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Infectious diseases
Mar 30, 2005
Robbins and Cotran Chapte
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Tumor immunity
Immune surveillance
Cancer immunoediting Tumor-specific antigens Tumor-associated antigens
Anti-tumor effector mechanisms CTL NK cell
Macrophages
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Oncogene products:
Normal self proteinsMutated self protein
Overexpressed or
aberrantly expressed
self protein
Product of oncogene
or mutated tumor
suppressor gene
MHC
Class I CD8+ CTL
CD8+ CTL
No T cell
response
Overexpressed:Various mutant proteins H
T cell
T cell T cell T cell
Normal host cell
displaying multiple
MHC-associatedself antigens
Tumor cells expressing different
types of tumor antigens
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T cell T cellT
Anti-tumor
immunityImmune evasion by tumors
Tumor cell
Tumor
antigen
T cell specific
for tumor antigen
T cell
MHC
molecule
Antigen-loss
variant of tumor
cell
Failure to produce tumor
antigen
Mutations in MHC
genes or genes needed for
antigen processing
im
Class I
MHC-deficient
tumor cell
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Kochs postulates
1) The organism is found in lesions o
disease2) The organism can be isolated as scolonies on solid media
3) Inoculation of the organism causein experimental animals4) The organism can be recovered fr
experimental animal
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Toxin Terminology
Exotoxin = protein toxins of bacte
contrast to endotoxin (LPS) Not all exotoxins are secreted; someaccumulate inside the bacterium and a
released by bacterial lysis Cytotoxin = target a wide range of
types, in contrast to neurotoxins,
leukotoxins, hepatotoxins, cardioto
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More Toxin Terminolog
Toxins can be named for the bacte
species that produce them, such astoxin, Shiga toxin, diphtheria toxintetanus toxin
Toxins can be named for their actisuch as adenylate cyclase, lecithina Toxins can be simply given letter
designations, such as exotoxin A
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Toxin Classification by Mech
Type I toxins bind to the host cell
but they are not translocated into cell (i.e. superantigens [Sag]) Type II toxins disrupt eukaryotic c
membranes (i.e. phospholipases, andforming toxins) Type III toxins are A-B toxins, wh
a binding (B) component and activecomponent
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Superantigens (Type I) To
Toxic shock syndrome toxin (TSST) (toxsyndrome)
Streptococcal pyrogenic exotoxin (Spe) shock-like syndrome and scarlet fever)
Staphylococcal enterotoxin (food poison
Hormone Analog
STa (heat-stable toxin) (diarrhea)
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Superantigens (Type I To
APCAPC Helper T cellHelper T cell
FeFe
PeptidePeptide
MM
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Membrane-Disrupting (Typ
Toxins Alpha-toxin (gas gangrene)
Alpha-toxin (necrosis) Listeriolysin O (LLO) (listeriosis)
Pneumolysin (pneumonia)
Streptolysin O (SLO) (rheumatic f
Hemolysin A (Hly A) (urinary tract
infections and peritonitis)
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Membrane-Disrupting (Typ
Toxins Two types of membrane-disrupting
Pore-forming toxins insert holes in thmembrane Enzymes cleave bonds in membrane ph
Erythrocytes provide a convenient to assay activity, so these toxins acalled hemolysins
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Role of Membrane Disrup
Toxins In some cases, the primary role ap
be killing of professional phagocyteas neutrophils and macrophages
In other cases, they are used by in
bacteria to escape from a phagosoenter the host cell cytoplasm
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A-B (Type III) Toxins
Diphtheria toxin (diphtheria)
Cholera toxin (cholera) LT (heat-labile toxin) (infant diarrtravelers diarrhea)
Shiga toxin (dysentery and hemolyuremic syndrome [HUS])
Botulinum toxin (botulism)
Tetanus toxin (tetanus)
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A-B (Type III) Toxins
First toxins studied
Historically more interest in A-B toxiType I or type II
Simple A-B toxins are synthesized single polypeptide Often A and B portions are separated
processing by proteolytic cleavage
Compound A-B toxins are composedmultiple B monomers
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A
B
BindingBinding
B
A
EndocytosisEndocytosis
B
TraTra
B
ATranslocationTranslocation
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More About A-B Toxin
Often the surface receptor for thsubunit is the carbohydrate moietyglycoconjugate
Distribution of receptor determine
cell specificity In some cases, the A subunit needsenzymatically activated within the
cytoplasm by host cell proteins
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Mechanisms of Action of
Toxins Although A-B toxins target many d
cell types, many of them catalyze treaction
ADP-ribosylation, the transfer of A
ribose from NAD to a target protechanges the behavior of the target Diphtheria toxin inactivates elongatio Cholera toxin constitutively activates
binding protein that regulates adenyla
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NIAID Category A & B Pri
(Bacterial) PathogensCategory A
Bacillus anthracis Clostridium botulinum Yersinia pestis Francisella tularensis
Category B Burkholderia
pseudomallei
Coxiella burnetti
Rickettsia pr Ricin toxin Epsilon toxin
Clostridiumperfringens
Staphylococcenterotoxin
Food and wat
bacteria E coli Vibr
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Select Agents (Partial Li
Rickettsia prowazekii
Rickettsia rickettsii
Yersinia pestis
Ricin toxin
Shiga-like toxins Bacillus anthracis
Brucella abortus
Brucella melitensisB ll i
Burkholderiapseudomallei
Coxiella burn Francisella t
Botulinum ne
Clostridiumperfringenstoxin
Shiga toxin
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Infection and cancer
During the past 20 years, 4 new infectioof cancer have been discovered Helicobacter pylori, hepatitis C virus (HCV),
papillomavirus, and human herpesvirus 8 (HHV
H. pyloricauses gastric cancer (2nd most
important cause of cancer death worldwi Papillomavirus causes the vast majority ocancer (2nd most important cause of canwomen)
Liver cancer caused by hepatitis viruses
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Between 15 and 20% of can
due to underlying infect
Source:
Parsonnet, Julie. Microbes and Malignancy. 1st ed. Oxford, UK: Oxford UniveISBN: 0195104013.
Image removed due to copyright reasons.
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Viruses linked to human neo
Virus Acute infection T
Human Tlymphotropic virus-1
Smolderingleukemia
Adult Tleukemi
Epstein-Barr virus Infectious
mononucleosis
B cell ly
Burkitt
Hepatitis B virus
Hepatitis C virus
Hepatitis B
Hepatitis C
Hepatoccarcinom
Human papilloma Squamous intra Cancer
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Transformation by high-ris
Please see:
Scheffner, M., and NJ. Whitaker. Human papillomavirus-induced ca
ubiquitin-proteasome system. Seminars in Cancer Biology 13 (2003)
Image removed due to copyright reasons.
f
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HPV tropism for squamo
epithelium
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Infectious group 1 carcino
Organism Cancer Dist
Helicobacterpylori
Gastric cancer World
Schistosomahaematobium Urinary bladdercancer AfricaMiddle
Opisthorchis
vivirreni
Bile duct cancer Northe
Thaila
G hi l di ib i
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Geographical distribution
schistosomiasis
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Helicobacter pylori
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Aliment Pharmacology Therapy 18, Supplement 1 (200
Image removed due to copyright reasons.
Please see:
Haruma, K., and M. Ito. Review article: clinical significance of mucosal-protective agen
carcinogenesis and rebamipide.
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