Transcript Obligate anaerobes

109-A10
http://www.usmle-forums.com/usmle-step-1-bits-pieces/1702-aerobes-anaerobes.html
(Anaerobes)
These are microorganisms that can live without oxygen.
Facultative anaerobes can live without oxygen but they use it if it available. Most of the bacteria we
know falls in the facultative anaerobes category (e.g E. Coli).
Obligate anaerobes are harmed by the presence of oxygen and these usually utilize fermentation to
produce their necessary ATP.
Examples of obligate anaerobes:
Actinomyces
Bacteroides
Clostridium
Good way to remember these is ABC
Yet, there's another sub category of anaerobes and these are called aerotolerant anaerobes. These
bugs unlike the obligate ones, are not harmed in the presence of oxygen.
Examples of aerotolerant anaerobes:
Propionibacterium and Lactobacillus (both are normal human flora)
(Aerobes)
Obligate aerobes require oxygen to in order to oxidize nutrients and they usually have catalase and
superoxide mutase. They cannot survive without oxygen.
Examples of obligate aerobes:
Nocardia
Pseudomonoa (remember aerogenosa)
Mycobacterium
Bacillus
A good mnemonic to remember these is Nagging Pets Must Breath
Microaerophilics are those organisms that may use oxygen but only when it's in low concentrations
and the two most commonly tested bugs in this category is Campylobacter and Helicobacter (both of
which are GI bugs).
109-A13
• 重症熱性血小板減少症候群
• SFTS: severe fever with thrombocytopenia
syndrome
• SFTSウイルス：Bunyaviridae科Phlebovirus属
• マダニ媒介
• 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 included fever,
thrombocytopenia, gastrointestinal symptoms, and
leukocytopenia; high initial case fatality rate of 30%
•Multi-organ failure developed RAPIDLY—elevated serum
alanine aminotransferase, aspartate aminotransferase,
creatine kinase, lactate dehyrogenase; proteinuria, hematuria.
From Dr. O’Callaghan Virology Journal Club April 29, 2011
Family Bunyaviridae
5 genera
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 (HPS)
Tospovirus
Plant virus, no known human disease
Encephalitis
Hemorrhagic
Fever
Pneumonia
BUNYAVIRIDAE; Bunyamwera in Uganda
Virion:
ENV, 120nm; 3 Helical capsids; three 1X RNAs
California
Sin Nombre
CCHF
5 Genera. 2 genera
have ambisense
RNAs; Phelbovirus
& Tospovirus
Rift Valley
S+M RNAs = ambi
Tospovirus genus = tomato spotted wilt virus
M&S
RNAs are ambisense. NSm 34K protein = movement. Forms tubules
that penetrate thru plasmadesmata so capsids can enter neighboring
cell. NSs 52K protein binds 2X RNA that can generate siRNAs .
Transmitted by THIRPS
Infects tomato, peanuts, watermelon, zucchini, impatiens
Dr. O’Callaghan Journal Club 4/20/12
Hantavirus (HFRS contact with rodents)
Nairovirus (CCHF-tick)
Orthobunyavirus (LAC mosquito)
Phlebovirus (Rift Valley Fever; mosquito)
Tospovirus (Tomato spotted wilt ; thrips)
thrips
PHLEBOVIRUS: 68 serotypes.
Two Groups:
1. Phlebotomus Fever Group 55 (sandflies)
2. Uukuniemi Group 13 (ticks)
Eight members linked to disease humans
Alenquer
Punta Toro
Chaniru
Rift Valley Fever
Chagres
Sicilian
Naples
Toscana
These leaves show
symptoms of tomato
spotted leaf virus. /
Kathie Rowell/The Times
May 12, 2011
SFTS Virus is new GROUP of PHLBOVIRUS Genus.
9th Phlebovirus to cause disease in humans
From Dr. O’Callaghan Virology Journal Club April 29, 2011
109-A38
• 血球貪食症候群 Hemophagocytic syndrome （
HPS)
• 血球貪食性リンパ組織球症 Hemophagocytic
lymphohistiocytosis (HLH)
• EBV関連血球貪食症候群 EBV-associated
hemophacotytic syndrome
– EBVに感染したT細胞が増殖し、大量のサイトカインを
分泌、これによって活性化したマクロファージがサイトカ
インの分泌や血球を貪食して起こす
– 標準微生物学 第12版 ｐ423
Some deficiencies can lead to
lymphoproliferative diseases (Table 4.2)
•Familial hemophagocytic lymphohistiocytosis (FHL or FHLH) is caused by an
inherited deficiency 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
•Hemophagocytic lymphohistiocytosis (HLH)
=Hemophagocytic syndrome (HPS)
=Macrophage activation syndrome
•
In FHL, mutations prevent NK cells and
cytotoxic T cells from releasing their
cytoplasmic granules, which leads to
uncontrolled proliferation 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
•
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-γ,
TNF, IL-6, IL-10,
macrophage colonystimulating factor (MCSF)
Treatment: control the
cytokine burst by
chemotherapy and
immunotherapy with
etoposide,
corticosteroids and
cyclosporine, followed
by bone marrow
transplantation
Hemophagocytic lymphohistiocytosis (HLH)
Hemophagocytic syndrome (HPS)
Genetic hemophagocytic lymphohistiocytosis
=primary hemophagocytic syndrome
Familial hemophagocytic lymphohistiocytosis (FHL or FHLH) (Table 4.2)
FHL1: unidentified 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 (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 (Table 4.3a)
Chediak-Higashi 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
•Phagocytes have enlarged granules and impaired intracellular killing ability
•Partial albinism, abnormal platelet function, severe immunodeficiency
http://www.jpeds.or.jp/saisin/saisin_100604.html
http://www.nurs.or.jp/~academy/igaku/t1/t1241.htm
Ototaka Higashi, 東音高
109-A60 含み声
•
•
•
•
muffled voice, hot potato voice
くぐもったような、手で口を押さえてしゃべったときのような声
のどの奥からうるんだようなような声がれが出ること
急性喉頭蓋炎、扁桃周囲膿瘍など
https://www.youtube.com/wat
ch?v=96n_nrgBV44
109-B16
• 原発性免疫不全症
• 慢性肉芽腫症 Chronic granulomatous disease
(CGD)
Primary Immunodeficiency Expert Committee
http://www.iuisonline.org/iuis/index.php/primary-immunodeficiency-expertcommittee.html
5. Congenital defects of
phagocytes
MSMD: Mendelian
susceptibility to
mycobacterial disease
Immunodeficiencies of phagocytic cells
Myeloid deficiencies primarily affect the innate immune system
Phagocyte immunodeficiencies can be grouped into 4 types: Deficiency in
1. Phagocyte production: Development – defect in gene
required for myeloid progenitor cell differentiation
2. Phagocyte adhesion
3. Phagocyte activation: Phagocytosis
4. Killing
Defects in phagocytic cells are associated with
persistence of bacterial infection
5.1: Defects of
neutrophil
differentiation
5.2: Defects of
motility
6.2, 6.3: IRAK4,
MyD88 deficiency
5.3: Defects of
respiratory burst
Table 4.1: Immunodeficiency with
hypopigmentation
Leukocyte adhesion deficiency (LAD) (Table 5.2)
•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 β2 integrins due to CD18 gene mutations
•LAD type 2 (LAD-2): absence of sialyl Lewis X: ligand on neutrophils required for binding to Eselectin 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
LAD type 1
•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, cytotoxicity
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
– ヘルペスウイルスとは無関係
– グルテン過敏腸症
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 the 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 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
Skin IgA deposition
Dermatitis herpetiformis
109-D14
急性リウマチ熱
Acute rheumatic fever (ARF)
 A multisystem 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 resulted
in reduced transmission of group A streptococci + antibiotics and
improved medical care
Harrison’s Online
http://www.accessmedicine.com/content.aspx?aID=2881862
Molecular mimicry in rheumatic fever
RHD :rheumatic
heart disease
•Streptococcal M protein are immunologically similar to myosin, tropomyosin, keratin, actin, 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 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 damage 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
Epitope spreading
 Self-antigen is released from damaged
tissue can be taken up by antigen
presenting cells (APCs), processed
and presented to autoreactive T cells
 Further tissue destruction by activated
T cells causes the release of more selfantigen 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
109-D44
Mumps
急性耳下腺炎
Mumps
Child with parotitis (CDC web site:
http://www.cdc.gov/mumps/about/photos.h
tml)
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. Encephalitis
Viral Meningitis
Viral Encephalitis
(Enteroviruses, HIV, HSV type
2, Arboviruses)
• Headache
• Stiff neck
• Photophobia
• Little alteration in
consciousness
• No focal signs
(HSV, Arboviruses, Rabies,
Nipah virus)
•
•
•
•
Altered consciousness
Focal neurological signs
Seizures
Meningeal signs
Dr. John E. Greenlee, MD,
University of Utah
https://www.youtube.com/watc
h?v=bj2CNkjvY4o
109-E50
慢性炎症性脱髄性多発根神経炎
109-E52
クループ
Paramyxoviridae Human Diseases
Family includes numerous human disease-causing members:
PaRaMyxovirus: Parainfluenza, Respiratory syncytial virus, Rubeola
(Measles), Mumps
Subfamily Paramyxovirinae
• Morbillivirus (measles) – fever, cough, conjunctivitis 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) – 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://www.edexitvideo.com/patient/videoplayer/7xDM8vuVEPo
109-E52
急性喉頭蓋炎：選択肢
正常
2016年近畿大学６年
寺田徹さんクリクラ
109-F13
選択肢：手足口病
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
Coxsackievirus
• 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: from 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-mouth 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 genus
Coxsackie; coxsackievirus
echo; echovirus;
HAV; hepatitis A virus
polio; poliovirus
rhino; rhinovirus.
Picornavirus
pathogenesis
The target tissue
infected by the virus
determines the
predominant disease
caused by the virus.
109-I67
SSPE
亜急性硬化性全脳炎
ADEM, demyelination; MIBE; inclusion body and viral antigen
ADEM, acute disseminated encephalomyelitis
MIBE; measles inclusion body encephalitis
Acute
Subacute
Chronic
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
•Clonal 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 gliosis [´´ + osis,
proliferation
the immune system, anti-virus antibodies other than M protein condition]:
of astrocytes= scar in
the CNS.
Brain atrophy, gliosis and mononuclear cell infiltration, and rarefied and gliotic white matter
• 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)
• 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
disorders 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 measles virus. You should
suspect which of the following?
(A) Acute Lyme disease
(B) Fifth disease
(C) Possible hepatitis B infection
(D) Possible subacute sclerosing
panencephalitis (SSPE)
(E) Susceptibility to chicken pox
Answer (D)
伝染性紅斑
=Erythema infectiosum
=fifth disease
109-I68
サイトメガロウイルス
フクロウの目
Cytomegalic cells
Cytomegalovirus (CMV) encephalitis
Inclusion bodies known as “owl eye” inclusions
109-I69
クロイツフェルト・ヤコブ病
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 death 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 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