Innate immune system


The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, prokaryotes, and invertebrates.
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.
  • initiates and regulates inflammatory responses by releasing inflammatory mediators, 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 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.
Anatomical barrierAdditional defense mechanisms
SkinSweat, cathelicidin, desquamation, flushing, organic acids, skin flora
Gastrointestinal tractPeristalsis, gastric acid, bile acids, digestive enzyme,
flushing, thiocyanate, defensins, gut flora, lysozymes
Respiratory airways and lungsMucociliary escalator, surfactant, defensins
NasopharynxMucus, saliva, lysozyme
EyesTears
Blood–brain barrierendothelial cells. P-glycoprotein

Epithelial Barrier Theory

The epithelial barrier hypothesis 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 A. 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 include:
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

is one of the first responses of the immune system to infection or irritation. Inflammation is stimulated by chemical factors released by injured cells. It establishes a physical barrier against the spread of infection and promotes healing of any damaged tissue following pathogen clearance.
The process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells, and mast cells. These cells present receptors contained on the surface or within the cell, named pattern recognition receptors, which recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns. At the onset of an infection, burn, or other injuries, these cells undergo activation and release inflammatory mediators, like cytokines and chemokines, which are responsible for the clinical signs of inflammation. PRR activation and its cellular consequences have been well-characterized as methods of inflammatory cell death, which include pyroptosis, necroptosis, and PANoptosis. These cell death pathways help clear infected or aberrant cells and release cellular contents and inflammatory mediators.
Chemical factors produced during inflammation sensitize pain receptors, cause local vasodilation of the blood vessels, and attract phagocytes, especially neutrophils. Neutrophils then trigger other parts of the immune system by releasing factors that summon additional leukocytes and lymphocytes. Cytokines produced by macrophages and other cells of the innate immune system mediate the inflammatory response. These cytokines include TNF, HMGB1, and IL-1.
The inflammatory response is characterized by the following symptoms:
  • redness of the skin, due to locally increased blood circulation;
  • heat, either increased local temperature, such as a warm feeling around a localized infection, or a systemic fever;
  • swelling of affected tissues, such as the upper throat during the common cold or joints affected by rheumatoid arthritis;
  • increased production of mucus, which can cause symptoms like a runny nose or a productive cough;
  • pain, inflammatory mediators directly stimulate and sensitize nociceptive nerve endings, resulting in local pain, such as painful joints or a sore throat, or affecting the whole body, such as body aches; and possible dysfunction of involved organs/tissues.

    Complement system

The complement system is a key mechanism of innate immunity that utilize proteins to identify and eliminate pathogens, while also maintaining homeostasis by clearing dead and damaged cells.. Once a pathogen enters the body through the epithelial barrier, soluble plasma proteins called complement proteins become activated. These complement proteins trigger a cascade of reactions that target and kill extracellular pathogens.
In the classical pathway, The antibody in the classical pathway is produced by B cells during the adaptive immune response, and once it binds to a pathogen, it allows C1 to bind and activate the complement system.This then activates C4 and C2 which will both combine to form C3 convertase. C3 convertase will then split into C3a and C3b. C3a aids in promoting opsonization and increases inflammation by helping immune cells move to the infection site, whereas C3b helps in forming a protein complex which functions to insert itself into a pathogen’s membrane to cause cell lysis, killing the pathogen, known as the membrane attack complex, composed of proteins C5b-C9.
The alternative pathway follows a similar sequence as the classical pathway but begins with the spontaneous activation of C3. Activated C3 will bind directly to the pathogen’s surface and interacts with other proteins to form C3 convertase. At this point, the pathway will continue like the classical pathway and form the membrane attack complex and kill the pathogen via cell lysis.
C3 is mechanistically essential for complement function, and deficiencies in C3 severely impair immune responses. A lack of C3-mediated opsonization is associated with defective dendritic cell differentiation, weakened memory B-cell responses, and impaired regulatory T-cell development, highlighting how C3 influences not only pathogen clearance but also broader adaptive immune processes.
  • Lectin: starts when lectins bind to mannose on bacteria
Elements of the complement cascade can be found in many non-mammalian species including plants, birds, fish, and some species of invertebrates.

White blood cells

White blood cells are also known as leukocytes. Most leukocytes differ from other cells of the body in that they are not tightly associated with a particular organ or tissue; thus, their function is similar to that of independent, single-cell organisms. Most leukocytes are able to move freely and interact with and capture cellular debris, foreign particles, and invading microorganisms. Unlike many other cells, most innate immune leukocytes cannot divide or reproduce on their own, but are the products of multipotent hematopoietic stem cells present in bone marrow.
The innate leukocytes include: natural killer cells, mast cells, eosinophils, basophils; and the phagocytic cells include macrophages, neutrophils, and dendritic cells, and function within the immune system by identifying and eliminating pathogens that might cause infection.