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1、寄生蟲阿米巴第1頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三General Properties of the Protozoa第2頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Eukaryotic, unicellular animals with full vital functions.Smallest parasites, 2-200m, and best seen with a high power objective lens of a good microscope.Grow and reproduce very fast.General Introdu

2、ction to Protozoa第3頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三 4. Wide distribution in nature. Total species: about 200,000; Free-living: majority; Parasitic: around 10,000; Medical protozoa: minority about 40.General Introduction5. Medical Protozoa: resident in human fluid, tissue or cells, which may be harmful

3、to their hosts.第4頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三 3. Nucleus for reproduction; morphologically may be vesicular form or compact form.Basic Structures:2. Cytoplasm: Ectoplasm for locomotion & ingestion; Endoplasm for metabolism.1. Plasma membrane: related to independence, invasion, physiological balance

4、.4. Locomotive organelle: pseudopodium, flagellum, cilium.第5頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Locomotion: locomotive organelles:Pseudopodium: a temporary ectoplasmic extrusion, by means of which an amoeba moves about or engulfs food (Amoeba) PseudopodiumFlagellum: a long, mobile, whip like projection fro

5、m the free surface of a cell (Trichomonas vaginalis)Cilia: a minute vibratile(可振動(dòng)的), hairlike process projecting from the free surface of a cell (Ciliates)Physiological functionsFlagellumCilia第6頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Physiological functionsFeeding and digestion:Pinocytosis-engulfing soluble ma

6、tter in digestive vacuoles Phagocytosis-engulfing particulate matter in digestive vacuoles In some species, food is ingested at a definite site (cytostome, e.g. Plasmodium spp.)第7頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Mode of reproductionBinary fission results in 2 daughter cells (almost all )Schizogony multi

7、ple fissions resulting in multiple cells (malaria parasites)Budding: External budding - results in multi-cells (sporoblast sporozoite buds sporozoites)Internal budding Endopolyogony (compare to schizogony). A special case is endodyogony which results in 2 cells (Toxoplasma)AsexualSexual Conjugation

8、by conjugating and exchanging nuclear materials of 2 organisms and then separating into new individuals (Balantidium coli), only nuclei unite. Gametogony The process of producing gamets. This is followed by sexually differentiated cells uniting, resulting in zygote (Plasmodia), both cytoplasm and nu

9、clei unite. 第8頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Mode of reproductionAlternation of generations: parasites reproduce by alternatively going through asexual and sexual means, e.g. in Plasmodium, including asexual mode (schizogony) in human liver cells and red blood cells and sexual mode (gametogony) in mos

10、quitoes.第9頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Life cycle patternsTwo-host form Mammals mammals, e.g. ToxoplasmaMammals vector arthropods, e.g. Plasmodium One-host formOne stage form Trophozoite, e.g. Trichomonas vaginalisTwo-stage forms Trophozoite & Cyst, e.g. Amoeba第10頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Charact

11、eristics of Protozoan Infections*In-host proliferation parasitism*No larva and adult differentiation but stage differences (e.g. trophozoite, cyst)*May be intracellular lodgment (e.g. Plasmodium in hepatocytes or red blood cells; Leishmania in macrophages)*Opportunistic infection (the immune-comprom

12、ised host, e.g. AIDS patients who are easily infected by some protozoa, e.g. Pneumocystis, that are harmless to normal hosts, and develop severe symptoms, and may result in death.)第11頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Important medical protozoaIncluding four classes:Zoomastigophorea: The class (the flagel

13、lates), has one or more whip-like flagella and in some case, an undulating membrane (e.g. Trichomonas). These include intestinal and genitourinary flagellates (Giardia, Trichomonas), and blood and tissue flagellates (Trypanosoma, Leishmania).Being classified into three phyla: Sarcomastigophora: e.g.

14、 flagellates and amoebae Apicomplexa: Sporozoa ( e.g. Plasmodium) Ciliophora: ciliates (e.g. Balantidium coli)第12頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Lobosea : The class includes Entamoeba, Naegleria, Acanthamoeba. Sporozoa: The class includes Isospora, Toxoplasma, Cryptosporidium, Plasmodium species, Babas

15、ia species, Pneumocystis. Kinetofragminophorea(動(dòng)基裂綱): The class includes Balantidium coli. Classification第13頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Medically important protozoa: 1. Amoebae 2. Flagellates 3. Sporozoa 4. Ciliates第14頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三1. MorphologyProtozoan is a single cell eukaryotic a

16、nimal with all necessary basic physiological functions that it needs. Medical protozoa mean pathogenic or nonpathogenic ones which live in human body, having more than 40 species with a range of about 2-200m in size and with round, oval or irregular shape. The basic structure of protozoa is made up

17、of cell membrane, cytoplasm and nucleus. Functionally, the protozoas organelles can be divided into three types, i.e. cytoplasm organelles, nutrition organelles and locomotive organelles which mainly include pseudopodium, flagellum and cilium. The protozoa have two types of nuclei: vesicular nucleus

18、 and parenchymatous nucleus.Main points of the section concerning introduction to medical protozoa第15頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三2. Life cycleProtozoa have two kinds of reproductive ways, asexual and sexual, in their life cycle. The asexual reproduction includes binary fission, multiple fission and

19、 budding (budding fission), and gametogony and conjugation are involved in the sexual reproduction. The life cycle of protozoa has three types, including interpersonal propagating type, circulation propagating type and vector-mediated spreading type. 3. PathogenesisThe medical protozoa can cause dis

20、eases by the following ways that include breaking, pressing, blocking, diffusing, etc. In recent years, the pathogenesis caused by opportunistic protozoa such as Pneumocystis, Cryptosporidium and Toxoplasma, etc. is already paid close attention.Main points of the section concerning introduction to m

21、edical protozoa第16頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三LoboseaAmoeba第17頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Amoebae in HumanEntamoebaE. histolytica (pathogenic)E. disparE. coliE. hartmani E. gingivalis (oral)Endolimax nanaIodamoeba butschlii第18頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Free-living amoebaePathogenic free-living A

22、moebae: Naegleria Acanthamoeba第19頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Entamoeba histolyticaGerman zoologist Schaudinn correctlydescribed the trophozoites and cysts of E.histolytica in 1903. Schaudinn died at the age of 35 (1871-1906) ofoverwhelming amoebiasis, as a result of selftesting with this pathogen.

23、Entamoeba dispar Brumpt, 1925第20頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三E. histolytica is a medical important pathogen1. Intestinal amoebiasis: Amoebic dysentery Amoebic colitis2. Extra-intestinal amoebiasis: Amoebic abscess & UlcersCause amoebiasis:第21頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Medical importance4th leading

24、 cause of deaths from parasitic diseases worldwideOrganism# of deaths/yr# infectedEntamoeba 40,000100,000300 millionAscaris 200,000 480 millionSchistosoma750,000 200 millionPlasmodium2-3 million 500 million(Malaria)第22頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Contaminated water is a source of infection.第23頁(yè),共132

25、頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Infection is common in developing countries where sanitation is poor.第24頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Morphology of E. histolyticaIngested RBCNucleus with central karyosome and finely divided peripheral chromatinPseudopodTrophozoiteEctoplasmEndoplasm第25頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分

26、,星期三Trophozoites of E. histolyticaSingle nucleus with a central, dot-like karyosome第26頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三1-4 ring-like nucleiwith finely divided peripheral chromatinCyst wall and round shapeMature E. histolytica Cyst (quadrinucleate cyst)Morphology of E. histolytica第27頁(yè),共132頁(yè),2022年,5月20日,1

27、9點(diǎn)2分,星期三Cysts of E. histolyticaChromatoidal bodyChromatoidal bodyGlycogen vacuole第28頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三These photographs taken at an interval of 4 seconds illustrate stepwise the process of phagocytosis (starch granule) in Entamoeba. Phase contrast 1000Phagocytosis and motivationstarch gra

28、nule第29頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Micrograph of a trophozoite ingesting a red blood cell derived from its host.UroidRBC第30頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Morphologic comparison oftrophozoite and cyst(Eh)第31頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三E. coli trophozoite NucleusCytoplasmaKaryosomeEhEc第32頁(yè),共132頁(yè),2022年

29、,5月20日,19點(diǎn)2分,星期三E. Coli cystsEcEh第33頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Life cycle Basic form:Reproduction in human intestineCyst Lumen Trophozoite Cyst 第34頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三1. The life cycle of E. histolytica is comparatively simple, and includes a cyst stage and a multiplying trophozoite stage

30、. As the cyst matures, the number of nuclei changes from one to four, and this is the infective form.The cysts are ingested with contaminated food or water and they pass through the stomach and intestine. The mature cysts, which are resistant to acidic digestive juices of the stomach, pass to lower

31、part of the small intestine. In the alkaline medium of the caecum or lower part of the small intestine, the cyst wall is damaged by neutral or alkaline digestive juices or trypsin, liberating four-nucleated trophozoite that undergoes three rounds of cytokinesis and one round of nuclear division into

32、 eight metacystic trophozoites.Main points of the life cycle of Entamoeba histolytica第35頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三3. The trophozoites ingest bacteria and multiply by binary fission while moving downward to the colon, where they respond to unknown stimuli and develop into precystic form and re-enc

33、yst. The trophozoites are responsible for clinical syndromes, ranging from classical dysentery to extraintestinal diseases. 4. Cysts are evacuated periodically into the stool, completing their development cycle, and are discharged into environment. Cysts remain viable and infective for several days

34、in feces and water, but can be easily killed by desiccation.Main points of the life cycle of Entamoeba histolytica第36頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三PathogenesisFactors that determine invasion of amoebas:Factors favor parasites invasivenessthe number of amoebae ingested, the pathogenic capacity of the

35、parasite strain pathogenic & non-pathogenic species (E. dispar)host factors such as gut motility and immune competence, the presence of suitable enteric bacteria that enhance amoebic growth.第37頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Pathogenesis (cont.)General types of virulence factors and the course of invas

36、ionAdherence factors: surface lectin, 260 kDa galactose/N-acetyl-O-galactosamine (Gal/gal NAC) mediates adherence amoeba trophozoite to the intestinal mucosa Amoebapores : form pores in host cell membranesInvasion factors: cysteine proteinases are cytopathic for host tissue, resulting in degradation

37、 of mucosal membrane of the colon第38頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Pathogenesis (cont.)The lesion caused by trophozoites :Trophozoites attach to mucosal epithelial cells (MEC) Lyse MEC Ulcerate and invade mucosa Cause dysentery (diarrhea + blood)Metastasize via blood &/or lymph to form abscesses in ex

38、tra intestinal sites ( e.g. liver, brain, lung).第39頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Clinical Classification of Amoebiasis (World Health Organization) Asymptomatic (intestinal) Cyst Passers” Symptomatic Infection:Extra-intestinal Amoebiasis:Amoebic liver abscess (ALA)Amoebic pulmonary abscess Other sites

39、 (brain, skin) Intestinal Amoebiasis: (colon and rectum)Acute Dysenteric (dysentery)Chronic Non-Dysenteric (“self-cured”)第40頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Asymptomatic Amoebiasis Cyst Passers”Most commonInfection may continue without clinical symptoms for weeks to months .Cause: it may spontaneously r

40、esolve (self cure) orTwo species of Entamoeba may existE. dispar (non-pathogenic)E. histolytica (pathogenic)第41頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Intestinal AmoebiasisTwo typesAcute dysenteric (dysentery)Chronic non-dysenteric (“self-cured” or carrier state)第42頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Acute Dysenteric

41、 AmoebiasisAmoebic DysenterySymptoms:Bloody mucoid diarrheaRBCs and few WBCs in stoolsAbdominal pain weight loss Bloating, *tenesmus and cramps*After bowel movements one still want bowel movements, but there is no stool to be excreted. A painfully urgent but ineffectual attempt to urinate or defecat

42、e. 第43頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Amoebic DysenterySigns:Fever (33%)Tender (enlarged) liverIn liquid stools, positive for trophozoites,No cysts.第44頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Amoebic DysenteryNormal mucosa except for .Adherent pseudomembrane overlying the ulcers, but classic “Flask-Shaped” ulcer c

43、an be rarely seenSub-mucosal involvement is rare with early treatmentSigmoidoscopic (乙狀結(jié)腸鏡) appearance:第45頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三 Flask-shaped ulcer in the large intestine of amoebiasis patient第46頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Chronic Non-Dysenteric Amoebiasis:“self-cured” carrier state37% sympt

44、omatic, 5 yearsSymptoms and signs:Intermittent diarrhea with mucus, abdominal pain, flatulence (腸胃脹氣)and/or weight lossNo E. histolytica trophozoites (rarely cysts) in semi-formed or formed stoolsPositive serology and ulcerations 第47頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Extra-Intestinal AmoebiasisA. Hepatic

45、amoebiasis (Amoebic liver abscess)B. Cutaneous amoebiasisC. Amoebic lung abscess D. Amoebic brain abscess From the ulcer, the amoebae may enter blood vessels and be carried to liver, via hepatic portal system to other organs, such as lung, skin, or even brain, etc. to form the abscesses as following

46、s:第48頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Amoebic Liver Abscess (ALA)SymptomsSignsHistory of dysentery, weight loss, abdominal pain, chest or (right) shoulder pain fever, hepatomegalyDiagnostic aspiration: non-odorous, reddish-brown in color aspirate (chocolate jam) not commonSkin inflammation第49頁(yè),共132頁(yè),202

47、2年,5月20日,19點(diǎn)2分,星期三Ulcers caused by invasion of E. histolytica into the liver第50頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Pathologic sample of a human amoebic liver abscessThe pathological sample of ahuman amoebic liver abscess第51頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三 A patient with amoebic liver abscessThe patient with l

48、iver abscess Shows skin inflammation reaction (skin ulceration). 第52頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三X-ray of Amoebic Liver Abscess 第53頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Stool examination: Direct Fecal Smear: trophozoites (using normal saline) and cysts (using iodine staining)Sigmoidoscopy Imaging: X-ray; CT

49、Serologic Tests (for chronic disease): ELISA, IHA (indirect hemagglutination)Diagnosis of Intestinal AmoebiasisTechniques:Fecal concentration techniques - (cysts) ZnSO4 (Zinc sulfate) or formalin-ether sedimentationCultivation in medium第54頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Molecular diagnosis: PCR第55頁(yè),共13

50、2頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Laboratory Diagnosis of Hepatic AmoebiasisExamine stools for trophozoites/cysts (suggestive)Blood cell counts - leukocytosis?Radiologic Studies (X-ray, CT)Serologic tests (IHA or ELISA), Liver enzyme profile is usually normalCatheterize(將導(dǎo)管插入)abscess and aspirate: Examine red

51、dish-brown aspirate for trophozoites and do serologic testing for amoebic antigensCulture trophozoites in aspirate Chemotherapeutic Trial第56頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Treatment of Amoebiasis第57頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Prevention/Control of AmoebiasisDiagnosis and treatment of E. histolytica pa

52、tientsanimal reservoirs (other than humans) are known? (dog, cat, pig and monkey can be infected by E. histolytica, but there are some differences in shape in animals from that in human.)Safe drinking water (boiling or 0.22 m filtration)Cleaning of uncooked fruits and vegetablesPrevention of contami

53、nation of foodsIndividual measures:第58頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Prevention/Control of Amoebiasis Public services and utilitiesAdequate disposal of human stoolsSafe and adequate water supplyPrimary health care systemsHealth education (washing hands, cleaning and protecting food, controlling insect

54、s)Specific surveillance programs and control programs integrated into ongoing sanitation & diarrhea controlHealth RegulationsControl of food vendors and food handlersControl of flies and cockroachesCommunity measures:第59頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三1. Morphology and life cycleThe development stages

55、of E. histolytica in the feces include the trophozoite, precyst (transitional form), and cyst. The trophozoite has a wide, clear, refractile, hyaline ectoplasm, sharply separated from the endoplasm. Locomotion of the trophozoite depends on a single well-defined pseudopodium, extending rapidly, witho

56、ut clear differentiation between ectoplasm and endoplasm. The cyst is ingested with feces-contaminated food or water and passes through the stomach and intestine. The trophozoite emerges in the terminal ileum or as the cyst forms in the lumen of the large intestine, passes out in the feces, and is i

57、mmediately infective when the cyst has developed to maturity. Cysts are evacuated periodically into the stool, completing their development cycle, and discharged into the environment. Humans are the host for E. histolytica and can transmit the infection to other humans, primates and so on. Main poin

58、ts of the section concerning Entamoeba histolytica第60頁(yè),共132頁(yè),2022年,5月20日,19點(diǎn)2分,星期三Ingestion of the quadrinucleate cyst of E. histolytica from fecally contaminated food or water initiates infection. In the caecum or lower ileum, the cyst wall is damaged by trypsin, leading to excystation. Excystation

59、 in the intestinal lumen produces trophozoites. In invasive amoebiasis, trophozoites are responsible for the clinical syndrome, ranging from classical dysentery to extraintestinal disease, and they have the capacity to destroy almost all the tissues of human body. Several virulence factors contribut

60、e to pathogenesis of this parasite. Three pathogenic factors have been extensively studied and characterized at the molecular level, the galactose/N-acetyl-O-galactosamine (Gal/GalNAc) lectin that mediates adherence to host target cells, the amoebapores that form pores in host cell membranes, and th

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