INNATE IMMUNITY

Innate immunity is an invariable, hereditary response—an inborn defense. It is independent of previous exposure to disease causing agents and foreign substances. The innate immunity depends on the non-specific mechanisms, molecular defenses and the activity of the phagocytic cells. Innate immunity may be non-specific, when it indicates a degree of resistance to infection in general or specific, when resistance to particular pathogen is concerned.

Innate immunity may be considered at the level of species, race and individual. In species immunity, all individuals of a species are born with resistance to an infectious agent that causes disease in another species. For example, humans are immune to most infectious agents that causes disease in pets and other domesticated animals. Human beings are insusceptible to rinderpest or distemper, which the canines suffer. Similarly, the animals show innate immunity to many human pathogens. The mechanisms of species immunity are not clearly understood, but may be due to physiological and biochemical differences between the tissues of the different host species that determine, whether or not a pathogen can multiply in them.

Individuals in a race exhibit difference in innate immunity. The genetic basis of individual immunity is evident from studies on the incidence of infectious disease in twins. Homozygous twins exhibit similar degree of resistance or susceptibility to lepromatous leprosy and tuberculosis. An individual’s resistance to disease also depends on age, nutritional status, stress, hormone influence and general health in addition to genetic factor.


Mechanism of Innate Immunity

First line of defense


innate immunity

Physical barriers

Skin and mucous membrane form an important line of defense. Intact skin is impenetrable to most of the bacteria. Its low pH and presence of fatty acid makes the environment inhospitable for bacteria other than commensals. The continual shedding of the squamous epithelium also reduces bacterial load. If the continuity of the skin is compromised, the skin may be secondarily infected.

The mucous membranes form a less formidable barrier. The mucus with entrapped bacteria is swept away by cilia of the ciliated respiratory mucosa or the villi in the intestine particles are swallowed and coughed out by cough reflex.

The flushing effect of the body secretions reduces the microbial flora. Any slowing of urinary flow increases the chance of ascending infection. Saliva teeming with oral bacteria flows to the back of throat and is swallowed; gastric acidity destroys most swallowed bacteria. Commensal flora in the intestine prevents the colonization by pathogenic bacteria.


Chemical factors (Antimicrobial substances):

The barrier defense of skin and mucous membrane are reinforced by the presence of antibacterial substances.

Lysozyme, a hydrolytic enzyme, found in the mucus secretions and in tears, is able to cleave the peptidoglycan of the bacterial cell wall. Saliva contains antibacterial hydrogen peroxide (H2O2 ). The low pH of stomach and vagina is inimical to most bacteria. Cholera infection occurs more rapidly in association with achlorhydria.

Several substances, possessing antimicrobial property, have been described in blood and tissue. These include :-

  • Beta-lysine active against anthrax and related bacilli.
  • Basic polypeptides (leukin from leukocytes and plakin from platelets).
  • Lactic acid found in the muscle tissue and in the inflammatory zone.
  • Lactoperoxidase in the milk.
  • Virus inhibiting substances (antiviral substances) inhibit viral hemagglutinin.
  • A cysteine-rich peptide called defensins secreted by a variety of cells (epithelial cells, neutrophils, macrophages) in the skin and mucous membrane.
  • Other molecules with microbicidal functions include cathelicidin, deoxyribonuclease (DNases) and ribonuclease (RNases).

Interferons

A method of defence virus infection is the production of interferon (IFN) by cells stimulated by live or killed viruses and certain other inducers. IFN has been shown to be more important than specific antibodies in protection against and recovery from certain acute viral infections


Immunoglobulin

All classes of immunoglobulins (Ig) have been detected on mucous membranes, but IgA is the most important, because it is present in the greatest amount. IgA is a dimer, linked by secretory piece that not only aids transport, but also renders it resistant to proteolytic enzymes in the secretions. IgA is not involved in complement -mediated killing (classical pathway), but impedes adherence, an essential first step in colonization.


Complement system

The complement is a group of serum proteins that circulate in an inactive state. A variety of specific and non-specific immunologic mechanisms can convert the inactive form of complement proteins into an active form leading to lysis of bacteria, cells and viruses; promotion of phagocytosis (opsonization); triggering of inflammation; secretion of immune-regulatory molecules and clearance of immune complex from the circulation. In the innate immune system, complement can be activated by alternative pathway or via the mannanbinding lectin (MBL) pathway.


Cytokines and chemokines :

The cytokines are secreted by leukocytes and other cells and are involved in innate immunity, adaptive immunity and inflammation. Cytokines act in an antigen non-specific manner, triggering a wide range of biological activities from chemotaxis to activation of specific cells. Chemokines are subgroups of cytokines of low molecular weight involved in chemotaxis (chemical-induced migration).


Second line of defense

When the first line of defense fails, either because of congenital or acquired defects, then the way to deeper tissue is open to bacteria and the next lines of defense come to play. Ciliary dysfunction associated with respiratory infections is one of the congenital defects. There are many examples of acquired defects, the increasing use of indwelling devices provides niches for bacterial colonization and infection. Bacteria (e.g. Staphylococcus epidermidis) grow on these foreign bodies in a biofilm, protect them from host defense.


Cellular factors in innate immunity:

Natural defense against the invasion of the blood and tissue is mediated by phagocytic cells. Phagocytosis is the process by which the invading organisms are ingested by phagocytic cells, ingestion being followed by intracellular killing. Many cells are able to ingest the particles, e.g. endothelial cells, but three cells may be regarded as professional phagocytes. These are neutrophils, macrophages and to a much lesser degree eosinophils. Macrophages consist of histiocytes (wandering ameboid cells found in the tissue), the fixed reticulo -endothelial cells and blood monocytes.

The innate immune system provides a rapid, initial means of defense against infection using genetically programmed receptors that recognize these structural features of microbes that are not found in the host. Such receptors are known as pattern recognition receptors (PRRs), which are found on or in phagocytic cells, which bind to pathogenassociated molecular patterns (PAMPs). PAMPs are conserved, microbes-specific carbohydrates, proteins, lipids and/or nucleic acid (e.g. lipopolysaccharide, peptidoglycan, etc.). PRRs binding to PAMPs result in phagocytosis and enzymatic degradation of the infectious organisms (Figs 3.3A and B). Pattern recognition receptors engagement can lead to activation of the host cell and its secretion of antimicrobial substances. PRRs include :

  • Toll-like receptors (TLRs), which signals the synthesis and secretion of cytokines to promote inflammation by recruiting cells.
  • Scavenger receptors that are involved in internalization of bacteria and phagocytosis of host cells that are undergoing apoptosis.
  • Opsonins, the molecules (C3a, IgM), which bind to microbes to facilitate their phagocytosis.

Inflammation


Tissue injury, initiated by the entry of pathogens leads to inflammation, which is an important non-specific mechanism of defense. Hence, inflammation acts as a protective phenomenon.

  • Blood flow to the particular part is increased.
  • There is an outpouring of plasma, which dilutes the toxins and enzymes.
  • Chemotactic factors including C5a, histamine, leukotrienes, etc. will attract phagocytic cells to the site. The increased vascular permeability will allow easier access for neutrophils and monocytes. Vasodilation means more cells in the vicinity.
  •  There is formation of fibrin barrier, which limits the inflammation.
  • There is activation of complement and also the specific defenses.
  • A rise of temperature following infection, helps in following ways:

Fever

A rise of temperature following infection, helps in following ways:

  • Mobilization defenses.
  • Accelerate repairs.
  • Inhibits pathogens.
  • Stimulates the production of IFNs and helps in recovery from virus infection. Therapeutic induction of fever was employed previously for destruction of T. pallidum.

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