11.2 Innate Immunity

Innate immunity is your body's first line of defense against invaders. It's like a fortress with walls, guards, and traps that work together to keep you safe from harmful microbes and substances.

This system includes physical barriers like skin, chemical defenses like stomach acid, and specialized cells that attack intruders. It's always on duty, ready to respond quickly to protect you from harm.

Innate Immunity: Body's First Line of Defense

Non-specific and Rapid Response

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• Innate immunity is the body's first line of defense against pathogens and is non-specific, meaning it responds to any foreign substance or microorganism
• Innate immunity is present from birth and does not require prior exposure to a pathogen to be effective
• The innate immune response is rapid, usually occurring within minutes to hours of exposure to a pathogen

Interaction with Adaptive Immunity

• Innate immunity includes physical and chemical barriers, cellular components, and humoral factors that work together to prevent or limit the spread of infection
• The innate immune system can also activate the adaptive immune system, which provides a more specific and targeted response to pathogens

Physical and Chemical Barriers

Physical Barriers

• Physical barriers include the skin, mucous membranes, and the cilia in the respiratory tract, which act as mechanical barriers to prevent the entry of pathogens
• The skin is an effective barrier due to its thickness, toughness, and the presence of keratin, a fibrous protein that makes the skin water-resistant and difficult to penetrate
• Mucous membranes, found in the respiratory, digestive, and urogenital tracts, secrete mucus that traps pathogens and prevents their attachment to epithelial cells
• Cilia in the respiratory tract sweep mucus and trapped particles towards the throat, where they can be swallowed or expectorated

Chemical Barriers

• Chemical barriers include enzymes, acids, and antimicrobial peptides that create an inhospitable environment for pathogens
  • Lysozyme, an enzyme found in tears, saliva, and other secretions, can break down the cell walls of certain bacteria (Staphylococcus)
  • The low pH of the stomach (HCl) and vagina (lactic acid) creates an acidic environment that is hostile to many pathogens
  • Defensins and cathelicidins are antimicrobial peptides that can disrupt bacterial cell membranes and have broad-spectrum activity against various pathogens (E. coli, Salmonella)
• Sebum, an oily substance secreted by sebaceous glands in the skin, contains antimicrobial lipids that help prevent bacterial and fungal growth on the skin's surface

Innate Immune Cells: Macrophages vs Natural Killer Cells

Macrophages

• Macrophages are large, phagocytic cells that engulf and destroy pathogens and cellular debris
  • They are derived from monocytes and are found in various tissues throughout the body (liver, lungs, lymph nodes)
  • Macrophages can be activated by cytokines and pathogen-associated molecular patterns (PAMPs) to enhance their phagocytic and microbicidal activities
  • Activated macrophages secrete cytokines (IL-1, TNF-α) and chemokines that promote inflammation and recruit other immune cells to the site of infection
• Macrophages also play a role in antigen presentation, displaying fragments of digested pathogens on their surface to activate T cells and initiate the adaptive immune response

Natural Killer Cells

• Natural killer (NK) cells are large, granular lymphocytes that can recognize and kill virus-infected cells and tumor cells
  • NK cells do not require prior sensitization and can respond rapidly to infected or abnormal cells
  • They release cytotoxic granules containing perforin and granzymes, which induce apoptosis in target cells (virus-infected cells, cancer cells)
  • NK cells also secrete cytokines, such as interferon-gamma (IFN-γ), that enhance the innate and adaptive immune responses
• NK cells express activating and inhibitory receptors on their surface that allow them to distinguish between normal and abnormal cells
  • Activating receptors recognize stress-induced proteins on infected or tumor cells, triggering NK cell activation
  • Inhibitory receptors recognize self-MHC class I molecules, which are often downregulated on infected or tumor cells, leading to NK cell activation

Neutrophils

• Neutrophils are the most abundant type of white blood cell and are the first cells to be recruited to the site of infection
  • They are phagocytic cells that can engulf and destroy pathogens, particularly bacteria (Streptococcus, Staphylococcus)
  • Neutrophils contain granules filled with enzymes (myeloperoxidase, lysozyme) and antimicrobial substances (defensins) that help kill pathogens
  • They can also release neutrophil extracellular traps (NETs), which are web-like structures composed of DNA and antimicrobial proteins that trap and kill pathogens
• Neutrophils are short-lived cells and are continuously produced in the bone marrow to maintain adequate numbers in circulation and respond to infections

Inflammatory Response vs Complement System

Inflammatory Response

• The inflammatory response is a complex series of events that occur in response to tissue damage or infection
  • It is characterized by redness, swelling, heat, pain, and loss of function in the affected area
  • The inflammatory response is initiated by the release of cytokines and chemokines from damaged cells and innate immune cells, such as macrophages (IL-1, TNF-α, IL-6)
  • These mediators cause vasodilation, increased blood flow, and increased vascular permeability, allowing immune cells and plasma proteins to enter the affected tissue
• The inflammatory response helps to isolate the damaged area, prevent the spread of infection, and promote tissue repair
  • Neutrophils and monocytes are recruited to the site of inflammation, where they phagocytose pathogens and dead cells
  • Fibroblasts proliferate and produce collagen to repair damaged tissue
  • Angiogenesis occurs to restore blood supply to the affected area

Complement System

• The complement system is a group of plasma proteins that play a key role in the innate immune response
  • The complement proteins circulate in an inactive form and are activated by specific triggers, such as antibody-antigen complexes or bacterial cell surfaces
  • Activation of the complement system occurs through three main pathways: the classical, alternative, and lectin pathways
• The complement system enhances the innate immune response through several mechanisms:
  • Opsonization: Complement proteins (C3b) coat the surface of pathogens, making them more easily recognized and engulfed by phagocytic cells
  • Chemotaxis: Complement fragments, such as C3a and C5a, attract immune cells (neutrophils, monocytes) to the site of infection
  • Membrane attack complex (MAC) formation: The terminal complement components (C5b-C9) assemble to form pores in the membranes of target cells, leading to cell lysis (Gram-negative bacteria)
• The complement system also helps to link the innate and adaptive immune responses by enhancing antibody-mediated immunity and promoting the clearance of immune complexes
  • C3d, a fragment of C3, binds to antigens and enhances B cell activation and antibody production
  • Complement receptors on phagocytic cells facilitate the uptake and destruction of opsonized pathogens and immune complexes