University:
American Career College
Course:
NURS115 | Intermediate Medical
Academic year:

2021
Views:

55

Pages:

57
Author:

Opfer8fg

IMMUNE DEFICIENCY DISEASES X-Linked Agammaglobulinemia of Bruton Basic characteristic:  No B-cell in peripheral smear but pre B-cells in bone marrow  Depressed level of all Igs  Underdeveloped germinal centers of lymphnodes  No plasma cells  T-cells are normal  Autoimmune diseases in half of cases  Treatment: Immunoglobulin replacement  Digeorge’s Syndrome Congenital malformation of 3rd and 4th phar.pauch  Rudimentary thymus  No T-cell in peripheral smears, spleen and lymphnodes  Susceptible to viral, fungal, and protozoal infection  Abnl. In heart and blood vessels or facial abnormalities  Hypocalcemia  Not a familial disorder: Deletion of an unidentified gene in 22q11  SCID Humoral and cellular defects  Decreased lymphocytes (T and B cells) but primarily T-cell defect  Immature lymphocytes in peripheral smears  Hypoplastic thymus and lymph nodes  50-60% of cases: X-liked recessive:   Mutation in the common γ chain subunit of several cytokine (IL2, IL4, IL7, IL9. IL11 and IL15) receptors that is a transmembrane protein for signal transduction SCID ½ : autosomal recessive  50% of AR. Types: ADA deficiency decreased purin metabolism increased intracellular deoxyadenosine Toxic for T cells  Less common type of AR.: defect in T-cell activation: gene rearrangement, signal transduction, MHC II expression ….  Susceptible to all infections  Treatment: Bone marrow transplantation Gene therapy for ADA deficiency  Selective IgA deficiency Most common form of immunodeficiency  Incidence: 1/700  Defect in serum and secretory IgA  Most patients are asymptomatic but some develop respiratory infections, chronic diarrhea and asthma  Associated with autoimmune dx: SLE, RA  Some defect in IgG2, IgG4 infection  Anti IgA antibody in 44%  transfusion reaction  Acquired form: following toxoplasma or measles  Basic defect: IgA B cells IgA plasma cells  Common Variable Immunodeficiency        Heterogeneous group of disorders Common to all patients: Hypo γ, generally affecting all Ig classes but sometimes IgG Congenital or acquired sporadic or familial 2/3 B-cell (although normal in number) plasma cell impairment Hyperplastic B-cell areas Similarities with Bruton Dx: Bacterial infection, autoimmune diseases, lymphoid malignancies and gastric cancer Differences from Bruton:  Both sexes equally involve  Later onset of symptoms Wiskott-Aldrich syndrome       X linked recessive Eczema, thrombocytopenia and recurrent infection Poor Ab response : pneumococci, H-influenza T-cell and B-cell initially normal but later ↓T-cells Prone to malignant lymphoma Xp11.23 gene: WASP: link membrane receptors such as Ag receptors to cytoskeleton elements defect in cytoskeleton and signal transduction Hyper IgM syndrome A T-cell disorder: defect in induction of isotype switching  Defect in CD40- CD40 ligand  70% : mutations in gene for CD40L that maps to Xq26 (Xlinked form)  Recurrent pyogenic infection (opsonization defect)  Susceptible to P. carinii (defect in T-cell mediated immunity)  ↑In IgM and IgD but no IgA or IgE and very low IgG  Hyper IgM syndrome  Many IgM Abs react with blood cells: thrombocytopenia, neutropenia and anemia  In older patients: uncontrolled polyclonal proliferation of plasma cells with infiltration of GI tract Complement deficiency     C2 C4 and C1q deficiency: SLE like syndrome C3 deficiency: severe infection + GN MAC deficiency: Neisseria infection C1 inhibitor deficinecy:    C1inhibitor: a protease inhibitor of C1r, C1s, factor XII, kallikrein autosomal dominant, Hereditary angioedema: edema of skin and mucus membranes: GI, Larynx Acquired Immunodeficiency Syndrome Rertroviral disease with :  Immunosuppression  Opportunistic infection  Secondary neoplasm  Neurological manifestation AIDS       Homosexual or bisexual males(57%)  5% of which are drug abusers IV drug abusers (without previous homosexuality) (25%) Hemophiliacs: using factor VIII conc. (0.5%) Recipients of blood and blood components excluding hemophiliacs (1.2%) Heterosexual contact with other high risk gps. (10%) No risk factors (6%) Risk Groups Sexual contact (75% of cases)  Parenteral Tr. : IV drug abusers Hemophiliacs Random recipients HIV in Children: > 90% Vertical transmission 10%  Hemophiliacs Transmission by breast feeding All forms of sexual transmissions are enhanced by coexisting sexually transmitted diseases  Modes of Transmission HIV can not be transmitted by casual personal contact or insect bites Rate of needle stick the rate of seroconversion is 0.3% (30% in HBV) Antiretroviral therapy given within 24-48 hr of a needle stick can reduce the risk of infection eightfold  HIV: Retrovirus  Family of lentivirus  Two closely related but genetically different forms: HIV-1 and HIV-2  HIV-1: in USA, Europe, central africa  HIV-2: West Africa  Serologic cross reactivity between HIV-1and 2 :ELISA Etiology CD4 :High affinity receptor for HIV(gp.120)  T cells and Macrophages are susceptible  Astrocytes: have Galactosyl ceramide as receptor  Other cells: skin fibroblasts and intestinal epithelial cells (No CD4 receptor)  CD4, CXCR4 and CCR5 interaction with gp 120 and gp 41  Pathogenesis  Reverse transcriptase : RNA DNA  DNA integration Latent phase or low level infection Stimulation Inside the cell :  Direct cytolysis  Loss of T cell precursors  Fusion of infected and uninfected T cells  ballooning and death  CD4/CD8 = ½ consistent but not diagnostic finding Causes of T cell loss  Most of the monocytes remain in tissue  Most express low levels of CD4  Most contain large amount of virus in their cytoplasm Monocytes    Hyper γ and circulating IC due to polyclonal B cell activation because of:  CMV or EBV reinfection  Gp41: B cell growth and differentiation  HIV infected macrophages produce IL6  B cell activation Unable to Ag response to new Ag  Lack of T cell help  Other defects in B cells Susceptible to S. pneumonia and H. Influenza B cell abnormalities  Macrophages and microglia  HIV isolates from the brain are M tropic  Mechanism of damage of the brain is obscure  Might be related to the viral products and soluble factors: IL1, TNF and IL6 CNS involvement  Cervical cancer: HPV  Lymphomas: EBV  Systemic, primary CNS (x1000) and body cavity  B cell type  Cause: polyclonal B cell activation  Kaposi Sarcoma: KSHV Neoplasms  In 90% of autopsies  40-60% with clinical manifestation  Infections and neoplasms of CNS  Self limited meningoencephalitis  Aseptic meningitis, Vacuolar myelopathy, peripheral neuropathies and most common: progressive encephalopathy: AIDS dementia complex Neurologic Manifestation  Early stages: marked follicular hyperplasia  HIV particles can be detected within the GC by EM and in situ hybridization: on the villous processes of FDCs  Late stages: Follicular involution  Disruption of FDC network  Atrophic small lymph nodes Lymph nodes Amyloidosis Is not a chemically distinct entity or single disease  Abnormal proteinacious substance that deposits between the cells in variety of Dx Physical nature:  EM: nonbranching fibrils of indefinite length  X-ray crystallography and infrared spectroscopy: Protein fibrils as β pleated sheets 10nm X indefinite (95%)+ nonfibrilar pentagonal (doughnut shaped) (5%) Bisubstancerefringence in congo-red  Immunocyte dyscrasia and amyloidosis: Deposition of AL: Bence jones protein  Most common form of Am. In USA (more than 70% of cases)  1/ Multiple myeloma: M-spike on SPEP that is κ or λ Amyloidosis is seen in only 6-15% of MM  2/ Monoclonal γ pathy: BJ protein in serum without any B-cell neoplasm        Secondary to inflammatory Dx Before Antibiotic therapy: TB, Bronchiectasis and osteomyelitis In USA: RA. Collagen Vascular Dx, UC, Hodgkin’s, IV drug abuse Originates from Serum Amyloid Associated protein(SAA) that is an acute phase reactant: Inflammation: IL6, IL1 by macrophages liver SAA production  Soluble end product Reactive systemic amyloidosis Familial Meditranian Fever:  Autosomal Recessive, serositis, SAA Familial amyloid polyneuropathy:  Amyloid deposition in peripheral and autonomic nerve fibers  Amyloid is mutant transthyretin Hereditary amyloidosis  microglobulin which can not be filtered by dialysis membranes deposition in synovial joint and tendon sheath( causes CTS) Hemodialysis associated amyloidosis Senile cardiac amyloidosis:  Transthyretin deposition in Ventricle restrictive cardiomyopathy and arrhythmia  ANF deposition in atrium Senile cerebral amyloidosis:  β2 amyloid deposition in Alzheimer’s Dx Amyloid of aging  Medullary carcinoma  Islet cell tumors of pancreas  Pheochromocytomas  Islets of langerhans in type II diabetes Endocrine amyloidosis Morphology Systemic amyloidosis: most severe systemic involvement: kidney, liver, spleen, lymph node  Immunocyte dyscrasia: Heart, GI, PNS, skin, Tongue Gross pathology:  Affected organs are enlarged and firm and have a waxy appearance  Cut surfaces should be painted with iodine and sulfuric acid brown discoloration  Microscopic pathology:  Intercellular deposition near basement membrane  Immunocyte form: Perivascular and vascular deposition  Potassium permanganate treatment: AA will loose birefringence  DDx: IHC can differentiate various forms of amyloid Morphology Kidney:  Most common and serious involvement  ↑ , normal and ↓ in size  Main site of deposition: Glomeruli then interstitium, peritubular and perivascular  In Glomeruli: Mesangial matrix, and basement membrane vascular narrowing Morphology Spleen:  Moderate or marked engagement  Sago spleen: Deposition in white pulp  Lardaceous spleen: Dep. In sinuses Liver:  Enlargement  1st site of deposition: space of diss  Liver function is usually preserved Morphology Heart:  In localized or systemic (Immunocyte derived) amyloidosis  Subendocardial and myocardial deposits  myocardial atrophy Tongue: macroglossia Extensor tendons of wrist: CTS Morphology Related to the organ of involvement Renal involvement: major cause of symptoms and death in reactive systemic amyloidosis proteinuria but not HTN Hepatosplenomegaly Cardiac Am.  More common in Light chain deposit that R.S.A  Most common manifestation: CHF  Most serious aspect: conduction defect  Restrictive cardiomyopathy  Clinical manifestation        GI amyloidosis: +/- asymptomatic or malabsorption and diarrhea Biopsy: From organ suspected to be involved In generalized Am.: Rectal and gingival Bx Abdominal fat aspirate: congo red In multiple myeloma: Skull X-ray, Bone marrow biopsy, serum protein electrophoresis  Poor in systemic Am.  Immunocyte derived : 2 years but poorer in M.M.  In R.S.A: better prognosis and related to control of primary disease Prognosis