Innate immunity Knowledge-Based Study

Study notes

1. Overview of Innate Immunity

   The immune system protects the human body from pathogenic microorganisms, toxic substances, and abnormal cells. Immunity is fundamentally divided into two major arms: innate (non-specific) immunity and adaptive (specific) immunity.

   Innate immunity serves as the body's first and immediate response system. It is present from birth, acts rapidly upon encounter with a foreign agent, and does not depend on prior exposure to a pathogen. Unlike adaptive immunity, innate immunity does not confer immunological memory; its mechanisms respond with the same intensity and strategy upon repeated exposures.

   First Line of Defense: Physical and Chemical Barriers

   Before pathogens can invade internal tissues, they must breach external surface barriers:

   • Skin: The stratified, keratinized epithelial cells of the epidermis form a continuous physical barrier. Continual shedding of epidermal cells removes adherent microorganisms. Furthermore, sebum secreted by sebaceous glands lowers skin pH to between 3 and 5, inhibiting bacterial colonization.
   • Mucous Membranes: Lines body tracts exposed to the exterior (respiratory, digestive, urinary, and reproductive systems). Viscous mucus traps airborne particles and microbes. In the respiratory tract, coordinated movement of the ciliary escalator sweeps trapped particles toward the pharynx for swallowing or expulsion.
   • Chemical Secretions: Lysozyme, an antimicrobial enzyme found in tears, saliva, and mucus, cleaves peptidoglycan bonds in bacterial cell walls. Concentrated hydrochloric acid and proteolytic enzymes in gastric juice destroy the majority of ingested pathogens.

   Internal Defenses: Cellular Mediators

   When microorganisms breach surface barriers, internal cellular mechanisms of the innate response are mobilized immediately to control and clear the infection.

   Phagocytic Cells

   Phagocytosis is the ingestion and destruction of foreign particulate matter, dead host cells, and microorganisms by specialized leukocytes:

   • Neutrophils: The most abundant circulating white blood cells. Neutrophils are the earliest responders to migrate to an infection site, where they engulf microbes and release microbicidal agents via degranulation.
   • Macrophages: Derived from circulating monocytes, macrophages differentiate within tissues into resident or wandering phagocytes. They possess high phagocytic capacity and serve as vital antigen-presenting cells that subsequently inform the adaptive immune system.
   • Dendritic Cells: Stationed in peripheral tissues that encounter the external environment, dendritic cells phagocytose pathogens and migrate to regional lymph nodes to present processed antigens to T lymphocytes.

   Natural Killer (NK) Cells

   Natural killer cells are large granular lymphocytes that function in innate defense by surveying host tissues for virally infected cells and tumor cells. Unlike cytotoxic T lymphocytes, NK cells do not rely on specific antigen recognition via clonal receptors. Instead, they detect down-regulated or absent Major Histocompatibility Complex class I (MHC-I) molecules on aberrant cells. Upon target identification, NK cells release perforin to generate membrane pores and granzymes to induce apoptosis in the target cell.

   Soluble Defenses and Protective Inflammation

   In addition to cellular responders, the innate immune system deploys soluble antimicrobial proteins and coordinated tissue reactions to halt pathogen spread.

   Antimicrobial Proteins

   • The Complement System: A cascade of approximately thirty plasma proteins synthesized primarily by the liver. When activated via the classical, alternative, or lectin pathways, complement proteins mediate three primary outcomes: opsonization (coating pathogens with C3b to enhance phagocytosis), chemotaxis and inflammation enhancement (via C3a and C5a), and direct cell lysis through the assembly of the Membrane Attack Complex (MAC).
   • Interferons (Type I: IFN-alpha and IFN-beta): Cytokines secreted by virus-infected host cells. Interferons bind to membrane receptors of adjacent uninfected cells, stimulating the transcription of antiviral proteins that inhibit viral mRNA translation and degrade viral genomes upon entry.

   The Inflammatory Response

   Inflammation is a localized, protective tissue response triggered by physical trauma or infection. Tissue-resident mast cells and macrophages detect microbial components via Pattern Recognition Receptors (PRRs) like Toll-like receptors (TLRs), triggering the release of chemical mediators including histamine, leukotrienes, and prostaglandins:

   1. Vasodilation: Increases local blood flow, manifesting clinically as redness (rubor) and localized heat (calor).
   2. Increased Vascular Permeability: Allows fluid, clotting factors, and antibodies to enter interstitial spaces, producing swelling (tumor) and stimulating local nociceptors, resulting in pain (dolor).
   3. Phagocyte Extravasation: Leukocytes adhere to vascular endothelial walls (margination) and squeeze between endothelial cells (diapedesis) into the damaged tissue guided by chemotactic gradients.