Basic Immunology PDF

Basic Immunology Introduction Natural immunity  Consists of various barriers  1st line of defense  No memory  nonspecific Acquired immunity  Humoral and cell mediated immunity  Stimulation by foreign substances  Specific receptors on lymphocytes and presentation by MQ  Retain memory. The...

Basic Immunology Introduction Natural immunity  Consists of various barriers  1st line of defense  No memory  nonspecific Acquired immunity  Humoral and cell mediated immunity  Stimulation by foreign substances  Specific receptors on lymphocytes and presentation by MQ  Retain memory. The Immune system : consists of 1. Central organs (BM, Thymus) 2. Peripheral organs 3. Cells of Immune system: - Granulocyte (50-70%) - Lymphocyte (30-45%) - Mononuclear Phagocytic (3-8%). Types of Immune Responses:  Humoral ( Antibody mediated) - Neutralization - Opsonisation - Complement fixation  Cell mediated Response - Through Direct contact between Ag and Tc cells. Immunologically mediated Diseases Reaction to self Ag auto-immune Ds. Exaggerated IR producing damage –> hyper-sensitivity Ds. Inadequate IR  Immuno-deficiency Ds. Hyper-sensitivity allergic ds:  1. 2. 3. 4. There 4 types of hypersensitivity reactions: Type I: Anaphylaxis and Atopy (IgE) as drug allergy Type II: Cytotoxic (IgM, IgG) as transfusion reaction Type III: Immune complex ( IgM, IgG) as GN Type IV : Cell mediated by T-lymphocytes ( as TB and contact dermatitis) Type I: Anaphylaxis and Atopy (IgE) as drug allergy Diagnostic tests for immediate hypersensitivity include:  skin (prick and intradermal) tests  measurement of total IgE and specific IgE antibodies against the suspected allergens by ELISA. 1  There appears to be a genetic predisposition for atopic diseases and there is evidence for HLA (A2) association. Type II: Cytotoxic (IgM, IgG) as transfusion reaction  Detection of circulating antibody against the tissues involved ( eg Coomb's test).  The presence of antibody and complement in the lesion (biopsy) by immunofluorescence. Type III: Immune complex ( IgM, IgG) as GN:  Examination of tissue biopsies for deposits of immunoglobulin and complement by immunofluorescence microscopy.  The presence of immune complexes in serum and depletion in the level of complement are also diagnostic. Type IV : Cell mediated by T-lymphocytes (TB and contact dermatitis)  In vivo include delayed cutaneous reaction (e.g. Montoux test ).  In vitro tests for delayed hypersensitivity include assessment mitogenic response of T-lymphocytes and IL-2 production. Immunodeficiency Disease Classification:      Humoral immuno-deficiencies (B-cell immunodeficiency) Cellular immuno-deficiencies (T-cell immunodeficiency) Combined immuno-deficiencies Phagocytic immuno-deficiencies Complement immuno-deficiencies Cause of ID: - Genetic - Metabolic Deficiency - Vitamin Deficiency - Autoimmune Ds - Acquired secondary to infection, drugs, Radiation, cancer. Common clinical features of ID - Chronic infection - Recurrent infection - Unusual microbial agent - Incomplete clearing after infection 1-B-cell immunodeficiency diagnosis:  B-cell count (N.20-25% of lymphocytes)  B-cell functions:- Hypogamaglobulinaemia  Intact T-cell number and function 2  Selective IgA immunodeficiency: The commonest immunodeficiency. Only low IgA and normal another immunoglobulin and normal B-cell number. 2-T-cell immunodeficiency diagnosis:  T-cell count (N.70% of lymphocytes)  T-cell functions: Negative delayed hypersensitivity skin Mantoux test and IL2 production 3- Complement deficiency diagnosis:  Complement quantitation by Radial immunodiffussion 4- Phagocytic deficiency diagnosis :  Neutrophil count and phagocytosis test by Candida albicans killing test. Acquired immunodeficiency ds AIDS Cause:  HIV virus  Predilection to CD4 (helper)  defective immunity  Susceptible to a variety of infectious agents and certain tumors. Clinical features: Incubation 8-10 years Progress of ds Group I: acute 14 day (Mononucleosis –like syndrom) Group II: asymptomatic Group III: generalized lymph-adenopathy Group IV: AIDS a) Constitutional ds: fever, weight loss, diarrhea b) Neurological: dementia, neuropathy c) 2ry infections d) 2ry cancer as lymphoma and Kaposi sarcoma Diagnosis:     Early detection by detection of P24 Ag in blood Detection of HIV Ab ( 6-8 weeks) Lymphopenia (T helper) Decreased T cell function : as decreased delayed hypersensitivity response  HIV genome detection by PCR 3 Auto immune Ds  Self ag don’t induce lymphocyte stimulation, self tolerance.  Loss of self tolerance ( may be due to : Genetic, Cross reactive Ag, Alteration of Tc to Th cell ratio) results in auto immune ds Classification: A- Organ specific 1. Thyroid autoimmune dis B- Organ non specific 1. SLE 2- IDDM 3- Immune hemolytic anaemia 2- Rheumatoid arthritis I – Systemic Lupus Erythromatosis SLE Definition  Immune complex with consumption of C  Circulating Immune complex level correlates with ds SLE diagnosis : A-For diagnosis: 1-Serum ANA ( sensitive)…….Screening 2-Anti-DNA and Anti-Smith Ab (Specific)………diagnostic B- For activity ……ESR, C3,C4 and CIC C- For follow up…….Anti-DNA D- For follow up of organ involvement…..Hb, Platelets, Urine analysis , Kidney functions. II - Rheumatoid arthritis Diagnosis: A- Rheumatoid factor (75% patients) 1-Antiglobulin against Fc fragment of autologous IgG by Latex agglutination test 2-RF –ve don’t exclude R arthritis (Seronegative) and diagnosed by Anticycliccitrullinated peptides (Anti-CCP). are autoantibodies produced by the immune system that are directed against cycliccitrullinated peptides (CCP). B- CBC: NN anemia, high CRP & ESR C- Follow up: by CRP, ESR and not by RF titer. 4 III- Other autoimmune diseases: 1- Thyroid autoimmune diseases A- Hashimoto”s thyroidits diagnosis by: Detection of abs against thyroglobulin and thyroid microsomal Ag. B- Grave”s diseases diagnosis by: Detection of Anti-thyroid antibodies ( Thyroid stimulating immunoglobulin, Thyroid growth stimulating immunoglobulin, Thyroid binding inhibitory immunoglobulin). 2- Immune hemolytic anaemia - Diagnosed by Antiglobulin test ( Coomb”s test) - Pernicious anaemia by Anti-intrinsic factor Ab 3- IDDM: diagnosed by Detection of Anti-islet cell Ab early 4- Myasthenia Gravis by Anti-acetylcholin receptor Ab. 5- Autoimmune chronic hepatitis diagnosis 1- Liver function tests 2- Exclude of Viral hepatitis by viral marker 3- presence of one or more autoantibodies: - ANA - ASMA - Liver kidney microsomal ( LKM) - Soluble Liver Antigen 6- Primary Biliary Cirrhosis(PBC)  Liver function tests  Positive Anti-mitochondrial Ab( AMA) and this differentiate it from Primary sclerosing cholangitis ( -ve AMA) Tumor markers  Induced and Produced by tu cells  They are Released in blood or body fluids or are expressed on cell surfaces 1- tu derived: secreted by tu. 2- tu associated secreted as a result of the presence of the tu. Application:     Detection & screening in high risk population Diagnosis together with histo-pathologic studies Prognosis and staging , correlation to tu size Follow up 5 NB:     normal level does not exclude malignancy Single determination not definite Different markers combination Early indication of recurrence. it depends on change in tu marker conc. From recent base line  No tu marker is sensitive and specific enough to be used as screening test in an asymptomatic pt. Classification:       Hormones( as HCG in chriocarcinoma) Enzymes: ( as Acid phosphatase in cancer prostate) Proteins:(as Ig in multiple myloma) Tum: as in or Ag: as In following table Cell surface markers leukemias Metabolites: as Vanillyl mandelic acid in pheochromocytoma Breast Ovary Pancrease Liver Lung Stomach Colo-rectum Lymphoma Prostate Uterus Cervix Thyroid Leukaemia testis CA15.3 CA 125 Ca19-9 AFP CEA CEA CEA LDH PSA CEA CEA calcitonin B2M AFP CEA CEA CEA SCC-A CA72-4 CA19.9 ESR CA72-4 B2M CA125 CEA ferretin HCG 6 LDH Hepatitis B Hepatitis C 1. Biochemical test 1. Biochemical test Increased: ALT , AST, ALP , Mild elevation: ALT, AST, ALP, Bilirubin BIL 2. Serology 2. Serology a) HBs Ag: earliest, before symptoms a) Ab detection: IgG ELISA b) HBe Ag: , replication, - F-ve in early acute cases c) HBc Ab: - F+ve in autoimmune & RF early IgM (IgG for life), in window b) Viral RNA by PCR phase recent infection d)HBe Ab: conversion from Ag to Ab = good sign, no conversion from Ag to Ab = chronicity e)HBs Ab: past inf. + immunity 7