🤾🏻‍♂️Human Physiology Engineering Unit 12 – Immune System

Key Components of the Immune System

• Consists of a complex network of cells, tissues, and organs that work together to defend the body against infectious agents and other harmful substances
• Lymphoid organs include the thymus, spleen, lymph nodes, and bone marrow which produce, mature, and store immune cells
• Innate immune system provides immediate, non-specific defense against pathogens through physical and chemical barriers, inflammation, and phagocytosis
  • Includes skin, mucous membranes, and various immune cells (neutrophils, macrophages, and natural killer cells)
• Adaptive immune system develops specific, long-lasting immunity to particular pathogens through the action of lymphocytes (T cells and B cells)
  • Involves antigen recognition, clonal expansion, and memory cell formation
• Cytokines are signaling molecules that regulate and coordinate immune responses by facilitating communication between immune cells
• Complement system enhances the ability of antibodies and phagocytic cells to clear pathogens and damaged cells from the body

Types of Immunity

• Passive immunity provides temporary protection through the transfer of antibodies from another source
  • Naturally acquired passive immunity occurs when maternal antibodies are transferred to the fetus through the placenta or to the infant through breast milk
  • Artificially acquired passive immunity involves the administration of preformed antibodies (immunoglobulins) through medical interventions
• Active immunity develops when an individual's immune system produces antibodies in response to an antigen
• Naturally acquired active immunity results from exposure to a pathogen through infection, leading to the development of long-lasting immunity
• Artificially acquired active immunity is induced by vaccines, which contain weakened, killed, or fragmented pathogens or their toxins
  • Vaccines stimulate the immune system to produce antibodies without causing the disease itself
• Herd immunity occurs when a significant portion of a population becomes immune to an infectious disease, reducing the likelihood of its spread

Immune Response Process

• Antigen recognition is the first step, where immune cells identify foreign substances (antigens) through specific receptors
• Innate immune response is triggered immediately upon antigen detection, involving inflammation, phagocytosis, and the release of antimicrobial compounds
  • Macrophages and dendritic cells engulf and destroy pathogens while presenting antigens to T cells
• Adaptive immune response is activated when innate immunity is insufficient, leading to the proliferation and differentiation of antigen-specific lymphocytes
  • T cells mature into cytotoxic T cells that directly kill infected cells or helper T cells that regulate the immune response
  • B cells mature into plasma cells that secrete antibodies specific to the encountered antigen
• Clonal expansion occurs when activated lymphocytes rapidly divide and multiply to create a large pool of antigen-specific cells
• Memory cell formation follows the primary immune response, where a subset of activated lymphocytes becomes long-lived memory cells
  • Memory cells enable a faster and stronger secondary immune response upon subsequent encounters with the same antigen

Cellular and Molecular Mechanisms

• Antigen presentation involves the processing and display of antigenic peptides on the surface of antigen-presenting cells (APCs) via major histocompatibility complex (MHC) molecules
  • MHC class I molecules present intracellular antigens to cytotoxic T cells, while MHC class II molecules present extracellular antigens to helper T cells
• T cell activation requires both antigen recognition through the T cell receptor (TCR) and co-stimulatory signals provided by APCs
  • CD4+ helper T cells secrete cytokines to regulate the immune response, while CD8+ cytotoxic T cells directly kill infected or abnormal cells
• B cell activation occurs when B cells encounter their specific antigen and receive signals from helper T cells
  • Activated B cells differentiate into plasma cells that secrete large quantities of antibodies
• Antibodies neutralize pathogens, opsonize them for phagocytosis, and activate the complement system
  • There are five classes of antibodies (IgM, IgG, IgA, IgE, and IgD) with different functions and locations in the body
• Cytokine signaling orchestrates the immune response by regulating cell proliferation, differentiation, and effector functions
  • Pro-inflammatory cytokines (IL-1, IL-6, TNF-α) promote inflammation, while anti-inflammatory cytokines (IL-10, TGF-β) suppress immune responses

Disorders and Diseases of the Immune System

• Immunodeficiencies are disorders characterized by a weakened immune system, increasing susceptibility to infections
  • Primary immunodeficiencies are genetic disorders (severe combined immunodeficiency, X-linked agammaglobulinemia)
  • Secondary immunodeficiencies are acquired due to factors like malnutrition, certain medications, or HIV/AIDS
• Autoimmune diseases occur when the immune system mistakenly attacks the body's own tissues
  • Examples include rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis
• Allergies are hypersensitivity reactions to normally harmless substances (allergens) mediated by IgE antibodies
  • Symptoms range from mild (hay fever) to severe (anaphylaxis)
• Graft rejection occurs when the immune system recognizes transplanted tissue as foreign and mounts an immune response against it
  • Immunosuppressive drugs are used to prevent rejection in organ transplant recipients
• Cancer immunology explores the complex interactions between the immune system and tumor cells
  • Immunotherapies harness the immune system to fight cancer by enhancing its ability to recognize and destroy tumor cells

Engineering Applications in Immunology

• Vaccine development utilizes genetic engineering and recombinant DNA technology to create safer and more effective vaccines
  • Subunit vaccines contain purified antigens, while DNA vaccines deliver genes encoding antigenic proteins
• Monoclonal antibodies are engineered antibodies produced by identical immune cells, used for targeted therapies and diagnostics
  • Applications include cancer treatment (checkpoint inhibitors), autoimmune disorders (TNF-α inhibitors), and infectious diseases (antiviral antibodies)
• Immunoassays are diagnostic tools that detect the presence of specific antigens or antibodies in a sample
  • Enzyme-linked immunosorbent assay (ELISA) and lateral flow assays (rapid tests) are commonly used
• Biopharmaceuticals are drugs produced using living organisms, often involving the manipulation of immune system components
  • Examples include recombinant cytokines (interferon, interleukin-2) and fusion proteins (etanercept)
• Immunoengineering focuses on the design and manipulation of immune cells and molecules for therapeutic purposes
  • Chimeric antigen receptor (CAR) T cell therapy genetically modifies a patient's T cells to target and destroy cancer cells

Cutting-Edge Research and Future Directions

• Immunoinformatics applies computational methods to analyze and predict immune system functions and interactions
  • Involves the development of databases, algorithms, and models to study immunological data
• Systems immunology takes a holistic approach to understanding the immune system by integrating data from various levels (genes, proteins, cells, tissues)
  • Aims to unravel the complex networks and feedback loops that regulate immune responses
• Microbiome research investigates the role of the human microbiome in shaping immune system development and function
  • Dysbiosis (imbalance in the microbiome) has been linked to various immune-related disorders
• Personalized immunotherapy tailors treatments to an individual's unique immune profile and disease characteristics
  • Involves the use of biomarkers, genetic profiling, and patient-specific immune cell engineering
• Regenerative immunology explores the use of immune cells and molecules to promote tissue repair and regeneration
  • Macrophages and regulatory T cells have shown potential in enhancing wound healing and reducing fibrosis

Practical Implications and Case Studies

• Vaccine hesitancy and misinformation have hindered the success of immunization programs, as seen in the resurgence of measles outbreaks
  • Effective communication and public education are crucial to promote vaccine uptake
• The COVID-19 pandemic has highlighted the importance of rapid vaccine development and the role of the immune system in disease progression
  • mRNA vaccines (Pfizer-BioNTech, Moderna) and viral vector vaccines (AstraZeneca, Johnson & Johnson) were developed in record time
• Immunotherapies have revolutionized cancer treatment, with notable successes in melanoma and lung cancer
  • Ipilimumab (CTLA-4 inhibitor) and nivolumab (PD-1 inhibitor) have significantly improved survival rates in advanced melanoma patients
• Autoimmune diseases like rheumatoid arthritis and inflammatory bowel disease have benefited from targeted therapies that modulate the immune response
  • TNF-α inhibitors (infliximab, adalimumab) have been effective in reducing inflammation and improving quality of life
• The development of rapid diagnostic tests for infectious diseases, such as HIV and influenza, has enabled earlier detection and treatment
  • Point-of-care testing using lateral flow assays has increased access to diagnostics in resource-limited settings