The environment contains a variety of microbes, such as viruses, bacteria, fungi and parasites, any number of which can infect a host and cause pathological damage or cause the immune system to turn on itself. One example of such a microorganism is Klebsiella pneumoniae, an encapsulated, highly virulent Gram-negative bacteria that is a leading cause of both community-acquired and nosocomial pneumonia. K. pneumoniae can also spread from the lung into the bloodstream, resulting in widespread systemic dissemination and death.
Most organisms, such as mammals, i.e. humans, have developed an immune system to ward off such infections. The immune system is divided into two functional divisions, the innate immune system and the adaptive immune system. The innate and adaptive immune system consists of a variety of molecules and cells distributed throughout the body. The most important cells are leukocytes, which are categorized as phagocytes, including polymorphonuclear neutrophils (PMNs), monocytes and macrophages, and lymphocytes, which mediate adaptive immunity. The two main phagocytic cells that constitute pulmonary innate immunity are resident alveolar macrophages (AM) and recruited neutrophils (PMN) (Lipscomb et al., 1983; and Towes et al., 1980).
Inflammation is the body's response to invasion by an infectious microbial agent and includes three broad actions. First, the blood supply is increased to the area. Second, capillary permeability is increased, thereby permitting cells and larger molecules to reach the site of infection. Third, leukocytes, particularly PMNs, migrate out of the capillaries and into the surrounding tissue. Once in the tissue, the PMNs migrate to the site of infection or injury by chemotaxis. These events manifest themselves as inflammation.
Once at the site of infection, PMNs perform phagocytic and degradative functions to combat the infectious agent. As part of the response to the infectious agent, PMNs and activated macrophages rapidly consume oxygen in the “respiratory burst” and convert it to superoxide anion and subsequently hydrogen peroxide (H2O2), as well as significant amounts of singlet oxygen to kill infested material and adhere to epithelial cells of mucosal surfaces or vascular endothelial cells of the blood vessels. In some cases, the immune system of the host fails to mount a successful response and needs help in this regard. For these and other reasons, there is a need for the present invention.
U.S. Pat. Nos. 5,840,318 and 7,189,834 and 7,678,557 describe the fermentation and processing conditions to yield populations of harmless bacteria which have accumulated and retained significant levels of oligoribonucleotides (ORNs) smaller than 10 kDa, ORN<10 kDa which are released during invasion. An animal's immune system can be stimulated by feeding such bacteria or a preparation of the released ORN<10 kDa which contain the stimulating oligos. In addition, ORN<10 kDa can be injected without adverse visible side effects. Such treatments have been shown to significantly reduce the lethality of septic shock in mice and viral infections in shrimp and beef. See U.S. Pat. No. 5,840,318.
U.S. Pat. No. 7,678,557 describes that when bacteria are grown naturally without the usual commercial addition of base to maintain a neutral pH and high growth rates, the bacteria accumulate stimulating ORNs. Microbes release these ORNs as a survival response when entering physiological conditions e.g., saliva and its neutral pH.
For these and other reasons, there is a need for the present invention.
USPTO Backgrounds
USPTO Backgrounds