First Lines of Defense PDF

FIRST LINES OF DEFENSE DR I KAYE INFECTION Infection is about the reaction to invasion of bacterial toxin Symptoms and Signs Pathophysiology Pathology Chemopathology Genetic lysogeny NON SPECIFIC IMMUNITY First Lines of Defense Nonspecific innate immunity can be characterized...

FIRST LINES OF DEFENSE DR I KAYE INFECTION Infection is about the reaction to invasion of bacterial toxin Symptoms and Signs Pathophysiology Pathology Chemopathology Genetic lysogeny NON SPECIFIC IMMUNITY First Lines of Defense Nonspecific innate immunity can be characterized as a multifaceted system of defenses that targets invading pathogens in a nonspecific manner. Three categories: physical defenses chemical defenses cellular defenses NON SPECIFIC IMMUNITY 1.PHYSICAL Cell level Tight junctions Desmosomes Gap junctions  Very effective 98% exclusion of pathogenic bacteria. Epithelia – 3 layers 1.1 SKIN BARRIER Epidermis: simple vs stratified sites, types of cells, packing and desmosome tight junctions. Dry inhospitable, with massive turnover. Variation in endothelium and mucosal surfaces of lungs and orifices. Avascular, water tight. Presence of basal lamina, and baso lateral surface polarizes cell which lowers absorption. Defense: Keratin, desquamation, pH, temperature,hair,tactile senses, Langerhans cells, commensal biota, sphincters, O2-co2 rationing, UV, age. Colonization factors after birth from vaginal delivery.  1.2 MUCUS MEMBRANES Mucous membranes consist of a layer of epithelial cells bound by tight junctions. The epithelial cells secrete a moist, sticky substance called mucus, which covers and protects the more fragile cell layers beneath it and traps debris and particulate matter, including microbes. Mucus secretions also contain antimicrobial peptides, Defensins, IgA, MALT, lysozymes, surfactant, escalator mechanism 1.3 ENDOTHELIA The epithelial cells lining the urogenital tract, blood vessels, lymphatic vessels, and certain other tissues are known as endothelia. These tightly packed cells provide a particularly effective frontline barrier against invaders. The endothelia of the blood-brain barrier, for example, protect the central nervous system (CNS), which consists of the brain and the spinal cord. 1.4 ANTI MICROBIAL PEPTIDES The antimicrobial peptides (AMPs) are a special class of nonspecific cell- derived mediators with broad-spectrum antimicrobial properties. Some AMPs are produced routinely by the body, whereas others are primarily produced (or produced in greater quantities) in response to the presence of an invading pathogen. A family of AMPs called defensins can be produced by epithelial cells throughout the body as well as by cellular defenses such as macrophages and neutrophils. AMPs called bacteriocins are produced exogenously by certain members of the resident microbiota within the gastrointestinal tract. 1-5 AMPS 2. MECHANICAL DEFENSE Mechanical defenses physically remove pathogens from the body, preventing them from taking up residence. Examples of mechanical defenses include the flushing action of urine and tears, which carry microbes away from the body. 2.1 MECHANICAL SKIN DEFENSES  2.2 GLANDS Seborrheic and Sudoriferous vary by region. Respiratory, Urinary, Visual, Genital, and Integument. Secretions include lysozyme, mucus, watery diluents, fatty acids. Goblet cells produce mucus. Mucin is a non specific glycoprotein for trapping sticky bacterial surfaces. Ex bronchi, urethra Cilia: motile filaments transport mucus rapidly 2.3 SPECIFIC REGIONS Chemicals in tears, such as defensins, lactoferrin, and lysozyme, help to prevent colonization by pathogens. Lysozyme cleaves the bond between NAG and NAM in peptidoglycan, a component of the cell wall in bacteria. It is more effective against gram-positive bacteria, which lack the protective outer membrane associated with gram-negative bacteria. Lactoferrin inhibits microbial growth by chemically binding and sequestering iron. This effectually starves many microbes that require iron for growth. In addition, mucins facilitate removal of microbes from the surface of the eye. Bile emulsifies membranes. Lactoperoxidase produces superoxide which destroys sulfhydryl linkages 3. MICROBIOME Resident microbiota serve as an important first- line defense against invading pathogens. Through their occupation of cellular binding sites and competition for available nutrients, the resident microbiota prevent the critical early steps of pathogen attachment and proliferation required for the establishment of an infection. Disruption ex. antibiotics (Candida), diarrhea (C.difficile) 4. SPECIAL DEFENSE GIT: pH 1-2 , rapid transit, proteolytic enzyme. Problem achlorhydria Bile salt: emulsify and initiate digestion of lipid especial gram negatives’ outer membrane Pancreatic and duodenal Brunner enzymes: absorption process Normal resident microbiota in colon are beneficial. E.coli assist in Vitamin K B12 production not folic acid) Issues: Nosocomial, Acquired immune deficiencies, medication, extremes of age, resistance factors, surgical wounds-loops-stoma Resident flora becomes pathogenic if conditions change ex S. epidermidis. Compare commensalism, mutualism, and parasitism. Staphylococcus(miliaria) Micrococcus Corynebacterium Brevibacterium Dermabacter(acne, rosacea) Malasezzia (fungal infections) 4.1 SITE SPECIFIC DEFENSES 5. CONSEQUENCES OF A WALL BREACH  SUMMARY The physical defenses of innate immunity include physical barriers, mechanical actions that remove microbes and debris, and the microbiome, which competes with and inhibits the growth of pathogens. The skin, mucous membranes, and endothelia throughout the body serve as physical barriers that prevent microbes from reaching potential sites of infection. Tight cell junctions in these tissues prevent microbes from passing through. Microbes trapped in dead skin cells or mucus are removed from the body by mechanical actions such as shedding of skin cells, muco-ciliary sweeping, coughing, peristalsis, and flushing of bodily fluids (urination, tears) Antimicrobial peptides (AMPs) found on the skin and in other areas of the body are largely produced in response to the presence of pathogens. These include dermcidin, cathelicidin, defensins, histatins, and bacteriocins. Chemical mediators exhibit nonspecific antimicrobial functions. The resident microbiota provide a physical defense by occupying available cellular binding sites and competing with pathogens for available nutrients. ASSIGNMENT 1 1.1 In what sense are S. epidermidis infections an example of how changing human practices can provide new opportunities for bacterial pathogens? S. epidermidis is classified as an opportunist. Why is this the case? 1.2 Explain the role that mucin plays in host defense. 1.3 Lysozyme is more effective against growing bacteria. Why might that be so?