MANOJ KUMAR (SHELFORD)

Sunday, February 19, 2012

Innate immunity: elements of innate immune system

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1. Innate immunity is present from birth.
2. It provides the first line of defense against pathogens
3. It is not specific to any one pathogen, but rather acts against all foreign molecules.
4. It also does not rely to previous exposure to the pathogens.
5. Its response is functional since birth and has no memory.
Elements of innate immunity:
1. Physical barriers:
Physical barriers are the first line of defence against microorganisms. It includes:
  • Mucous membranes
  • The acidic pH of sweat and sebaceous glands; fatty acids and hydrolytic enzymes inhibit the growth of microorganisms.
  • The respiratory tract is lined by cilia (hair like projection) of epithelial membranes; the synchronous movement of cilia propels mucus entrapped microorganisms from these tracts.
  • Conjunctiva is also specialized, the tears contains lysozyme, lactoferin, IgA and thus provide chemical as well as physical protection
In spite of these barriers, some microorganisms are able to penetrate the physical barriers. Then it is up to the adaptive and innate immune system to recognize and destroy them, without harming the host.
2. Chemical mediator:
a. Complement: it is a heat labile component of blood plasma that augments phagocytosis. This activity was said to complement the antibacterial activity of the antibody/
It also bridges the innate and adaptive immunity. The complement system is composed of over 30 serum proteins. Activation of complement in response to certain micro-organism results a controlled cascade of enzymatic reactions which targets the membranes of pathogenic organisms and lead to their destruction. A variety of specific and non-specific immunologic mechanisms can convert the inactive form of complement proteins to active forms with the ability to damage the membranes of pathogenic organisms, either destroying the pathogens or facilitating their clearance. Reactions between the complement molecules or fragments of complement molecules and cellular receptor triggers the activation of innate or adaptive immune systems.
b. Cytokines: the term cytokine is a generic term for any low molecular weight soluble protein or glycoprotein released by one cell population which acts as intercellular mediator. Interferon is cytokines made by cell in response to viral infection which essentially induce generalized antiviral state in surrounding cells.
c. Pattern recognition molecule: many molecules involved in innate immunity have the ability to recognize a give class on molecule. I.e. recognize pattern. Pattern recognition molecule that recognizes pattern associated molecular pattern (PAMP) may be soluble circular proteins or cell surface receptors. E.g. Manose-binding lectin (MBL) and C - reactive protein (CRP) are soluble pattern recognition molecules that bind to microbial surface and promote their opsonization.
3. Cellular defence: leukocytes are responsible for both specific and nonspecific immunity. Many specialized cell such as neutrophils, macrophages, monocytes, NK cells, participate in innate host defense mechanism. Once the pathogen invades the physical and chemical barriers, the specialized cells play and important role in protection, phagocytosis is fundamental protective. The phagocytosis is enhanced by the opsonization of pathogens. (opsonization: the process by which particulate antigen are rendered more susceptible to phagocytosis is called opsonization)
After ingestion the foreign particle is trapped in the phagosome (phagocytic vacuole), which fused with lysosome forming phagolysosomes. Now the antimicrobial and cytotoxic substances present within lysosome destroys the phagocytized micro-organism. The destruction of phagocytized micro-organism takes place as follows.
i. Oxygen dependent killing: during this process the phagocytes increase their O­2 consumption (such as hydroxyl radicals, superoxide anions, hydrogen peroxide) which acts as antimicrobials.
ii. Oxygen independent killing: activated macrophages also synthesize lysozyme, defensin and various hydrolytic enzymes, who act without oxygen requirement
4. Inflammatory barriers:
  •   Inflammation is an important non-specific dense reaction to cell injury.
  •   The signs of inflammation are pain redness (erythema) swelling (edema) and heat.
  •   Pain is caused due to increased vascular diameter which leads to increased blood flow, thus causing heat and redness in the area.
  •   These blood vessels become permeable to fluid and proteins, leading to local swelling and an accumulation of blood proteins that aid in defence.
  •   The inflammatory responses are mediated by a variety of signaling molecules. Activated macrophages produce chemo attractants (known as chemokine).
  •   Some chemokine attract neutrophils, (which are the first cells, which are recruited in large numbers to the site of infection).
  •   Other chemokine attract the monocytes and dendritic cells. The dendritic cells pick up antigens from the invading pathogens and carry them to nearby lymph nodes, where they present antigens to lymphocytes to marshal the forces of adaptive immune system.
  •   Two principal mediators of inflammatory response are histamine (released by a variety of cells in response to injury of tissues), kinines (present in blood plasma in active form)

















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