1 / 24

Immunodeficiency:

Immunodeficiency: . Primary immune deficiency: -Caused by intrinsic or congenital defects . - Over 100 diseases of this type are known in humans, and for many of these diseases, the specific defective genes have been identified. -Types: 1-Defects in stem cells.

acton
Download Presentation

Immunodeficiency:

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Immunodeficiency: Primary immune deficiency: -Caused by intrinsic or congenital defects. -Over 100 diseases of this type are known in humans, and for many of these diseases, the specific defective genes have been identified. -Types: 1-Defects in stem cells. 2-Defects in T lymphocytes. 3-Defects in B lymphocytes. 4-Defects in phagocytes and NK cells. 5-Defects in complement system.

  2. Defects in stem cells: 1-Severe combined immune deficiency (SCID): Genetics: Mode of Inheritance: Autosomal recessive (chrom. 11). X-linked recessive. Defective genes: RAG 1,2 gene. IL2RG gene. Function:Rearrangement of DNA to form variable regions of Immunoglobulin and TCR. Production of γ chain (common cytokine receptor) : IL-2R, IL-4R, IL-9R, IL-15R, INFγR.

  3. N Effect: Defect in B and T lymphocytes maturation. Features: Lethal susceptibility to both viral and bacterial infections due to deficiency of both humoral and cellular immunity. 2-Ataxia telangiectasia: Genetics: AR -Rearrangement of gene at chromosome 7, 14. -Gene: T cell receptor genes. -Function: T lymphocyte clonal selection.

  4. N Feature: -Oculocutaneous telangiectasia (dilated blood vessels in the conjunctivae, ears, and face). - Low serum IgA, and IgG. -Thymus hypoplasia. - Recurrent infection: Sinusitis, and pneumonia. - Increased risk of Leukemia and Lymphoma.

  5. N 3-Wiskott-Aldrich syndrome: Genetics: - XR gene mutation. - Etiology: defect in lymphocyte cytoskeleton. Feature: Boys have eczema, diarrhoea and recurrent infections, thrombocytopenia, low IgM level, and Tc -Th function.

  6. Defect in T Lymphocytes: 1-bare Lymphocyte syndrome: Genetics:AR gene on Chromosome 1 or 16. Etiology: Type 1: Mutationin the TAP gene prevent export of Class I MHC to the cell surface. Type 2 : Defectsin MHC II specific transcription factor, cause defect in T-helper function. Features: -Increased susceptibility to infection. -CD4 and CD8 cells numbers decreased. - Intracellular infection could cause lethal effect.

  7. N 2-DiGeorge syndrome: Genetics: AD gene deletion in chromosome 22 q 11. Etiology: 1- Completeor partial absence of thymus. 2- Defectin T-cell clonal selection and maturation. Features: -Increased susceptibility to viral infection. -Reduced active T cell production.

  8. Defect in B Lymphocytes: 1-Bruton’sagammaglobulinaemia: Genetics: X-linked recessive gene (BTK). Etiology: Defective B-cell tyrosine kinase prevents the B cell maturation. Features: -Increased susceptibility to infection(capsulated bacteria). -Very low level of Immunoglobulin or lost level. -5-6 months boys develop lethal multiple infections of lung.

  9. N 2-Immunodeficiency with Hyper-IgM: Genetics : X-linked recessive gene (CD40L G). Etiology: 1-Defect in expression of CD40L on B lymphocyte. 2-Inability of B lymphocyte to undergo isotype switching. Features: -Elevated IgM and IgD in blood stream. -Decreased IgG, IgA, and IgEconcentration. -Increased susceptibility to pyogenic infection.

  10. N 3-Selective IgA deficiency: Genetics: Multiple genes and forms. Etiology: -Defect in IgA production in body fluids. Features: -No increased susceptibility to infection. -Low IgA level. -Normal level of other antibodies.

  11. Defect in Phagocytes and Natural Killer cell: 1-Chronic granulomatous disease (CGD): Genetics: -XR ;Beta-chain of cytochrome b oxidase. -AR (chr.1,7); NADPH oxidase. -AR (chr.16); alpha chain of cytochrome b oxidase. Etiology: -Inability of Phagocytes to generate superoxide metabolites. Features: -Granulomatous infection in skin, lymph nodes, lung, liver.

  12. N 2-Chediak- Higashi syndrome: Genetics: -AR (Chromosome 1) Gene (LYST). (Lysosomal trafficking regulator). Etiology: -Defect in fusion of lysosome to phagosomes. -Defect of release of cytotoxicgranules. Features: -Increased susceptibility to pyogenic bacteria. -Reduced ability of phagocytes to kill ingested microbes. - Decreased functions of NK cell (Cytotoxicity). -Risk for development of Lymphoma.

  13. N 3- Leucocyte adhesion deficiency: Genetics: AR gene (ITGB2 or CD18) The leukocyte surface integrin Beta chains. Etiology: -Defect in migration of WBCs from circulation to the site of infection (tissue). Features: -Increased susceptibility to infection. -Frequent abscesses. -Defective chemotaxis.

  14. Defect in complement system: 1- C1,2,3,…,9 immunodeficiency: Genetics: Autosomal recessive gene (Chr. 1,2,5,6,9,12,19). Etiology: C1,2,3,...,9 deficiency. Features: -Increased susceptibility to infection. -associated with lupus like syndrome. -Defect in production of MAC unit of Classical pathway.

  15. N 2-Hereditary angioneuroticedema: Genetics: Autosomal dominant gene (Chr. 11). C1 inhibitor protein. Etiology: Defect in inhibition of Classical pathway. Features: - Fluids accumulation in soft tissue and airways due to uncontrolled production of C2a. -Swelling of tracheal and bronchial passages that can be life-threatening.

  16. Secondary (acquired) immune deficiency: -The immunodeficiency that associated with exposure to environmental factors. -Not related to inheritance of genetic mutations. -Types: 1-Therapeutic immunodeficiency. 2-Malignant tumor- associated deficiency. 3-Infectious immunodeficiency.

  17. N Therapeutic immunodeficiency: Examples: -Some Anti-inflammatory drugs (corticosteroids) ; treatment of Rheumatoid arthritis : Interfere with production of some cytokines. -Immunosuppressive drugs (cyclosporine); used during organ transplantation: Interfere with production of some cytokines.

  18. N Malignant tumor- associated deficiency: Examples: -Multiple myeloma: Increased polyclonal B cell activation non-specifically. - Lymphoma (HK): Uncontrolled proliferation of B lymphocytes (E.B virus). -Chronic lymphocytic leukemia: Reduced production of Immunoglobulin.

  19. Infectious immunodeficiency: Examples: -Schistosoma species: Enzymatic degradation of immunoglobulins. -Herpesvirus: inhibits MHC class I maturation within E.R. -CMV: Interferes with TAP of E.R. Redirects MHC I into cytoplasm rather than to cell surface. -Chlamydia: prevents phagosomes-lysosomes fusion.

  20. N -Staphylococcus: -Kills phagocytes by its toxins. -Protein A prevents opsonization. -Mycobacterium: -Kills phagocytes. -Prevents phagosome-lysosome fusion. -Inhibits oxidative degradation within phagosome. -Plasmodiumspecies: -RBCs infection. -Human Immunodeficiency virus (HIV): -Kills CD4, Monocytes, and CD8 cells. -Nef gene redirects MHC I into lysosome.

  21. N Human Immunodeficiency Virus (HIV): HIV infection in humans is considered pandemic by the World Health Organization (WHO). From its discovery in 1981 to 2006, AIDS killed more than 25 million people . Tropism: Some immune cells have a specific HIV susceptibility due to presence of specific receptors. -Macrophages, and dendriticcells carry the chemokine receptor CCR5. -CD4 T helper cells express the chemokine receptor CXCR4.

  22. HIV Tropism: N

  23. HIV infection periods: N

  24. N 1-Asymptomatic period: CD4:8 Ratio= 2:1 2-Latency and chronic period : -The virus is preserved in the dendritic cells of Lymph nodes. -Late Latency : CD4:8 Ratio= 1:1 3-AIDS period: -No cytotoxic Tc response. -No Humoral immunity. -CD4:8 Ratio= 1:2 -CD4 count less than 200 cell per μL.

More Related