Innate immune system
The innate immune system or nonspecific immune system[1] is one of the two main immunity strategies (the other being the adaptive immune system) 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 (see Beyond vertebrates).[2]
The major functions of the innate immune system are to:
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.[5]
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 (PRRs), which recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). At the onset of an infection, burn, or other injuries, these cells undergo activation (one of their PRRs recognizes a PAMP) 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 (histamine, bradykinin, serotonin, leukotrienes, and prostaglandins) sensitize pain receptors, cause local vasodilation of the blood vessels, and attract phagocytes, especially neutrophils.[5] 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.[6]
The inflammatory response is characterized by the following symptoms:
The complement system is a biochemical cascade of the immune system that helps, or "complements", the ability of antibodies to clear pathogens or mark them for destruction by other cells. The cascade is composed of many plasma proteins, synthesized in the liver, primarily by hepatocytes. The proteins work together to:
The three different complement systems are classical, alternative and lectin.
Elements of the complement cascade can be found in many non-mammalian species including plants, birds, fish, and some species of invertebrates.[7]
Other vertebrate mechanisms[edit]
The coagulation system overlaps with the immune system. Some products of the coagulation system can contribute to non-specific defenses via their ability to increase vascular permeability and act as chemotactic agents for phagocytic cells. In addition, some of the products of the coagulation system are directly antimicrobial. For example, beta-lysine, a protein produced by platelets during coagulation, can cause lysis of many Gram-positive bacteria by acting as a cationic detergent.[3] Many acute-phase proteins of inflammation are involved in the coagulation system.
Increased levels of lactoferrin and transferrin inhibit bacterial growth by binding iron, an essential bacterial nutrient.[3]
Neural regulation[edit]
The innate immune response to infectious and sterile injury is modulated by neural circuits that control cytokine production period. The inflammatory reflex is a prototypical neural circuit that controls cytokine production in the spleen.[15] Action potentials transmitted via the vagus nerve to the spleen mediate the release of acetylcholine, the neurotransmitter that inhibits cytokine release by interacting with alpha7 nicotinic acetylcholine receptors (CHRNA7) expressed on cytokine-producing cells.[16] The motor arc of the inflammatory reflex is termed the cholinergic anti-inflammatory pathway.
Beyond vertebrates[edit]
Prokaryotes[edit]
Bacteria (and perhaps other prokaryotic organisms), utilize a unique defense mechanism, called the restriction modification system to protect themselves from pathogens, such as bacteriophages. In this system, bacteria produce enzymes, called restriction endonucleases, that attack and destroy specific regions of the viral DNA of invading bacteriophages. Methylation of the host's own DNA marks it as "self" and prevents it from being attacked by endonucleases.[32] Restriction endonucleases and the restriction modification system exist exclusively in prokaryotes.[33]
Invertebrates[edit]
Invertebrates do not possess lymphocytes or an antibody-based humoral immune system, and it is likely that a multicomponent, adaptive immune system arose with the first vertebrates.[34] Nevertheless, invertebrates possess mechanisms that appear to be precursors of these aspects of vertebrate immunity. Pattern recognition receptors (PRRs) are proteins used by nearly all organisms to identify molecules associated with microbial pathogens. TLRs are a major class of pattern recognition receptor, that exists in all coelomates (animals with a body-cavity), including humans.[35] The complement system exists in most life forms. Some invertebrates, including various insects, crabs, and worms utilize a modified form of the complement response known as the prophenoloxidase (proPO) system.[34]
Antimicrobial peptides are an evolutionarily conserved component of the innate immune response found among all classes of life and represent the main form of invertebrate systemic immunity. Several species of insect produce antimicrobial peptides known as defensins and cecropins.