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Immuno deficiency disorders


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Immuno deficiency disorders

  2. 2. DEFINITIONS • Immunity • Immune system • Components of Immune systems
  3. 3. IMMUNODEFICIENCY DISORDERS • Definition: Immunodeficiency- an abnormality of the immune system that renders a person susceptible to diseases normally prevented by a normal functioning immune system.
  4. 4. CLASSIFICATION • Immunodeficiency: • Primary or Congenital: • • • • Inherited (due to Mutation in genes controlling immune cells) Susceptible to recurrent, severe infection; starting in children 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 – Human Immunodeficiency Virus.
  6. 6. • Four Categories Immune Mechanisms • Humoral (Antibody or B-cell mediated) • Specific type of mechanism • Cell-mediated (T-cell mediated) • Specific type of mechanism • Complement system • Non-specific type of mechanism • Phagocytosis • Non-specific type of mechanism
  8. 8. DEFECTS IN HUMORAL MEDIATED IMMUNITY • Caused by the improper production of one or all of the immunoglobins (antibodies) • Results in an increased of infections from Staphylococcus, Streptococcus, Haemophilus, and Pseudomonas. • Humoral Immunodeficiencies include: • Bruton’s X-Linked Agammaglobinulinemia • Common Variable Immunodeficiency • Selective Immunoglobin A Deficiency
  9. 9. DEFECTS IN CELL MEDIATED IMMUNITY • Caused by defects in T lymphocyte development (both CD4+ helper cells and CD8+ cytotoxic killer cells) • Symptoms are more severe than with humeral immunodeficiencies • Children rarely survive beyond infancy or childhood • Cell Mediated Immunodeficiency disorders include: • DiGeorge Syndrome • X-Linked Immunodeficiency with Hyper-IgM
  10. 10. COMBINED T-CELL AND B-CELL IMMUNODEFICIENCIES • Severe Combined Immunodeficiency (SCID) • Ataxia Telangiecctasia • Wiskott Aldrich syndrome
  11. 11. • 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.
  12. 12. • Ataxia Telangiectasia: • Results from a mutation on chromosome 11 • 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 decreased ratio of CD4+ helper T cells to CD8+ cells. • Children are prone to recurrent upper and lower respiratory infections and an increased risk of malignancy. • Death from lymphoma is common
  14. 14. • Wiskott-Aldrich Syndrome: • Patient has decreased IgM and elevated levels of IgA and IgE. • T-cell dysfunction is initially mild then progressively worsens making child susceptible to Hodgkin’s disease and lymphoma • They are also susceptible to infections (including septicemia and meningitis) caused by encapsulated microorganisms • Signs and symptoms: • eczema • chronic infections • low platelet counts
  15. 15. 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.
  16. 16. • 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.
  17. 17. • Abnormalities of the control proteins of the alternative pathway (factor H, factor I, properdin) may result in recurrent infections. • Deficiency of complement inhibitors (C1 esterase inhibitor, carboxypeptidase N) 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.
  18. 18. 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.
  19. 19. 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, Occulocultaneous albinism in chediak higashi
  22. 22. EVALUATION OF IMMUNODEFICIENCY Often present Usually present 1. Recurrent respiratory tract infections 2. Severe bacterial infections 3. Recurrence of same type of bacteria 4. Paucity of lymph nodes and tonsils 1. Persistent sinusitis or mastoiditis 2. Failure to thrive 3. Intermittent fever 4. Skin lesions 5. Diarrhea 6. Hearing loss due to chronic middle ear infections 7. Chronic conjunctivitis 8. Bronchiectasis 9. Evidence of autoimmunity 10. Hematologic abnormality Occasionally present 1. 2. 3. 4. 5. 6. Lymphadenopathy Hepatosplenomegaly Severe viral illnesses Chronic encephalitis Deep infections Delayed umbilical detachment 7. Adverse reactions to vaccines
  24. 24. Characteristic T- cell defect B- cell defect Granulocyte defect Complement defect Age of onset of infection Early; 2-6 months After 5-7 months Early onset at birth Any age Specific pathogens Mycobacteria, Viruses, Fungus like Candida and parasites Pyogenic bacteria mainly Streptococci, Staphylococci Hemophilus enteroviruses Bacteria; Staphylococcus Pseudomonas Klebsiella Bacteria Systemic effects Failure to thrive, Extensive mucocutaneous Candidiasis Recurrent sinopulmonary infections Malabsorption Enteroviral encephalitis Skin abscesses, impetigo, cellulitis Recurrent sinopulmonary infections Meningitis Special features GVHD, Post vaccination disseminated BCG or Varicella Hypocalcemic tetany in infancy Autoimmunity Lymphoma Thymoma Post vaccination paralytic polio Prolonged attachment of umbilical cord Poor wound healing Autoimmune diseases
  25. 25. LABORATORY EVALUATION OF IMMUNODEFICIENCY DISORDERS • Routine investigations: • Total and differential leucocyte counts • Absolute lymphocyte count • Normal result rules out T- cell defect • Absolute neutrophil count • Normal study rules out granulocyte defect • Platelet count and morphology • Normal result rules out WAS • Howell- Jolly bodies • ESR
  26. 26. Suspected B cell defect Serum Electrophoresis Hypogammaglobulinemia Immunoglobulin pattern B cell count Low XLA Normal Abnormal Possible CVID Normal Consider complement or phagocytic dysfunction
  28. 28. • Acquired immunodeficiency syndrome (AIDS) is a secondary immunodeficiency • AIDS is a disease caused by the retrovirus Human Immunodeficiency Virus (HIV) which is a single stranded RNA virus • It is characterized by profound immunosuppression that leads to opportunistic infections, secondary neoplasms and neurologic manifestations.
  30. 30. TRANSMISSION OF HIV INFECTION • Sexual contact • Most frequent mechanism • 75-80% via unprotected sex • The virus can pass from semen and vaginal secretions into the bloodstream through mucous membranes and wounds in the skin. • Blood-to-blood contact • Needle stick injury • Sharing of needles or • Transfusion of blood and blood products.
  31. 31. • Perinatal transmission can occur in utero, during labor, or by breast feeding • Studies still show that HIV does not spread through casual contact or by vectors such as mosquitoes
  32. 32. 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
  33. 33. • Polyclonal B cell activation • Hypergammaglobulinemia and circulating immune complexes • Altered monocyte and macrophage function • Decreased chemotaxis • Diminished antigen presenting to T cells.
  34. 34. Infected helper T-cell The small blue globules are HIV particles.
  35. 35. CLINICAL MANIFESTATIONS OF AIDS • An infection by microorganism that normally does not cause disease but become pathogenic when the body’s immune system is impaired and unable to fight off the infection are “opportunistic infections” (OIs). • OIs are the hallmark of immunodeficiency with HIV • It is important to diagnose OIs as the acute infections are at times lifethreatening and effective prophylaxis and treatment renders better survival.
  36. 36. AIDS DEFINING OPPORTUNISTIC INFECTIONS AND NEOPLASMS • Infections: • Protozoal and helminthic infections • • • • Cryptosporidiosis or Isosporidiosis Pneumoncystitis jirovecii pneumonia or disseminated infection Toxoplasmosis Strongyloidiasis • Fungal infections • • • • Candiadisis (esophageal, tracheal or pulmonary) Cryptococcosis Coccidioidomycosis Invasive Aspergillosis • Bacterial infections • Mycobacteriosis (M. tuberculosis or atypical mycobacteriosis) • Nocardiosis (Pneumonia, Meningitis or disseminated) • Salmonellosis
  37. 37. • Viral infections • Cytomegalovirus (pulmonary, intestinal, retinitis or CNS infection) • Herpes- simplex virus and varicella – Zoster virus (localized or disseminated) • Progressive multifocal leucoencephalopathy • Neoplasms • • • • Kaposi’s sarcoma B cell non Hodgkin lymphoma Primary lymphoma of brain Invasive cancer of the cervix.
  38. 38. • There is a correlation between CD4 count and HIV related infections. > 500 cells/mm3 – Recurrent vaginal candidiasis 200-500 cells/mm3 – Pulmonary TB, Pneumococcal pneumonia, Herpes zoster, Oropharyngeal candidiasis, Recurrent Salmonellosis < 200 cells/mm3 – Pneumocystis jirovecii pneumonia, mucocutaneous Herpes simplex, Cryptosporidiosis, Esophageal candidiasis, Miliary/ Extrapulmonary TB. < 100 cells/mm3 – cerebral Toxoplasmosis, Cryptococcal meningitis < 50 cells/mm3 – CMV retinitis & gastrointestinal disease and disseminated Mycobacterium avium intercellulare
  39. 39. Laboratory parameters during the course of the illness
  40. 40. • Tests to detect the presence of infection • Detection of viral antigens in the serum • Detection of antibodies to viral antigens in the serum • Detection of viral genomic material in the blood • Tests to determine the extent of the disease • Total CD4+ helper T-cell count • Quantitative viral RNA copies in blood. • Tests to detect the presence of various opportunistic infections.
  41. 41. TREATMENT
  42. 42. PRIMARY IMMUNODEFICIENCIES • B cell deficiencies: • IV Immunoglobulin 200-800mg/kg • Culture and sensitivity of organisms causing infection • Early drainage of abscess • Early control of infection • T cell deficiencies: • Early treatment of infection • Transplantation of foetal thymus or HLA matched bone marrow • Topical and systemic antifungal therapy • Stem cell transplantation is definitive therapy for SCID and most of phagocytic disorders like LAD, CGD and Chediak- Higashi disease
  43. 43. • More recently Gene therapy has been attempted as an alternative to the bone marrow transplant • Transduction of the missing gene to hematopoietic stem cells using viral vectors is being tested in ADA SCID and X-linked SCID • In 1990, four-year-old Ashanthi DeSilva became the first patient to undergo successful gene therapy. Researchers collected samples of Ashanthi's blood, isolated some of her white blood cells, and used a virus to insert a healthy adenosine deaminase (ADA) gene into the defective cells. • These cells were then injected back into her body, and began to express a normal enzyme. This, augmented by weekly injections of ADA, corrected her deficiency.
  44. 44. SECONDARY IMMUNODEFICIENCIES • Prompt and early instillation of anti retroviral therapy will help in control of the disease • Prophylaxis to prevent development of opportunistic infections.
  45. 45. Mobile: 99899 10303 Email ID: