Mechanism of Non-Specific Immune Response against Antigens

SCENARIO 1 The body's defense when initially exposed to an antigen SCENARIO The body has a defense system that can recognize antigens or pathogens. The body's initial defense system is always ready and has a non-specific response that can destroy pathogens. These immune components can be in the form of skin, mucosal epithelium, mucous membranes, respiratory tract cilia movement, IgA. 4. Explain the mechanism of non-specific immune response to destroy antigens Guidance Questions for LO 4: a. How can the nonspecific immune system destroy antigens? Non-specific/natural immune system cells function as protectors to detect microbes and damaged cells in tissues and perform several functions that are important for the body's defense against microorganisms. Epithelial barrier An intact epithelial surface forms a physical barrier between microbes in the external environment and host tissue, and epithelial cells produce antimicrobial chemicals that further inhibit microbial entry.The protective function of the epithelial barrier is largely physical. Epithelial cells form tight junctions with each other, inhibiting the entry of microbes between the epithelial cells. The outer layer of keratin, which accumulates as keratinocytes on the surface of dead skin, functions to block the penetration of microbes into the deeper layers of the epidermis. Mucus, a viscous secretion containing a glycoprotein called mucin, is produced by respiratory, gastrointestinal, and urogenital epithelial cells and physically interferes with microbial invasion. The function of this barrierenhanced by the action of cilia in the bronchial tree and peristalsis in the intestine, which facilitates the elimination of microbes. Although these physical properties themselves are essential in host defense, other epithelial defense mechanisms have evolved to complement the mechanical barrier.Epithelial cells as well as some leukocytes produce peptides that have antimicrobial properties. Two structurally distinct families of antimicrobial peptides are defensins and cathelicidins. Defensinproduced by mucosal surface epithelial cells and by granule-containing leukocytes, including neutrophils, NK cells, and cytotoxic T lymphocytes. The protective actions of defensins are direct toxicity against microbes, including bacteria, fungi and enveloped viruses, and activation of cells involved in the inflammatory response to microbes. Defensins kill microbes by various mechanisms, generally depending on their ability to enter and damage the function of microbial membranes. Cathelicidinproduced by neutrophils and epithelial cells in the skin, digestive tract, and respiratory tract. Active cathelicidins protect against infection by various mechanisms, including direct toxicity to various microorganisms and activation of various responses in leukocytes and other cell types that aid in the process of microbial eradication. The C-terminal fragment, called LL-37, can bind and neutralize LPS, a toxic component of the outer wall of gram-negative bacteria. LL-37 also plays an anti-inflammatory role by binding to DNA and blocking activation AIM2 inflammasome. Dendritic cells Dendritic cells doantigen recognitionand the role of effectors in non-specific immunity. Dendritic cells are uniquely able to stimulate and direct immune responses mediated by T lymphocyte cells, activated effector T lymphocyte cells and their processes are highly dependent on the process of non-specific immune responses to antigens/microbes. This ability reflects the ability of dendritic cells to recognize and capture microbial antigen proteins and then transport them to the lymph nodes where naive T cells reside, and to present the antigen proteins in a form that can be recognized by the T cells. Macrophage Cells Monocyte cells are non-specific immune cells that circulate in the blood. When monocyte cells migrate to infected or damaged tissue, these cells will differentiate into macrophage cells. The function of macrophage cells is to phagocytize microbes, as APCs (antigen presenting cells) which present antigens to T helper cells, producing several cytokines which play a role in destroying intracellular bacteria. This is a process by macrophage cells which can destroy antigens/microbes which can be carried out by macrophage cells. Natural Killer (NK) Cells Natural Killer (NK) cells are natural lymphoid cells that play an important role in the natural immune response, especially against viruses and intracellular bacteria. The effector function of NK cells is to kill infected cells and produce IFN-γ, which activates macrophages to destroy microbes by phagocytosis. The mechanism of NK cellmediated cytotoxicity is essentially the same as CD8+ (cytotoxic T cells). When NK cells are activated, granule exocytosis releases proteins adjacent to the target cells. One NK cell granule protein, whichcalledperforin, facilitating the entry of another granule protein, calledgranzyme, into the cytosol of target cells. Granzymes are enzymes that initiate a sequence of signaling events that cause target cell death through apoptosis. By killing cells infected by viruses and intracellular bacteria, NK cells eliminate the reservoir of infection. Inflammatory response The primary way the nonspecific immune system deals with infection and tissue injury is by stimulating acute inflammation, which is the accumulation of leukocytes, plasma proteins, and blood-derived fluid at the site of infection or extravascular tissue injury.Acute inflammation can develop within minutes to hours and last for days. Chronic inflammation is a process that takes over from acute inflammation if the infection is not eliminated or tissue injury is prolonged. It usually involves recruitment and activation of monocytes and lymphocytes. Sites of chronic inflammation also frequently undergo tissue remodeling, with angiogenesis and fibrosis. Although innate immune stimulation may contribute to chronic inflammation, the adaptive immune system may also be involved because cytokines produced by T cells are potent inflammatory stimuli. TNF, IL-1, and IL-6 produced during the natural immune response to infection or tissue damage have systemic effects that contribute to host defense and are responsible for many clinical manifestations of infections and inflammatory diseases. Inflammation is also the result of complement activation of the non-specific immune system.