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1、109-A13,重症熱性血小板減少症候群 SFTS: severe fever with thrombocytopenia syndrome SFTS：Bunyaviridae科Phlebovirus属 媒介 四類感染症,March to July 2009, Emerging infectious disease identified as the severe fever with thrombocytopenia syndrome (SFTS) in rural central China. Cause was unknown. Major clinical symptoms inclu
2、ded fever, thrombocytopenia, gastrointestinal symptoms, and leukocytopenia; high initial case fatality rate of 30%,Multi-organ failure developed RAPIDLYelevated serum alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehyrogenase; proteinuria, hematuria.,From Dr. OCallag
3、han Virology Journal Club April 29, 2011,Genus Human disease Orthobunyavirus La Crosse encephalitis, California encephalitis Phlebovirus Rift Valley fever (RVF) Nairovirus Crimean-Congo hemorrhagic fever (CCHF) Hantavirus Hemorrhagic fever with renal syndrome (HFRS) Hantavirus pulmonary syndrome (HP
4、S) Tospovirus Plant virus, no known human disease,5 genera,Family Bunyaviridae,Encephalitis,Hemorrhagic Fever,Pneumonia,Dr. OCallaghan Journal Club 4/20/12,From Dr. OCallaghan Virology Journal Club April 29, 2011,thrips,These leaves show symptoms of tomato spotted leaf virus. / Kathie Rowell/The Tim
5、es May 12, 2011,109-A38,血球貪食症候群 Hemophagocytic syndrome （HPS) 血球貪食性組織球症 Hemophagocytic lymphohistiocytosis (HLH) EBV関連血球貪食症候群 EBV-associated hemophacotytic syndrome EBV感染T細胞増殖、大量分泌、活性化分泌血球貪食起 標準微生物学 第12版 423,Familial hemophagocytic lymphohistiocytosis (FHL or FHLH) is caused by an inherited deficien
6、cy of perforin Hemophagocytosis: ingestion of red blood cells by macrophages Pfp-/- mice infected with some types of viruses result in a disease similar to FHL because the immune system is uncontrolled demonstrates that perforin plays an important role in regulating the immune response Hemophagocyti
7、c lymphohistiocytosis (HLH) =Hemophagocytic syndrome (HPS) =Macrophage activation syndrome,Some deficiencies can lead to lymphoproliferative diseases (Table 4.2),In FHL, mutations prevent NK cells and cytotoxic T cells from releasing their cytoplasmic granules, which leads to uncontrolled proliferat
8、ion of lymphocytes and macrophages These cells phagocytose blood cells and release huge amounts of proinflammatory cytokines Cytokine burst explains the inflammation, fever and systemic illness T cell and macrophage infiltration in liver, spleen, lymph nodes, bone marrow, and central nervous system
9、T cells and macrophages respond strongly to microbes to compensate for the CTL and NK cell defects?,Anemia Thrombocytopenia Hemophagocytosis in bone marrow, spleen, lymph node Increased cytokine release: interferon-, TNF, IL-6, IL-10, macrophage colony-stimulating factor (M-CSF) Treatment: control t
10、he cytokine burst by chemotherapy and immunotherapy with etoposide, corticosteroids and cyclosporine, followed by bone marrow transplantation,Hemophagocytic lymphohistiocytosis (HLH) Hemophagocytic syndrome (HPS),Familial hemophagocytic lymphohistiocytosis (FHL or FHLH) (Table 4.2) FHL1: unidentifie
11、d gene on chromosome 9 FHL2: perforin (PRF1) mutation FHL3: Munc13-4 (UNC13D) mutation FHL4: syntaxin 11 (STX11) mutation FHL5: syntaxin binding protein (STXBP) 2 (Munc 18-2) mutation All four proteins are involved in the granule-mediated cytotoxic pathway of lymphocytes Immune deficiency syndromes
12、(Table 4.1) Chediak-Higashi syndrome 1: LYST (=CHS1) mutation Griscelli syndrome 2: RAB27A mutation LYST and RAB27A: role in vesicle trafficking in CTL X-linked lymphoproliferative syndrome: SH2D1A mutation NK cell inhibition leads to severe EB virus infection and sustained proliferation of CTL (Tab
13、le 4.3a),Genetic hemophagocytic lymphohistiocytosis =primary hemophagocytic syndrome,A defect in LYST (=CHS1), which is involved in intracelluar vesicle formation and trafficking Reported by Moises Chediak (1954) and Ototaka Higashi (1956) A failure of lysosomes and phagosomes to fuse properly Phago
14、cytes have enlarged granules and impaired intracellular killing ability Partial albinism, abnormal platelet function, severe immunodeficiency,Chediak-Higashi syndrome,Ototaka Higashi, 東音高,http:/www.nurs.or.jp/academy/igaku/t1/t1241.htm,http:/www.jpeds.or.jp/saisin/saisin_100604.html,109-A60 含声,muffl
15、ed voice, hot potato voice 、手口押声 奥声出 急性喉頭蓋炎、扁桃周囲膿瘍,https:/ 慢性肉芽腫症 Chronic granulomatous disease (CGD),Primary Immunodeficiency Expert Committee http:/www.iuisonline.org/iuis/index.php/primary-immunodeficiency-expert-committee.html,MSMD: Mendelian susceptibility to mycobacterial disease,5. Congenital
16、 defects of phagocytes,Immunodeficiencies of phagocytic cells,Myeloid deficiencies primarily affect the innate immune system Phagocyte immunodeficiencies can be grouped into 4 types: Deficiency in Phagocyte production: Development defect in gene required for myeloid progenitor cell differentiation P
17、hagocyte adhesion Phagocyte activation: Phagocytosis Killing,Defects in phagocytic cells are associated with persistence of bacterial infection,5.3: Defects of respiratory burst,6.2, 6.3: IRAK4, MyD88 deficiency,5.2: Defects of motility,5.1: Defects of neutrophil differentiation,Table 4.1: Immunodef
18、iciency with hypopigmentation,The most significant problem is the inability of cells to attach to the vascular endothelium and migrate to sites of inflammation LAD type 1 (LAD-1): deficient expression of 2 integrins due to CD18 gene mutations LAD type 2 (LAD-2): absence of sialyl Lewis X: ligand on
19、neutrophils required for binding to E-selectin and P-selectin on endothelium Caused by fucose transporter gene mutation: the failure to transport fucose into the Golgi complex results in failure to synthesize sialyl Lewis X LAD type 3, deficiency of Kindlin-3, required for firm adhesion,Leukocyte ad
20、hesion deficiency (LAD) (Table 5.2),Leukocyte adhesion deficiency (LAD) results from mutation in the CD18 molecule the b2 chain of the integrin family The result is a loss of surface expression of key integrin molecules: Abnormal functions: endothelium adherence, neutrophil chemotaxis, phagocytosis,
21、 cytotoxicity,LAD type 1,Mac-1 p150:95,109-D4,解答：d. 落葉状天疱瘡 選択肢：e. 疱疹状皮膚炎 dermatitis herpetiformis 無関係 過敏腸症,Celiac disease (Celiac sprue gluten sensitive enteropathy),Chronic small intestinal immune-mediated enteropathy precipitated to dietary gluten A common cause of malabsorption in Caucasians In t
22、he US, estimated incidence: 1:113 Onset; from the first year through the eight decade Diarrhea, steatorrhea, weight loss, consequence of nutrient depletion (anemia and metabolic bone disease) Gliadin, a component of gluten (wheat, barley, rye) Serum antibodies: antigliadin IgA, anti-transglutaminase
23、 IgA HLA-DQ2 allele present in 80-95% of patients; HLA-DQ8 Associated with dermatitis herpetiformis (IgA deposition in the skin), diabetes mellitus type I, thyroiditis, IgA deficiency Enteropathy-associated T-cell lymphoma,After gluten-free diet,Dermatitis herpetiformis,Skin IgA deposition,A multisy
24、stem disease resulting from an autoimmune reaction to infection with group A streptococci Almost all of the manifestations in many parts of the body resolve completely Exception is cardiac valvular damage: rheumatic heart disease (RHD) Disease of poverty: less crowded housing and better hygiene resu
25、lted in reduced transmission of group A streptococci + antibiotics and improved medical care,109-D14 急性熱 Acute rheumatic fever (ARF),http:/ Online,Molecular mimicry in rheumatic fever,RHD :rheumatic heart disease,Streptococcal M protein are immunologically similar to myosin, tropomyosin, keratin, ac
26、tin, laminin, vimentin, and N-acetylflucosamine Antibodies that recognize cardiac myosin in the myocardium also recognize the valve endothelium and laminin Once disease has become chronic in the valve, other proteins in the valve such as laminin, vimentin, collagen and others may be presented to the
27、 immune system and epitope spreading would be predicted to occur,12-4 Epitope (determinant) spreading,In animals, autoimmune disease can be generated by immunizing autoantigen (protein X) in adjuvant First response is dominated by T cell response to one peptide derived from protein X Later, tissue d
28、amage release protein X and other self proteins (protein Y) Further activate T cell responses to proteins X and Y Example: 12-7 Experimental allergic encephalomyelitis (EAE), animal model for multiple sclerosis,Self-antigen is released from damaged tissue can be taken up by antigen presenting cells
29、(APCs), processed and presented to autoreactive T cells Further tissue destruction by activated T cells causes the release of more self-antigen from tissues The response can then spread to involve T cells (or antibodies) specific for other self-antigens in a process known as epitope spreading,Epitop
30、e spreading,109-D44 Mumps 急性耳下腺炎,Mumps,Child with parotitis (CDC web site: http:/www.cdc.gov/mumps/about/photos.html) Mumps causes salivary gland swelling, particularly the parotid gland,Mumps; “Otafuku” in Japanese Otafuku, Japanese mask(“fuku” = swelling),109-D49 項部硬直 髄膜炎,Viral Meningitis vs. Ence
31、phalitis,Viral Meningitis (Enteroviruses, HIV, HSV type 2, Arboviruses) Headache Stiff neck Photophobia Little alteration in consciousness No focal signs,Viral Encephalitis (HSV, Arboviruses, Rabies, Nipah virus) Altered consciousness Focal neurological signs Seizures Meningeal signs,Dr. John E. Gre
32、enlee, MD, University of Utah,https:/ 慢性炎症性脱髄性多発根神経炎,109-E52 ,Paramyxoviridae Human Diseases,Family includes numerous human disease-causing members: PaRaMyxovirus: Parainfluenza, Respiratory syncytial virus, Rubeola (Measles), Mumps Subfamily Paramyxovirinae Morbillivirus (measles) fever, cough, con
33、junctivitis leading to macropapular rash; can be fatal; Subacute sclerosing panencephalitis (SSPE) Rubulavirus (mumps) fever leading to salivary (parotid) gland swelling; can be testicular and central nervous system (CNS) involvement; occasionally fatal Rubulavirus (human parainfluenza virus 2/4a/4b
34、) acute respiratory tract disease; fever leading to bronchitis and possibly pneumonia Respirovirus (human parainfluenza virus 1/3) acute respiratory tract disease; fever leading to bronchitis and possibly pneumonia; “croup” in infants 6 mos.,Croup,http:/ 急性喉頭蓋炎：選択肢,正常,2016年近畿大学年 寺田徹,109-F13 選択肢：手足口病
35、,Hand, foot and mouth disease (HFMD),Vesicular lesions on the hands, feet, mouth, and tongue Occurs in children Caused by enteroviruses, including coxsackievirus A16, 10, and enterovirus 71 Mildly febrile, and the illness subsides in a few days,http:/pathmicro.med.sc.edu/virol/picorna.htm,Coxsackiev
36、irus,The first strains were isolated from two paralyzed boys in the village of Coxsackie, New York Meningitis and encephalitis Myocarditis,Aphtho: from Greek aphtha, “vesicles in the mouth“; English: aphtho, “thrush” Entero: from Greek enteron, “intestine” Hepato: from Greek hepatos, “liver“ Kobu: f
37、rom Japanese Kobu “hump or knob“ Rhino: from Greek rhis, rhinos, “nose“,The two original human rhinovirus species have been moved to the genus Enterovirus; the genus Rhinovirus no longer exists.,Whitton et al., Nature Reviews Microbiology 2005 v. 3 p. 765,Genus Aphthovirus Type species: Foot-and-mou
38、th disease virus (FMDV) Infect cloven-hoofed animals (cattle, goats, pigs, sheep) Rarely infect humans 7 serotypes, each with subtypes Lose infectivity at low pH values of less than 6.8,The “type species”: the virus initially necessitated the creation of the genus and best defines or identifies the
39、genus,Picornavirus pathogenesis,The target tissue infected by the virus determines the predominant disease caused by the virus.,Coxsackie; coxsackievirus echo; echovirus; HAV; hepatitis A virus polio; poliovirus rhino; rhinovirus.,109-I67 SSPE 亜急性硬化性全脳炎,ADEM, acute disseminated encephalomyelitis MIB
40、E; measles inclusion body encephalitis,ADEM, demyelination; MIBE; inclusion body and viral antigen,Subacute,Chronic,Acute,SSPE, subacute sclerosing panencephalitis,Occurs years or decades after an initial measles infection 0.4 to 9.7 per million patients with measles Mutations in the M protein Clona
41、l expansion of the mutated virus within the brain M protein is not produced, no budding Cell fusion by the F and H proteins is maintained, allowing the virus to spread within the brain by local cell fusion; virus evades the immune system, anti-virus antibodies other than M protein,Brain atrophy, gli
42、osis and mononuclear cell infiltration, and rarefied and gliotic white matter,gliosis + osis, condition: proliferation of astrocytes= scar in the CNS.,A rare disease in the US, with fewer than 10 cases per year, since the introduction of measles vaccine (0.4 to 9.7 per million patients with measles)
43、 Most patients had their measles infection prior to the age of 2 years the onset of disease occurs between the ages of 5 to 15 years in 85% of patients The disease usually begins with poor school performance, personality changes and then dementia (stage I). Myoclonus, seizures, and movement disorder
44、s occur in stage II. Eventually the comatose and akinetic mutism stages ensue (stage III and IV). Death usually occurs in 1 to 3 years (subacute).,Myoclonus in SSPE,A pediatric patient with progressively developing degenerative neurologic disease/disorder has an elevated CSF antibody titer to measle
45、s virus. You should suspect which of the following? Acute Lyme disease Fifth disease Possible hepatitis B infection Possible subacute sclerosing panencephalitis (SSPE) Susceptibility to chicken pox Answer (D),伝染性紅斑 =Erythema infectiosum =fifth disease,109-I68 目,Cytomegalic cells,Inclusion bodies kno
46、wn as “owl eye” inclusions,Cytomegalovirus (CMV) encephalitis,109-I69 病,Sporadic Creutzfeldt-Jakob disease,The most common human prion disorder 1 in 1 million per year 85% of all cases of human prion disease Age of patients: ave. 65 years Time between disease onset and death: 2.5 6 months,Age of dea
47、th in sporadic CJD. Most cases in the seventh decade of life. Uncommon under the age of 40 years,Laboratory tests of CJD,The electroencephalogram (EEG): 60% to 95% of patients have periodic synchronous discharge (PSD) occurring on the average of one per second The stress protein, 14-3-3, elevated in
48、 85% of sporadic CJD CSF samples MRI: 90% of patients show increased intensity in the basal ganglia and cortical ribboning,MRI of Creutzfeldt-Jakob disease,striatal lesions (A), cerebral cortical lesions (B), a combination of both lesions (C),Dorsomedial and pulvinar thalamic hyper intensity “hockey stick sign” in variant CJD,