Institutional Pharmaceutics (PHRM361) Lecture Notes PDF

INSTITUTIONAL PHARMACEUTICS (PHRM361) Mbuso Faya, PhD. Discipline of Pharmaceutical Sciences, UKZN, South Africa MICROBIAL PATHOGENICITY  MICROBIAL PATHOGENICITY Two qualities of pathogenic microbes by which they cause disease to the host: 1. Invasiven...

INSTITUTIONAL PHARMACEUTICS (PHRM361) Mbuso Faya, PhD. Discipline of Pharmaceutical Sciences, UKZN, South Africa MICROBIAL PATHOGENICITY  MICROBIAL PATHOGENICITY Two qualities of pathogenic microbes by which they cause disease to the host: 1. Invasiveness is the ability to invade tissues. It consists of colonization, production of extracellular substances which facilitate invasion and ability to bypass or overcome host defense mechanisms. 2. Toxigenesis is the ability to produce toxins. Bacteria may produce two types of toxins called exotoxins and endotoxins. Exotoxins are released from bacterial cells and may act at tissue sites removed from the site of bacterial growth. Endotoxins are cell- associated substance. The bacterial toxins, both soluble and cell- associated, may be transported by blood and lymph and cause cytotoxic effects at tissue sites remote from the original point of invasion or growth.  MICROBIAL PATHOGENICITY VIRULENCE FACTORS COLONIZATION FACTORS: specific recognition of receptor sites on target cells enhances pathogenic advantage 1. CAPSULE: nonspecific attachment 2. SURFACE RECEPTORS/TARGET SITES: Receptors on both bacteria (adhesins) and host (target) Examples include: i) fimbriae (formerly known as pili) of Enterobacteriaceae ii) Chlamydia binds host N-acetyl-D-glucosamine which is a cell surface lectin (polysaccharide target receptor) iii) Protein adhesin of Mycoplasma located in specialized tip structure; adheres to sialic acid-containing cell receptors  VIRULENCE FACTORS INVASIVE FACTORS (invasins): enable a pathogenic microorganism to enter and spread throughout the tissues of the host body; specific recognition of receptor sites on target cells enhances pathogenic advantage DEGRADATIVE ENZYMES: a class of protein capable of catalytic reactions; bacterial and host enzymes both play roles in the disease process  VIRULENCE FACTORS (cont.) TOXIGENICITY: the ability of a microorganism to cause disease as determined by the toxin it produces which partly determines its virulence 1. ENDOTOXIN: a complex bacterial toxin that is composed of protein, lipid, and polysaccharide (LPS) which is released only upon lysis of the cell 2. EXOTOXINS: a potent toxic substance formed and secreted by species of certain bacteria VIRULENCE FACTORS (summary) Adherence Factors: Many pathogenic bacteria colonize mucosal sites by using pili (fimbriae) to adhere to cells. Invasion Factors: Surface components that allow the bacterium to invade host cells can be encoded on plasmids, but more often are on the chromosome. Capsules: Many bacteria are surrounded by capsules that protect them from opsonization and phagocytosis. Endotoxins: The lipopolysaccharide endotoxins on Gram-negative bacteria cause fever, changes in blood pressure, inflammation, lethal shock, and many other toxic events. Exotoxins: Exotoxins include several types of protein toxins and enzymes produced and/or secreted from pathogenic bacteria. Major categories include cytotoxins, neurotoxins, and enterotoxins. Siderophores: Siderophores are iron-binding factors that allow some bacteria to compete with the host for iron, which is bound to hemoglobin, transferrin, and lactoferrin. HOST RESISTANCE and DEFENCE SYSTEM  Non-specific resistance Prevention of entry Lysozyme Mucous Skin Respiratory tract Gastrointestinal tract Urogenital tract Conjunctiva Commensals of the natural flora Phagocytosis Inflammatory response Fever Biochemical and tissue constituens  Specific Non-Specific resistance resistance Antibodies Inflammation Inflammatory Process  Inflammatory Process (Cont…) Three major events occur during this response: 1) Congestion phase: Initially, the capillaries become engorged and dilated with blood. This increases capillary permeability caused by the reaction of the endothelial cells. This increases amount of blood, hyperemia, causes the heat and redness associated with inflammation Inflammatory Process 2) Leakage - Leukocytes migrate out of the capillaries into the surrounding Tissues. In the earliest stages of inflammation, neutrophils are particularly prevalent, but later monocytes and lymphocytes also migrate towards the site of infection. Neutrophils line up within the capillary wall. Monocytes will clear up the debris. 3) Phagocytosis- specialized cells that defend the body against invading microorganisms and speed healing by engulfing cell debris in injured tissues Inflammation - causes, symptoms, diagnosis, treatment, pathology https:// youtu.be/LaG3nKGotZs Serous fluids associated with inflammation Serous Transudates - is fluid pushed through the capillary due to high pressure within the capillary Serous exudates – is fluid that leaks around the cells of the capillaries caused by inflammation.