Transplantation Immunology Lecture Notes PDF

SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE IMMUNOLOGY & SEROLOGY TRANSPLANTATION IMMUNOLOGY  1. Compare the mechanisms of direct and indirect alloantigen recognition....

SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE IMMUNOLOGY & SEROLOGY TRANSPLANTATION IMMUNOLOGY  1. Compare the mechanisms of direct and indirect alloantigen recognition. 2. Distinguish between an allograft, autograft, xenograft, and syngeneic graft (isograft) 3. Compare the immunologic mechanisms LEARNING involved in hyperacute, acute, and chronic graft rejection. OBJECTIVES 4. List the major classes of By the end of the lesson, the immunosuppressive agents and their effects on the immune system. students are expected to: 5. Deduce the suitability of a possible donor for a transplant recipient based on HLA typing. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE IMMUNOLOGY & SEROLOGY  SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE TOPIC IMMUNOLOGY & SEROLOGY OUTLINE ▪ Transplantation: ▪ Host responses to transplantation ▪ Types of grafts ▪ Types of rejection of transplanted organ DEFINITION TRANSPLANTATION ▪ The transfer of cells or tissues from one individual to another or from one site to another in the same individual. ▪ A potentially lifesaving treatment for end- stage organ failure, cancers, autoimmune diseases, immune deficiencies, and a variety of other diseases. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. DEFINITION TRANSPLANTATION ▪ The genetic match between the donor and host is the most important factor that determines whether a transplant will be successful. ▪ The closer the genetic match between the donor and recipient in terms of HLA types, the lower the risk of rejection. ▪ However, even with a good HLA match, rejection can occur due to minor histocompatibility antigens (mHAs), which are encoded by genes outside the MHC. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. TRANSPLANTATION IMMUNOLOGY HLA SYSTEM/MHC ▪ Composed of: ▪ Class I: HLA-A, HLA-B, and HLA-C ▪ Expressed on all nucleated cells ▪ Presents to CD8+ T cells (Cytotoxic T cells) ▪ Class II: HLA-DR, HLA-DQ, and HLA-DP ▪ Expressed on antigen-presenting cells ▪ Presents to CD4+ T cells (Helper T cells) ▪ Short arm of chromosome 6 in MHC. ▪ Inherited as haplotypes from parental chromosomes ▪ 25% HLA identical ▪ 50% HLA haploidentical ▪ 25% HLA nonidentical ▪ 50 allelic variants) ▪ Expression ▪ Expressed on: endothelial cells, keratinocytes, fibroblasts, epithelial cells, dendritic cells, and monocytes ▪ Not expressed on: T or B lymphocytes. ▪ MICA antibodies: associated with rejection episodes and decreased graft survival. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY TRANSPLANTATION IMMUNOLOGY MHC CLASS I-RELATED CHAIN A (MICA) ANTIGENS SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY TRANSPLANTATION IMMUNOLOGY ABO BLOOD GROUP ANTIGENS ▪ The only blood group system that affects clinical transplantation. ▪ Can cause hyperacute rejection (occurs within minutes to hours) ▪ Anti-A or anti-B antibodies develop in individuals lacking the corresponding blood group antigens. ▪ As such, recipient–donor pairs must be ABO identical or compatible to avoid this adverse outcome. ▪ Remedy: plasma exchange and intravenous immunoglobulin administration SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY TRANSPLANTATION IMMUNOLOGY ABO BLOOD GROUP ANTIGENS SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY TRANSPLANTATION IMMUNOLOGY KILLER IMMUNOGLOBULIN-LIKE RECEPTORS (KIRs) ▪ Regulate the activity of NK lymphocytes ▪ The KIRs contain activating and inhibitory receptors that vary in number and type on any individual NK cell. ▪ Normally: ▪ Interaction between the MHC protein and the inhibitory KIR maintains the NK cells in a quiescent state. ▪ If an NK cell encounters a cell with absent or decreased HLA class I expression, inhibitory receptors are not engaged, and a loss of negative regulatory activity occurs, resulting in NK cell activation. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY TRANSPLANTATION IMMUNOLOGY KILLER IMMUNOGLOBULIN-LIKE RECEPTORS (KIRs) ▪ Stem cell donors have been selected for recipients who lack a corresponding class I MHC protein for the donor’s inhibitory KIR type. ▪ This results in alloreactivity by NK cells that repopulate the recipient after transplant. ▪ These alloreactive NK cells have been shown to mediate a graft-versus- leukemia (GVL) reaction and prevent relapse after transplantation for certain types of hematologic malignancies. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE IMMUNOLOGY & SEROLOGY ALLORECOGNITION DEFINITION ALLORECOGNITION ▪ When a recipient receives a transplant, their immune system may recognize the donor's HLAs as foreign, initiating an immune response that can lead to graft rejection. ▪ Types of graft: ▪ Autograft: the transfer of tissue from one area of the body to another of the same individual. ▪ Syngeneic graft (isograft): the transfer of cells or tissues between individuals of the same species who are genetically identical, for example, identical twins. ▪ Allograft: the transfer of cells or tissue between two genetically disparate individuals of the same species. Most transplants fall into this category. ▪ Xenograft: the transfer of tissue between two individuals of different species. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY ▪ McPherson, Richard A. and Pincus, Matthew R., "Henry's Clinical Diagnosis and Management by Laboratory Methods, 24th ed" (2021). DEFINITION ALLORECOGNITION SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY DEFINITION ALLORECOGNITION ▪ Two main pathways of allorecognition: ▪ Direct allorecognition: ▪ Recipient T cells directly recognize intact foreign MHC molecules on donor cells. ▪ Indirect allorecognition: ▪ This involves the uptake, processing, and presentation of foreign HLA proteins by the recipient’s antigen-presenting cells (APCs) to recipient T cells, leading to the production of antibodies and cell-mediated responses against the graft. ▪ The effector responses against transplanted allogeneic tissue include: ▪ Direct cytotoxicity ▪ Delayed-type hypersensitivity responses ▪ Antibody-mediated mechanisms SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY MECHANISM ALLORECOGNITION SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY MECHANISM ALLORECOGNITION SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Garcia, M.,Yebra, B., Flores, A., Guerra, E., "The Major Histocompatibility Complex in Transplantation", Journal of Transplantation, vol. IMMUNOLOGY & SEROLOGY 2012, https://doi.org/10.1155/2012/842141 TYPES OF TRANSPLANTS ORGAN TRANSPLANTATION ▪ Kidneys ▪ the most common type of organ transplant, and it's often performed ▪ Factors for graft survival: to treat end-stage renal disease caused by conditions like diabetes, ▪ Source of organ glomerulonephritis, and polycystic kidney disease. ▪ Type of organ ▪ Liver ▪ for conditions such as cirrhosis, biliary atresia, and hepatitis C infection. ▪ Heart ▪ for patients with cardiomyopathy, congenital heart disease, and coronary artery disease. ▪ Lungs ▪ for patients with end-stage lung diseases like cystic fibrosis and emphysema. ▪ Pancreas ▪ can help patients with type 1 diabetes achieve insulin independence. ▪ Intestine ▪ for patients with intestinal failure. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ McPherson, Richard A. and Pincus, Matthew R., "Henry's Clinical Diagnosis and Management by Laboratory Methods, 24th ed" (2021). TYPES OF TRANSPLANTS CORNEAL TRANSPLANT ▪ High Success Rate ▪ Avascularity ▪ Low Antigen Concentration ▪ Relatively low concentration of MHC class I antigens ▪ Almost complete absence of class II antigens ▪ Immune Privilege ▪ Aqueous Humor Barrier ▪ Immunosuppressive Mechanisms ▪ Minimal Immunosuppression ▪ Graft Size and Placement SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Punt, Jenni, Stranford, Sharon A, Jones, Patricia P, Owen, Judith A. (2019). Kuby Immunology (8th). New York: Macmillan Learning. TYPES OF TRANSPLANTS BONE TRANSPLANT ▪ Bone matrix autografts or allografts are common. ▪ Bone matrix transplantation is used: ▪ Replace or repair bone fractures ▪ After limb-sparing tumor resections ▪ To correct congenital bone abnormalities ▪ Freezing bone offers these benefits: ▪ Preservation ▪ Reduced antigenicity ▪ Minimal Immunosuppression ▪ Criteria for bone donation ▪ Lack of infection ▪ No history of IV drug use ▪ No prolonged steroid therapy or human growth hormone treatment SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Punt, Jenni, Stranford, Sharon A, Jones, Patricia P, Owen, Judith A. (2019). Kuby Immunology (8th). New York: Macmillan Learning. TYPES OF TRANSPLANTS INTESTINAL TRANSPLANT ▪ Procedure ▪ Isolated Intestinal Transplant: only the small intestine is transplanted. ▪ Composite Allograft: Intestinal transplants are often performed with other organs, either as a composite allograft (where the organs are transplanted together) or as separate organs from the same donor. ▪ Donor criteria ▪ Inclusion: ▪ Stable Cardiopulmonary Status and Liver Function ▪ Exclusion: ▪ Systemic Infection and Malignancy ▪ Recipient: individuals with short gut syndrome. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Punt, Jenni, Stranford, Sharon A, Jones, Patricia P, Owen, Judith A. (2019). Kuby Immunology (8th). New York: Macmillan Learning. TYPES OF TRANSPLANTS LIVER TRANSPLANT ▪ Exclusion: ▪ Recipients should be free of diseases or infections affecting organs other than the liver. ▪ The most common recipients are those with: ▪ Congenital biliary atresia ▪ End-stage liver disease, Cirrhosis ▪ HLA crossmatching and Immunosuppressive regimens increases chances of survival in recipients ▪ Tacrolimus ▪ is the preferred drug for liver transplantation, potentially due to its hepatotrophic properties, meaning it may promote liver regeneration and function. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Punt, Jenni, Stranford, Sharon A, Jones, Patricia P, Owen, Judith A. (2019). Kuby Immunology (8th). New York: Macmillan Learning. TYPES OF TRANSPLANTS LUNG TRANSPLANT ▪ Most difficult to transplant out of all organs ▪ Challenges and considerations: ▪ Bronchial Circumference Matching ▪ Ischemic Damage Sensitivity ▪ Susceptibility to Infection ▪ High Rejection Rate ▪ Intensive Immunosuppression ▪ High Mortality SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Punt, Jenni, Stranford, Sharon A, Jones, Patricia P, Owen, Judith A. (2019). Kuby Immunology (8th). New York: Macmillan Learning. TYPES OF TRANSPLANTS KIDNEY TRANSPLANT Recipient Selection ▪ Exclusions: ▪ Individuals with active sepsis, a history of malignancy (except for CNS malignancies), or conditions where immunosuppression could reactivate chronic infections. ▪ Older patients ▪ Blood Type Compatibility ▪ HLA Typing and Matching: ▪ Donor-recipient HLA matching, especially at HLA-B and -DR loci, is crucial for long-term graft survival. ▪ Crossmatching SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Punt, Jenni, Stranford, Sharon A, Jones, Patricia P, Owen, Judith A. (2019). Kuby Immunology (8th). New York: Macmillan Learning. TYPES OF TRANSPLANTS KIDNEY TRANSPLANT Donor Selection ▪ Ideal Donors: ▪ Young trauma victims with no history of chronic renal disease, sepsis, or systemic diseases like diabetes, hypertension, and tuberculosis. ▪ Donors younger than 65 years old. ▪ Living donor transplants offer better chances of graft survival. Siblings are often the best matches. ▪ Due to organ shortage: ▪ Include donors older than 55 years and those with a history of hypertension or diabetes. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Punt, Jenni, Stranford, Sharon A, Jones, Patricia P, Owen, Judith A. (2019). Kuby Immunology (8th). New York: Macmillan Learning. TYPES OF TRANSPLANTS HEART AND HEART VALVE TRANSPLANTS ▪ Heart transplantation is considered the preferred treatment for patients facing end- stage heart failure. ▪ Donor Selection ▪ Sustained irreversible brain death while maintaining near-normal cardiac function. ▪ HLA matching is often not a primary consideration in heart transplantation. ▪ Recipient Selection ▪ The presence of active infections is a major exclusion criterion for heart transplantation. ▪ HLA antibody assessments are crucial to determine the recipient's sensitization level, which serves as an indicator of immunological risk. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Punt, Jenni, Stranford, Sharon A, Jones, Patricia P, Owen, Judith A. (2019). Kuby Immunology (8th). New York: Macmillan Learning. TYPES OF TRANSPLANTS PANCREAS TRANSPLANT ▪ Either as a whole organ or isolated islet cells ▪ Is a viable treatment option for individuals with diabetes, especially those seeking insulin independence. ▪ Three types of pancreatic transplantations can be done: ▪ Pancreas–kidney transplantation (SPK, the most common; 73%) ▪ Pancreas transplantation after kidney transplantation (PAK; 18%) ▪ Pancreas transplantation alone (PTA; 9%). SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Punt, Jenni, Stranford, Sharon A, Jones, Patricia P, Owen, Judith A. (2019). Kuby Immunology (8th). New York: Macmillan Learning. TYPES OF TRANSPLANTS SKIN TRANSPLANT ▪ Skin grafting is a common surgical procedure used to repair damaged skin resulting from burns, trauma, infections, or surgical removal of diseased tissue. ▪ Autologous grafts: most common type of skin transplant. ▪ High rejection phenomenon due to high density of MHC class I antigens in skin ▪ Thus procedure must be supported with immunosuppressive therapy SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Punt, Jenni, Stranford, Sharon A, Jones, Patricia P, Owen, Judith A. (2019). Kuby Immunology (8th). New York: Macmillan Learning. TYPES OF TRANSPLANTS HEMATOPOIETIC OR PERIPHERAL BLOOD STEM CELL TRANSPLANTS ▪ Bone marrow transplant, peripheral stem cell transplant, cord blood transplant ▪ Goal: achieve potential cure in hematologic disorders, malignancies, or myeloablation ▪ Source: ▪ Bone marrow: aspiration from posterior/anterior iliac crest to collect 10% (1- 2 hours) ▪ Peripheral blood stem cells: done by apheresis / leukapheresis; G-CSF is given prior ▪ Umbilical cord blood: preserved and frozen from birth; relatively recent development SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Punt, Jenni, Stranford, Sharon A, Jones, Patricia P, Owen, Judith A. (2019). Kuby Immunology (8th). New York: Macmillan Learning. TYPES OF TRANSPLANTS HEMATOPOIETIC OR PERIPHERAL BLOOD STEM CELL TRANSPLANTS ▪ Bone marrow transplant, peripheral stem cell transplant, cord blood transplant ▪ Goal: achieve potential cure in hematologic disorders, malignancies, or myeloablation ▪ Source: ▪ Bone marrow: aspiration from posterior/anterior iliac crest to collect 10% (1- 2 hours) ▪ Peripheral blood stem cells: done by apheresis / leukapheresis; G-CSF is given prior ▪ Umbilical cord blood: preserved and frozen from birth; relatively recent development SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Punt, Jenni, Stranford, Sharon A, Jones, Patricia P, Owen, Judith A. (2019). Kuby Immunology (8th). New York: Macmillan Learning. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE IMMUNOLOGY & SEROLOGY TRANSPLANT REJECTION TYPES OF TRANSPLANT REJECTION HYPERACUTE REJECTION ▪ Timing: ▪ Occurs minutes to hours after vascular supply is established. ▪ Mechanism: ▪ Mediated by preformed antibodies reacting with donor vascular endothelium. ▪ Target antigens: ABO, HLA, and specific endothelial antigens. ▪ Causes of Preformed Antibodies: ▪ Blood transfusions ▪ Prior transplantation ▪ Maternal exposure to paternal fetal antigens during pregnancy ▪ Pathophysiology: ▪ Antibody binding activates complement and clotting cascades. ▪ Results in thrombus formation, ischemia, and necrosis. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY TYPES OF TRANSPLANT REJECTION HYPERACUTE REJECTION SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Transplant: immunology and treatment of rejection Davis, Connie L American Journal of Kidney Diseases, Volume 43, Issue 6, 1116 - IMMUNOLOGY & SEROLOGY 1134 TYPES OF TRANSPLANT REJECTION HYPERACUTE REJECTION ▪ Rare in Clinical Practice due to preventive measures: ▪ ABO compatibility matching ▪ Pre-transplant HLA antibody screening ▪ Crossmatch tests to confirm the absence of donor HLA-specific antibodies ▪ Accelerated Rejection ▪ Timing: Occurs over several days in patients with very low levels of donor- specific antibodies pre-transplant. ▪ Accelerated rejection happens when a recipient is re-exposed to donor tissue antigens. This second exposure triggers a rapid reactivation of both B-cell and T-cell responses (primarily). ▪ Similar Features: Involves intravascular thrombosis and necrosis, like hyperacute rejection. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY TYPES OF TRANSPLANT REJECTION ACUTE REJECTION ▪ Timing: Occurs days to months after transplantation. ▪ Types: ▪ CELLULAR ALLORESPONSE (ACR) ▪ Mechanism: ▪ Parenchymal and vascular injury. ▪ Predominantly CD8+ T cells, along with CD4+ T cells and macrophages. ▪ Role of Cells: ▪ CD4+ T helper cells release cytokines that stimulate inflammation and recruit other immune cells to the graft site ▪ CD8+ cytotoxic T lymphocytes directly kill donor cells SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY TYPES OF TRANSPLANT REJECTION ACUTE REJECTION ▪ Timing: Occurs days to months after transplantation. ▪ Types: ▪ ANTIBODY-MEDIATED RESPONSE (AMR) ▪ Mechanism: ▪ Antibodies bind to vessel walls, activating complement. ▪ Results in transmural necrosis and inflammation. ▪ Diagnostic Criteria: ▪ Histological findings characteristic of AR. ▪ C4d deposition in peritubular capillaries. ▪ Detection of donor-specific HLA antibodies. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY TYPES OF TRANSPLANT REJECTION ACUTE REJECTION SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Transplant: immunology and treatment of rejection Davis, Connie L American Journal of Kidney Diseases, Volume 43, Issue 6, 1116 - IMMUNOLOGY & SEROLOGY 1134 TYPES OF TRANSPLANT REJECTION CHRONIC REJECTION ▪ Occurs months or years after the transplant ▪ Progressive graft arteriosclerosis with fibrosis, scarring, and narrowing of vessel lumen due to smooth muscle proliferation. ▪ Leading cause of graft loss after the first year post-transplant; difficult to treat. ▪ Mechanism: ▪ Delayed-type hypersensitivity to foreign HLA proteins. ▪ This reaction is driven by the indirect pathway of allorecognition ▪ Cytokine and Growth Factor Effects: ▪ Secreted by endothelial cells, smooth muscle cells, and macrophages activated by IFN-γ. ▪ Stimulate smooth muscle cell accumulation in graft vasculature. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY TYPES OF TRANSPLANT REJECTION CHRONIC REJECTION SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ J Clin Invest. 2019;129(1):24-33. https://doi.org/10.1172/JCI122132. IMMUNOLOGY & SEROLOGY TYPES OF TRANSPLANT REJECTION CHRONIC REJECTION SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ J Clin Invest. 2019;129(1):24-33. https://doi.org/10.1172/JCI122132. IMMUNOLOGY & SEROLOGY TYPES OF TRANSPLANT REJECTION CHRONIC REJECTION SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Transplant: immunology and treatment of rejection Davis, Connie L American Journal of Kidney Diseases, Volume 43, Issue 6, 1116 - IMMUNOLOGY & SEROLOGY 1134 TYPES OF TRANSPLANT REJECTION GRAFT-VERSUS-HOST DISEASE (GVHD) ▪ Common Transplants Involved: ▪ Hematopoietic stem cell (HSC) transplants (most common) ▪ Lung and liver transplants (less common) ▪ Mechanism of GVHD ▪ Process: ▪ Donor T cells in the graft attack the host/recipient. ▪ Targets: Host HLA proteins (mismatched transplants) or minor histocompatibility antigens (mHAs) (matched transplants). SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. IMMUNOLOGY & SEROLOGY ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. TYPES OF TRANSPLANT REJECTION GRAFT-VERSUS-HOST DISEASE (GVHD) ▪ Acute GVHD ▪ Timing: Occurs within the first 100 days post- transplant. ▪ Affected Organs: Skin, gastrointestinal tract, liver. ▪ Pathophysiology: ▪ Cytokine release due to donor cell activation by mismatched MHC proteins. ▪ Tissue destruction via infiltration of donor T cells. ▪ Chronic GVHD ▪ Timing: Beyond 100 days post-transplant. ▪ Characteristics: Resembles autoimmune disease. ▪ Affected Areas: Skin, eyes, mouth, and mucosal surfaces. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY TYPES OF TRANSPLANT REJECTION GRAFT-VERSUS-HOST DISEASE (GVHD) GRAFT-VERSUS-LEUKEMIA EFFECT ▪ Refers to the beneficial ability of donor immune cells, primarily T cells, to recognize and eliminate residual leukemia cells in a recipient after an allogeneic hematopoietic stem cell (HSC) transplant. ▪ Donor T cells attack the recipient's malignant cells. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY TYPES OF TRANSPLANT REJECTION GRAFT-VERSUS-HOST DISEASE (GVHD) ▪ PREVENTION ▪ HLA Matching ▪ Immunosuppressive Therapy ▪ T Cell Depletion ▪ Umbilical Cord Blood Transplantation ▪ Blood Product Irradiation SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY SUMMARY IMMUNOSUPPRESSIVE DRUGS MECHANISM OF LIMITATIONS/ CLASS USES ACTION SIDE EFFECTS Block cytokine Maintenance Can cause high production, inflammatory immunosuppressi blood pressure, mediators, on; Acute increased chemoattractants, and rejection susceptibility to CORTICOSTEROIDS adhesion molecules; treatment (high infection, and reduce macrophage doses). osteoporosis. function and alter leukocyte trafficking. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. SUMMARY IMMUNOSUPPRESSIVE DRUGS MECHANISM OF LIMITATIONS/ CLASS USES ACTION SIDE EFFECTS Complexes with Mainstay of Nephrotoxicity at cyclophilin A to inhibit immunosuppressive high doses, calcineurin, blocking T- therapy in stimulation of cell cytokine transplantation, used TGFβ production production, including IL- for prophylaxis and leading to renal CYCLOSPORINE 2. treatment of fibrosis. (CYCLOSPORIN A) Also affects dendritic transplant rejection. cells, inhibiting functions like antigen processing and cytokine production. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. SUMMARY IMMUNOSUPPRESSIVE DRUGS MECHANISM OF LIMITATIONS/ CLASS USES ACTION SIDE EFFECTS Inhibits nucleic acid A commonly used Toxicity to other synthesis, preferentially drug given before dividing cells, affecting T-cell-mediated and after especially in the AZATHIOPRINE reactions. transplantation to gut and liver. diminish B- and T-cell proliferation. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. SUMMARY IMMUNOSUPPRESSIVE DRUGS MECHANISM OF LIMITATIONS/ CLASS USES ACTION SIDE EFFECTS CALCINEURIN Inhibit calcineurin, A T-cell-specific Tacrolimus = INHIBITORS blocking T-cell cytokine immunosuppressive Nephrotoxicity at production and dendritic drug used in high doses Tacrolimus cell activities. prophylaxis and (FK506) It is more potent than treatment of cyclosporine but also transplant rejection. Sirolimus nephrotoxic at high (Rapamycin) doses. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. SUMMARY IMMUNOSUPPRESSIVE DRUGS MECHANISM OF LIMITATIONS/ CLASS USES ACTION SIDE EFFECTS Target specific Induction therapy; Risk of anti-mouse lymphocyte surface severe rejection antibody MONOCLONAL molecules (e.g., CD25, episodes. response; reduced ANTIBODIES CD52) to inhibit T-cell with humanized activation or deplete antibodies. lymphocytes. Deplete circulating Induction therapy; Risk of serum POLYCLONAL lymphocytes by targeting severe rejection sickness due to ANTIBODIES T cells (anti-T-cell episodes. foreign antibody). immunoglobulin. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE IMMUNOLOGY & SEROLOGY CLINICAL HISTOCOMPATIBILITY TESTING DEFINITION CLINICAL HISTOCOMPATIBILITY TESTING ▪ Specialized laboratory procedures used to determine the compatibility between a transplant donor and recipient. ▪ The goal of clinical histocompatibility testing is to minimize the risk of rejection and improve the chances of successful transplantation. ▪ Types: ▪ HLA typing ▪ HLA phenotyping ▪ HLA genotyping ▪ HLA antibody screening and identification. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY CLINICAL HISTOCOMPATIBILITY TESTING HLA TYPING ▪ Identification of HLA antigens or genes in transplant candidates or donors. ▪ Determines phenotypes or genotypes of classical transplant antigens/genes. ▪ Key HLA Antigens/Genes Tested: ▪ HLA-A, HLA-B, HLA-Cw, HLA-DR, HLA-DQ ▪ Purpose: ▪ To identify the most suitable donor-recipient pair from an immunologic perspective. ▪ General rules for recipient compatibility ▪ Donor with no HLA antibodies for ▪ Donor with compatible blood type SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY ▪ Turgeon, M. L. (2018). Immunology & Serology in Laboratory Medicine (Sixth edition). Elsevier. HLA TYPING HLA PHENOTYPING ▪ Complement-dependent cytotoxicity (CDC) test ▪ Microlymphocytotoxicity assay ▪ Uses antisera/antibodies to detect HLA antigens on lymphocytes. ▪ T and B cells for HLA class I; purified B cells for HLA class II. ▪ Key Steps: ▪ Incubate lymphocytes with specific antisera in a microtiter plate. ▪ Add rabbit complement to activate cell killing if HLA antigen is present. ▪ Use vital dye (e.g., eosin red) to distinguish dead (colored) vs. live cells (colorless). SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY HLA TYPING HLA PHENOTYPING SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ McPherson, Richard A. and Pincus, Matthew R., "Henry's Clinical Diagnosis and Management by Laboratory Methods, 24th ed" (2021). IMMUNOLOGY & SEROLOGY HLA TYPING HLA PHENOTYPING SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ McPherson, Richard A. and Pincus, Matthew R., "Henry's Clinical Diagnosis and Management by Laboratory Methods, 24th ed" (2021). IMMUNOLOGY & SEROLOGY HLA TYPING HLA PHENOTYPING SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ McPherson, Richard A. and Pincus, Matthew R., "Henry's Clinical Diagnosis and Management by Laboratory Methods, 24th ed" (2021). IMMUNOLOGY & SEROLOGY HLA TYPING HLA GENOTYPING ▪ Uses PCR-based amplification of HLA genes to identify specific alleles/allele groups. ▪ Resolves limitations of CDC-based phenotyping (e.g., no need for viable cells). ▪ Key Methods: ▪ PCR-SSP (Sequence-Specific Priming): ▪ Amplifies specific alleles/groups using primer pairs. ▪ Detection via agarose gel electrophoresis. ▪ PCR-SSOP (Sequence-Specific Oligonucleotide Probe Hybridization): ▪ Generic amplification followed by hybridization with allele-specific DNA probes. ▪ SBT (Sequence-Based Typing): ▪ Gold standard: sequences entire HLA gene region. ▪ Uses Sanger sequencing with fluorescent dideoxy terminators. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY CLINICAL HISTOCOMPATIBILITY TESTING HLA ANTIBODY SCREENING, IDENTIFICATION, AND CROSSMATCHING ▪ HLA Antibody Screening ▪ Antibody Development: ▪ Triggered by blood transfusions, HLA-mismatched transplants, or pregnancies (paternal antigens). ▪ Screening Purpose: ▪ Detect HLA antibodies to avoid donor-recipient incompatibility. ▪ Monthly testing for solid-organ transplant candidates. ▪ Post-Transplant Monitoring: ▪ Assists in diagnosing and treating antibody-mediated rejection. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY CLINICAL HISTOCOMPATIBILITY TESTING HLA ANTIBODY SCREENING, IDENTIFICATION, AND CROSSMATCHING ▪ HLA Antibody Detection Methods ▪ ELISA (Enzyme-Linked Immunosorbent Assay) ▪ HLA antigens bound to microtiter plate wells. ▪ Detects bound antibody with enzyme-labeled anti-immunoglobulin reagent. ▪ Procedure: ▪ Purified HLA antigens are bounded to the wells of microtiter plates ▪ Patient serum is added to the wells of the plate ▪ If HLA-specific antibody is present in patient’s serum , binding to the HLA antigens on the wells will happen ▪ Enzyme-labeled anti-immunoglobulin reagent is added to detect the binding of Ag- Ab reaction ▪ Add substrate and wash to remove excess. Visualization is seen via color change (%PRA) SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY CLINICAL HISTOCOMPATIBILITY TESTING HLA ANTIBODY SCREENING, IDENTIFICATION, AND CROSSMATCHING ▪ HLA Antibody Detection Methods ▪ Flow Cytometry ▪ Incubates serum with HLA-coated beads (pooled, donor-specific, or single-antigen). ▪ Detects bound antibody using FITC- labeled anti-IgG reagent. ▪ Multiplex bead arrays enable simultaneous detection of multiple HLA antigens. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY CLINICAL HISTOCOMPATIBILITY TESTING HLA ANTIBODY SCREENING, IDENTIFICATION, AND CROSSMATCHING ▪ HLA Antibody Detection Methods ▪ Flow Cytometry ▪ Incubates serum with HLA-coated beads (pooled, donor-specific, or single-antigen). ▪ Detects bound antibody using FITC- labeled anti-IgG reagent. ▪ Multiplex bead arrays enable simultaneous detection of multiple HLA antigens. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY CLINICAL HISTOCOMPATIBILITY TESTING HLA ANTIBODY SCREENING, IDENTIFICATION, AND CROSSMATCHING ▪ HLA Antibody Detection Methods ▪ Flow Cytometry ▪ Incubates serum with HLA-coated beads (pooled, donor-specific, or single-antigen). ▪ Detects bound antibody using FITC- labeled anti-IgG reagent. ▪ Multiplex bead arrays enable simultaneous detection of multiple HLA antigens. SAN PEDRO COLLEGE SCHOOL OF MEDICAL LABORATORY SCIENCE REFERENCES: ▪ Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspective. F.A. Davis. IMMUNOLOGY & SEROLOGY