Alida R Harahap & Farida Oesman Department of Clinical Pathology Faculty of Medicine, University of Indonesia

Alida R Harahap & Farida Oesman Department of Clinical Pathology Faculty of Medicine, University of Indonesia

Foreign molecules = antigens Immune response Immune system non-specific specific cellular humoral

Immune deficiency Immune system defect Auto immune

IMMUNE SYSTEM defect IMMUNE DEFICIENCY Increased susceptibility to infection

IMMUNE DEFICIENCY PRIMARY CONGENITAL humoral cellular combined humoral and cellular SECONDARY ACQUIRED malnutrition malignancy immunosuppresive drug infection of cell of immune system

IMMUNE DEFICIENCY QUALITY Function QUANTITY Number

PRIMARY IMMUNE DEFICIENCY Caused by defect in Innate immunity CELLULAR Phagocytic dysfunction disease HUMORAL Complement defficiency Adaptive immunity CELLULAR T cell defficiency B cell defficiency T & B cell defficiency HUMORAL Antibody

IMMUNE DEFICIENCY

IMMUNE DEFICIENCY Quantity Absolute lymphocyte count general assessment of T cell presence T cell enumeration measure number of circulating T cells T cell subset enumeration CD4+ (helper), CD8+ (cytotoxic)

IMMUNE DEFICIENCY Quality Delayed hypersensitivity skin test to recall antigens (PPD, Candida) in vivo ability of T cell to respond to previously encounter antigen Lymphocyte reaction to mitogen or antigen Cytokine production T cell ability to secrete lymphokine Proliferation

IMMUNE DEFICIENCY Quantity B cell enumeration measure number of circulating B cells

IMMUNE DEFICIENCY Quality Ig quantitation (IgG, IgA, IgM) general assessment of B cell function Isohemagglutinin titer (anti-a & -B) general indicator of IgM production Specific Ab level following immunization (tetanus toxoid, typhoid, paratyphoin) in vivo ability to response to a known Ag

IMMUNE DEFICIENCY Phagocytic dysfunction Complement defficiency

IMMUNE DEFICIENCY Quality Motility Chemotaxis Recognition & adhession adhession molecules (integrin, selectin ligand) Ingestion Degranulation Intracellular killing nitroblue tetrazolium superoxide production Quantity Absolute count neutrophil monocyte

IMMUNE DEFICIENCY Quality Complement activity Quantity Complement level Total hemolytic complement assay (CH50)

IMMUNE DEFICIENCY Recurrent bacterial infection B cell count Neutrophil count Complement level Antibody level Specific antibody responses Complement activity Neutrophil function QUANTITATIVE NORMAL QUALITATIVE Severe viral or fungal infection Lymphocyte count T cell count T cell subset DTH

autoimmune disease tis s ue da m a g e s elf tis s ue/ a ntig en s elf tis s ue/ a ntig en tolerance X im m une res pons e Autoimmune reaction im m une s ys tem

Failure or breakdown of the mechanism normally responsible for maintaining self tolerance in B cell, T cell or both Major factors that contribute: genetic susceptibility environmental trigger infection

CLASSIFICATION NON-ORGAN SPECIFIC SYSTEMIC Systemic Lupus Erythematosus Rheumatoid Arthritis Sjogren Syndrome Scleroderma Polyomyositis - Dermatomyositis Autoummune hemolytic anemia ORGAN SPECIFIC Type I Diabetes Mellitus Autoimmune thyroid disease Grave s disease Hashimoto Autoimmune Hepatitis

Autoimmune disease Auto antibodies systemic organ specific Immune complexes circulating immune complex complement level Inflammation acute phase reactant (apr) cytokine

AUTOANTIBODIES Anti Nuclear Ab Anti Neutrophil Cytoplasmic cytoplasmic perinuclear Anti Phospholipid Ab Anti Cardiolipin Ab Anti β2 Glycoprotein1 Lupus Antikoagulan ANA ANCA C-ANCA P-ANCA APA ACA β2gp-1 LA DISEASES SLE, RA, SS, Scleroderma Wegener s Granulomatosis Crohn s disease, Ulcerative colitis Antiphospholipid Syndrome

ANTINUCLEAR ANTIBODIES SPECIFICITY ANTIGEN DISEASES double strand DNA (ds-dna) histone Smith (sm) Sjogren Synd a (SS-a) Sjogren Synd b (SS-b) RiboNucleoProtein (RNP) Topoisomerase1 (Scl-70) Jo-1 Mi-2 SLE Drug induced LE, SLE SLE Sjogren Syndrome, SLE Sjogren Syndrome SLE Scleroderma Polyomyositis Dermatomyositis

nucleoli perifer Speckled = dotted homogen perifer

SYSTEMIC LUPUS ERYTHEMATOSUS AUTOANTIBODIES ASSOCIATED ANA SS-a SS-b Histone RNP ACA β2-gp1 SPECIFIC ds-dna Sm Anti Nucleosome (ANuA) Anti Ribosomal P Protein (ARPA)

RHEUMATOID ARTHRITIS AUTOANTIBODIES ASSOCIATED ANA Rheumatoid Factor (RF) SPECIFIC Anti Keratin Ab (AKA) Anti Perinuclear Factor (APF) Anti Filaggrin (AFA) Anti Cyclic Citrunilated Peptide (CCP)

ORGAN ANTIGEN ANTIBODY Thyroid Hepar Pancreas Stomach Muscle thyroid peroxidase TSH receptor thyroglobulin mitochondria antibodies smooth muscle liver kydney microsomes-1 soluble liver antigen liver cytosolic antigen-1 glutamic acid decarboxylase islet cell antigen insulin parietal cell intrinsic factor Acethylcholine receptor anti TPO TRAb TAb AMA ASMA anti LKM-1 anti SLA anti LC-1 anti GAD anti ACA IAA anti PCA anti IF anti AchR

LABORATORY CRITERIA for SLE RENAL proteinuria > 3+ ( > 0,5 g/dl ) cellular casts HEMATOLOGY hemolityc anemia direct coomb s test (+) leukopenia < 4000/ul lymphopenia < 1500/ul IMMUNOLOGY abnormal titer ANA anti ds DNA anti Sm APA ACA, LA, false (+) VDRL

INFLAMMATION PROINFLAMMATORY CYTOKINES IL-1, IL-6, TNF-α ACUTE PHASE PROTEIN FIBRINOGEN HAPTOGLOBIN C3 SERUM AMYLOID A C-REACTIVE PROTEIN

CYTOKINE AND CRP LEVEL IL-6 CRP PLASMA LEVEL TNFα 1 2 6 12 24 48 72 TIME (hours)