Understanding Primary Immunodeficiency: Types, Causes, and Inflammation
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
- Type I (Immediate): Release of inflammatory mediators, allergy, immediate hypersensitivity, IgE on mast cells or basophils.
- Type II (Antibody-Mediated Cytotoxicity): IgG or IgM mediated, examples include hemolytic anemia, Rh incompatibility between mother and child, autoimmune hyperthyroidism, and myasthenia gravis.
- Type III (Immune Complex-Mediated): IgG and IgM immune complexes, leading to anaphylatoxin production, chemotaxis, and necrosis.
- 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.