Chapter 128. Pneumococcal Infections (Part 2) pptx

Chapter 128. Pneumococcal Infections (Part 2) Nonimmunologic Mechanisms Nonimmunologic mechanisms that protect against pneumonia include filtration of air as it passes through the nasopharynx, the glottal reflex, laryngeal closure, the cough reflex, clearance of organisms from the lower airways by ciliated cells, and ingestion by pulmonary macrophages and PMNs of small bacterial inocula that manage to reach alveolar spaces. Respiratory virus infection, chronic pulmonary disease, or heart failure compromises these mechanisms, predisposing to the development of pneumococcal pneumonia. Immunologic Mechanisms Innate Immunity Innate immune mechanisms participate in clearance of pneumococci from the nasopharynx as well as in phagocytosis by PMNs and macrophages via the microbial pattern recognition receptor Toll-like receptor 2 (TLR2). Humoral Immunity Immunologically specific humoral mechanisms provide the best protection against pneumococcal infection. Most healthy adults have antibody to constituents of S. pneumoniae, such as PspA, PsaA, and the cell wall; however, there is no convincing evidence for an opsonic role of these antibodies, especially at their usual concentrations. Most healthy adults lack IgG antibody to the majority of pneumococcal capsular polysaccharides. Antibody appears after colonization, infection, or vaccination. In the first few weeks after colonization, nonspecific mechanisms probably protect the host from infection. Thereafter, newly developed anticapsular antibody provides a high degree of specific protection. Adults who are at risk of aspirating pharyngeal contents and/or who have diminished mechanisms of lower airway clearance are at risk of developing pneumonia before antibody is produced. Persons with a diminished capacity to form antibody probably remain susceptible as long as they are colonized. The risk of serious pneumococcal infection is greatly increased in persons with conditions that compromise IgG synthesis and/or the phagocytic function of PMNs and macrophages. Most patients hospitalized for pneumococcal pneumonia have one or more of these conditions (Table 128-1). Once a pneumococcal infection has been initiated, the absence of a spleen predisposes to fulminant disease. The liver can remove opsonized (antibody-coated) pneumococci from the circulation; in the absence of antibody, however, only the slow passage of blood through the splenic sinuses and prolonged contact with reticuloendothelial cells in the cords of Billroth can result in bacterial clearance. Patients without spleens tend to develop overwhelming pneumococcal disease that rapidly progresses to death. Table 128- 1 Conditions that Commonly Predispose to Pneumococcal Infection Increased risk of exposure Day-care centers Military training camps Prisons Shelters for the homeless Respiratory infection, inflammation Influenza, other viral respiratory infections Air pollution Allergies Defective complement function Defective bacterial clearance a Congenital asplenia, hyposplenia Splenectomy Sickle cell disease Multifactorial conditions Infancy and aging Cigarette smoking Chronic obstructive pulmonary disease Other causes of chronic pulmonary inflammation or obstruction Anatomi cal disruption of meninges (dural tear) Defective antibody formation Common variable hypogammaglobulinemia Selective IgG subclass deficiency Multiple myeloma Chronic lymphocytic leukemia Lymphoma Chronic disease Alcoholism Prior hospitalization Malnutrition HIV infection Chronic lung disease Glucocorticoid treatment Cirrhosis of the liver Renal insufficiency Diabetes mellitus Anemia Coronary artery disease Fatigue, stress, and/or exposure to cold a The absence of a spleen predisposes to more fulminant infection (see text). . Chapter 128. Pneumococcal Infections (Part 2) Nonimmunologic Mechanisms Nonimmunologic mechanisms that protect against. without spleens tend to develop overwhelming pneumococcal disease that rapidly progresses to death. Table 128- 1 Conditions that Commonly Predispose to Pneumococcal Infection Increased risk. pneumococcal infection is greatly increased in persons with conditions that compromise IgG synthesis and/or the phagocytic function of PMNs and macrophages. Most patients hospitalized for pneumococcal