Immunology Overview: Lymphokines and Antibodies

Lymphokines

• Regulate the immune response
• Control the growth, mobility, and differentiation of leukocytes

Immune System Regulation

• Suppressor cells: Inhibit immune responses
• Immune response genes: Control individual immune responses
• Antigen regulation: Regulate amount and type of antigens
• Passive immunity: Transfer of antibodies, providing temporary protection

Antibody Types

• Autoantibodies: Target the body's own cells & tissues
• Alloantibodies: Attack the tissues of other individuals
• Heteroantibodies: Attack non-human antigens

Immunoglobulin Classes

• IgG: Most common type, found in blood and tissues; protects against bacteria, viruses, and toxins
• IgA: Found in mucosal areas (e.g., respiratory and gastrointestinal tracts) and body secretions; protects against infections
• IgM: First antibody produced in response to infection; activates complement
• IgD: Found on the surface of B cells; role in B cell activation
• IgE: Involved in allergic and parasitic infections

Immunoglobulin Structure

• Heavy chain: 2 polypeptide chains with approximately 450 amino acids
• Light chain: 2 polypeptide chains with approximately 214 amino acids
• Constant region: The portion of the antibody’s polypeptide chain that determines its class
• Variable region: The portion of the antibody that binds to a specific antigen; recognizes and interacts with specific antigens
• Hinge region: Flexible region connecting the Fab and Fc regions; allows antibodies to bind to antigens in different conformations
• Fab (Fragment antigen-binding): The portion of the antibody that binds to the antigen; contains the variable region to recognize antigens
• Fc (Fragment crystallizable): The portion of the antibody that interacts with other immune cells; contains the constant region, determining the antibody's effector function
• J chain: A small polypeptide chain that links two IgA molecules together to form dimers, or connects IgM molecules to form pentamers
• Disulfide bond: A covalent bond that stabilizes the immunoglobulin structure by joining polypeptide chains

Primary vs. Secondary Response

• Primary response: Initial encounter with an antigen; slower response with lower antibody production
• Secondary response: Subsequent exposure; faster, stronger response due to memory cells; higher antibody levels

Immunity Types

• Passive active immunity: Transfer of antibodies from another individual (e.g., maternal antibodies)
• Natural active immunity: Exposure to an infectious agent; results in long-lasting specific immunity
• Artificial passive immunity: Injection of pre-formed antibodies; provides temporary protection
• Artificial active immunity: Vaccination with weakened or attenuated pathogens or antigens; leads to long-lasting immunity

Complement Function

• Destroy pathogens: Lyses cells and triggers inflammatory responses
• Enhance phagocytosis: Opsonize pathogens
• Trigger inflammation: Recruit immune cells to the site of infection
• Eliminate immune complexes: Clear antigen-antibody complexes from circulation

Complement Pathways

• Classical pathway: Activated by antigen-antibody complexes
• Alternative pathway: Activated by microbial surfaces and foreign particles

Granuloma Formation

• Occurs when the immune system cannot contain an infection
• Formation of a mass of macrophages, lymphocytes, and other cells

Inflammation

• Definition: Nonspecific response to injury or infection
• Characteristics: Redness, swelling, pain, heat, and loss of function

Classical vs Alternative Complement Pathways

• Classical pathway: Requires antigen-antibody complexes to initiate activation; more specific and slower
• Alternative pathway: Activated by microbial surfaces and foreign particles; less specific and faster

Complement Biological Activities

• Lysis of cells directly destroys bacteria and other pathogens
• Opsonization coats pathogens, enabling phagocytes to recognize and engulf them
• Inflammation recruits immune cells like neutrophils to the site of infection
• Immune complex clearance removes antigen-antibody complexes from the circulation

Immune Response to Infections

• Bacterial infections: Antibody production, complement activation, phagocytosis
• Toxigenic bacterial infections: Neutralization of toxins by antibodies
• Viral infections: Antibody production (neutralization of viruses), cell-mediated immunity (killing of infected cells)
• Parasitic infections: Eosinophils, IgE, and mast cells play a crucial role; hypersensitivity reactions
• Fungal infections: Adaptive immune responses, macrophages, and neutrophils; granuloma formation

Tolerance and Immunosuppression

• Immunologic Tolerance: A state of unresponsiveness to a specific antigen; prevents the immune system from attacking self-antigens.
• Peripheral tolerance: Mechanism that eliminates or inactivates self-reactive immune cells
• Immunosuppression: Suppression of the immune response; used in organ transplantation and autoimmune diseases
• Immunopotentiation: Enhancement of the immune response; used to treat certain infections and cancers
• Suppressor cells: Specialized immune cells that regulate the immune response and suppress the activation of other immune cells
• Proliferate: Rapid and uncontrolled growth of cells
• Neoplasm: Abnormal growth of cells
• Benign: Non-cancerous; does not spread
• Malignant: Cancerous; spreads to other tissues or organs
• Dyscrasia: Disorder of the blood or bone marrow
• Aplasia: Defective formation or lack of development
• Metastatic/Metastasis: The spread of cancer cells to other parts of the body

Immunoproliferative Diseases

• Leukemia: Cancer of the blood-forming cells in bone marrow
• Lymphomas: Cancers that affect the lymphatic system
• Plasma cell dyscrasias: Disorders involving proliferation of plasma cells:
  • Multiple myeloma: Cancer of plasma cells
  • Waldenstrom's macroglobulinemia: Cancer involving the production of IgM antibodies
  • Heavy chain disease: Disorder involving the production of abnormal heavy chain antibodies
  • Amyloidosis: A condition where amyloid protein deposits in tissues

Immunodeficiency Diseases

• T cell deficiency: Defective T cell function; impaired cell-mediated immunity
• B cell deficiency: Defective B cell function; impaired antibody production
• SCID (severe combined immunodeficiency): Defects in both T and B cell function; severe impairment of the immune system
• Phagocytic dysfunction: Defective phagocytic cells; impaired ability to engulf and destroy pathogens
• Neutropenia: Low neutrophil count; increases susceptibility to bacterial infections
  • Congenital neutropenia: Inherited form of neutropenia
  • Acquired neutropenia: Develops due to certain medications or infections
  • Cyclic neutropenia: Neutrophil counts fluctuate over time
• Complement deficiency: Defective complement system; increased susceptibility to infections

Hypersensitivity Reactions

• Type I: Immediate hypersensitivity; allergies; mast cell degranulation
• Type II: Cytotoxic hypersensitivity; antibody-dependent cell-mediated cytotoxicity; destruction of cells
• Type III: Immune complex hypersensitivity; formation of immune complexes; damage to tissues
• Type IV: Delayed-type hypersensitivity; cell-mediated immunity; T cell activation and release of cytokines

HLA System

• Involves more than 200 genes
• Functions: Tissue typing and immune regulation
• Importance: Tissue compatibility for transplantation, susceptibility to certain diseases

Transplantation

• Eligible tissues/organs: Kidneys, heart, liver, lungs, pancreas

Transplant Complications

• Rejection: Immune response against the transplanted organ triggered by the recipient's immune system
• GvHD (graft-versus-host disease): Immune cells in the donated graft attack the recipient's tissues

Oncogenes & Tumor Antigens

• Oncogene: A gene that can cause cancer; often mutated forms of normal cellular genes (proto-oncogenes).
• Anti-oncogene: A gene that normally suppresses tumor growth; loss of function can trigger cancer
• Viral oncogene: A gene from a virus that can transform a normal cell into a cancerous cell
• Tumor antigen: An antigen present on the cell surface of a tumor; can be used to identify and target cancer cells

Tumor Markers

• CEA (Carcinoembryonic antigen): Found in some cancers, including colorectal cancer
• AFP (Alpha-fetoprotein): Found in some cancers, including liver and testicular cancer
• PSA (Prostate-specific antigen): Indicates prostate cancer
• Ectopic: Production of a hormone or protein by a tissue that normally does not produce that substance

Types of Tumor Antigens

• Tumor-associated antigens: Found on normal cells, but expressed at higher levels in tumor cells; e.g., CEA
• Tumor-specific antigens: Found only on tumor cells; e.g., mutated proteins
• Differentiation antigens: Found on certain types of cells during their development and differentiation; can be used to diagnose specific types of cancer
• Onco-viral antigens: Viral proteins expressed in cells infected by cancer-causing viruses; example: HPV proteins in cervical cancer