Understanding Primary Immunodeficiency: Types, Causes, and Inflammation

Posted on Mar 15, 2025 in Microbiology

Primary Immunodeficiency: T and B Cell Disorders

Primary immunodeficiency involves disorders affecting T cells (related to infection organic level) and B cells (related to airway pyogenic infections).

Severe Combined Immunodeficiency (SCID)

SCID is characterized by the absence of T and B lymphocytes, leading to a lack of immune response. It results in infections from opportunistic pathogens and failure of lymphoid stem cell maturation. SCID can be associated with the X chromosome. A defective IL-7 signal prevents T lymphocyte maturation, affecting IL-2, B lymphocytes, T, and NK cells.

Congenital Thymic Aplasia: DiGeorge Syndrome

DiGeorge Syndrome is an embryonic defect of the 3rd and 4th pharyngeal arches, causing defects in the thymus, parathyroid, and cardiac outflow tract. It results in profound T lymphocytopenia, affecting the maturation of the T cell lineage.

X-Linked Agammaglobulinemia

This condition primarily affects males, leading to pyogenic bacterial and viral infections. It affects the maturation of the B cell lineage (pre-B cells) due to a defective BTK gene product.

Adenosine Deaminase (ADA) Deficiency

ADA deficiency inhibits normal lymphocyte proliferation, causing T and B cell cytopenia.

Purine Nucleoside Phosphorylase (PNP) Deficiency

PNP deficiency results in functional T cell abnormalities.

Chronic Granulomatous Disease

This X-linked condition, primarily seen in children, damages granulocyte function, leading to skin infections. Common pathogens include S. aureus. NADPH oxidase deficiency is a key feature, and gastrointestinal and genitourinary obstruction can occur.

Common Variable Immunodeficiency

This condition typically affects adults, leading to airway infections and decreased immunoglobulin production. It results from defects in B cell differentiation, increased T lymphocyte production, and decreased IL-2 production.

Hyper IgM Immunodeficiency

Characterized by elevated IgM levels and decreased IgA and IgG levels. It can be autosomal or X-linked, with defective expression of the T-cell marker CD154.

Hyper IgE Immunodeficiency (Job Syndrome)

Symptoms include boils, cellulitis, otitis, and sinusitis, often caused by S. aureus. There is deficient Ig production and B cell dysfunction, leading to abnormal T cell cytokine production.

Inflammation Types

Acute Inflammation: Characterized by PMN cells and macrophages.

Chronic Inflammation: Characterized by plasma cells, lymphocytes, and fibroblasts.

Subacute Inflammation: A less defined, intermediate state.

Exudate Types

  • Acute Serous: Variable protein content, often bacterial in origin, seen in blisters.
  • Acute Fibrinous: Rich in protein, alters membrane impermeability, leading to pseudomembrane formation.
  • Acute Suppurative: Characterized by pus (purulent exudate) containing PMNs, often bacterial.
  • Purulent Catarrh: Superficial mucosal inflammation with exudation and leucodiapedesis.
  • Empyema: Localized inflammation with pus accumulation.
  • Cellulitis: Poorly delimited inflammation in solid tissue, often with necrosis.
  • Abscess: Well-delimited area of tissue destruction with pus accumulation.
  • Ulcer: Focal necrosis of an organ or conduit, with excavation of necrotic tissue (skin, mucosa), containing PMNs.
  • Acute Hemorrhagic: Characterized by diapedesis and rupture, necrosis of vessel walls.
  • Acute Putrid: Bacterial infection with gray-green, foul-smelling exudate due to hydrogen sulfide.

Chronic Inflammation

  • Polymicrobial/Nonspecific/Polyetiological: Involves plasma cells, lymphocytes, and macrophages.
  • Specific/Granulomatous: Involves modified macrophages (epitheloid cells), macrophages, fibroblasts, and Langhans giant cells.

Hypersensitivity Reactions

  1. Type I (Immediate): Release of inflammatory mediators, allergy, immediate hypersensitivity, IgE on mast cells or basophils.
  2. Type II (Antibody-Mediated Cytotoxicity): IgG or IgM mediated, examples include hemolytic anemia, Rh incompatibility between mother and child, autoimmune hyperthyroidism, and myasthenia gravis.
  3. Type III (Immune Complex-Mediated): IgG and IgM immune complexes, leading to anaphylatoxin production, chemotaxis, and necrosis.
  4. Type IV (T Cell-Mediated): Delayed-type hypersensitivity (not Ig-mediated), T lymphocytes involved, examples include transplant rejection, leprosy, tuberculosis, tuberculin skin test, and contact dermatitis.