Mohammad Emaneini, PhD

Transcription

1 Mohammad Emaneini, PhD Professor in Microbiology Department of Microbiology School of Medicine Tehran University of Medical Sciences

2 اهداف اختصاصي پس از پايان اين جلسه انتظار مي رود فراگير: مراحل مختلف استقرار يک عفونت را توضيح دهد. تفاوت اتصال و کلونيزاسيون را بيان کند. نقش سيستم ترشحي تيپ III در فرايند بيماريزايي را ذکرنمايد. روش هاي نفوذ باکتري ها به بافت مخاطي را توضيح دهد. مکانيسم هاي مورد استفاده توسط ميکرب ها براي فرار از سيستم ايمني را بيان کند. انواع توکسين هاي ميکربي را نام برده تفاوت و تشابه ا ن را توضيح دهد. تفاوت عفونت هاي بيمارستاني و خارج بيمارستاني را ذكر نمايد. راههاي انتقال عفونت در بيمارستان را با ذكر مثال بيان نمايد با ذكر مثالي نحوه كنترل عفونت و نقش پزشك در اين مسير را توضيح دهد.

3 Port of Entries Skin Hard to penetrate (keratin) Requires usually lesion or injection Mucus membranes Respiratory tract Gastrointestinal tract: food, drink Urogenital tract Transplacental

4 Penetration: Mucous Membranes 1) Directed Uptake by an Epithelial Cell Endocytosis Non-phagocytic cells Delivery of Effector Molecules to Host Cells Changes cell membrane (ruffling) 2) Exploitation of Antigen-Sampling Processes

5 Avoiding the Host Defenses Hiding within a host cell Avoiding complement Avoiding phagocytes - Prevent uptake - Prevent degradation Avoiding antibodies

6 Prevent of complement activation Masking surface [LPS & teichoic acid] A) Capsule Pneumococci, meningococci Complement activation B) Coated with IgA Do not activate the complement Meningococci

7 Membrane attack complex (MAC) Serum resistant Neisseria gonorrhoeae Sialic acid in the LOS Inactivation of any C3b

8 Preventing encounters with phagocytes Destroy C5a : Chemoattractant, S. pyogenes Membrane damaging toxins : Streptolysin O kill phagocytes Capsule: Block alternative pathway; S. pneumoniae, N. meningitidis M protein: Inactivates C3b Fc receptors: Foil opsonization, bind Fc region of antibodies

9 Surviving within the phagocyte 1. Escape from phagosome Shigella dysenteriae Listeria monocytogenes 2. Preventing phagosome-lysosome fusion Salmonella, Chlamydia, Mycobacterium 3. Surviving within phagolysosome Coxsiella burnetii The sequential events in phagocytosis. (1) Phagocyte is attracted to bacteria. (2) Close-up view of process showing bacteria adhering to phagocyte receptors by their PAMPs. (3) Vacuole is formed around bacteria during engulfment. (4) Phagosome digestive vacuole results. (5) Lysosomes fuse with phagosome, forming a phagolysosome. (6) Enzymes and toxic oxygen products kill and digest bacteria. (7) Undigested particles are released.

10 Avoiding antibodies 1- IgA protease Cleaves IgA antibodies Neisseria gonorrhoeae 2- Antigenic variation Alteration of surface antigens Allows bacteria to stay 3- Mimicking host molecules Capsule of Streptococcus pyogenes

11 Damage to the Host Facilitates dispersal of organisms Vibrio cholerae (diarrhea) Bordetella pertussis (coughing) Direct: Toxin production Indirect: Immune response

12 Direct Damage Toxins Exotoxins Endotoxin Other bacterial cell wall components PTG & other cell wall components elicit symptoms: Fever, Drop in blood pressure

13 Toxins Property Bacterial Source Endotoxins Gram-negative Exotoxins Gram positive & Gram negative Chemistry Lipid A of LPS Proteins Heat Stability Toxicity Fever-Producing Immunology Lethal Dose Stable Can withstand autoclaving (121 C for 1 hour) Low Fever by induction of interleukin 1 Weakly immunogenic Effective toxoids cannot be made Not easily neutralized by antitoxin Considerably larger Unstable Can usually be destroyed at C (except staphylococcal enterotoxin) High Not pyrogenic Highly antigenic Can be converted to toxoids Neutralized by antitoxin Small

14 The many activities of Endotoxin (LPS)

15 Exotoxins 1- AB toxin Neurotoxins Enterotoxins 2- Membrane-damaging toxins 3- Superantigens Structure. 1997;5(8):991-6.

16 Toxins Bacterium Disease Exotoxin Mechanism Clostridium botulinum Botulism A-B Neurotoxin prevents transmission of nerve impulses; flaccid paralysis results. Clostridium tetani Tetanus A-B Neurotoxin blocks nerve impulses to muscle relaxation pathway; results in uncontrollable muscle contractions Corynebacterium diphtheriae Diphtheria A-B Cytotoxin inhibits protein synthesis, especially in nerve, heart, and kidney cells. Vibrio cholerae Cholera A-B Enterotoxin causes secretion of large amounts of fluids and electrolytes that result in diarrhea Bacillus anthracis Anthrax A-B Two A components enter the cell via the same B. The A proteins cause shock and reduce the immune response Clostridium difficile Membranedisrupting Antibioticassociated diarrhea Enterotoxin causes secretion of fluids and electrolytes that results in diarrhea; cytotoxin disrupts host cytoskeleton Staphylococcus aureus Toxic shock syndrome (TSS) Superantigen Toxin causes secretion of fluids and electrolytes from capillaries that decreases blood volume and lowers blood pressure

17 Indirect Damage 1- Inflammation Inflammatory response (due to phagocytic cells) Cells release enzymes & toxic products into tissue Bacterial meningitis 2- Antibodies Antigen-antibody complexes Complexes form & settle in joints & kidneys Destructive inflammation Cross-reactive antibodies Promotes autoimmune response

18 Question كداميك از ويژگي هاي زير در مورد اگزوتوكسين باكتري ها صحيح الف) ليپوپلي ساكاريدي بدون خاصيت تب زايي است است ب) پروتي يني بوده در برابر حرارت پايدار است ج) قابليت تبديل شدن به توكسوي يد دارد د) باعث انعقاد داخل عروقي منتشر مي شود

19 Infection Control

20 Infections Health care-associated (or nosocomial) infections (HAIs) Community-acquired infection

21 HAIs Definition Is acquired in a hospital or health care facility An onset of symptoms 48 h after admission Infection Rates 5 to 10% Infection Sites Urinary tract infections (UTI): 30 to 40% of all HAIs Surgical wound:15 to 20% of HAIs Lower respiratory tract infections:15 to 20% of HAIs Bloodstream infections: 5 to 15% The vast majority of HAIs are associated with medical devices

22 Predominant Pathogens Infection site Catheter-associated urinary tract infection Surgical-site infection pathogens Escherichia coli Enterococcus spp. Candida spp. Pseudomonas aeruginosa Klebsiella pneumoniae/ Klebsiella oxytoca Staphylococcus aureus CoNS Enterococcus spp. Escherichia coli Pseudomonas aeruginosa % of total Reported to the National Healthcare Safety Network from 2009 to 2010 CoNS, coagulase-negative staphylococci Infect Control Hosp Epidemiol 2013;34(1):1-14

23 Predominant Pathogens Infection site Ventilator-associated pneumonia Bloodstream infection pathogens Staphylococcus aureus Pseudomonas aeruginosa Klebsiella pneumoniae/ Klebsiella oxytoca Enterobacter spp. Acinetobacter baumannii CoNS Enterococcus spp. Candida spp. Staphylococcus aureus Klebsiella pneumoniae/ Klebsiella oxytoca % of total

24 Key elements of & effective Infection Control Program

25 Microbial skin flora Normal human skin harbors bacteria, usually between CFU/cm 2 Resident flora Colonizes deeper skin layers and is more resistant to mechanical removal than transient flora CoNS & corynebacteria, with a population density between 10 2 and 10 3 CFU/cm 2 Resident flora generally has lower pathogenic potential than transient flora Transient flora Colonizes the superficial skin layers for short periods Is usually acquired by contact with a patient or contaminated environment Are easily removed by mechanical means such as hand washing Is responsible for most HAIs and the spread of antimicrobial resistance

26 Hand transmission

27 Areas missed!

28 And by the way

29 Infection Control

30 Infection Control The global impact of SAVE LIVES: Clean Your Hands - Jan health-care facilities from 126 countries

31 How to clean your hands