Pathology lecture mmunodeficency disorders.ppt
- 1. IMMUNO DEFICIENCY DISORDERS Dr. Al-Farah Asst. Professor
- 2. Learning objectives Define immunodeficiency. Classify immunodeficiency according to its types. Discuss various clinical presentations of immunodeficiency diseases.
- 6. CLASSIFICATIO N Immunodeficiency • Primary or Congenital: • Inherited (due to Mutation in genes controlling immune cells) • Susceptible to recurrent, severe infection; starting in childhood • Cannot recover without treatment • > 125 immunodeficiency disorders • Secondary or Acquired: • As a consequence of other diseases or environmental factors • E.g: Infection, Malignancy, Aging, Starvation, Medication & Drugs • Acquired Immuno Deficiency Syndrome – HIV.
- 7. Primary or congenital Immunodeficiency Classification B-Cell (Humoral) Immunodeficiencies T-Cell (Cellular) Immunodeficiencies B-Cell & T-Cell (Combined) Immunodeficiencies Disorders of Complement Disorders of Phagocytosis
- 12. X-Linked Hypogammaglobulinemia (Bruton’s Agammaglobulinemia) • Occur in infants at about 6 months of age, when maternal antibody is no longer present in sufficient amount to be protective.
- 13. Selective Immunoglobulin Deficiencies: IgA deficiency The cause of IgA deficiency may be a failure of heavy chain gene switching because the amounts of IgG and IgM are normal.
- 14. Thymic Aplasia (DiGeorge’s Syndrome) Pneumonia caused by Pneumocystis carinii and thrush caused by Candida albicans are two common infections in these patients.
- 16. Hyper-IgM Syndrome Mutation is in the gene encoding the CD40 ligand in the CD4-positive helper T cells
- 18. COMBINED T-CELL AND B-CELL IMMUNODEFICIENCIES • Severe Combined Immunodeficiency (SCID) • Wiskott Aldrich syndrome • Ataxia Telangiecctasia
- 19. Combined B-Cell & T-Cell Deficiencies Severe Combined Immunodeficiency Disease (SCID) Group of inherited diseases, all of which are due to a defect in the differentiation of an early stem cell. There are two types: X-linked defect in the IL-2 receptor on T cells. They lack the γ chain of the IL-2 receptor that is essential for the development of T cells. This is the most common form of SCID in the United States. Autosomal mutation in the gene encoding a tyrosine kinase called ZAP-70 that plays a role in signal transduction in T cells.
- 20. Combined B-Cell & T-Cell Deficiencies Severe Combined Immunodeficiency Disease (SCID) Because immunity is so profoundly depressed, these children must be protected from exposure to microorganisms, usually by being enclosed in a plastic “bubble.” Live, attenuated viral vaccines should not be given. Bone marrow transplantation may restore immunity. It is interesting that because infants with SCID do not reject allografts, bone marrow transplants do not require immunosuppressive drugs.
- 21. Severe Combined Immunodeficiency Disease (SCID)
- 29. Phagocyte Deficiencies Chronic Granulomatous Disease (CGD)
- 30. Chronic Granulomatous Disease (CGD) Patients with this disease are very susceptible to opportunistic infections with certain bacteria and fungi (e.g., S. aureus); enteric gram-negative rods, especially Serratia and Burkholderia; and Aspergillus fumigatus.
- 31. Chédiak-Higashi Syndrome Recurrent pyogenic infections, caused primarily By staphylococci and streptococci, occur.
- 35. • Severe Combined Immunodeficiency (SCID) • Caused by diverse genetic mutations resulting in the absence of ALL immune function • Infants with this disease lead a short life (~ 2 years) with chronic opportunistic infections • There is a milder form known as combined immunodeficiency syndrome having a low, but not absent T-cell function.
- 36. Ataxia Telangiectasia: • Autosomal recessive disease • Condition consists of worsening ataxia (lack of coordination) and telangiectasia (dilated capillaries and arterioles) on the skin and conjunctiva. • Children have reduced levels of IgA, IgE, and IgG, and lymphopenia. • Children are prone to recurrent upper and lower respiratory infections and an increased risk of malignancy.
- 37. DISORDERS OF COMPLEMENT SYSTEM • Complement system is an important part of the non-specific immune response. • Complement promotes chemotaxis, opsonization, and phagocytosis of invasive pathogens, bacteriolysis, and anaphylactic reactions.
- 38. • Primary complement disorders are caused by genetic problems • Deficiency of C1 to C4 are not at increased risk for infection because alternate pathways can be activated. • These patients are more prone to autoimmune diseases such as Lupus Erythematosus and increased susceptibility to pyogenic infections • Deficiency of late complement components (C5, C6, C7, C8) results in systemic Neisseria infections such as meningococcal sepsis, meningitis and disseminated gonococcal infections.
- 39. • Abnormalities of the control proteins of the alternative pathway (factor H, factor I, properdin) may result in recurrent infections. • Deficiency of complement inhibitors (C1 inhibitor) leads to Hereditary Angioneurotic Edema. • Secondary Disorders of Complement • Occur in persons with normal complement systems who have rapid activation or turnover of complement components • Can also occur with conditions where there is a decreased production complement components such as in liver cirrhosis or malnutrition.
- 40. DISORDERS OF PHAGOCYTOSIS • Phagocytic system: • Composed primarily of: • Neutrophils, Eosinophils and Monocytes. • Phagocytic cells function to migrate to site of infection, adhere to the tissue, engulf invading material, and then digest it. • A defect in the phagocytic system results in a decreased number of phagocytic cells. • Persons are prone to bacterial infections, often by Candida and filamentous fungi.
- 41. Disorder Inheritance Clinical Features 1) Chronic granulomatous disease X-linked (66%); autosomal recessive (33%) Infections with catalase producing bacteria and fungi affecting skin, lungs, liver; granuloma formation 2)Myeloperoxidase deficiency Autosomal Recessive Fungal infections (candidiasis) in deep tissues, especially in presence of diabetes 3)Leukocyte adhesion deficiency Auto-somal recessive Delayed separation of the umbilical cord; skin infections; otitis media; pneumonia; gingivitis; periodontitis 4)Abnormal chemotaxis -Hyper IgE -chediak-Higashi Variable Recurrent skin infections with staphylococci. enteric bacteria, Neuropathy, Occulo- cultaneous albinism in chediak higashi
- 42. SECONDARY OR ACQUIRED IMMUNODEFICIENCY B-cell deficiencies Common variable hypogammaglobulinemia Malnutrition T-cell deficiencies Acquired immunodeficiency syndrome radiation or chemotherapy from drugs or severe infections Measles Complement deficiencies Liver failure Malnutrition Phagocytic deficiencies Neutropenia
- 45. Acquired Immunodeficiency Syndrome (AIDS) AIDS is a disease caused by the retrovirus human immunodeficiency virus (HIV) and characterized by profound immunosuppression that leads to opportunistic infections, secondary neoplasms, and neurologic manifestations.
- 46. MAJOR ABNORMALITIES OF IMMUNE FUNCTION IN AIDS • Lymphopenia • Predominantly due to selective loss of CD4+ helper inducer T cell subset and reversal of CD4:CD8 ratio • Decreased T cell function • Preferential loss of memory T cells • Susceptibility to opportunistic infections and neoplasms • Decreased type IV hypersensitivity
- 47. • Polyclonal B cell activation • Hypergammaglobulinemia and circulating immune complexes • Altered monocyte and macrophage function • Decreased chemotaxis • Diminished antigen presenting to T cells.