Physiologic Barriers - Innate and Adaptive Immunity

Physiologic  Barriers

The following act as physiologic barriers of innate immune response:

1.     Antibodies against blood group antigens

2.     Alternate pathway of complement system

3.     Macrophages

4.     Interferons

5.     γδ Cells

6.     CD5-B Cells

Also, the physiologic barriers that contribute to innate immunity include temperature, pH and various soluble factors. Many animal spe-cies are not susceptible to certain diseases simply because their normal body temperature inhibits the growth of the pathogens. Chicken for example have innate immunity to anthrax because their high body tem-perature inhibits the growth of the bacteria. Gastric acidity acts as physi-ologic barrier to infection because very few ingested microorganisms can survive the low pH of the stomach contents. In the mouth, strepto-cocci produce peroxides that compete with bacteria for iron and en-hance respiratory activity in neutrophils. Many soluble factors contrib-ute to nonspecific immunity such as the enzyme lysozyme, interferon, and complement.

The flushing action of urine combined with the low pH of the urinogenital tract prevents the pathogens from establishing in the uro-genital tract. Desquamation of epithelial cells from the vaginal wall in adult women provides a substrate for lactobacilli growth. These bacte-ria produce lactic acid, and also compete with pathogenic bacteria for nutrients and space.

The flushing action of milk in the mammary gland that contains lactenins, bacterial inhibitors, iron binding protein lactoferrin lactoper-oxidase, and IgA enhancers also contributes to innate immunity. Ph-agocytic cells released into the mammary gland caused in response toirritation due to sucking contributes to phagocytic action, lactoferrins and hydrogen peroxide.

Antimicrobial peptides: Cells of many animals produce anti-microbial substances that act as endogenous natural antibiotics or dis-infectants. These micropeptides take many forms.

α-Defensins:There are six known human alpha defensins. Fourbelong to neutrophils and the other two are present in vagina and cer-vix

β-Defensins:Large amounts of β-Defensins appear in Henley’sloop, distal and collecting tubules of kidney and also in the vagina, cervix, uterus and fallopian tubes. These peptides have broad spec-trum, salt-sensitive antibacterial activity and show synergy with lysozyme and lactoferrin.

Cathelicidins: Humans express only one cathelicidin, aprepropeptide that is released after neutrophil elastase action.

Protegrins: They are broad-spectrum antimicrobial peptidesfound in porcine neutrophils, where they are stored as cathelin contain-ing precursors.

Granulysin: They are found in granules of human cytolytic Tlymphocytes and natural killer cells. They act in combination with perforins, gain access to intracellular compartment of microbes and kill them.

Histatins: These are small histidine-rich human salivary proteinsthat display moderate activity against Candida albicans at acidic pH and also have antifungal actions.

Lysozyme: It is a hydrolytic enzyme found in mucus secretionsand tears, and is able to cleave the peptidoglycan layer of the bacterial cell wall.

Interferon: comprises a group of proteins produced by virus-infected cells. One of the many functions of the interferons is the ability to bind to nearby cells. It also induces a generalized antiviral state. There are three different types of interferons IFN-α, IFN-β and IFN-γ. They are synthesized by leucocytes on exposure to viruses, fibro-blasts and effector T cells on induction respectively. The second effect of interferons in host defense is to increase expression of the MHC class I complex and TAP transporter proteins, enhancing the ability of virus-infected cells to present viral peptides to CD-8 cells. The third property is the activation of natural killer cells.

Complement is a group of serum proteins that circulate in aninactive state. A variety of specific and nonspecific immunologic mecha-nisms can convert the inactive forms of complement proteins into ac-tive form. When activated complement can cause damage to the mem-branes of pathogenic organisms, so that they are either destroyed or phagocytosed and cleared