Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Ebola virus disease wikipedia , lookup
Plant virus wikipedia , lookup
Viral phylodynamics wikipedia , lookup
Introduction to viruses wikipedia , lookup
Social history of viruses wikipedia , lookup
Oncolytic virus wikipedia , lookup
History of virology wikipedia , lookup
Virus quantification wikipedia , lookup
Ind iv i dua l M icro bio lo g y G + Cocci GG----- Aerobe Bacilli and G facultative anaerobe + staphylococcus streptococcus pneumococcus meningococcus Gonococcus -- enteric bacilli corynebacterium M.tuberculosis diphtheria Spirillar bacteria ----V.cholera obligate anaerobe spore-forming anaerobic bacteria non-spore-forming anaerobic bacteria Content 1.biological characteristics 2.pathogenicity------pathogenic factor phathogenesis 3.immunity 4.laboratory diagnosis(bacteriological methods) 5.prevention and treatment P a t h o g e n i c Co c c i G+ cocci – Staphylococcus, Streptococcus, Pneumococcus. G-cocci – Meningococcus, Gonococcus. Section1. Purulent Infection St a p h y l o c o c c u s I. Biological characteristics 1. Morphology: Gram positive cocci, arranged in irregular, grape – like clusters No special structure 2.Culture blood agar----- haemolysis Colony : 1~2 mm, circular, smooth, shiny surface, opaque, various pigments 3. Classification: 1 Major properties of three species of staphylococci Main property Staph. aureus Pigmentation Coagulase Hemolysin SPA Pathogenicity Golden yellow + + + +++ Staph. Epidermidis White _ _ _ -/+ Staph saprophyticus Citrine _ _ _ _ 4. Antigenic structure: (1) SPA (staphylococcal protein A) i) cell wall protein ii) it combines nonspecifically with the Fc-portion of human IgG iii) antiphagocytosis iv) coagglutination 5. Resistance: (1) resistant to dry; heat (80℃,30min); salt(10~15%) (2) sensitivity to: basic-dyes(crystal violet); antibiotics and sulfonamides (antibiotic resistance) II. Pathogenicity 1.pathogenic factor 1).Invasiveness (1)Surface structure: SPA (2)Enzyme Coagulase: A enzyme that convers fibrinogen in citrated human or rabbit plasma into fibrin. (1).Extracellular coagulase ----an extracellular enzyme which activates a coagulase-reacting factor (CRF) normally present in plasma , causing the plasma to clot by the conversion of fibrinogen to fibrin (in tube). (2).Bound coagulase----fibrinogen fibrin ( in slide) ---Roles: to inhibit the phagocytosis of macrocytes and damage of bacteriacide substances in humor by coating the organisms with fibrin 2)Toxin---exotoxin (1) . Staphylolysin: impairment of membrane permeadility; cytotoxic effects on phagocytic and tissue cells Protein Staphylolysin-: main pathogenic substance Form hemolysing-ring around the colony (2) .Leukocidin: Kill PMNs and M (3). Enterotoxin:Protein; five types: A-E; Heat stable (boiling for 30 min)Cause a food poisoning characterized by severe vomiting and diarrhea (4).Toxic shock syndrome toxin-1 (TSST-1): Induces multisystsm effects; superantigen effects (5).Epidermolytic toxin: Cause blistering of skin 4. pathogensis 2 1) purulent infection (1). local infection skin infection: hair folliculitis; boil; carbuncle; impetigo. (think pus; limited local area) (2).organ infection: pneumonia meningitis. (3).Systemic infection: Septicemia; pyemia 2) toxin diseases (1). Food poisoning (enterotoxin) (2). TSS (Toxic shock syndrome) (3). SSSS(staphylococcal scalded skin syndrome): 3) Staphylococcal enteritis: dysbacteriosis (superinfection) III. Immunity IV. Laboratory diagnosis specimen: *pus * sputum (low respiratory tract infection) * blood (septic shock, osteomyelitis, endocarditis) * food/faeces or vomit (food poisoning) * mid-stream urine (pyelonephritis or cystisis) *direct smear :gram stain *isolation and identification: blood agar *coagulose test *Enterotoxin test and animal test V. Treatment Section 2. St r e p t o c o c c u s I.Biological characteristics 1.Morphology & cultural properties: (1).G+ cocci, arranged in chains, no special structure(capsule of hyaluronic acid in the early period). (2).high nutritive requirement (blood & serum) blood agar: *tiny colony ( 0.5~0.7 mm) * hemolyze erythrocytes in vitro in varying degrees *faculation/obligate anaerobe 2.Classsification: It is classified based on the hemolyzation phenomenon and antigenic structure. (1).Hemolytic activity: (i) -hemolytic streptococcus *Incomplete hemolysis, green colotation of the medium surrounding the colony. *Opportunistic pathogens – subacute bacterial endocarditis (SBE). (ii) -hemolytic streptococcus (or pyogenic streptococcus) Complete hemolysis, major human pathogens (iii) -streptococcus No hemolyzation, no pathogenicity. 3 (2).Antigenic structure: (i) Polysaccharide antigen (group-specific antigen). 19 groups Group A streptococci are main human pathogens (ii) protein antigen (type-specific antigen). M protein: *presents in cell wall (group A) *Anti-phagocytosis *adhere to epithelial cells *clump platelet and leukocyte *heat steable; acid steabl (pH 2) 3.Resistance *heat labile: 60℃,30 min *antibiotics sencitivity: panicillin G ,etc. II.phathogenicity 1. Pathogenic substances (invasiveness & exotoxin): (1).Invasiveness (i).surface structure *LTA(lipoteichoic acid): adhere to sensitive cell (epithelial cell; platelet; RBC; WBC; lymphocyte; mucous membranes) * M-protein : ◆anti-phagocytotic ◆M-Ag Ab hypersensitivity(glomerulonephritis) ◆Common antigen---heart muscle cell(rheumatic fever) (ii).enzyme *Hyaluronidase (spreading factor): Splits hyaluronic acids bacteria spread * Streptokinase (SK ): Lyse fibrin, prevent plasma clotting bacteria spread * Streptodornase (SD): Resolve DNA bacteria spread (2).Toxins---exotoxin (i) Streptolysin (hemolysin) Streptolysin O (SLO) Streptolysin S(SLS) oxygen-labile hemolysin oxygen stable O2 O2 (-SH -S-S-) (-SH -SH) antigenicity-----ASO weak antigen (antistreptolysin O) destroy WBC, pletelet destroy WBC virulence of MΦ, N.C virulence of many tissues protein polypeptide MW 60,000 28 amino-acid (ii) Erythrogenic toxin (or pyrogenic toxin /scarlet fever toxin) *produced by most strains of group A streptococci *cause scarlet fever *possess antigenicity, antitoxin specifically neutralize the toxin 4 * protien heat stable 2. Diseases of streptococcal infection 1). Infections of group A (-hemolytic streptococci) (1). local purulent infections: *pharyngitis, *erysipelas *puerperal fever (2). systemic infection : * septicemia *scarlet fever (3). poststerptococcal diseases (hypersensitive disease) (i) acute glomerulonephritis ( group A) mechanism: *type III hypersensitivity (most) *type II hypersensitivity M protein- Ab complex common Ag (ii) Rheumatic fever (many types of group A streptococci) mechanism: *immune complex (deposition) heart, joints type III hypersensitivity *common Ag cross –reaction heart type II hypersensitivity 2) Infections of -hemolytic streptococci: normal flora : throat/nasapharyn *SBE(subacute bacterial endocarditis) damaged heart valve fever, heart murmure;enlarged spleen; anemia. I V. I m m u n i t y V. L a b o r a t o r y d i a g n o s i s 1. Isolation & identification of pathogen 2. ASO test: ASO titer > 1: 400 units, help to diagnose rheumatic fever. VI. Prevention & treatment *Treat the pharyngitis and tonsillitis in time, avoid the post streptococcal diseases. *Antibiotics and chemical agents: penicillin G for the first choice Section 3. P n e u mo c o c c u s 1. Belong to the Streptococcus ( Streptococcus pneumoniae ), 2. G+, diplococcus, lancet shape, arranged in pair, capsule of polysaccharide 3. Blood agar, 0.1% glucose, 5~15%CO2 4. small colony, α- haemolysis, smooth colony (virulent strain) ‘draughtsman’colony(incubation over 24 hour) 5. Pathogenic factor: capsule( antiphagocytosis)(S→R); pneumolysin 6. Disease: pneumonia , bacteraemia; meningtis 7. Treatment: sensitive to a wide range of antimicrobia agent. eg.Penicillins*, Section 4. Neisseria Gram negative cocci, usually arranged in pairs. Some are normal inhabitants in respiratory tract. Others are human pathogens (eg: gonococcus,meningococcus ) Common biological characteristics 1.Gram negative cocci, kidney-shaped, in pairs have capsules and pili 5 2.Need enriched medium (chocolate blood agar ) 3. 5~10%CO2 4.Resistance: very weak “fragile”, extremely sensitive to drying, heat, cold… Neisseria meningitidis I. biological characteristics II.Pathogenicity and immunity 1. Pathogenicity: (1) Human is the only natural host for pathogenic meningococci. Child: susceptible (lacking specific Abs) (2) Pathogenic factor: *Pili– attach to nasopharyngeal mucosa *capsule – antiphagocytosis *endotoxin – main pathogenic substance capillary tube, small blood vessel 2.Pathogenesis: epidemic cerebrospinal meningitis clinical typing: common, outbreak,septicemic type 3.Immunity: group-specific antibody, cross-immunity between groups. III. Laboratory diagnosis 1. specimen: spinal fluid, blood, nasopharyngeal swabs . (*note: “fragile” bed-side inoculation) 2. direct smear : smear Gram stain (G- diplococci, within white cells) 3. isolation and identification: specimen serum broth chocolate blood agar plate (5~10% CO2 ,37C ) Gram stain and biochemical, serological identification 4. serologic test : to detect the unknown Ag with given Ab IV. Prevention and treatment 1. Polysaccharide vaccine (group A, C) 2. Penicillin; cefotaxime; chloramphenicol Neisseria gonorrhoeae 1. Pathogenic factors: * Pilli: attach to epithelial cells (urinary-gentital, RBC) * IgA 1-protease: break down surface IgA antibodies. *Outer membrane protein (OMP): 2. Diseases: *Gonorrhea (STD: sexually transmitted disease) acute urethritis(male); pelvic inflammatory(female) *ophthalmia neonatorum→blindness 3. Laboratory diagnosis: Specimen: purulent secretion of genitourinary tract Isolation and identification: direct smear, culture, biochemical tests 4. Prevention and treatment *penicillin----- Gonorrhea *silver nitrate---- ophthalmia neonatorum 6 ------ Cheng Yizhe Enteric Bacilli I. Common properties: 1. Similar shape: G- rods, most possess flagella and pilli. No spores, certain members possessing capsules. 2. Biochemical reactions are active and diverse. Many kinds of carbohydrates and proteins can be utilized and form various products. Differentiation: e.g. Lactose fermenting bacteria – enteric nonpathogens Non-lactose fermenting bacteria – enteric pathogens 3. antigenic structure is complex (1) *O antigen - specific polysaccharides of LPS: Repeating sequence of carbohydrates, different enteric bacilli vary in the constitution and their arrangement. Basis of serological classification *S-R variation: Smooth colony (virulent) lose O-specific polysaccharides rough colony (non-virulent) (2) Surface Ag: Polysaccharides that cover the O Ags (e.g. capsule Ag) Main surface Ags: Vi antigen (S. typhi), K antigen (E. coli) Inhibit specific agglutination of O antiserum Associated with invasiveness of enteric bacilli (3) H Ag – flagella protein: Specificity of H antigen is determined by the arrangement and stereoscopic form of amino acids within polypeptides. Basis of serological classification. 4. Resistance: (1) Killed by heating at 60C for 30 min. (2) Some strains resistant to the action of bile salts. (3) Antibiotics and other chemotherapy agents are effective against members of the family, but the susceptibility pattern frequently varies in strains. 5. Produce endotoxins and/or exotoxins 6. Final identification depend upon their chemical and serological reaction Section I. Escherichia coli I. Biological characteristics: 1. Shape and structure: G- rods, possess flagella and pilli. 7 2 .Biochemical reactions (extremely active and complex): (1) Lactose fermentation test: “+” Differential media : EMB(eosine methylene blue) –metallic green MacConkey agar plate – red color (2) IMViC test: + + - 4. Antigenic structure: O Ag---- more than 164 cross -rection H Ag ---- more than 60 specific (flagellar) K Ag (L, A and B) ---- more than 100 e.g. serotype is expressed as O111:K58 (B4):H2 II. Pathogenicity 1. pathogenic factors (1) invasiveness: K Ag; Pili (fimbriae) ; CFA (colonization factor Ag) Specifically adheres to the epithelial cell lining the small intestine (2) endotoxin: cell wall lipopolysaccharide ; fever / shock (3) O Ag, K Ag: anti-complement; anti-phagocyte (4) enterotoxin (exotoxin) protein, under genetic control of a tansmissible plasmid; consists of LT and ST LT (heat labile enterotoxin) ST(heat stable enterotoxin) Heat: labile 65 ℃,30min stable 100℃,30 min MW: 73,000 4,000~5,000 Ag: Ag→Ab no Structure: 1A(A1,A2) and 5B a and b Mechanish: 2. Infection (1). extaintestinal infections ----caused by E. coli opportunistic pathogens *urinary tract infection (the most common ) *G- bacteremia ;septicemia * neonatal meningitis (new born) (2). diarrheal diseases------caused by certain serotypes of E.coli ① Enterotoxigenic E.coli (ETEC) LT and/orST ; Diarrhea; children(under 5 years),adult(travellers) Nausea, vomiting, abdominal cramps ② Enteropathogenic E.col i(EPEC) No exterotoxin; Diarrhea; infantile enteritis severe→death Less in adults ③ Enteroinvasive E.coli(EIEC) No exterotoxin; endotoxin Diarrhea, like dysentery;(several organisim. Children, adults Large intestine) 8 ④ Enterohemorrhagic E. Coli(EHEC) or Vero cytotoxin-producing E.coli(VTEC) endotoxin; hemorrhagic colitis; III. Laboratory diagnosis 1. Specimen: feces, blood, pus, …… 2. Isolation and identification: * Biochemical reactions * serologic identification IV. Investigation in public health bacteriology – indicator of fecal pollution (food/water) 1.Detecting number of coliform bacteria: Normal number < 3 / 1000 ml sample. 2.Detecting total number of bacteria: Normal number < 100 colonies / ml (g) sample. V . Tre a t me n t a n d c o n t ro l I. Section 3. Biological characteristics Shigella 1. G-, non-motile, possesses pili 2. biochemical reaction lactose fermentation: (shigella sonnei late fermentation), 3. antigenicity: O Ag (pili Ag), K Ag 4. Classification: 4 groups, 43 serotypes 5. Resistant: Sonnei > flexneri > dysenteriae 6. Variation: (1). antibiotic-resistance (R plasmid); EMB---non color colony (2). SR II. Pathogenesis and Immunity Human beings – the only natural hosts 1. Pathogenic factor: Infecting dose: 10~100 organisms (1).Pili – adhesion ileum intestinum end epithelial cell (2).Endotoxin – fever, shock; inflammatory; rectal cramp (3).Exotoxin: S. dysenteriae I, II shiga toxin 2.Course: organisms oral route suddenincubation 2~3 days/12 hour abdominal colic watery diarrhea fever, malaise local inflammation ulceration bloody mucopurulent stool, abdominal cramp, tenesmus *acute dysentery(bacillary dysentery) 9 diarrhea , 39℃,blood stool more than ten times, vomit *chronic dysentery : diarrhea 3.Immunity IgA persistent short, no IgG III.Laboratory diagnosis 1.Isolation and identification Stool / rectal swabs selective media biochemical, serological, and animal tests 2.Rapid diagnosis A. Fluorescence-bacterial particle method B. Co-agglutination I V. T r e a t m e n t Section 4. I. Biological characteristics: Salmonella 1. Morphology and biochemical reactions: (1) Morphology: G-, peritrichous, non spore-forming (2) Culture: grow in simple cultural media, EMB,non-color colony (3) Biochemical reactions: --------the basis of classification and identification 2.Antigenic structure and classification (1). O antigen (somatic antigen) group specific Ag: 42 groups (2). H antigen (flagella antigen) Type specific Ag: a. Phase 1 – specific phase b. phase 2 – nonspecific phase (3). Vi antigen(virulent Ag) surface polysaccharide; Ag leak; antiphagocytosis 3.Variation (1) S→R Variation: lose O-specific polysaccharides (2) H→O Variation: lose of flagella (3) V→W Variation: lose of Vi-Ag. 4.Resistance 60℃ 1 hour ; 65℃ 15~20min living: 2~3 weeks in water , 1~2 month in feces resistance to certain chemicals, e.g. brilliant green II. Pathogenesis and immunity 1. Pathogenic factors (1) Invasiveness Pili---adhance Vi antigen ---antiphagocytosis (2) Endotoxin WBC↓; shock ; activited complement→inflammant (3) Enterotoxin S.typhi murium: LT/ST 2. Pathogenesis 10 (1) Septicemia: (S. Choleraesuis) Pneumonia; osteomyelitis; meningitis(neonates, very young child) (2) Enterocolitis (Food poisoning) World wide; incubation period: 8~48 hour headache, abdominal pain, nausea, vomiting, fever , watery diarrhea (3) Enteric fever: Organism typhoid (caused by S. typhi) paratyphoid (caused by S. Paratyphi A,B,C) infective dose: 106~109 organism; 103or less than 100 Courses of the disease (3 stages): Organism comtaminate water or food via eating ingestion(some destroy by gastric acid) adhere in the small intestine by pili phagocytosis by tntestinal lymphnodes (macrophages) growing thoratic duct Blood stream ----------------------------------------primary bacterimia Organs and tissues (liver, kidneys, spleen, bone marrow, gall bladder) phagocytosis multiplication Blood stream-------------------------------------Secondary bacterimia (high fever, enlargment of spleen, slow pulse) organs : capillaryrose spots done narrowanemia kidneyorganism excret out gall bladderintestinal tructsexcret out Major intestinal lymphnode necrosis ulcer (Hypersensitivity IV) testinal wall necrosis, ulcer enterobrosis(intestinal perforation) Recover dead. Characteristics of the disease: two times of bacteremia, continuous fever, liver and spleen enlargement, rose spots, severe complications. 3. Immunity Enteric fever: *persistant immunity after disease. *The main anti-infectious immunity is CMI. *humoral immunity destroy the organism which into the blood 11 Ab titer can continue for a long time after recover gastroenteritic: local Ab septicemia: monophagocytocis, Ab III. L a b o r a t o r y d i a g n o s i s 1. Bacteriological methods (1) *Enteric fever: collect specimen according to the stages of the disease, 1st week----blood; 2nd~3rd week ------ feces or urine. *Food poisoning: collect feces, food. *septicemia: blood (2) Systemic biochemical and serologic identification. 2. Serological methods (Widal test) (1) To detect the unknown Ab with given Ag(O,H,HA,HB) – tube agglutination. (2)Normal serum titer: O < 1:80; H < 1:160; H (A/B) < 1:80 IV. Prevention and treatment 1. Vaccination – Triple vaccine (TAB) 2. Antibiotics: chloramphenicol (oral, 14 days) and other Bacteremia-----high dose ampicillin, 10~14 days -------Cheng yizhe Vibrio (V. cholera) V. cholera – cause cholera (an outbreak infectious disease) – two biotypes: classical biotype eltor biotype I. Biological characteristics: 1. Gram negative, short curved rods, single polar flagellum, pili, sexpilis 2. Culture (facultative)Aerobe, 37℃ halophilic, grow in high pH (8.5 – 9.5) medium, 3. Antigenic structure O Ag stable heat group specificity(130 serogroup, V. Cholera O-1) H Ag labile heat non- specificity 4. biochemical reaction five sugar fermentation test: + - + + + 5. resistant *live for 1~3 weeks in water *resistant basic, cold *sensitive to heat(55℃ 15min,100℃ 1~2min) dry acid(gastric acid 4min) Antibiotics II. Pathogenicity: 12 1. Pathogenic factor (1).Invasiveness: flagellum, pili (2).Cholera enterotoxin (similar to LT) MW: 84,000 *B subunits (five) – 56,000; Ag high; bound unit, attaches to the receptor (GM1) on the epithelial cells of small intestine. *A subunits (A1 ,A2) –28,000; Ag weak ;active unit, enters the cell, stimulates adenylate cyclase cAMP . 2. Disease-----cholera Organisms oral route (contaninated water, food) stamoch(gastric acid) attach to the small intestine epithelial cells(non-penetration) multiplication cholera toxin adenylate cyclase cAMPconcentration secreting effect devere diarrhea (rice-water stools ) *patient may lose as much as 10 to 15 liters of liquid peir day *rapid dehydration and hypovolaemic shockdeath in 12-24 hour *“rice-water stools”---mucus, epithelial cells, large number of vibrios * recover: gallbladder have some organism III.Immunity 1. Nonspecific immunity: Gastric acid 2. Specific immunity: Abs (SIgA) 3. Persistent immunity to the same serotype I V. L a b o r a t o r y d i a g n o s i s 1. Rapid diagnosis rice-water stools--- directly smear: Hanging-drop observation; Gram stain 2. Isolation Basic peptone water, 37℃, 3~6 hours, grow on the surface 3. Identification Slide agglutination test fermentation reaction V. P r e v e n t i o n a n d t r e a t m e n t 1. Vaccine 13 *Inoculation of dead bacteria-vaccine *Live attenuated oral vaccines(against O1 , O139) *Genetic engineering vaccine is being studied. (subunit vaccine + toxoid) 2. give the life-saving replacement of fluid and electrolytes 3. Antibiotics: tetracycline; chloramphenicol -------Cheng yizhe A n a e ro b i c b a c t e r i a Section 1. I n t ro d u c t i o n 1. Anaerobic bacteria: Spore-forming anaerobes-----Clostridium(G+ bacilli) Non-spore-forming anaerobes-----polymorphic more than 30 genera (G+ and G- cocci, G+ and G- bacilli) 2. Distribution: Clostridium: endospores, in nature Non-spore-forming anaerobes: members of normal flora (1011 bacterium in 1g feces) 3. Infection: Spore-forming anaerobes Non-spore-forming anaerobes Exogenous Exotoxin Typical clinical symptoms endogenous endotoxin & other invasive factor inflammation similai sympotems abscess Septicemia Treatment by antitoxin Treatment by antibacterial drug 4.Anaerobic culture 1).biological method-----beef medium 2). Physical method------anaerobic jar 3). Chemical method------chemical reaction(blood agar) Section 2. Spore -f orming anaerobic bacteria – C lostridium I. Clostridium tetani 1. Biological characteristics: *Peritrichate, endospore – round, terminal spore(“drum-stick”) *culture: blood agar----completely hemolysin; ‘feather’ colony *resistance: several years in soil (spore) sensitive to penicillin(vegetative form) 14 2. Pathogenesis: 1).condition *deep ,narrow and mixture with soil Wound+spore *necrotic tissue *pyogenic bacteria mixture infection (puncture; gun shoot; burn; animal bite) 2).pathogenic substance * tetanospasmin (neurotoxin) protein 150,000 ; α toxin subunit, β bound subunit 1μg----lethal Ag→Ab(tetanus antitoxin TAT) potent neurotoxin 3).mechanism : Spores vegetative bacteria grow locally ↓ tetanpspasmin (neurotoxin) ↓ blood anterior horn cells of spinal cord ,binds to ganglioside receptor and blocks release of inhibitory mediators (eg. glycine) causes convulsive contraction of voluntary muscle. 4).Clinical manifestation: *local muscle apasm – lock jaw ; sardonic grin *progressive spasm – opisthotonus, respiratory failure 3. immunity humoral immunity-----antitoxin 4. diagnosis *morphology not value *clinical picture 5. Prevention and control: *Active immunization: toxoid DPT (Diphtheria, Pertussis, Tetanus) *Passive immunization: TAT (tetanus antitoxin), early & enough * wound---debridement *antibiotics (penicillin) II. Clostridium botulinum 1. Biological characteristics: 1). Morphology * Large rod ; *endospore: oval, sub-terminal; no capsul; pertrichous 2). Culture * blood plate-------hemolysis 3).resistant *living in gastroliquid for 24 hr 15 *spore: 180℃ 5~15min ; 100℃ 3~5h ; 120℃ 5min 2. Pathogenesis: 1).pathogenicity substance-----Botulin *the most toxic exotoxin 1 mg botulin can kill two million mice. Lethal dose for human being is about 1 g). *Eight types of C. botulinum: A, B, C, C, D, E, F, G A, B, E, F – main pathogens to human being *Neurotoxin inducing muscle paralysis in three steps: binding to receptor on nerve synapse entrance into nerve cell blocking release of acetylcholine from the cell *heat labile 100℃ 10min *protein 2).disease *food poisoning (Neurotoxin) ----- fatal *C.botuliumcontaminated food ↓growing producing botulin ↓ ingestion ↓ intestinal tract ↓absorb blood ↓ CNS ↓ inhibitin the release of acetylcholine ↓ paralysis *clinical manifestation: eye and throat paralysis (early signs) respiratory and cardiac failure death 3. Immunity: no induce antitoxin; no immunity 4. Laboratory diagnosis: * anaerobic culture of food; * toxin test----- feces ; vomit 5. Prevention and treatment *food boiling * to neutralize unfixed toxin by give polyvalent antitoxin Section 3. Non-spore-forminga n a e ro b i c b a c t e r i a 16 *70-80% infection of oral, intestinal tract, urogenital tract are caused by non-spore-forming anaerobic bacteria I. Biological characteristics: 1. G+ bacilli : polymorphic, no- motile, growing slow, biochemical react slowly * Bifidobacterium * Lactobacillus 2. G- bacilli : capsul, pili, no motile, *Bacteroides--- B. fragilis; B. melaninogenicus *Fusobacterium---F. nucleatum + 3. G cocci: *peptococcus *peptostreptococcus cause infection with other bacteria 4.G cocci: *Veillonella cause infection with other bacteria II. Pathogenesis: *Infection mixed with other aerobes *Anaerobic environment pathogenic condition chronic consumptive disease maligmant tumor immunity function lower diabetes radiotherapy chemotherapy barrier destruction dental extraction enterobrosis open fracture tissue necrosis local anaerobic environment ischemia flora disequlibrium *Pathogenic factors: LPS, capsule, enzymes * diseas nonspecific infection: chronic; purulent local inflammation, abscess, tissue necrosis, septicemia III. Laboratory diagnosis: Direct smear; Anaerobic culture IV. Prevention and control: *Surgical treatment *Antibiotics : penicillin metronidazole 17 -------Cheng yizhe Mycobacterium Types of Mycobacterium: M. tuberculosis M. Bovis M. africanus *Non-tuberculosis mycobacteria *M. leprae *M. tuberculosis Section 1. M. tu bercul osis I. Biological characteristics: 1. morphology *thin , straight or slightly curved rod , *G+; acid-fast stain----red *non-motile; non- sporing; non-capsulate *thick, complex, lipid-rich-waxy cell wall 2. culture *obligate aerobes; *Special nutrient requirement: whole eggs(yolk), glycerol, asparagine, malachite green, potate *Slow growth: generation time – 18 h~24h(primary isolation—8 weeks) Colony: “cauliflower” Pellicle on surface of liquid media 3.Resistant *Resistant to drying (especially in sputum, 6-8 months) *resistant to: acid( 3% HCl, 6% H2SO4) alkalis( 4% NaOH) *Sensitive to : moist heat---60℃ 30min,70℃ 3min disinfectants-- alcohol, glutaraldehyde, formaldehyde (5%lysoform: no sputum---5min, sputum---1-12h) drugs---rifampin, para-aminosalicyclic acid, streptomycin, isoniazid, pyrazinamide U.V. 4.Variation: *drug resistance variation *virulent variation ------BCG (Bacliie Calmette-Guerin) II. Pathogenicity 1. Pathogenic substance: (1) Lipid Possess 40% of the cell dry weight, or 60% of the cell-wall dry weight Phosphatide 18 Stimulate monocytes proliferation---form tubercle Inhibit proteinase--- form caseous necrosis Mycolic acid A large fatty acid Associated with acid-fast property Cord factor Associated with virulence Inhibit migration of leukocyte to form chronic granuloma Bind to mitochondrial membranes, cause functional damage to respiration and oxidative phosphorylation Wax D----Act as an adjuvant Sulfatides-----Inhibit the fusion of phagosome and lysosome (2) Protein-----Ag; protein-Wax D→allergic response (3) Polysaccharide(capsul?) Connected with Wax D 2. Disease: tuberculosis Usually a respiratory infection, others as wound, food can cause infection---lung, intestin, kidney, skin, lymphonode, bone, joint Pulmonary tuberculosis: primary tuberculosis organism→respiratory tract→pulmonary alveolar→lesions →hilar lymph nodes→swelling→fibrosis→natural cure post-primary tuberculosis organism→infection again→inflammation→necrosis→tubercle →fibrosis/caseation necrosis pathogenic mechanism infiltration ----------PMN, monocyte tubercles-------monocyte→phagocytose bacteria lipid epithelioid cell fuse multinuclear giant cell surrounded by lymphocyte tubercles fibrosis------a little bacterium, immunity→calcium diposis caseation necrosis----immunity↓,bacterium multiplication, allergy →necrotic tissue in a semisolid cheesy state or necrotic tissue effluvium→cavities III. immunity 1. The main anti-infectious immunity is CMI 2. Infection immunity 3. CMI and DTH I V. T u b e r c u l i n t e s t 19 *OT (old tuberculin): TB Glycerol broth 4-8 weeks 100C, 1 h filtration concentration (1/10) *PPD (purified protein derivative): TB special media 6-8 weeks TCA precipitation 1. Principle: DTH 2. Result and interpretation PPD injection 24-48h induration, erthyema “-”--- < 5mm: no TB infection early stage of primary infection miliary tuberculosis or tuberculosis meningitis; virus infection; tumor, AIDS; use of immunosuppressive agents “+”--- 5mm <15mm: hypersensitive to M. tuberculosis ; immunity “++”--- 15mm: active TB perhaps 3. Application * Basis of BCG inoculation, detect immunity effect *Diagnosis for young children tuberculosis *Epidemiological investigation *cellular immunity test of patients with tumor V. L a b o r a t o r y d i a g n o s i s 1. Specimen: sputum, urine, CSF, etc. direct smear----acid-fast stain 2. culture---specimen concentration sputum 4% NaOH/3% HCl/6% H2SO2 , 30 minkH2PO3, 15-30min centrifuged deposit inoculate media 8 weeks 3. Animal test---guinea pig 4. Immunity diagnosis----ELISA 5. PCR VI. Prevention and control 1. Specific prevention: BCG 2. Prophylactic chemotherapy: isoniazid -----Cheng yizhe ChlamydiaeI. Biological propertiessmall non-motile prokaryotic microbes, filterable (0.2-0.4um) , 2. cell wall, G- similar to G- bacillus, 3.contain DNA and RNA , 20 4.obligate intracellular parasite, 5.unique life-cycle , 6.classification, unique life-cycle :Elementary body : very little (0.3μm in diameter), dense , infectious form;Initial body: larger (1μm in diameter), less dense, non-infectious, replication form Elementary body → phagocytic engulfment → replication form →initial body →inclusion body →lots of elementary body →release from cell, infect another cell, 40hrs inclusion body---consisted of replicating initial body and descendant elementary body in the infected cell classification 1. Chlamydia trachomatis : (1) biovar trachoma : 14 serotypes(A-K ) (2) biovar lymphogranuloma Venereun(LGV):4 serotypes(L1, L2, L2a,L3 ) (3) biovar mouse 2.Chlamydia pneumoniae: 1 serotype 3. Chlamydia psittaci Ⅱ Pathogenicity 1.pathogenic factor : (1) surface structure : LPS and MOMP (2) endotoxin -like substance 2.Disease (1) C.trachomatis ① Trachoma ② Inclusion Conjunctivitis ③ Genital-tract infection –NGU ⑤ Lymphogranuloma Venereun (LGV)(2) C. pneumonia infantile pneumonia -------Cheng MycoplasmaⅠ yizhe Introduction1.the smallest free-living prokaryotic organisms that can grow in artificial media. 2. distributed extensively --Human, animals, plants, insects and sewage. 21 3. Non-cell wall, pleomorphic. 3. pleuro-pneumonia-like organisms—PPLO Ⅱ Biological properties1. size: 0.2~0.3um, pass through 0.45filters.polymorphic: coccoid, coccobacillary,Giemsa stain: purpleStructure : three layer of membrane: two protein membrane, one lipid membrane terminal structure: some mycoplasma have specialized structures at one or both ends by which they adhere to respiratory or genital tract mucosal surfaces 5. Propagation pattern: binary fission 6. Both DNA and RNA 7. culturefried-egg colony: 8. classification (1) Mycoplasmataceae: mycoplasma , (2) Acholeplasmataceae Ureaplasma (3) Spiroplasmataceae9. Resistant resistant to penicillin, polymyxinsensitive to tetracycline, Ⅲ Pathogenicity1.M. pneumoniae[MP] 2.Ureaplasma urealyticum [UU] 1.M. pneumoniae[MP] (1)Terminal structure → adherence epithelial cell, RBC → damage Cell Membrane →release products (H2O2, toxic enzyme) →toxic enzymetic →injure cell(RBC, tracheal epithelial cell) (2)Primary atypical pneumonia [PAP] (a) PAP often in school children and adolescent;(b) Spread by respiratory, incubation 2~3 weeks; (c) Headache, cough, fever, malaise; (d) Rarely fetal;(e) Tetracycline --adolescent, Erythromycin --children, pregnant women.2.Ureaplasma urealyticum [UU] (1) genitourinary tract infection—STD (3) vaginitis,cervicitis→premature birth, (4) arthritis (2) nongonococcal urethritis (NGU) abortion, sterility Erythromycin,Tetracycline,Doxycycline -----Cheng yizhe 22 Rickettsia Ⅰ Biological properties 1. small G- bacilli, 2. Giemsa stain: violet or blue;3.They are obligated intracellular parasites ; 4. binary fission ;5. have both DNA and RNA;6. Culture: susceptible animal (guinea pig), yolk sac of chick embryo, cell culture;7. Rickettsiae normally enter the body (mammalian reservoir) through the bite or feces of an infected arthropod vector. Arthropod vector : mite , tick , louse , flea 8. resistance: week, sensitive to antibiotic 9. Antigen: type-specific Ag-- stimulate antibody 10. weil-Felix reaction Proteins: Proteus strains OX-2, OX-19, OX-K tilter:>1:160 and progressive rise 11.Classification:(1) Typhus group : Epidemic typhus (R.prowazekii) Endemic typhus (R. mooseri) (2) Spotted fever group (3) Tsutsugamushi group Epidemic typhus (R.prowazekii)(1) louse-borne ; substandard living condition, poor sanitation; overwhelming bacterimia (2) transmitted way (3) fever(temperature rises to 40℃); (4) treatment: sanitation, eradication of human lice; vaccine , tetracycline transmitted way: Rickettsiae →arthropod vector, bite →human skin,wound →multiply in epithelial cells of small blood vessule →toxin released in the blood →toxemia →many organs →pathogenesis Endemic typhus(R. mooseri) flea-borne; murine typhus transmitted way : rat human louse 23 rat flea rat louse rat flea Human rat human human louse fever; headach; maculopapular rash II.Pathogenicity Rickettsiae diseases are transmitted from animal to animal by the bite of an arthropod vector .Rickettsia disseminated through the bloodstream, enter endothelial cells by induced phagocytosis escape from the phagosome, intracellular multiply and eventually destroy their host cell ------Cheng yizhe Spirochetes Introductionmonocellular organism , flexible, helical, possess an axial filament (active motile)2.situs is between bacterium and protozoa 3.general structure : envelope , axial filament , protoplast 4.sensitive to antibiotics (penicillin etc.) 5.Fontana silver stain:brown classification: pathogenic organisms Borrelia-------B.recurrentis----relapsing fever Treponema—T. pallidium----syphilis Leptospira---Leptospirosis, systemic infection Section I. Leptospira I. Biological properties 1. Morphology 1) tightly coiled spiral, long (6~12μm) 2) 3) active motility---rhythmic contraction of axial filament 4) 2.culture 1) grow in artificial medium 2) hooked in one or both ends silver-stain aerobic growth;A Antigen P Ag (peptidopolysacharides)---- type-specific : 180 serotypes S Ag (lipidosaccharides) -- generous-specific: 19 serotypes 24 II. Pathogenicity 1. pathogenic substance hemolysin-----lysis RBC Cytotoxicity factor-----cytopathogenic effect endotoxin-like component(ELS)------cause fever, inflammation, necrosis III. Disease infected animal → discharge urine → water/soil → human skin → blood stream →septicemia→recovery or fatality(30%) Clinical type :jaundice—hemorrhage type influenza—typhoid type pulmonary—hemorrhage type renal—failure type meningoencephalitis type IV. Immunity Humoral—immunity; after two weeks, specific Ab can be examed V. Treatment and prevention 1.penicillin, tetracycline, streptomycin or erythromycin (in large enough doses early in the infection) 2.rodent control 3.vaccination of domestic animal Section 2 Treponema pallidium I. Biological properties 1. fine, culture 4. long, tightly coiled organism 2. silver-stain: brown 3. difficult to sensitive to temperature (41℃ 1hr); dry (1~2hr); soapsuds; penicillin, tetracycline II. Pathogenicity T. pallidum is the causative agent of syphilis, a common sexually transmitted disease found world-wide. It is generally transmitted by genital/genital contact. Transmission in utero or during birth can also occur. The syphilis(lues) is usually acquired: 1.during sexual contact----venereal disease 2.contact with mucous-membrane lesions 3.blood transfusion----rare (causative treponema will not survive more than 48 hours under the condition of blood storage) 4. congenital syphilis---organism pass through the placenta to infect fetus. Acquired syphilis----sexual contact *primary syphilis (10-60 days)---- chancre *secondary syphilis(2-10 weeks later) *tertiary syphilis(several years later) Treatment 25 No vaccine exists antibiotic therapy (usually penicillin G) is usually highly effective. Actinomyces 1) .Filamentous prokaryotic microbes, form hyphae 2). Cell structure is similar to bacteria 3). sensitive to antibiotics 4). Actinomyces colonies ---Sulphur granules ---- cheng yi zhe 26 Individual Virology Respiratory viruses Characteristic properties of common respiratory viruses viruses Diameter (nm) Shape and strecture Nucleic Envolope acid Influenza virus 80-120 ssRNA + Parainflue-nz a virus 100-250 ssRNA + Measles virus 120-250 ssRNA + Mumps virus 110-360 ssRNA + 90-130 ssRNA + 50-70 ssRNA 15-30 H,N No.of serotypes variable 3 4 H(+) N(-) diseases Influenza, Common cold, Bronchitis Common cold Croup Pneumonia 1 Measles, SSPE 1 Mumps, Menungutis, Orchitis 1 Bronchiolitis, Pneumonia + 1 Postnatal and congenital rubella ssRNA _ >110 Common cold 80-100 ssRNA + >3 Common cold Reovirus 60-90 dsRNA _ 3 Adenovirus 70-90 dsRNA _ 33 Respirato-ry syncytial virus Rubella virus Rhinovirus Coronavirus _ Upper resp. tract infection, diarrhea Acute resp. disease, Pneumonia, Conjunctivitis Section 1 Influenza virus Comprises influenza A,B and C, viruses. Influenza A viruses can infect a variety of different species (aquatic birds, chickens, horses etc) and can cause worldwide epidemics of influenza (occur approximately every 10-20years). Influenza B only infects humans and can cause major outbreaks of influenza. influenza C mainly infects humans and can cause mild respiratory tract infections ,but does not cause outbreaks of influenza ⅠBiological characteristics 27 1.Morphology and structure Spherical, 100-120nm in diameter, enveloped, spikes 1)core: -ssRNA, segmented(7- 8 pieces ) 2) NP: surround and bind the RNA, type-specific, stable. 3) envelope:M1、M2、lipid bilayer membrane 4)spikes:HA、NA Hemagglutinin ( HA ): 2units: HA1and HA2 * agglutinate human and some animal RBC * be related to the adsorption of viruses (receptor : neuraminic acid ) * antigenicity: show great variability Abs to the HA are protective,neutralize viral infectivity. Neuraminidase ( NA ) * be related to the release of viruses: hydrolyze the terminal neuraminic acid of glycoprotein on surface of cell. * antigenicity: variable 2.Type and variation Based on antigenicity of NP and MP: Influenza A, B, C. Based on HA, NA: subtype * Antigenic drift: which are minor changes based on mutations in the genome RNA. * Antigenic shift: which are major changes based on the reassortment of segments of the genome RNA. 3.Cultivation Culture in chicken embryo. Culture in cell culture (non-CPE) 4.Resistance Inactivated 56℃ 30min. ⅡPathogenesis and immunity *is spread via respiratory droplets. *virus particles binds to cells of the respiratory epithelium ⅢClinical features: *respiratory tract symptoms: sore throat, cough etc; *systemic symptoms: headache, fever, myalgias (muscle pains). Ⅳ.Control Vaccine: Whole inactivated virus vaccines ----including H1N1,H3N2 and a B subtype. 28 Section 2 Avian Influenza 1.Blong to type A influenza viruses; 2.can infect birds, pigs, horses, seals and whales, etc; 3.Avian influenza infections in humans: 1997: Hong Kong, (H5N1) 1999: Hong Kong, H9N2 2003: Hong Kong , H5N1 2003: Netherlands, H7N7 2003: Hong Kong, H9N2 4.serotypes including H5 and H7 are associated with disease in poultry. Section 3 SARS-associated coronavirus (SARS-CoV) 1.A novel coronavirus; 2.60-220nm, +ssRNA(29.7kb), enveloped; 3.Major structures: N, S, M, E 4.Transmission: close person-to-person contact 5.Associated diseases: Severe Acute Respiratory Syndrome (SARS) -----Qi mei 29 Enteroviruses ⅠClassification: 1)Poliovirus: 3 serotypes 2) Coxsackievirus: Group A and Group 30serotypes 3)ECHO virus: 34 serotype 4)New Enteroviruses : serotype 68.69.70.71.72 ⅡCommon Properties: 1) Spherical , 20-30nm, icosahedral symmetry, nonenveloped, +ssRNA 2)cell culture ( cause CPE) 3) resistance : more stable, resistant to lipo-solvents, pH3-5, resist 56℃ 30min 4)Pathogenesis:virus---enteron--- viremia --- different trarget tissue. Eg: Poliovirus: V—enteron –viremia– CNS (anterior horn cells , cytocidal effect) ---cause Poliomyelitis Coxs. Viruses ( group B ): V— enteron – viremia –cardiacmuscular (immunopathological reactions) ---- cause viral myocarditis 5) the virus-neutralizing epitopes reside mainly in VP1, although the actual sites may cover VP2 and/or VP3 Poliovirus 1. Three serotypes, non-cross reaction 2.fecal –oral tramission , 3. Cause Poliomyelitis incubation period : 7 - 14 days (range 3 - 35 days). Following ingestion---- oropharyngeal and intestinal mucosa( lymphatic system) a transient viraemia. CNS following dissemination. outcomes following poliovirus infection: Subclinical infection (90 - 95%) Abortive infection (4 - 8%) Major illness (1 - 2%) 4.Immunity: neutralization Ab 5. Vaccine: attenuated-live vaccine (Sabin vaccine) This vaccine uses live attenuated virus that is given by mouth, sometimes as liquid drops in a sugar cube. Rotaviruses 1.65-75nm, icosahedral, double-shelld capsids (inner capsid, wheel-like) 2.dsRNA: 11segments, 3.Culture: difficult 4.Type: basic on outer capsid, 7 groups(A-G), most of the human rotavirus are of group A 5.Transmission: fecal-oral route 6.mainly infect young children (6 months-2 years) -----Qi mei 30 Hepatitis A-E Viruses Section 1 Hepatitis A virus ( HAV ) A Picornavirus, now classified as a heptovirus, formerly known as enterovirus 72 ⅠBiological properties 1.spherical, 27nm, icosahedral, non-enveloped 2. +ssRNA, 7400bp. 3. One serotype 4. Chimpanzee and marmoset(绒猴)are susceptible. 5.Culture: difficult, no CPE, grow slowly. 6.Stable: resistance to 60℃ 1h, pH 3; inactivated at 100℃ 5min. ⅡPathogenesis and immunity 1.Source of infection: patients, subclinical infected person. 2.Transmission: fecal-oral route.(from fecally contaminated water or food) 3.Children are the most frequently infected group 4.Pathogenic mechanism: HAV----mouth----intestine----blood----liver 5.Mechanism of hepatocyte damage: Cause acute hepatitis. 1) viral direct effect 2) immunol injure ⅢControl 1.ã-globulin for urgent prevention. 2.Vaccine: inactivated vaccines are commonly used (The virus is grown in human cell culture and inactivated with formalin). Section 2 Hepatitis B virus ( HBV ) Globally, more than 300 million people are chronically infected with HBV and about 75% of them are Asian. ⅠBiological properties 1.structure: 1).partially dsDNA, circular 3200bp the long strand is complete, variable length of the short strand. 2)layer capsids: inner capsid: icosahedral, carry HBcAg, HBeAg outer capsid: carry HBsAg, pre-S Ag. 31 2. Three different particles : 1)Dane particle: intact virion, 42nm. 2)Small spherical particle: 22nm, carry HBsAg. 3)Tubular particle: consists of HBsAg. 3.Gene and encoded proteins S, C, P, X regions, located in the long strand. 1)S region: HBsAg, pre-S1 protein, pre-S2 protein. 2)C region: HBcAg, HBeAg. 3)P region: DNA polymerase(has both RNA-dependent and DNA-dependent activity). 4)X region: X protein. -----Qi mei 32 4.Replication: There are some parallels between the HBV and the retroviruses.(reverse transcription) 5.Ags & Abs 1)HBsAg: *4 subtypes: adr, adw, ayr, ayw; ayw predominates in N.Europe, N.America and Australia ; adr in China and Japan *4 genetypes: A, B, C, D; *HBsAg ( + ): indicates that the patient is infected with HBV, either as a recent acute infection or as a carrier; *anti-HBs: protective. 2)pre-S1 Ag and pre-S2 Ag: * be related to the adsorption of virus; * enhance the antigenicity of S protein. *anti-pre-S1: protective, neutralizing Ab *anti-pre-S2: protective, neutralizing Ab 3) HBcAg: *not easily detective in serum *anti-HBc: not protective *anti-HBc ( + ): viral multiplication, active infection, infectious. 4)HBeAg: *C gene and preC gene encode HBeAg protein *Lies in inner capsid and easily detected in serum *HBeAg ( + ): viral multiplication, active infection, infectious. variable *anti-HBe: not protective, viral multiplication and active infection are reduced, has less infectious 5)HBxAg: associated with cancer. 6.Can not grow in any cell culture. 7.Resistance stable 60℃1h , 100℃10-15 min. Ⅱ.Pathogenesis & immunity 1.Source of infection: patients, HBsAg-carrier( Who has HBsAg persisting in their blood for at least 6 months). 2.Transmission way: ① By blood or blood products; ② Sexual transmission; ③ Vertical transmission: from mother to child(during birth or breast feeding). 3.Mechanism of pathogenesis: *hepersensitivity reactions ( type Ⅱ, Ⅲ,Ⅳ ) *Variation HBV preC mutate----HbeAg----immunal escape 33 Ⅲ.Microbiological detection 1.Detecte Ags & Abs: HBsAg, anti-HBs, anti-HBc, HBeAg, anti-HBe. 2. HBV DNA HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy. 3. Sera DNA polymerase Ⅳ.Control 1.Vaccination - highly effective recombinant vaccines are now available. *Serum derived - prepared from HBsAg purified from the serum of HBV carriers *Recombinant HBsAg - made by genetic engineering in yeasts 2.Treatment *Interferon – *Lamividine - a nucleoside analogue reverse transcriptase inhibitor. Section 3 Hepatitis C virus ( HCV ) 1. +ssRNA , lipo-enveloped. 2.Can not culture. 3. easy variation. 4. Transmission: transmitted mainly by blood and blood products. 5. HCV is closely related to hepatoma. 6.Microbiological detection: Detect anti-HCV; Detect viral RNA: RT-PCR. 7.Control:Neither active nor passive immunization is available. Section 4 Hepatitis D virus ( HDV ) 1. Spherical, 35-37nm. 2.–ssRNA, circle, 1700bp. Outer capsid is HBsAg. 3.One serotype. 4.Defective virus. 5.Human and chimpanzee are susceptible to HDV. 6.Transmission: same as HBV. 7.Infecious mode: *Coinfection – severe acute disease. – low risk of chronic infection. *Superinfection – usually develop chronic HDV infection. 34 – high risk of severe chronic liver disease. – may present as an acute hepatitis. 8.Detect HDAg & anti-HDV. Section 5 Hepatitis E virus ( HEV ) 1 Spherical, 27-38nm. 2 +ssRNA, 8.5kb. 3 Not stable. 4 Not grow in cell culture. 5 Transmission: fecal-oral route. 6 Mainly involve young and adults. 7 Incubation period: average 40 days. 8 Cause acute hepatitis, 4-6 weeks recovery, no chronic. 9 Mortality 1-2%, pregnant woman 10-20%. 10. Detect viral Ag in faeces: Detect anti-HEV IgM in serum: -----Qi mei 35 Retrovirus Retroviridae include 3 Oncovirinae: Lentivirinae: Spumavirinae: subfamilies: HTLV (Human T-cell Lymphotropic Virus) HIV (Human Immunodeficiency Virus) Human immunodeficiency virus ( HIV ) *Pathogen of AIDS ( Acquired Immunodeficiency Syndrome ). *HIV-1 is found worldwide, HIV-2 is found primarily in West Africa. Ⅰ.Biological properties 1. Spherical, enveloped, spikes. 2. Structure: *Core: 2 copies of +ssRNA ( to be diploid ); reverse transcriptase; *Capsid protein: P24 *Matrix protein: P 17. *Envelope: gp41:mediates fusion of the viral envelope with the cell membrane,and the virion enters the cell. gp120: 1)be associated with adsorption (binding site for CD4 molecule of T cells). 2)be able to stimulate the production of neutralizing antibodies. 3)easy variation. 3.Genes: *Structural genes: gag: coding for capsid proteins ( p17, p24, p7 ) pol: coding for protease that cleaved the various viral precursor proteins, reverse transcriptase etc. env: coding for gp120, gp41. *Regulatory genes: tat: regulating the synthesis of viral proteins ( + ).(enhance viral gene transcription) rev: regulating the synthesis of viral proteins ( + ). nef: regulating the synthesis of viral proteins ( - ). *LTR: contain promotor and enhancer sequences. 4.Resistance: 56℃inactivated. 5.Replication: *absorption : 36 gp120 bind for CD4 molecule of T4 cells the necessary co-receptors (chemokine receptors) for HIV-1 entry: CXCR4 (fusion) for T-cell line (T)-tropic strains CCR5 for macrophage (M)-tropic strains. *Penetration: membrane fusion *Uncoating: *Biosythesis: RNA---cDNA--- RNA:DNA hybrid molecule ---dsDNA(provirus) integrated into host DNA--- stay latent ----- enter a productive cycle *assembly and release: budding Ⅱ.Pathogenesis & immunity 1.Infectious source: patients (symptomatic), infectious people(anti-HIV(+), asymptomatic). 2.Transmission pathway: 1) By blood or blood products; 2) By Sexual contact; 3) Vertical transmission: from mother to child. 3.Pathogenesis: * gp120 of HIV select CD4 molecule of T4 cells ---viruses multiply in T4 cells---cell-mediated immunodeficiency---opportunistic infections and tumors occur---death *Destruction of T4 cells is achieved by: ① Viral replication ②Syncytium formation via membrane gp120 binding to cell CD4 antigen ③Cytotoxic T cell lysis of infected cells ④Cytotoxic T cell lysis of T4 cells carrying gp120 released from infected cells ⑤ Natural killer cells ⑥ Antibody-dependent cell cytotoxicity. ⑦Induce appoptosis. 4.Clinical features Exposure---Seroconversion---Asymptomatic---PGL(persistent generalized lymphadenopathy, ) or ARC(AIDS-related complex) ---AIDS a.Opportunistic Infections: Fungal, Bacterial, Viral b. Opportunistic Tumours Kaposi's sarcoma, is observed in 20% of patients with AIDS. Ⅲ. Diagnosis 1. The detection of the antibody to HIV 2. The detection of viral components or detection of viral 3. Isolation of the virus in culture RNA 37 Ⅳ.Control 1.Vaccines: Several vaccines are under trial. 2. Treatment (1.) Nucleoside analogues reverse transcriptase inhibitors. AZT, DDC, DDI and lamuvidine. (2.) Non-nucleoside analogue reverse transcriptase inhibitors e.g. Nevirapine( 抑制 DNA 合成) (3.) HIV Protease inhibitors e.g. Ritonavir, Indivavir. They are the most potent inhibitors of HIV replication to date. -----Qi mei Herpesviruses Ⅰ.Classification: Classification and associated diseases of herpesviruses( 表 -) Classification and associated diseases of herpesviruses Viruses Herpes simplex virus 1 ( HSV-1 ) Herpes simplex virus 2 ( HSV-2 ) Varicella-zostervirus ( VZV ) Epstein-Barr virus (EBV ) Cytomegalovirus (CMV ) Human herpesvirus 6 ( HHV 6 ) Clinical illness Gingivostomatitis Labial herpes Keratoconjunctivitis Herpesencephalitis Genital herpes Neonatal herpes Cervical carcinoma Varicella Zoster Infectious mononucleosis Burkitt′s lymphoma Nasopharyngeal carcinoma Cytomegalic inclusion body disease Mononucleosis Congenial deformity Roseola 38 Ⅱ.Common properties 1.Linear dsDNA. 2.120-200nm, Icosahedral , Enveloped . 4.Most can grow in HDC, cause CPE. 5.Various infectious expression: apparent infection latent infection integrating infection congenital infection -----Qi mei 39 Human papillomaviruses ( HPV ) 1.dsDNA, non-enveloped. 2.Can not culture. 3.More than 80 types have been identified. 4. Pathogenesis: HPV type 16, type 18 (high-risk type) --- malignant tumor HPV type 6, type 11 (low-risk type) --- condyloma acuminatum Arboviruses Ⅰ.Common properties 1.+ssRNA, icosahedral, enveloped, hemagglutinin. 2.Sensitive to heat, lipo-solvents, acid. 3.Intra-cytoplasmic multiplication, newborn mice are susceptible. 4.Reproduce in arthropods, arthropods are vector and reservoir host. 5.Epidemics with marked geographical and seasonal distribution.. Ⅱ.Diseases caused by arboviruses 1.Encephalitis: e.g. B encephalitis. 2.Systemic infection: e.g. denge fever 3.Hemorrhagic fever: e.g. epidemic hemorrhagic fever. 4.Hepatitis associated infection: e.g. yellow fever. Rabies virus 1.Bullet shaped 2. –ssRNA, helical symmetry, enveloped. 3. Cytoplasmic inclusions ( Negri bodies ). 4. one serotype. 5.Pathogenesis: * The cause: bite of rabid animal. * Incubation period: average 3-8 weeks. (depending on the severity and site of wound ) * viruses ( in saliva of rabid animal )---wound--- never fiber ---CNS --- fatal encephalitis. 6.Control: * Treat the wound: clean, infiltrate with antirabies serum. * Vaccines: inactivated vaccines Hantaviruses 1.cause haemorrhagic fever with renal syndrome (HFRS) or, more recently hantavirus disease (HVD). 2.Genome consists of 3 stranded segments; L, M, S. 3.At least 6 serotypes are known 4.The virus is found in the lungs, spleen and kidneys for long periods in the rodent, 40 perhaps for life. Saliva appears to play an important role in the horizontal transmission of the virus between rodents. 5. Transmission (1) through the respiratory route( via aerosols of virus particles excreted by rodents in their lungs, saliva, urine and faeces. ) (2) bites by rodents. 6. multisystem pathology: damage to capillaries and small vessel walls, resulting in vasodilation and congestion with hemorrhages. Mechanisms: immunopathological mechanisms, viral cellular destruction. -----Qi mei Prion ⅠDefinition: A protein particle that is capable of causing an infection or disease. Like viruses, prions are not capable of reproduction by themselves. Unlike viruses, prions do not contain genetic material (DNA or RNA). ⅡThe prion protein PrP exists in two different conformational forms. *PrPc is thought to be the benign form of the protein and is found in normal, healthy cells. *PrPsc is thought to be the infectious "scrapie" form which causes neurodegenerative diseases such as bovine spongiform encephalopathy (BSE), Creutzfeldt-Jakob disease (CJD), kuru, and Gerstmann-Straussler syndrome. Ⅲ.Human prion diseases: Form Phenotype (Clinical & pathological features) Sporadic Creutzfeldt-Jakob disease (CJD), Familial insomnia (FI) Familial Creutzfeldt-Jakob disease (CJD), Fatal Familial Insomnia (FFI), Gerstmann-Sträussler-Scheinker Syndrome (GSS) Acquired Creutzfeldt-Jakob disease (CJD), Kuru, new variant Creutzfeldt-Jakob disease (nvCJD) -----Qi mei 41