The following points highlight the four main components of innate immunity. The components are: 1. Physical and Chemical or Anatomical Barriers 2. Phagocytic Barriers 3. Blood Proteins 4. Cytokines.
Component # 1. Physical and Chemical or Anatomical Barriers:
Physical and Chemical or Anatomical barriers that tend to prevent the entry of pathogens are an organism’s first line of defense against infection. The skin and the surface of mucous membranes are included in this category because they provide an effective barrier to the entry of most microorganisms.
Skin:
The skin consists of two distinct layers: a relatively thin outer layer—the epidermis—and a thicker inner layer—the dermis. The epidermis contains several layers of tightly packed epithelial cells. The outer epidermal layer consists of dead cells and is filled with a water-proofing protein called keratin.
The skin acts as a major barrier to various invading microorganisms. Breaks in the skin results from scratches, wounds or abrasions. These breaks are the routes of infection. The skin may also be penetrated by biting insects e.g., mosquitoes, mites, ticks, fleas and sandflies.
On the surface of the skin, dense population of resident bacterial growth occurs. Growth of these bacteria is accelerated by the improper entrance due to the presence of sebum (from sebaceous glands of dermis), desiccation, etc.
Gastro-intestinal tract:
The gastro-intestinal tract contains residential bacteria, which not only help in digestion of certain polysaccharides (as cellulose in herbivores) but also play an important role in the control of potential pathogens.
The natural development of the immune system depends on continuous antigenic stimulus provided by those sufficiently low pH which is maintained within the stomach by gastric juices and has bactericidal and viricidal actions. In the intestine, low pH and anaerobic condition are maintained.
Urinogenital tract:
The flow of the urine and low pH provides the lumen of the urinogenital tract sufficient protection. In women, the vaginal wall is lined by squamous epithelium which is composed of rich amount of glycogen. In response to oestrogen, glycogen is deposited upon the epithelial surface just prior to ovulation. This is degraded anaerobically by the lactobacilli to produce lactic acid which act as a deterrent of pathogenic infection.
Mammary gland:
Milk contains bacterial inhibitors called lactenius. The lactenius include complement, lysozymes, an iron-binding protein called lactoferrin and an enzyme called lacto-peroxidase. Lactoferrin competes with bacteria for iron and thus inhibits their growth. In the presence of exogenous hydrogen-peroxide, lacto-peroxidase reacts with thiocyanate ions of milk and convert them into sulphurdicyanide, which is bacteriostatic.
Respiratory tract:
The walls of the respiratory tract are mucous covered when the suspended particles (~5 μm) present in the air enter the respiratory tract, they get stuck to these mucous covered walls. The mucous layer of the upper respiratory tract is provided with antiseptic properties by virtue of the presence of lysosomes and IgA in it.
The epithelial lining of GI, respiratory and genitourinary tracts produce various micro-peptides, which act as endogenous, natural antibiotics or disinfectants. Antimicrobial peptides are also produced in glandular secretions and by the phagocytes and other cells. These are defensins, cathelicidins, protegrins, granulysin, histamin, secretory leuco-protease inhibitor (SLPI).
Component # 2. Phagocytic Barriers:
The function of ingesting and destroying microbes is mediated by phagocytes, like neutrophils, macrophages and natural killer cells (NK cells).
Neutrophils:
Neutrophils or polymorphonuclear leukocytes are the most abundant population of circulating white blood cells. Neutrophils are spherical cells of about 12-15 μm diameter and with numerous ciliary projections. The cytoplasm is granular. The granules are of two types. Specific granules are filled with degradative enzymes, such as lysozyme, collagenase and elastase.
Macrophages:
Macrophages and their precursors, called the monocytes play a central role in both innate and acquired immunity. Macrophages may assume different morphologic forms, some develop abundant cytoplasm and are called epitheloid cells. Macrophages are found in sub-epithelial connective tissue, in the interstice of parenchymal organs, in the lining of the vascular sinusoids in the liver and spleen and in the lymphatic sinuses of lymph nodes.
Endocytosis, phagocytosis and killing of microbes:
Innate immunity is that defense mechanism which ingest extracellular macromolecules via endocytosis and particulate material via phagocytosis. In endocytosis, macromolecules within the extracellular tissue fluid are taken by cell via the invagination and pinching off a small regions of the plasma membrane.
Endocytosis occurs through either pinocytosis or receptor-mediated endocytosis, both help to internalize extracellular macromolecules either by nonspecific membrane invagination or by binding to specific membrane receptors (Fig. 6.1).
After that endocytic vesicles fuse with each other and ultimately fuse with endosomes. These help to dissociate ligands of macromolecules from their receptors so that they can fuse with primary lysosomes to form secondary lysosomes.
Primary lysosomes originate from Golgi, primary lysosome includes degrading enzyme with proteases, nucleases, lipases and hydrolytic enzyme, which digest macromolecules within secondary lysosomes and break into certain small products.
Phagocytosis is a cytoskeleton dependent process of engulfment of large particulate material which may also include the whole pathogenic molecules (Fig. 6.2). During phagocytosis the plasma membrane expands around the particulate material to form large vesicle called phagosome.
Before forming phagosome, macrophages and neutrophils are attracted by and more towards a variety of substances generated in an immune response. Phagosomes are several times larger than endocytic vesicles.
The phagosome vesicles contain the ingested foreign particles and or which break away from the plasma membrane and enter into the endocytic pathway. Then the phagosome moves toward the interior of the cell, fuses with lysosome or lysomes to form phagolysosome.
Natural killer cells (NK cells):
A third lymphoid lineage cell distinct from B and T-cells and their progeny is the natural killer (NK) cell. These large, non-phagocytic, granular lymphocytes are named for their ability to kill abnormal (e.g., infected or malignant) host cells. They account for 5% to 10% of all lymphocytes in the circulation.
NK cells are lymphocytes and are described as large, granular, non-T and non-B lymphocytes. Although they do contain cytoplasmic granules, these are considerably less prominent than those found in granulocytes (basophils, eosinophils, neutrophils).
NK cells are derived from bone marrow precursors and appear as large lymphocytes with numerous cytoplasmic granules. These cells constitute 5-20% of the mononuclear cells in the blood and spleen. Nor are NK cells members of the monocyte family.
Component # 3. Blood Proteins:
The Complement system:
Several blood plasma proteins, known as complement proteins, serve the function of linking microbe recognition to effector functions and also the development of inflammation by the “classical pathway” and “alternative pathway” create pores in the virus-infected target cells and granzymes enter through these pores to induce apoptosis of the target cells. Thus the NK cells eliminate the reservoir of the infection.
The complement system uses three different strategies for recognizing microorganisms, each of which initiates a pathway of complement activation that leads to the covalent bonding of complement proteins to microbial surfaces.
The classical pathway of complement activation is triggered by antibodies bound to antigens on a microbial surface. Here the complement proteins work together with antibodies to enhance the clearance of antigen: antibody complexes from the body. The two other pathways provide for complement activation in the absence of antibody and are considered part of the innate immune defenses.
They are the alternative pathway of complement activation, which is triggered directly by constituents of bacterial cell surfaces, and lectinmediated pathway, which is activated by the binding of mannose-binding protein present in blood plasma to mannose-containing proteoglycans on the surfaces of yeast and bacteria.
Complement deposited on the surface of certain pathogens can also lead directly to the lysis of the coated through the assembly of terminal complement components that makes a hole in the cell membrane and destroys its integrity (Table 6.3).
Component # 4. Cytokines:
Cytokines are proteins produced in response to microbes and other antigens that mediate and regulate immune and inflammatory reactions. In innate immunity, the principal sources of cytokines are macrophages, neutrophils and NK cells. Endothelial cells and some epithelial cells may also produce some cytokines (Table 6.4).
