15. Autoimmunity - Notes taken from the lecture of Sir Joseph Joy Banzon, RMT PDF

Preview

Summary

IMMUNOLOGY & SEROLOGY AUTOIMMUNITY AUTOIMMUNITY - conditions in which damage to organs or tissues results from the presence of Autoantibody or Autoreactive cells - when B-cells & T-cells lost its tolerance to your self-Ag - Etiology: Defect in mechanisms underlying se...

Description

IMMUNOLOGY & SEROLOGY

AUTOIMMUNITY AUTOIMMUNITY - conditions in which damage to organs or tissues results from the presence of Autoantibody or Autoreactive cells - when B-cells & T-cells lost its tolerance to your self-Ag - Etiology: Defect in mechanisms underlying self-recognition Possible Mechanisms:  Loss of self-tolerance by B-cells or T-cells  The response to self-reactive antigens  Molecular memory  Release of maturation antigen (sequestered antigen)  Deficiency of T-suppresor cells  Polyclonal B-cell activation - most Autoimmune Disease exhibit marked familial incidence suggesting genetic predisposition - Autoimmune responses are often related to the presence of specific major histocompatibility complex (MHC) genes General Signs of Autoimmune Diseases that may have Diagnostic Value:  Elevated serum gamma globulin  Presence of diverse antibodies  Depressed levels of serum complement  Immune complexes in serum  Depressed levels of T-cells  Lesions detected on biopsy resulting deposition of immune complexes Other facts about Autoimmune Diseases:  Patient may have one autoantibody and in fact, may suffer from multiple autoimmune disease  Although SLE is associated primarily with anti-nuclear antibodies & rheumatoid arthritis primarily with Rf, both types of antibodies may be found in both diseases  Autoantibodies are not uniqiue to autoimmune disease  Autoimmune diseases are also grouped into two:  HUMORAL / ANTIBODY-MEDIATED  CELL-MEDIATED / T-CELL MEDIATED Diagnosis of Autoimmune Diseases: 1. Enzyme-linked Immunosorbent Assay (ELISA) 2. Radioimmunoassay (RIA) 3. Indirect Immunfluorescence (IIF) 4. Immunoblotting 5. Immunodiffusion, Binding Assays

JOYCE ANN S. MAGSAKAY

|

BS MEDICAL LABORATORY SCIENCE

|

OLFU VALENZUELA

IMMUNOLOGY & SEROLOGY

AUTOIMMUNITY CLINICAL TYPES: 1. ORGAN SPECIFIC - lesions from damaged tissue & autoantibodies are directed towards a single target organ AUTOIMMUNE DISEASE ANTIGENS / TARGET ORGANS OR CELLS Addison’s Disease Microsomal proteins of Adrenal cells Acute disseminated Encephalomyelitis Basic protein of Myelin Hashimoto’s Thyroiditis Thyroglobulin, Microsomal antigen (Thyroid Peroxidase) Type 1 Diabetes Mellitus Islet cells of Pancreas Goodpasteur’s Syndrome Type IV collagen of basement membrane Grave’s disease TSH receptors Myasthenia gravis Acetylcholine receptors Autoimmune chronic active hepatitis Smooth muscles Pernicious Anemia Gastric partial cell antigens, intrinsic factor Sjogren’s Syndrome Salivary gland nucleolar antigens Primary Billiary Cirrhosis Mitochondria Autoimmune Myocarditis Striated cardiac muscle Pemphigus Vulgaris Epidermal antigens Bullous Pemphigoid Skin basement region antigens Autoimmune rheumatic fever Heart & joint tissue antigen Autoimmune glomerulonephritis Glomerular basement membrane Multiple Sclerosis Myelin sheath of nerves 2. SYSTEMIC / NON-ORGAN SPECIFIC - sometimes called “Collagen vascular disease” - lesions from damaged tissue & autoantibodies are not confined to any organs a. RHEUMATOID ARTHRITIS - chronic, inflammatory joint disease with systemic involvement - hallmark feature: presence of Rheumatoid factors—an anti-IgG produced by B-cells & Plasma cells in the Synovial membrane b. SYSTEMIC LUPUS ERYHTEMATOSUS (SLE) - chronic, inflammatory multi-organ disorder that predominantly affects young women of childbearing age * LUPUS ERYTHEMATOSUS (LE) PHENOMENON - it was observed that when peripheral blood from a patient is incubated @ 37°c for 30-60 mins, the WBC swells & extrudes their nuclear material - this nuclar material is opsonized by anti-DNA & Complement & is then phagocytized by Neutrophil In this case, it is now called “LE Cell” ORGAN-SPECIFIC Antibodies & lesions are directed towards a single target organ Clinical & serological overlap (Ex: Thyroid, Stomach, Adrenal glands, Kidney) Antigens are only available to lymphoid system in low concentration

JOYCE ANN S. MAGSAKAY

|

SYSTEMIC Antibodies & lesions are not confined to any organ Overlap of SLE, RA, & other connective tissue disorders Antigens are accessible at higher concentration

BS MEDICAL LABORATORY SCIENCE

|

OLFU VALENZUELA

IMMUNOLOGY & SEROLOGY

AUTOIMMUNITY Antigens evoke organs specific antibodies in normal animals with complete Freund’s adjuvant Familial tendency to develop organ-specific autoimmunity Lymphoid invasion, parenchymal destruction by questionable cell-mediated hypersensitivity or antibodies Tendency to develop Cancer in organ

No antibodies produced in animals with comparable stimulation Familial tendency to develop connective tissue disease * Questionable abnormalities in Ig synthesis in relatives * Lesions caused by deposition of Antigen-Antibody (immune complexes) Tendency to develop Lymphoreticular neoplasia

POSITIVE PATTERNS UNDER FLUORESCENCE MICROSCOPE IMMUNOFLUORESCENT PATTERN ANTIBODY INVOLVED AUTOIMMUNE DISEASE - Drug-induced SLE - Rheumatoid arthritis Homogenous Fluorescence - Chronic Active Hepatitis Anti-nucleoprotein - staining of the entire nucleus - Sjogren’s Syndrome - Myasthenia gravis Membranous /Shaggy/Peripheral Anti-DNA / native DBA (double stranded) Staining - SLE Anti-nucleoprotein (soluble) - staining around the nucleus

Speckled fluorescence - numerous minute fluorescence points throughout the nucleus Nucleolar fluorescence - fluorescence on the nucleolus only Fine speckled pattern of fluorescence

Non-DNA nuclear constituents / anti-ENA (extractable nuclear antigen) a. Anti-SM b. Anti-RNP

- SLE - Scleroderma - Sjogren’s Syndrome - Mixed connective tissue disease

Anti-RNA

- SLE - Scleroderma

Anti-centromere antibody

- CREST Syndrome (a variant of SLE)

Interpretation: 1. HOMOGENOUS (solid, diffused) - whole nucleus fluoresces evenly gold - detects antibodies to nDNA, dsDNA, ssDNA, DNP, or Histones - high titers: suggestive of SLE - low titers: found in SLE, RA, Sjogren’s Syndrome, MCTD 2. PERIPHERAL (ring, membranous shaggy, thread) - sharp, ring-gold fluorescence of outer edge on nucleus with a gradually darkening inner border blending with a dark nuclear center - detects Antibodies to nDNA, dsDNA, DNP - seen in active stage of SLE 3. SPECKLED (mottled) - numerous round speckles of green-gold nucleoli of various sizes against a dark background, “pepper dots” - detects Antibodies to ENA (SM and RNP) - Anti-RNP: indicative of other Rheumatic diseases 4. NUCLEOLAR JOYCE ANN S. MAGSAKAY

|

BS MEDICAL LABORATORY SCIENCE

|

OLFU VALENZUELA

IMMUNOLOGY & SEROLOGY

AUTOIMMUNITY - multiple, round, smooth, green-gold fluorescing nucleoli of various sizes - detects Antibodies to nRNA - present in 50% patients with Scleroderma, Sjogren’s Syndrome, & SLE - also observed in illnesses manifesting Raynaud’s phenomenon 5. ANTI-CENTROMERE ANTIBODY (ACA) - discrete & speckled pattern - detects Antibodies to centromeric chromatin of Metaphase & Interphase cells - highly selective of CREST variant of progressive Systemic Sclerosis - infrequently found in SLE and other MCTD

JOYCE ANN S. MAGSAKAY

|

BS MEDICAL LABORATORY SCIENCE

|

OLFU VALENZUELA...