Autoimmune and histocompatibility testing Flashcards
examples of autoimmune disease
-brain- multiple sclerosis, guillaun-barre syndrome, autism
-thyroid- thyroiditis, hashimoto’s disease, graves disease
-bones- rheumatoid arthritis, ankylosing spondylitis, polymyalgia rheumatica
-muscles- muscular dystrophy, fibromyalgia
-skin- psoriasis, vitiligo, eczema, scleroderma
-nerves- peripheral neuropathy, diabetic neuropathy
-GI tract- celiacs, crohns, ulceratic colitis, diabetes type 1
-blood- leukemia, lupus erythematosus, hemolytic dysglycemia
autoimmune
-Receptors on T & B cells of the immune system are antigen specific with diversity derived from gene recombination
-Cells have memory and on a subsequent engagement with an antigen the cells exhibit more rapid and robust responses
-Immune response to self-antigens as in autoimmune & failure to recognize pathogens and eliminate
-Autoimmune Diseases: immune response to self antigens occur in the context of a genetic predisposition resulting in disease expression. Can be organ or system.
-Immunodeficiency: Primary are a direct consequence of structural or functional derangement in the immune network. Secondary are a consequence of an alteration in the immune status resulting in manifestation of infectious disease.
systemic autoimmune diseases: connective tissue: systemic Lupus Erythematosus
-Multisystem autoimmune disease, associated with the production of antibodies to a variety of nuclear and cytoplasmic antigens
-Antibodies to ds DNA, causes inflammation to skin, joints, kidney, cardiovascular system, ervous system,lung and hemopoietic cells.
-Diagnosis with criteria of signs (rash, arthritis, oral ulcers, etc) proteinuria, cytopenia
-+ anti-ds DNA
-+ antiphospholipid antibody
-+ anti-Sm antibody
-false positive syphilis (boards q)
-abnormal (speckled) ANA -> usually first test
-butterfly rash
-arthritis, raynauds, lupus nephritis, heart problems, pleural effusions
systemic autoimmune diseases: connective tissue: sjogren syndrome
-Systemic connective tissue disorder
-MC in women than is men
-an autoimmune exocrinopathy involving the lacrimal GLANDS, salivary glands and less often the pancreas
-Inflammation contributes to sicca syndrome, dry eyes and mouth.
-Positive ANA, positive SS-A, positive SS-B, positive rheumatoid factor
-Can be primary or associated with another autoimmune disorder.
-Test for sicca
-Dry eye Schirmer test- tissue paper put up to eye to measure how far down the wet travels
-Biopsy of salivary gland
-2.5% develop non-Hodgkin Lymphoma
-joint pain, abnormal liver, digestive problems, muscle pain, vaginal dryness, neurological problems, recurrent bronchitis
-fertility problems due to lack of fluid
systemic autoimmune diseases: connective tissue: scleroderma
-Excessive and widespread deposition of collagen in many organ systems of the body
-3 characteristics of tissue fibrosis, a proliferative and occlusive vasculopathy of the small blood vessels, and a specific autoimmune response associated with distinctive autoantibody profile.
-Involvement of skin, GI tract, kidney(renal ischemia), lung and muscles
-Subtypes including CREST (Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly and Telangiectasia)
-pulmonary HTN -> CHF, lung problems -> can die
-Positive ANA, antibody Scl-70
-Calcinosis- calcium deposits in skin
-Raynauds phenomenon
-Esophageal dysfunction- acid reflex and decrease motility
-Sclerodactyly- thickening and tightening of skin on fingers and hands
-Telangiectasis- dilation of capillaries causing red marks on surface of skin
systemic autoimmune diseases: connective tissue: inflammatory muscle diseases
-3 types:
-1. dermatomyositis. Heliotrope rash, shawl sign, Gottron papules. Complement vasculopathy.
-2. Polymyositis. T-cell medicated muscle injury
-3. Inclusion body myositis. Older
-Pulmonary interstitial fibrosis in 10%,
-3/5 criteria present -> proximal muscle weakness, muscle pain and tenderness on palpation, EMG abnormal, elevated serum/plasma concentrations of muscle enzymes, muscle bx with cellular inflammation
-Positive ANA, anti-Jo
-calcification in skin, joint pain, arthritis, arrhythmias, myocarditis, pericarditis, gastroesophageal reflex disease, dysphagia, aspiration pneumonia
-progressive muscle wasting
-fever, fatigue, weight loss
systemic autoimmune diseases: connective tissue: mixed connective tissue disease
-Combined features of SLE, sclerosis, and polymyositis
-Arthralgias, myalgias, fatigue & Raynaud phenomenon.
-Pulmonary (interstitial pneumonitis, Pulmonary HTN, Intersitital Fibrosis, diaphragm & esophagus disfucntion)
-Dx by clinical features, positive ANA, anti-U1 RNP
-scleroderma, rheumatoid arthritis, lupus, sjogrens
systemic autoimmune diseases: connective tissues: rheumatoid arthritis
-primarily affects the synovial joints often starting as a synovitis.
-Young women.
-3/7 criteria with morning stiffness.
-Increased serum Rheumatoid Factor, anti- CCP
systemic autoimmune diseases: connective tissue: amylodosis
-Extracellular deposition of low-molecular-weight fibrils from a soluble circulating precursor giving a waxy appearance to the infiltrated organs.
-Congo red stain on microscopy, abdominal fat pad,
-Multiorgan involvement Factor X coagulopathy
-Male 2:1, onset 40’s
-fatigue
-SOB
-protein in urine
-BP changes
-dizzy
-pain
-kidney issues
-stiff heart
-diarrhea/constipation
-weight loss
systemic autoimmune diseases: connective tissue: cryoglobulinemia
-Immunoglobulins in the serum that precipitate at a temp below 37C, resolves on warming.
-Immune complex vascultitis, arthritis, neuropathy, renal involvement
-Wintrobe tube collects cyroglubulin reported as a cryocrit.
-occurs at cold and resolves with warm
-red blotchy rash
positive ANA flow chart
-order the whole panel at once
-anti-jo differentiation is based on symptoms
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diseases of immune system: X-linked agammaglobulinemia
-Absence of b lymphocytes in males
-Recurrent infections
omosis chart
disease of immune system: common variable immunodeficiency
-Male & females in adult
-B cells are dysfunctional
-Recurrent infections, immune hemolytic anemia, neutropenia, pernicious anemia, B cell Lymphoma
-chronic cough
-swollen lymph nodes
-breathing trouble
-pain in ear
-nausea, vomiting, and diarrhea, weight loss
disease of immune system: hyper IgM syndrome
-low IgG and IgA with normal IgM OR high IgM, normal B cells
disease of immune system: selective IgA deficiency
-MC primary immunodeficiency syndrome
-asymptomatic to allergies, autoimmune disorders, recurrent infections, GI diseases
-IgA < 5 with normal IgG and IgM
diseases of immune system: DiGeorge Syndrome
-Chromosome 22 deletion
-Catch 22 (Cardiac abnormality, abnormal facies, thymic hypoplasia, cleft palate & hypocalcemia) -> board question
-T cell abnormalities and B Cell dysfunction, parathyroid abnormal
diseases of the immune system: severe combined immunodeficiency syndrome
-Cellular and humoral immunity defects
-Bubble babies
-Bone marrow transplant
-Neonate heel prick test.
deficiencies in complement
-Complement protects against pathogens and non-self antigens. Cytokine release, stimulation of phagocytes, inflammation, cell killing attack.
-Deficiencies result in susceptibility for infections and predispose to autoimmune diseases.
-CH50 test. Hemolyze antibody coated sheep red cells.
-Low if depleted of complement or congenitally deficient.
-AH50 , addition of complement restore hemolytic activity
perform CH50 chart
she barely went over this…
HLA genes and gene products
-Organ rejection is primarily a consequence of the interactions between the immune system of the transplant recipient and the histocompatibility antigens present on the transplanted cells.
-Histocompatibility antigens are encoded by a complex of closely linked genes called the major histocompatibility complex (MHC). Found on the short arm of chromosome 6 and encodes for the human leukocyte antigen (HLA) system
HLA class 1, 2, and 3 (the surface antigen)
-CLASS 1 GENES HLA-A, HLA-B, HLA-C
-Interacts with t-lymphocytes, (cytotoxic T-cells, T suppressor cells) CD 8
-Found on surface of all cells with nucleus (not RBC)
-Healthy cell verses infected cell
-Antigen of infection binds to the Class I HLA surface antigen and triggers an immune reaction
-CLASS 2 GENES HLA-DP, HLA,DQ, HLA-DR
-Interacts with t-lymphocytes (T helper cells) CD4
-Found on surface of B-lymphocytes, macrophages, dendritic cells and some T cells
-Help immune cells communicate with each other!
-When a macrophage attacks an organism the antigen binds from the pathogen which releases interlukin 1 calls the helper T cells which release interlukin 2 which calls B cells (antibodies) an T cells (cytotoxic)
-CLASS 3
-cyotkines
-complement proteins
positive antigen findings**
-HLA-A 3 : hemochromatosis
-HLA-B 8 : graves, addisons, myasthenia gravis
-HLA-B 27: PAIRS (psoriasis, ankylosing sponylitis, IBS, reiter’s syndrome)
-HLA-D R2: MS, SLE
-HLA-D R3 & HLA-D R4: DM type 1
-HLA-D R5: hashimoto
-HLA-D Q2: celiac disease
matching HLA with siblings
-Each person gets one halotype from each parent. The two haplotypes represent the HLA genotype
-Four genotypes are possible in the offspring
-25% chance of tow siblings being identical
-50% of sharing one haplotype
-Currently 17,500 HLA alleles
histocompatibility testing assays: HLA typing
-microlymphocytotoxicity assay.
-T lymphocytes for class I antigens
-B lymphocytes for class II antigens
-Antibody in the serum binds to antigen causing cell lysis.
-DNA Polymerase chain reaction -Used for specific antigen
histocompatibility testing assays: HLA antibody screening
-Serum screened for antibodies from prior exposure
-Percent panel reactive antibody
-High PRA must wait for a donor 0% PRA
-These patients have a higher risk of rejection
Histocompatibility Testing Assays: crossmatching
-Lymphocyte cross match
-Renal, heart, lung transplants
-If recipient has HLA antibodies against donor antigens the cells will be lysed… then no transplant match.
histocompatibility: solid organ transplants
-kidney- ABO blood group compatibility, cross match donor lymphocytes with recipient serum
-liver- ABO blood group compatibility, donor specific HLA antibodies are not a contraindication
-heart- ABO blood group compatibility, if HLA high antibodies in recipient, then virtual crossmatch
-lung- ABO blood group compatibility, if HLA high antibodies in recipient, then virtual crossmatch
-pancreas- ABO blood group compatibility, cross match donor lymphocytes with recipient serum
-cornea- no HLA or ABO matching
histocompatibility: cell transplants
-Normal hematopoietic cell transplantation is a therapeutic option in which normal hematopoietic stem or progenitor cells are used to replace abnormal hematopoietic cells or to reconstitute the bone marrow of patients undergoing high-dose cytotoxic therapy for malignancy.
-Harvested from the bone marrow or from the peripheral blood after giving the donor growth factors.
-HLA matching, 2%graft failure even with match
HLA typing and non-transplantation related applications
-Clinically HLA typing can be used to help identify increased risk of a drug hypersensitivity.
-Hypersensitivity to : Carbamazepine ( Tegretol), allopurinol, abacavir (Ziagen)
