2- Microbial Pathogenesis and normal flora.pdf
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2024
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Ninevah University Medicine College Microbiology Department 2024 - 2025 Dr. Saba Abdul Salam Hamid Al-Sultan [email protected] 2. Microbial Pathogenesis and normal flora The lecture overview about 1. Microbial Pa...
Ninevah University Medicine College Microbiology Department 2024 - 2025 Dr. Saba Abdul Salam Hamid Al-Sultan [email protected] 2. Microbial Pathogenesis and normal flora The lecture overview about 1. Microbial Pathogenesis (Principles of Pathogenesis Why Do People Get Infectious Diseases?) 2. Normal flora Concept of Normal Flora, of the Skin, Respiratory Tract, Intestinal Tract,and Genitourinary Tract P:2 Pathogen The term Pathogen refers to those microbes capable of causing disease, especially if they cause disease in immunocompetent (Healthy) people. The term Opportunistic pathogen refers to microbes that are capable of causing disease only in immunocompromised people. Virulence is a measure of a microbe's ability to cause disease (i.e., a highly virulent microbe requires fewer organisms to cause disease than a less virulent one). The ID50 is the number of organisms required to cause disease in 50% of the population. The 50% lethal dose (LD50) is the number of organisms needed to kill half the hosts P:3 The infectious dose of an organism required to cause disease varies greatly among the pathogenic bacteria. For example, Shigella and Salmonella both cause diarrhea by infecting the gastrointestinal tract, but the infectious dose of Shigella is less than 100 organisms, whereas the infectious dose of Salmonella is on the order of 100,000 organisms. The infectious dose of bacteria depends primarily on their virulence factors e.g.: Pili allow them to adhere well to mucous membranes, Exotoxins or Endotoxins, Capsule to protect them from phagocytosis, and whether they can survive various nonspecific host defenses such as acid in the stomach). P:4 Whether a person gets an infectious disease or not is determined by the balance between the number and virulence of the microbes and the competency of that person's host defenses. Many infections are asymptomatic or inapparent because our host defenses have eliminated the microorganism before it could multiply to sufficient numbers to cause the symptoms of disease P:5 The term infection: has two meanings: (1) the presence of microbes in the body and (2) the symptoms of disease. Important Note: The presence of microbes in the body does not always result in symptoms of the disease. Bacteria cause the symptoms of disease by two main mechanisms: (1): production of toxins (both exotoxins and endotoxins) and (2): induction of inflammation. Most bacterial infections are communicable (i.e., capable of spreading from person to person), but some are not communicable ( e.g., botulism and Legionella pneumonia). P:6 Three epidemiologic terms are often used to describe infections: Endemic infections are those that occur at a persistent, usually low level in a certain geographic area, Epidemics are those infections that occur at a much higher rate than usual, and Pandemics are those infections that spread rapidly over large areas of the globe. P:7 Determinants of Bacterial Pathogenesis Transmission The modes of transmission of microbes include both human-to human and nonhuman- to-human processes. Non-human sources include animals, soil, water, and food. Human-to-human transmission can occur either by direct contact or indirectly via a vector such as an insect(ticks or mosquitoes). Animal-to-human transmission can also occur either by direct contact with the animal or indirectly via a vector. The main "portals of entry" into the body are the respiratory tract, gastrointestinal tract, skin, and genital tract. Human diseases for which animals are the reservoir are called zoonoses. P:8 Adherence to Cell Surfaces (1) Pili are the main mechanism by which bacteria adhere to human cells, that mediate attachment to specific receptors on cells. (2) Glycocalyx is a polysaccharide "slime layer" secreted by some strains of bacteria that mediates strong adherence to certain structures such as heart valves, prosthetic implants, and catheters. Invasion, Inflammation, & intracellular Survival The invasion of tissue is enhanced by enzymes secreted by bacteria. For example, (1): Hyaluronidase produced by Streptococcus pyogenes degrades hyaluronic acid in the subcutaneous tissue, allowing the organism to spread rapidly. P:9 (2): IgA protease degrades secretory IgA (3): The capsule surrounding bacteria is antiphagocytic Mutant strains of many pathogens that do not produce capsules are nonpathogenic. (3): Inflammation is an important host defense induced by the presence of bacteria in the body. There are two types of inflammation, Pyogenic inflammation, the host defense against pyogenic (pus- producing) bacteria such as S.pyogenes. Granulomatous inflammation, the host defense against intracellular, granuloma-producing bacteria, such as Mycobacterium tuberculosis. (4) Intracellular survival (i.e., bacteria that can live within cells are protected from attack by macrophages and neutrophils). Note that many of these bacteria (e.g., M tuberculosis) P : 10 (5): Toxins: Exotoxins are polypeptides secreted by certain bacteria that alter specific cell functions resulting in the symptoms of disease. They are produced by both gram-positive and gram-negative bacteria, Exotoxins are antigenic and induce antibodies called antitoxins. Exotoxins can be modified to form toxoids, which are antigenic but not toxic. Toxoids, such as tetanus toxoid, are used to immunize against disease. Endotoxins are lipopolysaccharides (LPS) located in the outer membrane only of gram-negative bacteria, poorly antigenic, do not induce antitoxins, and does not form toxoids· which ' causes the symptoms of septic shock, such as fever and hypotension. P : 11 Typical stages of an Infectious Disease There are often four discrete stages. ( After the1): The incubation period is the time between the moment the person is exposed to the microbe (or toxin) and the appearance of symptoms. (2): The prodrome period is the time during which nonspecific symptoms occur. (3):The specific period is the time during which the characteristic features of the disease occur. (4):The recovery period is the time during which symptoms resolve and health is restored. the recovery period, some people become chronic carriers of the organism and in others, latent infections develop. Some people have subclinical infections during which they remain asymptomatic. The presence of antibodies reveals that a prior infection has occurred. P : 12 CONCEPT OF NORMAL FLORA Normal flora is the term used to describe the various bacteria and fungi that are permanent residents of certain body sites, especially the skin, oropharynx, colon, and vagina. Viruses and parasites (protozoa and helminths), which are the other major groups of microorganisms, are usually not considered members of the normal flora, although they can be present in asymptomatic individuals. The normal flora organisms are often referred to as commensals. Commensals are organisms that derive benefit from another host but do not damage that host. P : 13 Normal Flora Definition (microbiota, indigenous microbial population, microflora, microbial flora ) Normal flora is the mixture of microorganisms (bacteria and fungi) that are regularly found at any anatomical site of the human body: P : 14 Types of Symbiosis Symbiosis = "intimate living together" between different species Commensalism One benefits, one (host) is not obviously affected either positively or negatively Parasitism One benefits, the other (host) is (potentially) harmed Mutualism Both benefit from the association P : 15 Type of Normal flora Commensals Microorganisms that have natural relationship with the host. Found in low number and has no benefit or harm. Mainly associated with the GIT. Residents Consist of relatively fixed types of microorganisms. Regularly found in a given area at invariable period. If disturbed promptly reestablish itself. Transients Consist of nonpathogenic or potential pathogenic microorganisms that inhabit the skin or mucous membrane for hours or days, excluded by host defense or competition from residents’ flora. Carrier flora Potentially pathogenic that are carried by the individual without causing disease. However, it is the source of infection to other susceptible ( non immune ) individual. , eg. Streptococcus pneumoniae, Neisseria meningetidis in throat of healthy individual P : 16 Resident flora Reflects age of person Resident flora Reflects Normal flora nutrition of person Normal Flora Resident flora Acquired rapidly during & after birth Resident flora Reflects sex of person Normal Flora Resident flora Changes continuously Resident flora Reflects through out life. environment of person Resident flora Reflects genetics of person P : 17 There are 2 groups of pathogens that are known to cause diseases. They are strict and opportunistic pathogens. strict pathogens: are organisms always associated with human disease. A few infections are caused by these pathogens. A few examples of strict pathogens include:- ❖ Neisseria gonorrhea (gonorrhea) ❖Francisella tularensis (tularemia) ❖Mycobacterium tuberculosis (tuberculosis) ❖Plasmodium spp. (malaria) ❖Rabies virus (rabies). P : 18 opportunistic pathogens: are organisms that are typically members of the patient’s normal microbial flora. Most human infections are caused by these pathogens. If a patient’s immune system is defective, that patient is more susceptible to disease caused by opportunistic pathogens. A few examples of opportunistic pathogens include :- ❖Staphylococcus aureus ❖Escherichia coli ❖Candida albicans P : 19 9/17/2024 20 P : 20 Normal flora of the Upper Respiratory Tract (URT) and Lower Respiratory Tract (LRT) Although many microorganisms enter the URT & LRT through the air, most of them are removed by the mucous and cilia lining of the respiratory tract. Furthermore, mucous also consists of lysozyme that kills many microorganisms of the mucous. Some microorganisms that can attach to the mucous membrane form the resident flora of the URT. P : 21 Normal flora of the mouth: 9/17/2024 22 P : 22 Normal flora of the Gastrointestinal Tract (GIT): Gastrointestinal tract (GIT) consists of the esophagus, stomach, small intestine (duodenum, jejunum, and ileum), and large intestine. Since different regions of GIT differ in their environmental, physical, and chemical properties, the amount and type of normal flora are different in these regions. P : 23 Normal flora of the stomach: The Stomach receives many microorganisms from the mouth along with the food. However, the bacterial activity of HCl in the stomach kills most of them. Only a few organisms can tolerate this low pH in the stomach and form the resident flora there. Common normal resident flora of the stomach includes Lactobacillus, Candida albicans, Helicobacter pylori. But Helicobacter pylori is pathogenic. P : 24 Normal flora of GI tract: SMALL INTESTINE streptococci, lactobacilli, enterococci, enterics, anaerobic rods and cocci 9/17/2024 25 P : 25 Normal flora of GI tract: LARGE INTESTINE Bacteroids, clostridia, bifidobacteria, lactic acid bacteria, enterococci, enterics 9/17/2024 26 P : 26 Normal flora of the genito-urinary tract: In a healthy person, kidneys, urinary bladder, and ureters are free of microorganisms. However, the anterior urethra of both males and females contain a small number of the same types of organisms found in the skin and perineum. These organisms regularly appear in normal voided urine in the numbers of 102-104/ml. After menopause, lactobacilli diminish, and a mixed flora returns to the vagina. P : 27 Dr. Saba Al-Sultan P : 28