Page 128 Complete Your CE Test Online - Click Here ● ● The incidence of sepsis increases overall in the winter months, attributable to an increased number of respiratory etiologies (Danai, Sinha, Moss, Haber, & Martin, 2007). ● ● There is a 13% higher incidence of mortality from sepsis in winter months than in summer months (Danai et al., 2007). ● ● Mortality rates are between 25% and 30% of patients with sepsis. If sepsis progresses to septic shock, mortality rates rise to 40% to 70% (Gauer, 2013). Associated costs The care and treatment of patients with sepsis is skyrocketing, and it is ranked as the most costly of hospital stays (O’Brien, 2015). It is estimated that sepsis costs in U.S. hospitals have reached $24 billion annually, or over $65 million per day (Sepsis Alliance, n.d.). Medicare costs associated with a sepsis diagnosis are rising, as patients 65 years of age and older are 13 times more likely to develop sepsis than their younger counterparts are (Artero et al., 2012). An increase in direct Medicare spending on sepsis hospitalizations rose from $6.03 billion in 1996 to $15.73 billion in 2008 (Iwashyna, Cooke, Wunsch, & Kahn, 2012). There are other costs to consider when evaluating the financial burden of sepsis, such as direct health care costs from disability, lost productivity, and the need for a caregiver, whether a paid worker or a family member who may lose wages to stay home and care for the sepsis survivor (Iwashyna et al., 2012). The treatment, length of stay, and personal financial impacts of sepsis have significant financial implications on health care costs. REVIEW OF THE IMMUNE SYSTEM RESPONSE When the body comes into contact with an infectious pathogen, the immune system is activated. There are two types of immunity that our body uses to help fight a foreign invader, or antigen. The first line of defense is known as innate immunity, and the second line of defense is known as acquired or adaptive immunity. Innate immunity Innate immunity is also known as natural immunity. It is the immunity we are born with and does not require previous exposure to an antigen to work effectively. Innate immunity includes phagocytic cells, natural killer cells, and polymorphonuclear neutrophils (PMNs); the complement system; and cytokines and chemokines. The following definitions provide a brief overview and function of these terms (Delves, 2017; Neviere, 2017; Jaffer, Wade, & Gourlay, 2010). Phagocytic cells ingest and destroy microbial components. Phagocytic cells include neutrophils present in blood and tissues, monocytes in blood, and macrophages in tissues. Natural killer cells are responsible for destroying tumor cells and cells infected with viruses. Leukocytes include neutrophils, eosinophils, basophils, monocytes, and macrophages. Leukocytes are the cells present in the inflammatory response. Polymorphonuclear neutrophils (PMNs) are the main cellular participants in the acute inflammatory process. Neutrophils are the first responders to the site of injury or infection. They are stored in the bone marrow, circulate via blood, and accumulate at the site of injury or infection. Complement system is a protein cascade that helps clear pathogens from the host. Cytokines are small proteins that are chemical mediators that recruit immune cells to the site of infection or injury. Cytokines are key in the proinflammation and antiinflammation response of the body and play a pivotal role in the development of sepsis. Chemokines are small molecules that direct the movement of leukocytes. Inflammatory chemokines are produced in response to bacterial toxins and inflammatory cytokines. Our innate immune response is known as the first line of defense against an invading organism and is an immediate response by our body. Upon the initial invasion of the harmful organism, blood vessels dilate and the injured tissue or site of infectious agent is flooded with fluid, coagulation factors, cytokines, chemokines, platelets, and inflammatory cells that include white blood cells (also known as leukocytes), such as neutrophils, monocytes, macrophages, eosinophils, and basophils. The increase of blood flow to the injured area is responsible for the heat and redness associated with the acute inflammatory response. Increased vascular permeability is responsible for localized edema. White blood cells—such as macrophages in the tissues, neutrophils in the blood and tissues, and monocytes in the bloodstream—recognize the invader and bind to it. There are three different ways this recognition and binding may occur (Neviere, 2017): 1. Pattern recognition receptors (PRRs): PRRs are located on the surface of immune cells and may recognize the invader by the molecular pattern of the pathogen. PRRs are responsible for alerting the immune cells of the body that there is an invading organism. To use an army analogy, PRRs are like the watchmen who are on the lookout for an approaching enemy army. They notice the enemy army by their uniform and call the troops (the immune cells) to fight the invaders. Following are the three families of PRRs: ○ ○ Toll-like receptors (TLRs). ○ ○ Nucleotide-oligomerization domain (NOD). ○ ○ Retinoic acid-inducible gene (RIG-1). 2. PRRs can also recognize danger signals or patterns associated with a given invader that is released during the inflammation process. 3. The triggering receptor on myeloid cells (monocytes, macrophages, and granulocytes, collectively) can recognize and bind to microbial components. In general, when the immune cells (the troops) are recruited to local tissues and bind to infectious agents for phagocytosis, the binding process activates inflammatory cytokines (Kawamoto & Minato, 2004; Neviere, 2017). More specifically, immune cells bind to the invader, and Toll-like receptors (TLRs) activate the nuclear factor (NF-kb) within the monocyte, which then leads to the production of proinflammatory cytokines known as tumor necrosis factor (TNF-a) and interleukin 1 (IL-1) (LaRosa, 2010). TNF-a and IL-1 also activate the coagulation cascade (explained below) and cause the production of prostaglandins, leukotrienes, platelet-activating factor, and phospholipase A2 (LaRosa, 2010). The function of cytokines is to regulate the inflammatory response, including the coagulation cascade, and trigger more inflammatory immune cells (leukocytes) to go to the location of infection (Shulte, Bernhagen, & Bucala, 2013). Chemokines, molecules that direct the movement of the immune cells to the site of injury or invasion, help out in a process known as chemotaxis. Normally, antiinflammatory cytokines are activated in the immune response. Their purpose is to regulate and suppress the immune system to prevent an exaggerated inflammatory response (Neviere, 2017). Antiinflammatory cytokines and regulatory proteins of the complement