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• Immunohematology or Blood Banking:

  • Study of immunologic principles of a reaction from Red Cell Antigens and Antibodies found in plasma and its application to transfusion medicine
  • Combination of Immunology, Serology, Hematology, Genetics, and Molecular Biology
  • Includes blood banking processes like blood typing, crossmatching, antihuman globulin testing, detection and identification of antibodies, screening of donors for blood donation, and bleeding techniques
• • Involves transfusion and transfusion therapy for treating patients with blood components and other blood products, emphasizing quality systems
• Reasons to study immunohematology:

  • Avoid transmission of diseases like Hepa, HIV, syphilis
  • Ensure blood products are safe for use
  • Biology plays a role in immunohematology
• • 1901: Dr. Karl Landsteiner discovered the ABO blood group
  • 1913: Reuben Ottenberg emphasized the importance of blood typing and compatibility testing
  • 1921: First blood donor service established by Percy Oliver
  • 1927: American Association of Immunologists adopted the current ABO terminology proposed by Dr. Landsteiner
  • 1939: Philip Levine published a case report of post-transfusion hemolysis in a blood group O patient
• History of Blood Transfusion:

  • 1492: Physician bled three boys and had an ill Pope drink blood, resulting in their deaths
  • 1628: Dr. William Harvey's book paved the way for blood investigation
  • 1656: Architect Sir Christopher Wren demonstrated intravenous injections using a quill of a goose
  • 1666: Dr. Richard Lower transfused blood from one dog to another
  • 1667: Dr. Jean Baptiste Denis performed the first animal-to-human transfusion
  • 1795: Dr. Philip Syng Physick performed the first human-to-human transfusion after a ban of 150 years
• Basic Immunology:

  • Study of molecules, cells, organs, and systems recognizing and disposing foreign materials
  • Resistance to disease and defense against non-self
  • Main stars of Immunology are Lymphocytes
  • Consequences of immunity include allergy, organ rejections, and autoimmune disorders
• Body Defense:

  First Line:

  • Unbroken skin with keratinization protection
  • Mucus membrane traps foreign materials
  • Sebum, lactic acid, earwax, and excretion remove microorganisms
  • Acidity in stomach, intestines, and vagina eliminates pathogens
  • Cilia in respiratory tract remove foreign materials
  • Tears and saliva combat microorganisms
  • Normal flora present in intestines and vagina

  Second Line:

  • Non-specific innate immunity with rapid response including phagocytes, neutrophils, complement, and acute inflammatory reaction

  Third Line:
• • Specific acquired immunity with recognition, memory, and response
  • Includes cellular (lymphocytes) and humoral (antibodies, complement) immunity
• Antigen:

  • Recognized as a foreign body
  • Can be a protein, carbohydrate, or lipid
  • Autoantigens are antigens of the host, no reaction in normal circumstances
  • Alloantigens are antigens of others
  • Heteroantigens are antigens from other species
  • Composition includes epitope (part that reacts with antibody), haptens (partial antigen), and carrier (responsible for molecular weight of the antigen)
• Factors of immunogenicity:

  • Foreignness: non-self vs. self
  • Number: there should be a sufficient number of immunogens to produce a response
  • Molecular weight: the higher the molecular weight, the more effective the antigen is
  • Complexity: more complex antigens are more effective
• Immunogen:

  • An antigen that can provoke an immune response
• Lipids and Nucleic acids are the weakest antigens

  Proteins and Polysaccharides (kind of) are the strongest antigens
• Major Histocompatibility Complex (MHC):

  • Formerly Human Leukocyte Antigen encoded from the gene found in the short arm of Chromosome 6
  • Found in all Nucleated Cells
  • Can cause an immune response if transplanted
  • Binds to peptides within the cell and transports it to the plasma membrane
  • Brings antigen to the cell surface for recognition by T-cells
• Class I MHC:

  • High levels on nucleated cells including lymphocytes
  • Low levels in Liver, Neural, Muscle, Sperm cells
  • Recognized by cytotoxic T-cells (CD8+)
  • HLA-A, HLA-B, HLA-C
• Class II MHC:

  • More restricted
  • Found in Antigen Presenting Cells (APC) such as B-cells, Macrophages, dendritic cells
  • Process extracellularly derived antigen
  • Recognized by T-Helper cells (CD4+)
  • HLA-DP, HLA-DQ, HLA-DR
• Antibodies:

  • Molecules that bind to Antigen and are very specific
  • Y-shaped with 4 protein chains (2 identical light chains and 2 heavy chains connected by disulfide bonds)
  • Found in plasma and other body fluids
  • Natural Antibodies occur without stimulus
  • Immune Antibodies occur with stimulus
• Immunoglobulin M (IgM):

  • Largest antibody with molecular weight 900,000 daltons
  • A Pentamer named after its heavy chain Mu heavy chain
  • Binds FC receptors, found on B-cell surface
  • Activates complement
  • First antibody made by infants
  • First antibody produced during infection, last to leave
  • Reacts best at room temperature and/or cold temperature
• Immunoglobulin D (IgD):

  • Monomer found on B-cell surface, blood, lymph
  • With a Delta Heavy Chain, molecular weight of 180,000 daltons
  • Second type of IG to appear
  • Heat and acid labile, susceptible to proteolysis
• Immunoglobulin A (IgA):

  • Found in serum as a monomer, in secretions as a Dimer
  • With an alpha heavy chain
  • Molecular Weight: 160,000-400,000 Daltons
  • Antibody that protects mucosal surfaces, major secretory IG
  • Present in Tears, Saliva, Milk
• Immunoglobulin G (IgG):

  • Major Serum Immunoglobulin
  • A monomer with Gamma Heavy Chain
  • Binds Fc receptors, activates complement, neutralizes toxins, enhances phagocytosis
  • Main antibody in secondary response
  • Can travel to the placenta and protect newborns
  • Reacts best at body temperature
  • With subclasses: IgG1, IgG2, IgG3, IgG4
• Immunoglobulin E (IgE):

  • A monomer with an extra domain
  • Molecular weight is 190,000 Daltons
  • With an epsilon Heavy Chain
  • Least abundant in serum
  • Binds to FC receptors of Eosinophils for the Major basic protein
  • Antibody for allergy (causes Type 1 hypersensitivity), parasitic infections
• Cytokines:

  • Polypeptide product of activated cells
  • Controls cellular response and regulates the immune system
  • Pleiotropic = multiple activities/effects
  • Binds to target cell receptors
  • Regulate receptor expression in T and B cells
  • Influence other Cytokines
  • Acts as hormones

  Examples: Interleukins, Interferons, Stem Cell Factor, Tumor Necrosis Factor, Chemokines
• Complement:

  • Non-specific proteins
  • Completes the process of Antibody-Antigen complex
  • Most are synthesized in the liver
  • Effects: Chemotaxis, Lysis of Cells, Mediators, Opsonization, Increase Vascular permeability
  • With 3 known pathways
• Classical Pathway:

  • Activated by the immune complexes of antibody and antigen
  • Process involves C1, C1q, C1r, C1s, C4, C2, C3, C5, C4a, C4b, C2a, C2b, C3a, C3b, C4b2a/2b/3b, C5a, C5b, membrane attack complex (MAC)
• C5 convertase is formed by C3bBb3b
• C5 convertase cleaves C5 into C5a and C5b
• C5b combines with C6, C7, C8, and C9 to form the membrane attack complex (MAC)
• Alternative Pathway:

  • Activated by bacterial cell membrane and IgA aggregate
  • Process involves cleaving C3 into C3a and C3b
  • C3b combines with C3bBb to form C3bBb3b, known as C5 convertase
  • C5 convertase cleaves C5 into C5a and C5b
• Properdin pathway:

  • Stabilizes the pathway and increases the half-life of C3 convertase to 90 seconds
• Lectin Pathway:

  • Antigen activates MASPS (Mannose-associated serine protease)
  • MASPS cleaves C2 and C4, similar to the classical pathway
• 1. Cells:

  • T-Cells make up 60-80% of circulating lymphocytes
  • Thymocytes live as immature Thymocytes in the Thymus
  • Thymocytes mature to Double Positive Thymocytes (CD4+ and CD8+ cells)
  • T-Helper cells (Th) are inducer cells and recognize antigens with MHC-II
  • T-Helper cells include Th1 and Th2 subsets
  • T-Regulatory cells regulate Th1 and Th2 activity
  • Cytotoxic T-Cells (Tc) destroy target cells
  • T-Suppressor cells shut down the immune response
• 1. Cells:

  • B-Cells develop in the bone marrow and mature to Plasma cells to produce antibodies
  • B-Cells interact with T-Cells for antibody production
  • Different types of antibodies (IgM, IgD, IgG, IgE, IgA) are produced based on immune responses
• Natural Killer Cells:

  • Third population of lymphocytes
  • Non-specific cells that target cancer cells and infected cells
• Eosinophils and Basophils:

  • Capable of phagocytosis and antigen presenting, mainly involved in hypersensitivity and allergy reactions
• Molecular Biology:

  • RNA and DNA are nucleic acids composed of bases, sugars, and phosphate
  • RNA is composed of ribonucleotides with ribose sugar, while DNA is genetic material with deoxyribonucleotides and a double helix structure
  • Genome, genetic polymorphism, and chromosomes are key concepts in molecular biology
  • Gene expression involves transcription, RNA splicing, and translation processes
• Molecular Basis of Blood Group Polymorphism:

  • There are around 33 blood group systems with over 300 blood antigens
  • Blood group variants result from single nucleotide polymorphisms and genetic variations
• Variants are results of one or more single nucleotide polymorphisms, including:

  • Gene deletion
  • Insertion
  • Intergenic recombination
  • Substitution
  • Translocation
  • Duplication
• Actions of genes are responsible for the traits and disease
• Antigens are made up of glycolipids (carbohydrates) because:

  • The binding sites of the amino acids are complementary to the carbohydrates or lipids needed
  • Over 300 blood antigens exist due to different mating in each generation, leading to variation
  • Polymorphism refers to variation on the genes
• RBC membrane:

  • Biconcave shape allows for a close to maximum surface to volume ratio and optimal gaseous exchange
  • Functions include deformability, osmotic balance, support for antigens, and gas exchange