* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Immunodeficiency - quantitative or qualitative defects of immune
Chagas disease wikipedia , lookup
Trichinosis wikipedia , lookup
Middle East respiratory syndrome wikipedia , lookup
Microbicides for sexually transmitted diseases wikipedia , lookup
Diagnosis of HIV/AIDS wikipedia , lookup
Leptospirosis wikipedia , lookup
Sarcocystis wikipedia , lookup
West Nile fever wikipedia , lookup
Hepatitis C wikipedia , lookup
Herpes simplex virus wikipedia , lookup
Sexually transmitted infection wikipedia , lookup
African trypanosomiasis wikipedia , lookup
Neisseria meningitidis wikipedia , lookup
Visceral leishmaniasis wikipedia , lookup
Marburg virus disease wikipedia , lookup
Oesophagostomum wikipedia , lookup
Antiviral drug wikipedia , lookup
Human cytomegalovirus wikipedia , lookup
Neonatal infection wikipedia , lookup
Schistosomiasis wikipedia , lookup
Coccidioidomycosis wikipedia , lookup
Hospital-acquired infection wikipedia , lookup
TO UNDERSTAND THE PATHOPHYSIOLOGY, LABORATORY,AND CLINICAL ASPECTS OF THE IMMUNODEFICIENCY DISORDERS Immunodeficiency - quantitative or qualitative defects of immune system • may involve the cells and components of: - natural defense system ( e.g. Defect of phagocytosis, complement mediated defense) - acquired immunity involving T- and B- cells • associated with an increase susceptibility of infection and lymphoproliferative disease • PRIMARY – congenital, mostly genetic deficiencies of one or more components of immune system • SECONDARY – numerous acquired deficiencies of one and more components of immune system caused by infection, malnutrition, drugs, irradiation, cancer or autoimmunity. • B cell deficiencies T- & B-cell deficiencies • X-linked agammmaglobulinemia ( Bruton) Hyper IgM syndrome • Common variable immunodeficiency DiGeorge syndrome • Isolated IgA deficiency Severe combined immunodeficiency D 02-03/06 TO UNDERSTAND THE PATHOPHYSIOLOGY, LABORATORY,AND CLINICAL ASPECTS OF THE IMMUNODEFICIENCY DISORDERS • X- linked agammaglobulinemia – Bruton type – is a sex linked recessive disease whose pathogenesis involves the failure of pre-B cells to differentiate into mature B cells. Failure to assemble complete immunoglobulin molecules is due to a mutation in btk (Brtuon tyrosinase kinase) gene located on X q21.2-22 chromosome. Maternally derived IgG protects the newborn for few months before affected infants begin to develop sinopulmonary disease associated with Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. Since cell-mediated immunity is intact there is an effective host defense against most viruses and fungi • Common variable immunodeficiency – onset in late childhood of hypogammaglobulinemia and recurrent infections. Boys and girls are affected equally. High frequency of malignancies – gastric cancer, lymphoma – later in life. • Isolated IgA deficiency – the most common hereditary immunodeficiency is due to an intrinsic defect in the differentiation of B cells committed to synthesizing IgA or to a defect in T cells that prevents B cells from synthesizing IgA. Because IgA is the major immunoglobulin found in mucosal secretions ( respiratory, GI tract), IgA immunodeficiency is characterized by recurrent sinusitis, pulmonary and urinary infections and recurrent diarrhea. D 02-03/06 TO UNDERSTAND THE PATHOPHYSIOLOGY, LABORATORY,AND CLINICAL ASPECTS OF THE IMMUNODEFICIENCY DISORDERS • X- linked hyper IgM syndrome – persons have high titers of IgM and IgD but low level of IgG, IgA and IgE antibodies, indicating defect in isotype switching. • primary defect in CD4+ T- cells • caused by mutation of X-chromosome gene coding Cd40L Patients suffer from pyogenic infections and are susceptible to infection with Pneumocystis carinii. • DiGeorge syndrome – is failure of third and fourth pouches to develop due to deletion of chromosome 21q11, with subsequent absence of all four parathyroid glands and thymus. Part of CATCH 22 syndrome : Cardiac abnormalities, T cell deficit, Cleft plate , Hypocalcemia. • Severe combined immunodeficiency – SCID X-chromosome linked – boys are typically affected Both humoral and cellular immunity responses are affected Susceptibility to severe, recurrent fungal, viral and bacterial infections • Wiskot-Aldrich syndrome – is sex linked recessive disease with triad of thrombocytopenia, eczema and recurrent sinopulmonary infections complicate by an increased risk for development of malignant lymphomas. •The most common diseases resulting from deficiencies of the complement system • C2 deficiency results in increased susceptibility to infections and SLE-like syndrome • C1-inhibitor deficiency give rise to hereditary angioedema D 02-03/06 TO UNDERSTAND THE PATHOPHYSIOLOGY, LABORATORY,AND CLINICAL ASPECTS OF THE IMMUNODEFICIENCY DISORDERS AIDS- is and infectious disease caused by human immunodeficiency virus –HIV. It is characterized by profound suppression the immune system and susceptibility to infection, neurological disorders and malignancies. HIV-1 and HIV-2 – two genetically different but closely related forms of human disease. RNA viruses belonging to retrovirus family HIV expresses cell surface protein gp 120 that binds to CD+ surface molecule of T-cells proviral DNA synthesized by a reverse transcription in infected cells is integrated into the host DNA Mode of transmission Sexual contact – homosexual, heterosexual Potential inoculation – iv drug abuser, transfusion of blood and blood products Passage from infected mother to child - transplacental spread, during delivery, during breast feeding The virus is carried by semen, contaminated blood or bodily secretions- any contact with them carries a potential risk for transmission of the disease. D 02-03/06 TO UNDERSTAND THE PATHOPHYSIOLOGY, LABORATORY,AND CLINICAL ASPECTS OF THE IMMUNODEFICIENCY DISORDERS Pathogenesis of AIDS • • • • • • CD4+ T- cell, macrophages & dendritic cells are primary targets for HIV HIV binds to CD+ cells which acts as a high-affinity receptor; infection requires coreceptors CCR5 and CXCR4 - chemokine receptors Once internalized , viral genome undergo reverse transcription leading to formation of proviral DNA, - cDNA cDNA in dividing cells intergrades in the host genome Proviral DNA is transcript and complete virus particles are produce which may lead to cell death This results in reduction of CD+ T-cells, persistent productive infection of macrophages, monocytes and Langerhans cells Clinical phases of HIV infection • • • Early, acute phase – self limited illness 3-6 weeks after infection. High level of virus production and widespread infection of lymphoid organs Middle, chronic phase – no symptoms or persistent lymphadenoptahy for several years. Minor infection Final, crisis – long lasting fever, severe opportunistic infections, secondary neoplasms, neurologic disease. It usually develops after 7-10 years of chronic phase. Laboratory test to confirmed diagnosis of AIDS Seroconversion – presence of HIV • antibodies in previously non-reactive individuals – occurs within 6 mints of exposure to HIV Detection of infection during • serological window before seroconversion requires detection of viral antigen or viral RNA D 02-03/06 TO UNDERSTAND THE PATHOPHYSIOLOGY, LABORATORY,AND CLINICAL ASPECTS OF THE IMMUNODEFICIENCY DISORDERS Opportunistic infection in AIDS Opportunistic infections account for the vast majority of deaths in patients with HIV infection. These are: • • • • • • Pneumocytis carinii pneumonia Candida albicans infection of mouth, esophagus, vagina, lungs Cytomegalovirus enteritis, pnuemonitis Atypical mycobacterial infection (M. avium intracellulare) of GI tract Cryptococcus meningitis Cryptosporidium enteritis Neoplasms associated with HIV infection • • • • Kaposi sarcoma Non Hodgkin lymphoma Carcinoma of uterine cervix Squamous carcinoma of the skin D 02-03/06 TO UNDERSTAND THE PATHOPHYSIOLOGY, LABORATORY,AND CLINICAL ASPECTS OF THE IMMUNODEFICIENCY DISORDERS Neurological consequences of HIV infection Involvement of the CNS is common (4060%) and may present in several forms: • • Opportunistic infection • Viral – CMV, Herpes simplex, fungal , protozoal Aseptic meningitis AIDS dementia complex Neoplasms • Lymphoma D 02-03/06 TO UNDERSTAND THE PATHOPHYSIOLOGY, LABORATORY AND CLINICAL ASPECTS OF AMYLOIDOSIS Amyloidosis Amyloidosis is a group of diseases characterized by deposition of amyloid in various organs Amyloid is a proteinaceous substance deposited between cells in various organs and tissue in a variety of clinical settings. • The name derives from starch-like staining properties • Amorphous, eosinophilic, hyline extracellular substance seen under microscope. • Chemically diverse. • Typical physical properties. All amyloidosis irrespective of their biochemical composition form non-branching long fibrils (7.5-10mm) By electron diffraction they are arranged in β-pleated sheaths. • Congo-red staining is typical. Under polarized light, Congo-red stained amyloid fibrils show an apple green birefringence. D 02-03/06 TO UNDERSTAND THE PATHOPHYSIOLOGY, LABORATORY AND CLINICAL ASPECTS OF AMYLOIDOSIS Biochemical forms of amyloid • Al – amyloid formed by immunoglobulin light chains. This form of amyloid is found in multiple myloma • AA – amyloid associated protein synthesized by liver – SAA ( serum amyloid A). This form of amyloid is seen in tissue of patients harboring chronic suppurative infection • Aβ - amyloid found in Alzheimer disease The deposition of amyloid may occur as a primary disease – multiple myloma. Or as a secondary form in the course of chronic inlammation or other disease. The disease may be limited to a single organ, or systemic, and some forms may be hereditary. D 02-03/06 TO UNDERSTAND THE PATHOPHYSIOLOGY, LABORATORY AND CLINICAL ASPECTS OF AMYLOIDOSIS Characteritics of primary amyloidosis • • • Systemic deposits of AL type amyloid Associated with plasma cell neoplasia and B-cell lymphoma Monoclonal gammapathy Characteristics of secondary amyloidosis • • Underlying disease –e.g. Tuberculosis, chronic ostemylitis, rheumatoid arthritis, cancer, or condition- e.g. heroin abuse Widespread deposition of AA protein in many organs Amyloidosis of aging • systemic deposition of amyloid in elderly patients • frequent involvement of heart – cardiac amyloidosis D 02-03/06 TO UNDERSTAND THE PATHOPHYSIOLOGY, LABORATORY AND CLINICAL ASPECTS OF AMYLOIDOSIS Morphological features in systemic amyloidosis • kidney: enlarged. Pale, waxy. Glomerular mesengial, interstitial and vascular deposition of amyloid • spleen: enlarged with either nodular (follicular) depositions- sago spleen, or map-like (red pulp) deposition – lardaceous spleen • liver: hepatomegaly, extracellular amyloid with pressure atrophy of hepatocytes • small blood vessels in many organs contain deposits of amyloid. Amyloid deposits in blood vessels can be observed in gingival or rectal biopsies – commonly preformed to diagnosis of disease. D 02-03/06