The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates (the other being the adaptive immune system). The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, prokaryotes, and invertebrates (see § Beyond vertebrates). The major functions of the innate immune system are to:
recruit immune cells to infection sites by producing chemical factors, including chemical mediators called cytokines activate the complement cascade to identify bacteria, activate cells, and promote clearance of antibody complexes or dead cells identify and remove foreign substances present in organs, tissues, blood and lymph, by specialized white blood cells activate the adaptive immune system through antigen presentation act as a physical and chemical barrier to infectious agents; via physical measures such as skin and mucus, and chemical measures such as clotting factors and host defence peptides. initiate and regulate inflammatory responses by releasing inflammatory mediators (such as cytokines and chemokines), thereby promoting immune cell recruitment, increasing vascular permeability, and enhancing local immune defense at sites of infection.
Anatomical barriers Anatomical barriers include physical, chemical and biological barriers. The epithelial surfaces form a physical barrier that is impermeable to most infectious agents, acting as the first line of defense against invading organisms. Desquamation (shedding) of skin epithelium also helps remove bacteria and other infectious agents that have adhered to the epithelial surface. Lack of blood vessels, the inability of the epidermis to retain moisture, and the presence of sebaceous glands in the dermis, produces an environment unsuitable for the survival of microbes. In the gastrointestinal and respiratory tract, movement due to peristalsis or cilia, respectively, helps remove infectious agents. Also, mucus traps infectious agents. Gut flora can prevent the colonization of pathogenic bacteria by secreting toxic substances or by competing with pathogenic bacteria for nutrients or cell surface attachment sites. The flushing action of tears and saliva helps prevent infection of the eyes and mouth.
Epithelial barrier theory The epithelial barrier hypothesis (also known as the epithelial barrier theory) is a medical concept suggesting that dysfunction of epithelial barriers, induced by environmental toxic substances such as air pollutants, detergents, food additives, microplastics, and nanoparticles, contributes to the development of chronic diseases. Barrier impairment occurs in the skin, respiratory tract, and intestines, and is often accompanied by microbial dysbiosis, bacterial translocation, tissue and systemic inflammation, and immune dysregulation. These processes have been proposed as contributing factors to allergic, autoimmune, metabolic, and neuropsychiatric disorders. The hypothesis was initially framed in the early 2020s by immunologist Cezmi Akdis and has since been discussed in independent peer-reviewed reviews in the fields of immunology, allergy, dermatology, and nutrition. Akdis introduced the concept to explain the rising prevalence of chronic inflammatory diseases in industrialized societies. It builds on earlier frameworks such as the hygiene hypothesis, and incorporates findings from microbiome research. Proposed mechanisms include:
Barrier damage: Environmental exposures including ozone, particulate matter, detergents, and synthetic particles may impair epithelial junctions, increasing permeability and allowing antigens to penetrate underlying tissues. Microbial dysbiosis: Barrier impairment can alter microbiota composition in the skin, gut, and airways, reducing microbial diversity and promoting overgrowth of opportunistic species. Immune activation: Cytokines such as interleukin-25, interleukin-33, and thymic stromal lymphopoietin are implicated in initiating type 2 inflammatory responses following barrier disruption. Disease contexts may include:
Allergic diseases: asthma, atopic dermatitis, food allergy, allergic rhinitis, eosinophilic esophagitis. Autoimmune and metabolic disorders: type 1 diabetes, multiple sclerosis, metabolic dysfunction-associated steatotic liver disease. Neuropsychiatric conditions: preliminary research suggests possible links to neuroinflammatory disorders, such as Alzheimer's disease. Critics of the theory argue that many associations remain correlative and emphasize the need for longitudinal human studies and standardized methods to assess epithelial barrier integrity.
Inflammation
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