CLM Week 4 Immunology PDF

Immunology Week #4 Hanzely, DMSc, PA-C, RD South College Where Dreams Find Direction  Instructional Objectives 1. Inventory antigens and antibodies/immunoglobulins including IgA, IgD, IgE, IgG, and IgM (LO7) 2. I...

Immunology Week #4 Hanzely, DMSc, PA-C, RD South College Where Dreams Find Direction  Instructional Objectives 1. Inventory antigens and antibodies/immunoglobulins including IgA, IgD, IgE, IgG, and IgM (LO7) 2. Illustrate the immune response including cell-mediated and humoral immunity (LO7) 3. Inspect the 4 types of hypersensitivity (LO7) 4. Compare autoimmune diseases and immunodeficiency diseases (LO7) 5. Define HIV, transmission, and significant testing to diagnose and monitor therapy (LO7) 6. Compare the major blood group systems of ABO and Rh types and briefly review other blood group systems. (LO7) 7. Contrast the formation of anti Rh antibodies and HDN. (LO7) 8. Differentiate Type and Cross Match, Type and Screen, Direct and Indirect Coombs laboratory testing. (LO7) Inventory indications for red cell, cryoprecipitate, platelet and fresh frozen transfusion and review possible transfusion reactions. (LO7) Refresh  Immune Response (Simplified) Local neutrophils encounter pathogens Begin phagocytosis, trigger cytokines Cytokines induce local vasodilation, monocytes and more neutrophils arrive Monocytes differentiate into macrophages Macrophages and neutrophils continue phagocytosis Macrophages act as antigen presenting cells (APCs), presenting to T-cells (cytotoxic T cells, helper T cells, and regulatory T cells) B-cells Memory B-cells (go dormant, can respond faster than naïve B-cells in the future) Plasma B-cells (secrete antibodies aka immunoglobulins) Immunoglobulins  Immunoglobulins Used synonymously with antibodies Technically called antibodies when secreted Measured in a blood test (mg/dL) Reference ranges vary according to age and method Can be used to monitor the course of hypersensitivity reactions, immune deficiencies, autoimmune diseases, chronic infections, vaccine responsiveness Serum Ig testing is not diagnostic but can indicate disease Follow up electrophoresis is sometimes required Electric current used to separate them according to their mass and charge Five isotypes IgG IgA IgM IgE IgD  First: Monoclonal vs Polyclonal Polyclonal Antibody subtypes that bind to different epitopes of the same antigen Monoclonal Antibodies of one type that bind to one epitope of the antigen Difference is useful in drug development, research, lab evaluation  IgG Constitutes approx. 75% of serum Ig’s Major circulating serum antibody Crosses placenta Four subclasses: various actions in fighting infections Neutralization: blocking binding sites for viruses and toxins Opsonization: binding to foreign particles to recruit phagocytes Complement activation: proteins that enhance immune response Antibody-dependent cytotoxicity: recruit cytotoxic cells like NK cells Increased Various disorders including rheumatologic, pulmonary, renal, and immune diseases Present: immune via natural or passive immunity Decreased IgG deficiency: frequent and/or more severe infections  IgA 15% of IG’s in the body Present in tears, blood, secretions of the respiratory and GI systems Protects mucosal tissues from pathogens and maintains homeostasis with microbiota Increased Several anti-inflammatory disorders: IgA nephropathy, immunoglobulin A vasculitis (Henoch-Schonlein purpura), acquired immune deficiency syndrome (AIDS), hepatitis, and more Decreased Leukemia, macroglobulinemia, IgA deficiency  IgM Primarily responsible for ABO blood grouping In lymph and blood Responds immediately to infection Involved in immunologic reaction to many infections First antibody produced in immune response Forms a “pentamer” which has 10 antigen- binding sites Effective at forming antigen-antibody complexes and activating complement system Does not cross placenta Elevated IgM in newborn indicates in utero infection  IgE Mediates allergic response and parasitic disease Measured to detect allergic disease and hypersensitivity Significant overlap between allergic and nonallergic individuals Not useful as a standalone test Not significant in the defense against bacterial infections Does not activate complement system or participate in opsonization Increased in various diseases Atopic dermatitis, asthma, immunodeficiency, parasitic infections, viral infections, chronic inflammatory diseases, cancer  IgD Not well understood Rarely evaluated Might have something to do with evaluating B-cell function without participating in direct immune responses Or maybe it does Don’t worry so much about it  Hypersensitivity Exaggerated immune response with varying severity Uncomfortable to fatal Classified into 4 types in the Gell and Coombs system Questionable clinical significance but widely used Type I Type II Type III Type IV  Type I Hypersensitivity Reaction IgE mediated Initial exposure to antigen (allergen): immune system sensitized IgE’s with receptors to allergen become linked to mast cells Mast cells contain granules rich in histamine (among other things) Re-exposure Immediate: degranulation of histamine Bronchoconstriction, vasodilation Sustained (long-term) response by prostaglandins and leukotrienes Chronic inflammation AKA immediate, bronchial asthma, allergic rhinitis, allergic dermatitis, food allergy, allergic conjunctivitis, drug allergy and anaphylactic shock  Type II Hypersensitivity Reaction IgM IgG mediated Two sub-types Self-cells recognized as foreign Antibodies bind to antigens on person’s own cells Leads to autoimmune cellular destruction Examples Transfusion reaction after receiving incompatible blood Graves's disease: antibodies target TSH receptors Immune thrombocytopenia: antibodies target platelets Many other autoimmune examples AKA antibody reaction Reactions to non-self cells too  Type III Hypersensitivity Reaction IgG mediated Antibodies bind to circulating antigens but are not effectively cleared Antigen-antibody complexes deposit in vessels and joints Leads to localized inflammatory reactions Examples Rheumatoid arthritis Post streptococcal glomerulonephritis Systemic lupus erythematosus AKA immune complex reaction  Type IV Hypersensitivity Reaction T-cell mediated (not antibody mediated) T-cells overreact to antigens which leads to exaggerated immune response, inflammation, tissue damage Examples Allergic contact dermatitis Type 1 DM: pancreatic beta cell destruction Inflammatory bowel disease AKA delayed reaction (takes days to develop)  Autoimmune vs Immunodeficiency Autoimmune Overreactive immune system T-cell and B-cell activity leading to harmful processes against own tissues In general Elevated inflammatory markers (ESR/CRP) Elevated WBCs Elevated antibodies sometimes PANCE Blueprint https://www.nccpa.net/become-certified/pance-blueprint/ Spread across different sections  Autoimmune vs Immunodeficiency Immunodeficiency Inadequate immune system Many disorders Clinical experience uncommon (disease is rare or patient dies from the disease) Grouping and memorization is difficult Pathology and testing varies widely “In general” Frequent, opportunistic, or exaggerated infections Ataxia-Telangiectasia. Chédiak-Higashi Syndrome. Chronic Granulomatous Disease (CGD) Decreased WBCs, decreased antibodies Chronic Mucocutaneous Candidiasis. Common Variable Immunodeficiency (CVID) DiGeorge Syndrome. Hyper-IgE Syndrome  Human Immunodeficiency Virus Virus that leads to progressive immune system failure, increasing risk of infections and cancers CD4 (“cluster of differentiation 4”) Protein on surface of immune cells, especially helper T cells Important in signaling CD8 which aids cytotoxic T cells HIV leads to progressive reduction in CD4+ T cells CD4 test not a direct test of HIV but used to measure progress Lower CD4 counts mean increased risk of opportunistic infections Increase in CD4 counts indicate successful treatment Relatively significant variation in normal values even in a single person CD4 count below 200 = AIDS  HIV dx & tx HIV differentiation immunoassay (HIV serology) Confirms HIV and distinguishes type Many types of tests HIV RNA quantification (HIV viral load) Quantifies HIV RNA in patients after diagnosis is confirmed Used with CD4 count to direct treatment approach x  HIV dx ELISA Enzyme-Linked ImmunoSorbent Assay Detect antibody to HIV and others CBC Leukopenia, lymphopenia Thrombocytopenia: infections can suppress bone marrow Lyme dz, COVID-19, RMSF, syphilis  Blood Types Blood types depend on surface antigens on erythrocytes ABO blood types Human erythrocytes have inherited antigens of A, B, or both A and B Or lack of AB surface antigens (O) Remember, antigens trigger an immune response Type A blood contains anti-B antibodies Type B blood contains anti-A antibodies Type AB blood contains no antibodies Type O blood contains anti-A and anti-B antibodies What blood type is compatible with what blood type?  Rh Factor Erythrocyte antigen first discovered in rhesus Blood Type Prevalence monkeys A+ 34% Antibodies to the antigen do not occur naturally, A- 6% developed after first exposure in Rh- individuals B+ 9% to Rh+ blood B- 2% There are many other human erythrocyte AB+ 3% antigen systems, except in extreme emergencies AB- 1% these are cross-matched before transfusion O+ 38% O- 7% https://www.youtube.com/watch? v=wckwUSuz8uk  Blood Types Transfusion reaction Exposure to incompatible blood Two antigen-antibody reactions Recipient’s plasma antibodies vs donor’s erythrocyte antigens Agglutination reaction (clumping) and hemolysis of RBCs Can be fatal Blocks vessels, released Hgb can block kidneys causing acute kidney failure Donor’s plasma antibodies vs recipient’s erythrocyte antigens Less important because donor’s antibodies are diluted by recipient’s plasma, causing little RBC damage  Coombs Tests Checks your blood for antibodies against RBCs (jaundice, anemia) Aka antiglobulin tests (AGT) Animal (rabbit) injected with human plasma. Develops anti-human antibodies. Antibodies against human antibodies = “Coombs reagent” RBCs and plasma separated Direct Tests the RBCs to detect antibodies “Are there antibodies against RBCs in this patient?” Indirect Tests the serum to detect antibodies “What are those antibodies attacking?” Only used in gravid women and testing prior to blood transfusion “Type & Screen”  Direct Coombs Test Direct Coombs test (DAT) Confirms immune-mediate hemolytic anemia Coombs reagent added to patient’s RBCs “Are there antibodies attacking this patient’s RBCs?” Yes: Coombs reagent will bind to the antibodies attacking RBCs = clumping =+DAT No: no clumping = -DAT Autoimmune hemolytic anemia, transfusion reaction, HDN, etc  Indirect Coombs Test Indirect Coombs test (IAT) Patient’s serum is systematically exposed to RBCs with predetermined antigens Example Serum with RBCs of types A B AB X Y Z etc Tests that result in clumping confirm presence of antibodies against those antigens If AB and A antigen tests result in clumping but not B or O then we know there are anti-A antibodies in patient’s plasma  Type and Screen/Cross Type and screen Determines ABO grouping and Rh typing Also, other more common antibodies Type and cross Includes type and screen + adding recipient plasma to donor blood to see if there is a reaction (indirect Coombs test) Ordered if there is high likelihood of transfusion Takes about 1 hour. May be skipped in emergencies. Risk of emergency condition outweighs risk of transfusion reaction O- blood may be used. Depends on institution’s policies.  Blood Product Indications Whole blood Not clinically efficient. Most patients require a specific element. Components can be separated and stored under separate ideal conditions. Packed red blood cells Very low Hgb, decreased O2 sat, need for additional O2 capacity (chronic anemia, cardiopulmonary disease, acute blood loss) Platelet rich plasma (PRP) Low platelets at risk of spontaneous bleeding. May be given before high-risk procedures, thresholds for risk and platelet count vary. Old method: 1 donor’s whole blood separated into 1 RBC, 1 platelet, 1 plasma. 6 platelets = “6 pack”. Could end up with 6 different donors = more risk for reactions. New method: single donor apheresis results in concentrated platelets from 1 donor (PRP). When referencing older material, if it says “6 pack of platelets” do NOT order 6 units of PRP  Blood Product Indications Fresh frozen plasma Contains clotting factors. Used for patients with bleeding and clotting factor deficiencies. Typically, INR at least 1.6. Cryoprecipitate FFP is thawed and centrifuged, precipitate is re-frozen. Fewer total clotting factors but more concentrated with select factors Factors VIII and XIII, fibrinogen, von Willebrand factor More useful than FFP if patient is deficient in those specific factors You can do it!  Midterm 1. GFR 15. Urine casts 29. Lymphocytes 43. Immunity 2. Cr/CrCl 16. Urine WBCs 30. Monocytes 44. Hypersensitivity 3. BUN 17. Urine RBCs 31. Eosinophils 45. Autoimmunity/ 4. BUN/Cr 18. RBC 32. Basophils immunodeficiency 5. Urine pH 19. Hgb 33. Blood smear 46. HIV monitoring 6. Urine SG 20. Hct 34. Iron 47. Blood groups 7. Urine protein 21. Platelets 35. TIBC/transferrin 48. Hemolysis 8. Urine leuk. est. 22. MCV 36. Ferritin 49. Blood testing 9. Urine nitrite 23. MCH 37. ESR 50. Blood products 10. Urine glucose 24. MCHC 38. CRP 11. Urine ketones 25. RDW 39. PT/INR 12. Urine bilirubin 26. Reticulocytes 40. PTT 13. Urobilinogen 27. WBC count 41. D-dimer 14. Urine crystals 28. Neutrophils 42. Immunoglobulins