🦠Microbiology Unit 17 – Innate Nonspecific Host Defenses

Key Concepts and Definitions

• Innate immunity provides immediate, non-specific defense against pathogens and foreign substances
• Consists of physical barriers, chemical barriers, and cellular components that work together to prevent infection
• Innate immune responses are genetically determined and do not require prior exposure to a pathogen
• Includes the inflammatory response, which is a complex series of events that helps to localize and eliminate pathogens
• Key cells involved in innate immunity include phagocytes (neutrophils and macrophages), dendritic cells, and natural killer cells
• The complement system is a group of plasma proteins that enhance the ability of antibodies and phagocytic cells to clear pathogens
• Innate immunity is the first line of defense against infection and plays a crucial role in activating adaptive immunity

Types of Innate Defenses

• Physical barriers include the skin, mucous membranes, and other mechanical barriers that prevent the entry of pathogens
• Chemical barriers consist of enzymes, acids, and antimicrobial peptides that create an inhospitable environment for pathogens
  • Examples include lysozyme in tears and saliva, low pH of the stomach, and defensins in the intestinal tract
• Cellular components involve various immune cells that recognize and respond to pathogens
  • Phagocytes (neutrophils and macrophages) engulf and destroy pathogens
  • Dendritic cells capture, process, and present antigens to T cells, linking innate and adaptive immunity
  • Natural killer cells destroy virus-infected and tumor cells without prior sensitization
• The inflammatory response is a complex cascade of events that helps to localize and eliminate pathogens
• The complement system enhances the ability of antibodies and phagocytic cells to clear pathogens

Physical and Chemical Barriers

• The skin is the largest organ and serves as a physical barrier against pathogens
  • Keratinocytes produce keratin, which forms a tough, waterproof layer
  • Langerhans cells in the epidermis capture and present antigens to T cells
• Mucous membranes line the respiratory, digestive, and urogenital tracts and secrete mucus, which traps pathogens
  • Cilia in the respiratory tract sweep mucus and trapped particles out of the lungs
• Tears, saliva, and other secretions contain lysozyme, an enzyme that breaks down bacterial cell walls
• The low pH of the stomach creates an acidic environment that kills many ingested pathogens
• Defensins are antimicrobial peptides found in the intestinal tract, respiratory tract, and skin
  • They create pores in bacterial cell membranes, leading to cell lysis
• Urine flow and vaginal secretions help to mechanically remove pathogens from the urogenital tract

Cellular Components of Innate Immunity

• Phagocytes are cells that engulf and destroy pathogens
  • Neutrophils are the most abundant type of white blood cell and are the first to respond to infection
  • Macrophages are long-lived cells that reside in tissues and continue to fight infection after neutrophils have died
• Dendritic cells are specialized antigen-presenting cells that capture, process, and present antigens to T cells
  • They link innate and adaptive immunity by activating T cells and initiating an adaptive immune response
• Natural killer (NK) cells are lymphocytes that destroy virus-infected and tumor cells without prior sensitization
  • They release cytotoxic granules containing perforin and granzymes, which induce apoptosis in target cells
• Eosinophils are granulocytes that defend against parasitic infections and play a role in allergic responses
• Basophils and mast cells release histamine and other mediators that contribute to inflammation and allergic reactions

Inflammatory Response

• Inflammation is a complex cascade of events that helps to localize and eliminate pathogens
• Triggered by tissue damage or infection, which causes the release of inflammatory mediators (cytokines, chemokines, and prostaglandins)
• Vasodilation increases blood flow to the affected area, causing redness and heat
• Increased vascular permeability allows fluid and immune cells to enter the tissue, causing swelling
• Pain results from the stimulation of nerve endings by inflammatory mediators
• Neutrophils are the first cells to arrive at the site of inflammation, followed by macrophages
  • They phagocytose pathogens and release additional inflammatory mediators
• The inflammatory response helps to localize the infection, prevent the spread of pathogens, and promote tissue repair
• Chronic inflammation can contribute to the development of diseases such as atherosclerosis, cancer, and autoimmune disorders

Complement System

• The complement system is a group of plasma proteins that enhance the ability of antibodies and phagocytic cells to clear pathogens
• Consists of three activation pathways: classical, alternative, and lectin pathways
  • The classical pathway is activated by antibody-antigen complexes
  • The alternative pathway is activated by microbial surfaces and does not require antibodies
  • The lectin pathway is activated by the binding of mannose-binding lectin to microbial carbohydrates
• All three pathways converge on the formation of C3 convertase, which cleaves C3 into C3a and C3b
• C3b opsonizes pathogens, enhancing phagocytosis by macrophages and neutrophils
• The terminal pathway leads to the formation of the membrane attack complex (MAC), which creates pores in the pathogen's cell membrane, causing lysis
• Complement activation also generates anaphylatoxins (C3a and C5a), which promote inflammation and recruit immune cells to the site of infection

Innate vs. Adaptive Immunity

• Innate immunity is the first line of defense against pathogens and provides immediate, non-specific protection
• Adaptive immunity is a slower, more specific response that develops after exposure to a pathogen
• Innate immunity does not confer long-lasting protection, while adaptive immunity provides immunological memory
• Innate immune responses are genetically determined, while adaptive immune responses are acquired through exposure to antigens
• Innate immunity involves physical barriers, chemical barriers, and cellular components (phagocytes, dendritic cells, and NK cells)
• Adaptive immunity involves T lymphocytes and B lymphocytes, which produce specific antibodies and cell-mediated responses
• Innate immunity plays a crucial role in activating adaptive immunity through antigen presentation by dendritic cells

Clinical Relevance and Applications

• Deficiencies in innate immune components can lead to increased susceptibility to infections
  • Chronic granulomatous disease is caused by defects in phagocyte oxidative burst, leading to recurrent bacterial and fungal infections
  • Leukocyte adhesion deficiency is caused by defects in neutrophil adhesion and migration, resulting in recurrent soft tissue infections
• Excessive or inappropriate activation of innate immunity can contribute to inflammatory and autoimmune diseases
  • Rheumatoid arthritis is characterized by chronic inflammation of the joints, mediated by innate immune cells and cytokines
  • Inflammatory bowel disease (Crohn's disease and ulcerative colitis) involves dysregulated innate immune responses in the gut
• Targeting innate immune pathways is a promising approach for the development of new therapies
  • Toll-like receptor (TLR) agonists are being investigated as vaccine adjuvants and cancer immunotherapies
  • Complement inhibitors are being developed for the treatment of inflammatory and autoimmune diseases
• Understanding the interplay between innate and adaptive immunity is crucial for the development of effective vaccines and immunotherapies