IMMUNOSEROLOGY

• The complement system is activated by the classical pathway, mannan-binding lectin (MBL) pathway, or alternative pathway.
• Immunology is the study of a host's reactions when foreign substances are introduced into the body
• A foreign substance that induces an immune response is called an immunogen
• Immunology has its roots in the study of immunity, the condition of being resistant to infection
• In the 1500s, the Chinese developed an immunological experimentation known as "variolation," where individuals were deliberately exposed to material from smallpox lesions
• In the 1700s, an English Doctor discovered the relationship between exposure to cowpox and immunity to smallpox, leading to the development of vaccination
• Cross-Immunity is the phenomenon where exposure to one agent produces protection against another agent
• In 1880-1881, a scientist discovered the first attenuated vaccine while working with bacteria that caused chicken cholera
• Natural immunity refers to the ability of an individual to resist infections through normally present body functions
• Acquired immunity is characterized by specificity for each individual pathogen or microbial agent
• The external defense system includes structural barriers like linings of the respiratory tract, skin, mucosal membrane surfaces, and secretions such as sweat, sebaceous glands, stomach acidity, tears, and saliva
• The internal defense system recognizes molecules unique to infectious organisms and includes functions like phagocytosis, inflammation, fever, and natural antimicrobial substances
• Cellular components of natural immunity include phagocytes, other white blood cells, NK cells, and LAK cells
• The humoral component of natural immunity involves cytokines, complement pathway, lysozymes, antimicrobial substances, and beta-lysin
• Neutrophils are a type of phagocyte that constitute 50-70% of circulating white blood cells and play a crucial role in the immune response
• Eosinophils, making up 1-3% of circulating white blood cells, are involved in allergic reactions and parasitic diseases
• Basophils, with bluish-purple granules containing histamine, are involved in immediate hypersensitivity reactions
• Mast cells, found in connective tissues, contain granules with various substances like ACP, ALP, and protease
• Monocytes, the largest white blood cells, possess granules with different enzymes and play a role in the immune response
• Macrophages, larger versions of monocytes found in tissues, have increased organelles and play various roles in immune defense
• Dendritic cells function to phagocytose antigens and present them to T-helper cells, playing a crucial role in the immune response
• PRR (Toll-like receptors) are proteins that play a role in antifungal immunity and are found in high concentrations in certain immune cells
• Pattern Recognition Receptors (PRRs) are involved in detecting specific molecular patterns associated with pathogens and inflammation
• NBS-LRR Proteins (Nucleotide-Binding Site and Leucine Rich Repeat) are part of the recognition mechanism
• Selected Pattern Recognition Receptors (PRRs):

  • TLR-1: Cell surface, Ligand: Lipoprotein, Cell types: Monocytes, macrophages, dendritic cells, B-cells
  • TLR-2: Cell surface, Ligand: Glycolipid, lipoteichoic acid, HSP-70, peptidoglycan, Cell types: Monocytes, macrophages, dendritic cells, mast cells
  • TLR-3: Intracellular compartment, Ligand: dsRNA, polyl:C, Cell types: Dendritic cells
  • TLR-4: Cell surface, Ligand: LPS, HSP, fibrinogen, Cell types: Monocytes, macrophages, dendritic cells, mast cells, B-cells
  • TLR-5: Cell surface, Ligand: Flagellin, Cell types: Monocytes, macrophages, dendritic cells
  • TLR-6: Cell surface, Ligand: Diacyl lipopeptides, Cell types: Monocytes, macrophages, B-cells
  • TLR-7: Intracellular compartment, Ligand: ssRNA, Cell types: Monocytes, macrophages, plasmacytoid cells, B-cells
  • TLR-8: Intracellular compartment, Ligand: ssRNA, Cell types: Monocytes, macrophages, dendritic cells, B-cells
• • TLR-9: Intracellular compartment, Ligand: Unmethylated CpG DNA, Cell types: Monocytes, macrophages, dendritic cells, B-cells
  • TLR-10: Intracellular compartment, Ligand: Unknown
  • TLR-11: Intracellular compartment, Ligand: Profilin, Cell types: Monocytes, macrophages
  • TLR-12: Intracellular compartment, Ligand: Unknown
  • TLR-13: Intracellular compartment, Ligand: Bacterial RNA, Cell types: Monocytes, macrophages, dendritic cells
  • C-lectin receptor: Cell surface, Ligand: Mannose, galactose, Cell types: Macrophages, dendritic cells
  • NOD-like receptor: Cytoplasm, Ligand: Peptidoglycan, Muramyl dipeptide
  • RIG-I-like receptor: Cytoplasm, Ligand: dsRNA
• Phagocytosis:

  • Engulfment of cells and particulate matter by leukocytes, macrophages, and other cells
• Chemotaxis:

  • Cells are attracted to the site of inflammation by chemical substances
  • Positive chemotaxis: Towards the stimulus
  • Negative chemotaxis: Away from the stimulus
  • Examples: C5a, C5b, C6, C7
• Opsonization:

  • Coating of Antibody and/or complement to facilitate phagocytosis
  • Examples of Opsonins: C3b, C4b, C5b, fibronectin, leukotrienes, immunoglobulins
• Steps of Phagocytosis:

  1. Physical contact between the WBC and the foreign particle

  2. Formation of phagosome

  3. Fusion with cytoplasmic granule to form phagolysosome

  4. Digestion and release of debris to the outside (exocytosis)
• Types of Phagocytosis:

  • Indirect: Via opsonin receptors that recognize opsonins such as IgG, CRP, and C3b bound to microorganisms
  • Direct: Via Pattern Recognition Receptors that recognize lipid and carbohydrate sequences on microorganisms
• Pathways of Killing Pathogens by Phagocytes:

  • Oxygen Dependent: Respiratory Burst occurs when the cytoplasmic pseudopods enclose the particle within a vacuole
  • Oxygen Independent: Production of nitric oxide from oxidation of L-arginine by NO synthase, produced by IFN-gamma activated cells
• Oxygen Independent:

  • Nitric oxide synthetase is induced when the phagocytic cell comes in contact with a microorganism
  • Nitric oxide is a soluble, highly labile, free radical gas capable of operating against invading organisms
  • In the presence of other reactive oxygen species within the phagosome, nitric oxide is converted to peroxynitrite and other products, highly toxic to bacteria, yeast, and viruses
• Inflammation:

  • The body's reaction to injury or invasion by an infectious agent
  • Involves cellular and humoral mechanisms
  • Tissue damage releases vasoactive and chemotactic factors triggering local increase in blood flow and capillary permeability
  • Permeable capillaries allow influx of fluids and cells
  • Phagocytes migrate to the site of inflammation
  • Phagocytes and anti-bacterial exudates destroy pathogens
• Acute Phase Reactants:

  • Produced primarily by hepatocytes within 12-24 hours in response to an increase in certain cytokines
  • Examples: C-reactive protein, Serum amyloid A, Alpha1-antitrypsin, Fibrinogen, Haptoglobin, Ceruloplasmin, Complement C3, Mannose-binding protein
• Humoral Component of Natural Immunity:

  • Includes cytokines (IL, IFN, TNF, G-CSF, GM-CSF), Complement Pathway, Lysozymes, Anti-microbial substances, Beta-lysin
• Interferon (IFN):

  • Originally named for interfering with viral replication in infected cells
  • Type 1 IFN: Produced primarily during initial innate response to viral infection (IFN-α by Mononuclear Phagocytes, IFN-β by Fibroblasts)
  • Type 2 IFN: Produced as part of the specific immune response to viral and other pathogens
• Tumor Necrosis Factor (TNF):

  • Major mediator of innate defense against gram-negative bacteria
  • Can trigger apoptotic death of tumor cells
  • Pro-inflammatory agent inducing secretion of APRs
  • Examples: TNF-α (cachectin, produced by macrophages), TNF-β (lymphotoxin, produced by CD4+ and CD8+ cells)
• Complement Pathway:

  • Complex series of more than 30 soluble and cell-bound proteins enhancing host defense mechanisms
  • Effects include activation of the immune system, opsonization, lysis of foreign cells and immune complexes
  • Chronic activation leads to inflammation and tissue damage
  • Most plasma complement proteins are synthesized in the liver as inactive precursors (zymogens)
  • Activated in three ways: Classical Pathway, Alternative Pathway, Lectin Pathway
• Immunity


  Physiological mechanisms that endow the animal with the capacity to recognize materials as foreign to itself and to neutralize, eliminate or metabolize them with or without injury to its own tissues