K80-K87).

  • Chronic liver disease

Psyche – nervous system (F00-F99; G00-G99)

  • Insomnia (sleep disorders)
  • Multiple sclerosis (MS) with exacerbation (worsening; resurgence of the disease) without treatment

Mouth, esophagus (food pipe), stomach, and intestines (K00-K67; K90-K93).

  • Protein loss syndromes (protein loss syndromes) such as.
    • Protein loss enteropathy
    • Intestinal – gastrointestinal tract-related – lymphagiectasia.

Musculoskeletal system and connective tissue (M00-M99).

  • Rheumatoid arthritis
  • Systemic lupus erythematosus (SLE) – autoimmune disease with formation of autoantibodies mainly against antigens of the cell nuclei (so-called antinuclear antibodies = ANA), possibly also against blood cells and other body tissues.

Neoplasms – tumor diseases (C00-D48).

  • Aplastic anemia – form of anemia (anemia) characterized by pancytopenia (synonym: tricytopenia; reduction of all three rows of cells in the blood; stem cell disease) and concomitant hypoplasia (functional impairment) of the bone marrow.
  • Tumor diseases of all kinds, especially of the lymphatic and hematopoietic systems.

Genitourinary system (kidneys, urinary tract – reproductive organs) (N00-N99).

  • Chronic kidney disease
  • Nephrotic syndrome – collective term for symptoms that occur in various diseases of the glomerulus (renal corpuscles); the symptoms are proteinuria (increased excretion of protein in the urine) with a protein loss of more than 1 g/m²/body surface/d; hypoproteinemia, peripheral edema due to hypalbuminemia of < 2.5 g/dl in serum, hyperlipoproteinemia (lipid metabolism disorder).
  • Protein loss syndromes (protein loss syndromes) such as.
    • Glomerulopathies – pathological changes affecting the renal corpuscles.
    • Tubulopathies – pathological changes affecting the renal tubules.

Injuries, poisonings and other consequences of external causes (S00-T98).

  • Burns

Medication

Environmental pollution – intoxications (poisoning).

  • Exposure to ionizing radiation
  • Noise
  • Radiation syndrome – complex of symptoms that may occur after therapy/exposure to ionizing radiation.

Further