Host defenses

Hydrocortisone and Prednisolone. Following the discovery of the antiinflammatory actions of cortisone (1) and cortisol (2), there was a need not only to develop highly efficient routes to the corticoids, but to discover novel stmctures with fewer side effects than those of the corticoids, eg, sodium and water retention, reduced carbohydrate tolerance (steroid diabetes), osteoporosis, and depressed host defense. 

Modem cancer therapy has been primarily dependent upon surgery, radiotherapy, chemotherapy, and hormonal therapy (72) (see Chemotherapeutics,anticancer Hormones Radiopharmaceuticals). Chemotherapeutic agents maybe able to retard the rate of growth, but are unable to eradicate the entire population of neoplastic cells without significant destmction of normal host tissue. This serious side effect limits general use. More recentiy, the immunotherapeutic approach to cancer has involved modification and exploitation of the cellular and molecular mechanisms in host defense, regulation of tissue proliferation, tissue differentiation, and tissue survival. The results have been more than encouraging. 

This wide range of pharmacokinetic properties, along with thek ease of administration, broad spectmm antimicrobial activity, and noninterference with host-defense mechanisms is responsible for thek widespread use five decades after thek discovery. 

Endotoxin and Muramyl Dipeptide Derivatives. Bacterial cell wall constituents such as the Hpopolysaccharide endotoxin and muramyl dipeptide, which stimulate host defense systems, show radioprotective activity in animals (204). Although endotoxin is most effective when given - 24 h before irradiation, it provides some protection when adrninistered shortiy before and even after radiation exposure. Endotoxin s radioprotective activity is probably related to its Hpid component, and some of its properties may result from PG and leukotriene induction (204). 

Reynolds, H. Y. (1988). Normal and defective respiratory host defenses. In Respiratory Infections Diagnosis and Management (J. E. Pennington, Ed.), pp. 1-33. Raven Press, New York. 

In both cases, a seeming virus stimulator (twinberry extract) and a virus inhibitor (tannic acid) operated in a more or less similar way in the cucumber-TMV system. They both affect the host defense mechanism against virus infection. The active component in twin-berry extract exhibits a mild and temporary interference, thus permitting virus to make further rounds of gain (ringlike patterns) while tannic acid produces a strong and permanent interference. 

The neutrophil is a primary cell type which interacts with and is influenced by the environment. Neutrophils are important in host defense and play a role in the phagocytosis of particulate material. We obtain these cells in highly purified form from human blood (1,2). 

IgE Mediates immediate hypersensitivity by causing release of mediators from mast cells and basophils upon exposure to antigen (allergen). Defends against worm infections by causing release of enzymes from eosinophils. Does not fix complement. Main host defense against helminthic infections. 

Cross A, Asher L, Seguin M, Yuan L, Kelly N, Hammack C (1995) The importance of a hpopoly-sacchaiide-initiated, cytokine-mediated host defense mechanism in mice against extraintesti-nally invasive escheiichia coh. J Clin Invest 96(2) 676-686 Dahan A, van Dorp E, Smith T, Yassen A (2008) Morphine-6-glucuronide (M6G) for postoperative pain relief. Eur J Pain 12(4) 403-411... 

Sharp BM (2003) Opioid receptor expression and intracellular signaling by cells involved in host defense and immunity. Adv Exp Med Biol 521 98-105 Sharp BM (2006) Multiple opioid receptors on immune cells modulate intracellular signaling. Brain Behav Immun 20 9-14... 

Aranyi C, O Shea WJ, Graham JA, et al. 1986. The effects of inhalation of organic chemical air contaminants on murine lung host defenses. Fundam Appl Toxicol 6 713-720. 

The selective stimulation of these cells is of importance because they are the most active effector cells in host defense mechanisms against bacterial and viral infections. 

Older individuals have decreased host defense mechanisms such as slowed gastric emptying and decreased saliva production. They may present with atypical symptoms such as chest pain, asthma, hoarseness, coughing, wheezing, or poor dentition. These patients often do not seek medical attention because they believe their symptoms are part of the normal aging process. 

Many areas of the human body are colonized with bacteria— this is known as normal flora. Infections often arise from one s own normal flora (also called an endogenous infection). Endogenous infection may occur when there are alterations in the normal flora (e.g., recent antimicrobial use may allow for overgrowth of other normal flora) or disruption of host defenses (e.g., a break or entry in the skin). Knowing what organisms reside where can help to guide empirical antimicrobial therapy (Fig. 66-1). In addition, it is beneficial to know what anatomic sites are normally sterile. These include the cerebrospinal fluid, blood, and urine. 

Disruption of host defenses owing to intravenous catheters, indwelling Foley catheters, burns, trauma, surgery, and increased gastric pH (secondary to antacids, H2 blockers, and proton pump inhibitors) may place patients at higher risk for infection. Breaks in and entry into the skin provide a route for infection because the natural barrier of the skin is disrupted. Increased gastric pH can allow for bacterial overgrowth and has been associated with an increased risk of pneumonia.18... 

Once through the blood-brain barrier, pathogens thrive and replicate due to limited host defenses in the CNS. Figure 67-1 depicts the pathophysiologic changes associated... 

Explain the host defenses that protect against infection. 

Local host defenses of both the upper and lower respiratory tract, along with the anatomy of the airways, are important in preventing infection. Upper respiratory defenses include the mucodliary apparatus of the nasopharynx, nasal hair, normal bacterial flora, IgA antibodies, and complement. Local host defenses of the lower respiratory tract include cough, mucodliary apparatus of the trachea and bronchi, antibodies (IgA, IgM, and IgG), complement, and alveolar macrophages. Mucus lines the cells of the respiratory tract, forming a protective barrier for the cells. This minimizes the ability of organisms to attach to the cells and initiate the infectious process. The squamous epithelial cells of the upper respiratory tract are not ciliated, but those of the columnar epithelium of the lower tract are. The cilia beat in a uniform fashion upward, moving particles up and out of the lower respiratory tract. 

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