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Anatomy/Physiology Bacterial Invasion via the Respiratory tract to Bloodstream Some bacteria enter the body through the

nose and mouth (e.g. Meningococcal bacteria). The nose is the 1st part of the respirator y system through which incoming air passes, and is warmed, moistened and filtered. The nose is line with a ciliated mucous membrane, which traps particles of dust and other impurities, such as microorganisms to prevent them from entering the lungs. Microorganisms can be carried at the back of the throat for weeks or months without causing illness. When the meningococcal bacteria invade, they release a chemical which destroys the cilia at the back of the nose. This allows the bacteria to then cross the mucous membrane and enter the bloodstream. When the meningococcal bacteria enter the bloodstream, they multiply rapidly, doubling in number every 30 minutes. As the bacteria multiply rapidly in the bloodstream they begin to release endotoxins from their slimy outer coating. These endotoxins are released in to the bloodstream as greasy bubbles. Endotoxins During an infection, certain types of bacteria can produce and release complex molecules, called endotoxins that may provoke a dramatic response by the body's immune system. Released in the bloodstream, endotoxins are particularly dangerous, because they become widely dispersed and affect the blood vessels themselves. Arteries and the smaller arterioles open wider, increasing the total volume of the circulatory system. At the same time, the walls of the blood vessels become leaky, allowing fluid to seep out into the tissues, lowering the amount of fluid left in circulation. This combination of increased system volume and decreased fluid causes a dramatic decrease in blood pressure and reduces the blood flow to the organs. Other changes brought on by immune response may cause coagulation of the blood in the extremities, which can further decrease circulation through the organs. Innate Immune System The normal host response to infection is a complex process that localizes and controls bacterial invasion, while initiating the repair of injured tissue. It involves the activation of circulating and fixed phagocytic cells, as well as the generation of proinflammatory and antiinflammatory mediators. Sepsis results when the response to infection becomes generalized and involves normal tissues remote from the site of injury or infection Innate immunity is an antigen-nonspecific defense mechanisms that a host uses immediately or within several hours after exposure to almost any microbe. This is the immunity one is born with and is the initial response by the body to eliminate microbes and prevent infection. Innate immunity can be divided into immediate innate immunity and early induced innate immunity. A. Immediate innate immunity

Immediate innate immunity begins 0 - 4 hours after exposure to an infectious agent and involves the action of soluble preformed antimicrobial molecules that circulate in the blood, our found in extracellular tissue fluids, and are secreted by epithelial cells. These include:

antimicrobial enzymes and peptides; complement system proteins; and anatomical barriers to infection, mechanical removal of microbes, and bacterial antagonism by normal flora bacteria

B. Early induced innate immunity Early induced innate immunity begins 4 - 96 hours after exposure to an infectious agent and involves the recruitment of defense cells as a result of pathogen-associated molecular patterns or PAMPS binding to pattern-recognition receptors or PRRs. These recruited defense cells include:

phagocytic cells: leukocytes such as neutrophils, eosinophils, and monocytes; tissue phagocytic cells in the tissue such as macrophages; cells that release inflammatory mediators: inflammatory cells in the tissue such as macrophages and mast cells; leukocytes such as basophils and eosinophils; and natural killer cells (NK cells).

These unique microbial molecules are called pathogen-associated molecular patterns or PAMPS and include LPS from the gram-negative cell wall, peptidoglycan and lipotechoic acids from the gram-positive cell wall, the sugar mannose (a terminal sugar common in microbial glycolipids and glycoproteins but rare in those of humans), bacterial and viral unmethylated CpG DNA, bacterial flagellin, the amino acid N formylmethionine found in bacterial proteins, double-stranded and single-stranded RNA from viruses, and glucans from fungal cell walls. In addition, unique molecules displayed on stressed, injured, infected, or transformed human cells also act as PAMPS. (Because all microbes, not just pathogenic microbes, possess PAMPs, pathogen-associated molecular patterns are sometimes referred to as microbeassociated molecular patterns or MAMPs.) Most body defense cells have pattern-recognition receptors or PRRs for these common PAMPS and so there is an immediate response against the invading microorganism. Pathogen-associated molecular patterns can also be recognized by a series of soluble pattern-recognition receptors in the blood that function as opsonins and initiate the complement pathways. In all, the innate immune system is thought to recognize approximately 103 of these microbial molecular patterns.