🐅Animal Physiology Unit 9 – Immune System: Our Body's Defense Shield

Key Components of the Immune System

• Consists of a complex network of cells, tissues, and organs that work together to protect the body from pathogens and other harmful substances
• White blood cells (leukocytes) play a central role in the immune system, including lymphocytes (T cells and B cells), monocytes, and granulocytes (neutrophils, eosinophils, and basophils)
• Lymphoid organs, such as the thymus, spleen, and lymph nodes, are essential for the development, maturation, and activation of immune cells
  • Thymus is the site of T cell maturation and selection
  • Spleen filters blood and serves as a reservoir for immune cells
  • Lymph nodes trap and filter pathogens from the lymphatic system
• Bone marrow is the primary site of hematopoiesis, producing all blood cells, including immune cells
• Mucous membranes (respiratory, digestive, and urogenital tracts) act as physical and chemical barriers, secreting mucus, enzymes, and antimicrobial peptides to prevent pathogen entry
• Skin serves as a physical barrier, with keratinocytes producing antimicrobial peptides and Langerhans cells acting as antigen-presenting cells

Types of Immunity

• Innate immunity is the first line of defense, providing rapid, non-specific protection against pathogens
  • Includes physical and chemical barriers (skin, mucous membranes), phagocytic cells (macrophages, neutrophils), and soluble factors (complement proteins, cytokines)
  • Recognizes pathogen-associated molecular patterns (PAMPs) using pattern recognition receptors (PRRs) like Toll-like receptors (TLRs)
• Adaptive immunity is a slower, more specific response that develops after exposure to a pathogen
  • Mediated by lymphocytes (T cells and B cells) that recognize specific antigens
  • T cells are involved in cell-mediated immunity, directly killing infected cells or activating other immune cells
  • B cells are responsible for humoral immunity, producing antibodies that neutralize pathogens and mark them for destruction
• Passive immunity is the transfer of preformed antibodies from one individual to another
  • Occurs naturally through the placenta (maternal antibodies) or breast milk
  • Can be artificially induced through the administration of immune globulins (e.g., for post-exposure prophylaxis)
• Active immunity is the development of an immune response following exposure to a pathogen or vaccine
  • Naturally acquired through infection
  • Artificially induced through vaccination, using inactivated, attenuated, or subunit antigens to stimulate an immune response

Immune System Responses

• Inflammatory response is a localized reaction to tissue damage or infection, characterized by redness, swelling, heat, and pain
  • Mediated by cytokines (IL-1, TNF-α) and chemokines that recruit immune cells to the site of injury
  • Vasodilation increases blood flow and vascular permeability, allowing immune cells and fluid to enter the affected area
• Complement system is a cascade of plasma proteins that enhance the immune response
  • Classical pathway is activated by antibody-antigen complexes
  • Alternative pathway is triggered by microbial surfaces
  • Lectin pathway is initiated by the binding of mannose-binding lectin to pathogen surfaces
  • Complement activation leads to opsonization (marking pathogens for phagocytosis), chemotaxis (attracting immune cells), and direct lysis of pathogens through the membrane attack complex (MAC)
• Cytotoxic T cell response involves the direct killing of infected or abnormal cells by CD8+ T cells
  • Activated by antigen presentation on MHC class I molecules
  • Release perforin and granzymes to induce apoptosis in target cells
• Antibody-mediated response is the production of specific antibodies by B cells (plasma cells) to neutralize and eliminate pathogens
  • Antibodies bind to antigens, preventing their entry into cells and marking them for destruction by phagocytes or complement activation
  • Different antibody classes (IgM, IgG, IgA, IgE, IgD) have specific functions and locations in the body

Cellular and Molecular Mechanisms

• Antigen presentation is the process by which antigen-presenting cells (APCs) display foreign antigens on their surface to activate T cells
  • Major histocompatibility complex (MHC) molecules are responsible for presenting antigens
    • MHC class I presents intracellular antigens to CD8+ T cells
    • MHC class II presents extracellular antigens to CD4+ T cells
  • Professional APCs include dendritic cells, macrophages, and B cells
• T cell activation requires two signals: antigen recognition by the T cell receptor (TCR) and co-stimulation by molecules like CD28 and CD80/86
  • Absence of co-stimulation can lead to T cell anergy or tolerance
• B cell activation and antibody production
  • B cells recognize antigens through their B cell receptor (BCR, membrane-bound antibody)
  • T-dependent activation requires interaction with helper T cells (CD4+) and cytokines
  • T-independent activation occurs through repetitive antigenic structures (e.g., polysaccharides) and does not require T cell help
  • Activated B cells differentiate into plasma cells, secreting large amounts of specific antibodies
• Cytokine signaling is crucial for immune cell communication and regulation
  • Produced by various immune cells (e.g., T cells, macrophages) and other cell types
  • Act as messengers to stimulate, regulate, or suppress immune responses
  • Examples include interleukins (IL-2, IL-4, IL-10), interferons (IFN-α, IFN-γ), and tumor necrosis factors (TNF-α)

Disorders and Diseases

• Autoimmune disorders occur when the immune system mistakenly attacks the body's own tissues
  • Examples include rheumatoid arthritis (joints), multiple sclerosis (central nervous system), and systemic lupus erythematosus (multiple organs)
  • Caused by a combination of genetic and environmental factors that lead to a breakdown in self-tolerance
• Immunodeficiencies are conditions characterized by a weakened or absent immune response
  • Primary immunodeficiencies are genetic disorders, such as severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA)
  • Secondary immunodeficiencies are acquired, resulting from factors like malnutrition, certain medications (e.g., chemotherapy), or infections (e.g., HIV)
• Allergies are hypersensitivity reactions to normally harmless substances (allergens)
  • Mediated by IgE antibodies and mast cells, leading to the release of histamine and other inflammatory mediators
  • Symptoms can range from mild (e.g., hay fever) to severe (e.g., anaphylaxis)
• Chronic inflammation is a prolonged inflammatory response that can contribute to various diseases
  • Associated with conditions like atherosclerosis, obesity, and neurodegenerative disorders
  • Characterized by the persistent presence of inflammatory cells and cytokines in affected tissues

Immune System Health and Maintenance

• Balanced diet provides essential nutrients (vitamins, minerals, antioxidants) that support immune function
  • Vitamin C aids in collagen synthesis and enhances phagocytic activity
  • Vitamin D modulates immune responses and has anti-inflammatory properties
  • Zinc is crucial for T cell development and function
• Regular exercise has immunomodulatory effects, enhancing immune surveillance and reducing inflammation
  • Moderate exercise increases the circulation of immune cells and anti-inflammatory cytokines
  • Excessive or prolonged exercise can temporarily suppress immune function
• Stress management is important, as chronic stress can impair immune responses
  • Stress hormones (cortisol, catecholamines) can suppress immune cell function and increase inflammation
  • Relaxation techniques (meditation, deep breathing) and adequate sleep can help mitigate the effects of stress on the immune system
• Vaccination is a critical tool for preventing infectious diseases
  • Stimulates the development of specific immunity without causing disease
  • Herd immunity occurs when a significant portion of a population is vaccinated, reducing the spread of disease and protecting those who cannot be vaccinated

Cutting-Edge Research and Developments

• Immunotherapy is a rapidly growing field that harnesses the immune system to treat various diseases
  • Cancer immunotherapy uses strategies like checkpoint inhibitors (anti-PD-1, anti-CTLA-4) and CAR T cell therapy to enhance anti-tumor immune responses
  • Monoclonal antibodies are engineered to target specific antigens, used in the treatment of autoimmune disorders (e.g., anti-TNF-α for rheumatoid arthritis) and cancer (e.g., rituximab for B cell lymphoma)
• Personalized medicine approaches aim to tailor immune-based therapies to an individual's genetic and immunological profile
  • Pharmacogenomics studies the influence of genetic variations on drug responses, helping to optimize treatment strategies
  • Neoantigen vaccines are designed to target patient-specific tumor mutations, eliciting a more targeted anti-tumor immune response
• Microbiome research investigates the role of the gut microbiota in shaping immune responses
  • Commensal bacteria can modulate immune cell development and function, influencing susceptibility to various diseases (e.g., inflammatory bowel disease, allergies)
  • Probiotics and fecal microbiota transplantation are being explored as potential therapies for immune-related disorders
• Systems immunology integrates high-throughput technologies (e.g., single-cell sequencing, mass cytometry) and computational methods to study the immune system as a complex network
  • Allows for the identification of novel immune cell subsets and their interactions
  • Helps to unravel the mechanisms underlying immune responses and diseases, facilitating the development of targeted therapies

Practical Applications and Case Studies

• Vaccine development and implementation have led to the eradication of smallpox and the significant reduction of diseases like polio, measles, and rubella
  • Current efforts focus on developing vaccines for emerging pathogens (e.g., SARS-CoV-2) and improving vaccine accessibility in low-resource settings
• Immunodiagnostics are tools that detect the presence of specific antibodies or antigens to diagnose infections or monitor immune responses
  • Enzyme-linked immunosorbent assay (ELISA) is widely used to detect antibodies against pathogens (e.g., HIV, hepatitis) or autoantibodies in autoimmune disorders
  • Flow cytometry allows for the rapid analysis of immune cell populations based on surface marker expression, aiding in the diagnosis of immunodeficiencies and leukemias
• Transplantation immunology focuses on managing the immune response to prevent graft rejection
  • Human leukocyte antigen (HLA) typing ensures compatibility between donor and recipient
  • Immunosuppressive drugs (e.g., cyclosporine, tacrolimus) are used to prevent graft rejection by inhibiting T cell activation and proliferation
• Immunotoxicology studies the adverse effects of chemicals and drugs on the immune system
  • Assesses the immunosuppressive or immunostimulatory potential of substances
  • Helps to establish safety guidelines and regulatory standards for environmental and occupational exposures