Chapter 8 – Infectious Diseases: General Principles of Microbial Pathogenesis Flashcards
CATEGORIES OF INFECTIOUS AGENTS
- * Prions :30–50 kD Intracellular
- * Viruses: 20–300 nm
- Obligate intracellular
-
Bacteria : 0.2–15 μm
- * Obligate intracellular
- * Extracellular
- Facultative intracellular
-
Fungi : 2–200 μm
- * Extracellular
- * Facultative intracellular
-
Protozoa 1–50 μm
- * Extracellular
- * Facultative intracellular
- * Obligate intracellular
-
Helminths : 3 mm–10m
- * Extracellular
- * Intracellular
What are prions?
Prions are composed of abnormal forms of a host protein, termed prion protein (PrP). [3]
These agents cause transmissible spongiform encephalopathies, including kuru (associated withhuman cannibalism), Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy(BSE; better known as mad cow disease), and variant Creutzfeldt-Jakob disease (vCJD; probably transmitted to humans from BSE-infected cattle).
What is a PrP and its pathophysiology?
PrP is normally found in neurons.
Diseases occur when the PrP undergoes a conformational change that confers resistance toproteases.
The protease-resistant PrP promotes conversion of the normal protease-sensitive PrP to the abnormal form, explaining the infectious nature of these diseases.
Accumulation ofabnormal PrP leads to neuronal damage and distinctive spongiform pathologic changes in thebrain.
Spontaneous or inherited mutations in PrP, which make PrP resistant to proteases, havebeen observed in the sporadic and familial forms of CJD, respectively. CJD can be transmittedfrom person to person iatrogenically, by surgery, organ transplant, or blood transfusion.
What are viruses?
Viruses are obligate intracellular parasites that depend on the host cell’s metabolic machinery for their replication.
They consist of a nucleic acid genome surrounded by a protein coat (called a capsid) that is sometimes encased in a lipid membrane.
How are viruses classified?
Viruses are classified by their:
- nucleic acid genome (DNA or RNA but not both),
- the shape of the capsid (icosahedral or helical),
- the presence or absence of a lipid envelope,
- their mode of replication,
- the preferred cell type for replication (called tropism),
- or the type of pathology.
Because of the very small size of the virus, they are best seen under the electron microscope.
At what instances do these viruses are seen under the light microscope.
Because viruses are only 20 to 300 nm insize, they are best visualized with the electron microscope.
However, some viral particles aggregate within the cells they infect and form characteristic inclusion bodies, whichmay be seen with the light microscope and are useful for diagnosis.
What examples of Viruses show inclusion bodies?
- cytomegalovirus (CMV)-infected cells are enlarged and show a large eosinophilic nuclear inclusion and smaller basophilic cytoplasmic inclusions
- herpesviruses form a large nuclear inclusion surrounded by a clear halo
- both smallpox and rabies viruses form characteristic cytoplasmic inclusions
What are bacteria?
Bacteria are prokaryotes, meaning that they have a cell membrane but lack membrane-boundnuclei and other membrane-enclosed organelles.
Most bacteria are bound by a cell wallconsisting of peptidoglycan, a polymer of long sugar chains linked by peptide bridges.
How are bacteria classifed?
Bacteria are classified by
- * Gram staining (positive or negative),
- * shape (spherical ones are cocci; rod-shaped ones are bacilli) ( Fig. 8-3 ),
- * and need for oxygen (aerobic or anaerobic).
- Many bacteria have flagella,long helical filaments extending from the cell surface that enable bacteria to move.
- Some bacteria possess pili, another kind of surface projection that can attach bacteria to host cells or extracellular matrix.
- Most bacteria synthesize their own DNA, RNA, and proteins, but they depend on the host for favorable growth conditions.
Thereare two forms of bacterial cell wall structures:
- thick wall surrounding the cell membrane that retainscrystal-violet stain (gram-positive bacteria) or
- a thin cell wall sandwiched between twophospholipid bilayer membranes (gram-negative bacteria) ( Fig. 8-2 ).
Normal healthy people can be colonized by as many as _____________ on the skin
10^ 12 bacteria on the skin
Normal healthy people can be colonized by as many as _____________ on the mouth.
10^ 10
bacteria in the mouth,
Normal healthy people can be colonized by as many as _____________ on the GIT
10 ^14 bacteria in the gastrointestinal tract
Bacteria colonizing the
skin include __________ and _______
Staphylococcus epidermidis and Propionibacterium acnes, the cause of acne.
the cause of acne.
Propionibacterium acnes,
Aerobic and anaerobic bacteria in the mouth, particularly ________ contribute to
dental plaque, a major cause of tooth decay
Streptococcus mutans,
What is facultative intracellular bacteria?
can survive and replicate either
outside or inside of host cells
What is an obligate intracellular bacteria?
some grow only inside host
cells
Obligate intracellular bacteria include____________ which replicate inside
membrane-bound vacuoles in epithelial and endothelial cells, respectively
These bacteria get
most or all of their energy source, ATP, from the host cell
Chlamydia and Rickettsia,
__________ is the most
frequent infectiouscause offemale sterility(byscarring and narrowing of the fallopian tubes)
and blindness (by chronic inflammation of the conjunctiva that eventually causes scarring and
opacification of the cornea).
Chlamydia trachomatis
What does Rickettsiae injure and causes what?
Rickettsiae injure the endothelial cells in which they grow, and so
cause a hemorrhagic vasculitis, often visible as a rash, but they may also injure the central
nervous system (CNS) and cause death (Rocky Mountain spotted fever [RMSF] and epidemic
typhus).
Rickettsiae are transmitted by ___________
arthropod vectors, including lice (epidemic typhus), ticks
(RMSF and ehrlichiosis), and mites (scrub typhus
Why do Mycoplasma organisms and those belonging to the related genus Ureaplasma are unique
among extracellular bacterial pathogens,
because they do not have a cell wall. These are the
tiniest free-living organisms known (125–300 nm).
What are Fungi?
Fungi are eukaryotes that possess thick chitin-containing cell walls and ergosterol-containing
cell membranes.
Bacteria ang PROKARYOTES
What is the content of the cell wall of fungi?
Fungi are eukaryotes that possess thick chitin-containing cell walls
What is the content of the cell membranes of Fungi?
ergosterol-containing
cell membranes.
Fungi can grow either as:
- *rounded yeast cells** or as slender filamentous
- *hyphae.**
Hyphae may be :
- septate (with cell walls separating individual cells)
- or aseptate, which is an important distinguishing characteristic in clinical material
Some of the most important
pathogenic fungi exhibit thermal dimorphism which means?
that is, they grow as hyphal forms at room
temperature but as yeast forms at body temperature
San nakikita ang YEAST kiban? Dba sa Katawan? Anong temp ng katawan? ok?
What is conidia?
Fungi may produce sexual spores or,
more commonly, asexual spores referred to as conidia. The latter are produced on specialized
structures or fruiting bodies arising along the hyphal filament.
Fungi may cause superficial or deep infections.
What is a dermatophyte?
Superficial infections involve the skin, hair, and nails. Fungal species that are
confined to superficial layers of the human skin are known as dermatophytes.
These infections
are commonly referred to by the term “tinea” followed by the area of the body affected (e.g.,
tinea pedis, “athlete’s foot”; tinea capitis, “ringworm of the scalp”).
Certain fungal species
invade the subcutaneous tissue, causing abscesses or granulomas ____________
(e.g., sporotrichosis and
tropical mycoses).
Deep fungal infections can spread systemically and invade tissues, destroying vital organs in
immunocompromised hosts, but usually heal or remain latent in otherwise normal hosts.
Some
deep fungal species are limited to a particular geographic region, give an example.
(e. g., Coccidioides in the
* *southwestern United States and Histoplasma in the Ohio River Valley**).
Opportunistic fungi ____________ by contrast, are ubiquitous organisms that
either colonize individuals or are encountered from environmental sources
(e.g., Candida, Aspergillus, Mucor , and Cryptococcus),
In immunodeficient
individuals,opportunistic fungi give rise tolife-threatening infections characterized by tissue
necrosis, hemorrhage, and vascular occlusion, with little or no inflammatory response.
AIDS
patients are often infected by the opportunistic fungus ________________
Pneumocystis jiroveci (previously called Pneumocystis carinii).
What is protozoa?
Parasitic protozoa are single-celled eukaryotes that are major causes of disease and death in
developing countries.
Protozoa can replicate intracellularly within a variety of cells ___________ .
(e.g., Plasmodium in red blood cells, Leishmania in macrophages)
Protozoa can replicate:
intracellularly or extracellularly in the urogenital
system, intestine, or blood
_________- are flagellated protozoal parasites that are
sexually transmitted and can colonize the vagina and male urethra
Trichomonas vaginalis
The most prevalent
intestinal protozoans:
Entamoeba histolytica and Giardia lamblia,
The most prevalent
intestinal protozoans, Entamoeba histolytica and Giardia lamblia, have two forms:
(1) motile trophozoites that attach to the intestinal epithelial wall and may invade,
and (2) immobile cysts that are resistant to stomach acids and are infectious when ingested.
Blood-borne protozoa
__________- are transmitted by insect vectors, in which
they replicate before being passed to new human hosts.
(e.g., Plasmodium, Trypanosoma, and Leishmania)
Intestinal protozoa are acquired by
ingestion of_____ from contaminated food or water.
cysts
Toxoplasma gondii is acquired either by
contact with ___________
oocyst-shedding kittens or by eating cyst-ridden, undercooked meat.
What are Helminths?
Parasitic worms are highly differentiated multicellular organisms.
Their life cycles are complex;
most alternate between sexual reproduction in the definitive host and asexual multiplication in
an intermediary host or vector.
Thus, depending on parasite species, humans could harbor adult worms (e.g., Ascaris lumbricoides) or immature stages (e.g., Toxocara canis) or asexual larval forms (e.g., Echinococcus species). Once adult worms take up residence in humans, they do not multiply but they produce eggs or larvae that are usually passed out in stool.
Often, the
severity of disease is in proportion to the number of organisms that have infected the individual
(e.g., 10 hookworms cause little disease, whereas 1000 hookworms cause severe anemia by
consuming 100 mL of blood per day).
In some helminthic infections, disease is caused by
inflammatory responses to the eggs or larvae rather than to the adults (e.g., schistosomiasis).
What are Ectoparasites?
Ectoparasites are insects (lice, bedbugs, fleas) or arachnids (mites, ticks, spiders) that attach to
and live on or in the skin.
Arthropods may produce disease directly by damaging the human host or indirectly by serving as the vectors for transmission of an infectious agent into a human
host.
Some arthropods cause itching and excoriations (e.g., ________- caused by lice attached
to hair shafts, or scabies caused by mites burrowing into the stratum corneum).
pediculosis
At the site of
the bite, mouth parts may be found associated with a mixed infiltrate of lymphocytes,
macrophages, and eosinophils.
In addition, attached arthropods can be vectors for other
pathogens. For example, deer ticks transmit the Lyme disease spirochete Borrelia burgdorferi.
SPECIAL TECHNIQUES FOR DIAGNOSING INFECTIOUS AGENTS
- Gram stain
- Acid-fast stain
- Silver stains
- Periodic acid–Schiff
- Mucicarmine
- Giemsa
- Antibody probes
- Culture
- DNA probes
Gram stain
Most bacteria
Acid-fast stain
Mycobacteria, nocardiae (modified)
Silver stains
- Fungi, l
- egionellae,
- pneumocystis
Periodic acid–Schiff
Fungi, amebae
Mucicarmine
Cryptococci
Giemsa
Campylobacteria, leishmaniae, malaria parasites
Antibody probes
All classes
Culture
DNA probes
All classes
Acute infections can be diagnosed serologically by detecting pathogen-specific antibodies in
the serum. The presence of specific ______ shortly after the onset of symptoms is often
diagnostic.
IgM antibody
Alternatively, specific antibody titers can be measured early (“acute”) and 4–6 weeks
(“convalescent”) after infection; a four-fold rise in titer is usually considered diagnostic
T or F
T
What are molecular diagnostics?
Nucleic acid–based tests, collectively called molecular diagnostics, have become routine
methods for detecting and quantifying several pathogens.
For instance, in people infected with
the human immunodeficiency virus (HIV), quantification of HIV RNA is an important guide to
antiretroviral therapy. [7]
The management of HBV and HCV infections is similarly guided by
nucleic acid–based viral quantification or typing to predict resistance to antiviral drugs.
Nucleic acid amplification tests, such as polymerase chain reaction (PCR) and transcriptionmediated
amplification, have become routine for diagnosis of _______________.
gonorrhea, chlamydial infection,
tuberculosis, and herpes encephalitis
In some cases, molecular assays are much more
sensitive than conventional testing. [8,] [9]
PCR testing of cerebrospinal fluid (CSF) for____________ has a sensitivity of about 80%, while viral culture of CSF has a
sensitivity of less than 10%.
herpes simplex virus (HSV) encephalitis
Similarly, nucleic acid tests for genital chlamydia detect 10% to 30%
more infections than does conventional chlamydia culture. In other cases, such as gonorrhea,
the sensitivity of nucleic acid testing is similar to that of culture.
Some infectious agents or their products can be directly observed in hematoxylin and eosin
–stained sections: give examples
(e.g., the inclusion bodies formed by CMV and herpes simplex virus (HSV
What stains blue H and E?
- bacterial clumps, which usually stain blue
- Candida and Mucor among the fungi
- most protozoans; and all helminths)
Many infectious agents, however, are best visualized by special
stainsthatidentify organismson the basis of particularcharacteristics of their cell wall or coat
—Gram, acid-fast, silver, mucicarmine, and Giemsa stains—or after labeling with specific
antibody probes
NEW AND EMERGING INFECTIOUS DISEASES
The
infectious causes of some diseases with significant morbidity and mortality were previously
unrecognized, because some of the infectious agents are difficult to culture; examples include
_____________
Helicobacter pylori gastritis, HBV and HCV, and Legionnaires pneumonia
NEW AND EMERGING INFECTIOUS DISEASES
Some infectious
agents are genuinely new to humans,
e.g., HIV, which causes AIDS, and B. burgdorferi, which
causes Lyme disease.
NEW AND EMERGING INFECTIOUS DISEASES
Other infections have become much more common because of immunosuppression caused by AIDS or therapy for transplant rejection and some cancers. Give examples.
(e.g., CMV, Kaposi sarcoma herpesvirus, Mycobacterium avium-intracellulare, P. jiroveci, and Cryptosporidium parvum
NEW AND EMERGING INFECTIOUS DISEASES
Finally, infectious diseases that are common in one area may be introduced into a new area.
For example,__________ has been common in Europe,
Asia, and Africa for years but was first described in the United States in 1999
West Nile virus
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1977 :Ebola virus
Manifestation:
Epidemic Ebola hemorrhagic fever
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1977 :Hantaan virus
Manifestation:
Hemorrhagic fever with renal syndrome
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1977 :Legionella
pneumophila
Manifestation:
Legionnaires disease
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1977 :Campylobacter jejuni
Manifestation:
Enteritis
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1980 HTLV-I
Manifestation:
T-cell lymphoma or leukemia, HTLV-associated
myelopathy
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1981 Staphylococcus aureus
Manifestation:
Toxic shock syndrome
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1982 Escherichia coli
O157:H7
Manifestation:
Hemorrhagic colitis, hemolytic-uremic syndrome
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1982 : Borrelia burgdorferi
Manifestation:
Lyme disease
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1983 HIV
Manifestation:
AIDS
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1983 :Helicobacter pylori
Manifestations
Gastric ulcers
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1988 Hepatitis E
Manifestations
Enterically transmitted hepatitis
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1989 Hepatitis C
Manifestations
Hepatitis C
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1992 Vibrio cholerae O139
Manifestations
New epidemic cholera strain
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1992 Bartonella henselaedisease
Manifestations
Cat-scratch
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1995 KSHV (HHV-8)
Manifestations
Kaposi sarcoma in AIDS
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
1999 West Nile virus
Manifestations
West Nile fever, neuroinvasive disease
TABLE 8-3 – Some Recently Recognized Infectious Agents and Manifestations
2003 SARS coronavirus
Manifestations
Severe acute respiratory syndrome
Human demographics and behavior are among the many variables that contribute to the
emergence of infectious diseases. AIDS was first recognized in the United States as
predominantly a disease of homosexuals and drug abusers, but heterosexual transmission is
now common. In sub-Saharan Africa, the area of the world with the highest number of AIDS
cases, it is predominantly a heterosexual disease
Changes in the environment
occasionally drive rates of infectious diseases. Reforestation of the eastern United States has
led to massive increases in the populations of deer and mice, which carry the ticks that transmit
Lyme disease, babesiosis, and ehrlichiosis
Failure of DDT to control the mosquitoes that
transmit malaria and the development of drug-resistant parasites have dramatically increased
the morbidity and mortality of Plasmodium falciparum in Asia, Africa, and Latin America.
Microbial adaptation to widespread antibiotic use contributed to the emergence of drug
resistance in many species of bacteria, including Mycobacterium tuberculosis, Neisseria
gonorrhoeae, Staphylococcus aureus, and Enterococcus faecium. Infections with antibioticresistant
bacteria are becoming a serious problem, such as methicillin-resistant staphylococcus
(discussed later).
AGENTS OF BIOTERRORISM has three categories:
What is Category A?
Category A agents pose the highest risk and can be readily disseminated or transmitted from
person to person, can cause high mortality with potential for major public health impact, might
cause public panic and social disruption, and might require special action for public health
preparedness
Explain why small pox belongs to category A
For example, smallpox is a category A agent because of its high transmissibility
in any climate or season, case mortality rate of 30% or greater, and lack of effective antiviral
therapy.
This agent can be easily disseminated because of the stability of the virus in aerosol
form and the very small dose needed for infection. Smallpox naturally spreads from person to
person mainly by direct contact with virus in skin lesions or contaminated clothing or bedding.
Symptoms appear after 7 to 17 days. Initially there is high fever, headache, and backache,
followed by the appearance of the rash, which first appears on the mucosa of the mouth and
pharynx, face, and forearms and later spreads to the trunk and legs and becomes vesicular
and later pustular.
Because people can be contagious during the incubation period, this virus has the potential to continue to spread throughout an unprotected population. Since
vaccination ended in the United States in 1972 and vaccination immunity has waned, the
population is highly susceptible to smallpox. Recent concern that smallpox could be used for
bioterrorism has led to a return of vaccination for selected groups in the United States and
Israel.
AGENTS OF BIOTERRORISM
What is category B?
Category B agents are moderately easy to disseminate, produce moderate morbidity but low
mortality, and require specific diagnostic and disease surveillance. Many of these agents are
food-borne or water-borne
What is Bioterrorism category C?
Category C agents include emerging pathogens that could be
engineered for mass dissemination because of availability, ease of production and
dissemination, potential for high morbidity and mortality, and great impact on health.
TRANSMISSION AND DISSEMINATION OF MICROBES
Microbes can enter the host by :
- *inhalation, ingestion**, sexual transmission, insect or animal bites,
- *or injection**.
What is the first defense against infection?
The first defenses against infection are :
intact skin and mucosal surfaces, which
provide physical barriers and produce antimicrobial substances.
In general, respiratory,
gastrointestinal, or genitourinary tract infections that occur in healthy persons are caused by
relatively virulent microorganisms that are capable of damaging or penetrating intact epithelial
barriers.
In contrast, most skin infections in healthy persons are caused by less virulent
organisms entering the skin through damaged sites (cuts and burns).
TRANSMISSION AND DISSEMINATION OF MICROBES
Routes of Entry of Microbes
- Skin.
- Gastrointestinal Tract.
- Respiratory Tract.
- Urogenital Tract.
How does skin protect us from microbeS?
The dense, keratinized outer layer of skin is a natural barrier to infection, and the low pH of the
skin (∼5.5)and thepresence of fatty acids inhibit growth of microorganisms other than residents
of the normal flora.
Human skin is normally inhabited by a variety of bacterial and fungal
species, including some potential opportunists, such as ________
S. epidermidis and Candida albicans
Although skin is usually an effective barrier, certain types of fungi ___________- can infect
the stratum corneum, hair, and nails, and a few microorganisms are able to traverse the
unbroken skin
(dermatophytes)
How does Shistosoma penetrate the skin?
Schistosoma larvae -released from freshwater snails penetrate
swimmers’ skin by releasing collagenase, elastase, and other enzymes that dissolve the
extracellular matrix
Most microorganisms, however, penetrate through breaks in the skin,
including superficial pricks __________,
(fungal infections)
Most microorganisms, however, penetrate through breaks in the skin,
including wounds________,
(staphylococci)
Most microorganisms, however, penetrate through breaks in the skin,
including burns ____________and diabetic and pressure-related foot sores (multibacterial infections).
(Pseudomonas
aeruginosa),
Intravenous catheters in hospitalized patients can produce ____________
local or systemic infection
(bacteremia).
Needle sticks can expose the recipient to potentially infected blood and may transmit _____________
transmit HBV, hepatitis C virus (HCV), or HIV
Some pathogens penetrate the skin via an insect
or animal bite.
For instance, bites by fleas, ticks, mosquitoes, mites, and lice break the skin and
transmit arboviruses causing_______________
(causes of yellow fever and encephalitis
Some pathogens penetrate the skin via an insect
or animal bite.
For instance, bites by fleas, ticks, mosquitoes, mites, and lice break the skin and
transmit causing:, ________- (Rocky Mountain
spotted fever [RMSF])
rickettsiae
Some pathogens penetrate the skin via an insect
or animal bite.
For instance, bites by fleas, ticks, mosquitoes, mites, and lice break the skin and
transmit
bacteria ____________,
(plague, Lyme disease)
Some pathogens penetrate the skin via an insect
or animal bite.
For instance, bites by fleas, ticks, mosquitoes, mites, and lice break the skin and
transmit
protozoa___________,
(malaria, leishmaniasis)
Some pathogens penetrate the skin via an insect
or animal bite.
For instance, bites by fleas, ticks, mosquitoes, mites, and lice break the skin and
transmit
and
helminths______
(filariasis).
Animal bites can lead to infections with bacteria or certain viruses such as
________-
rabies.
Most gastrointestinal pathogens are transmitted by _____________l.
food or drink contaminated with fecal
materia
Where hygiene fails, diarrheal disease becomes rampant.
_______ are important defenses within the gastrointestinal tract and are lethal
for many gastrointestinal pathogens.
Acidic gastric secretions
Healthy volunteers do not become infected by Vibrio
cholerae unless they are fed________-
10 ^11 organisms,
whereas volunteers given V. cholerae and
sodium bicarbonate have a 10,000-fold increase in susceptibility to cholera
In contrast, some
ingested agents, such as ________, are relatively resistant to gastric acid;
hence, as few as 100 organisms of each are sufficient to cause illness.
Shigella and Giardia cysts
Other normal defenses within the gastrointestinal tract include :
- (1) the layer of viscous mucus covering the intestinal epithelium
- (2) lytic pancreatic enzymes and bile detergents,
- (3) mucosal antimicrobial peptides called defensins,
- (4) normal flora, and
- (5) secreted IgA antibodies. IgA antibodies are made by plasma cells located in mucosa-associated lymphoid tissues (MALT).
What is an M cell?
These lymphoid aggregates are covered by a single layer of specialized epithelial cells called M
cells.
M cells are important for transport of antigens to mucosa-associated lymphoid tissues and
for binding and uptake of numerous gut pathogens, including poliovirus, enteropathic
Escherichia coli, V. cholerae, Salmonella typhi, and Shigella flexneri.
M cells are important for transport of antigens to mucosa-associated lymphoid tissues and
for binding and uptake of numerous gut pathogens, including :
- poliovirus,
- enteropathic
- Escherichia coli,
- V. cholerae,
- Salmonella typhi,
- and Shigella flexneri.
Infections via the gastrointestinal tract occur when local defenses are weakened or the
organisms develop strategies to overcome these defenses.
Host defenses are weakened by low
gastric acidity, by antibiotics that alter the normal bacterial flora (e.g., in ___________),
pseudomembranous
colitis
Infections via the gastrointestinal tract occur when local defenses are weakened or the
organisms develop strategies to overcome these defenses.
Host defenses are weakened by :
- low gastric acidity,
- by antibiotics that alter the normal bacterial flora
- or when there is stalled peristalsis
- or mechanical obstruction (e.g., in blind-loop
syndrome).
Most enveloped viruses are inactivated by bile and digestive enzymes, but
nonenveloped viruses may be resistant _____________
(e. g., the hepatitis A virus, rotaviruses, reoviruses, and
norovirus) .
Enteropathogenic bacteria elicit gastrointestinal disease by a variety of mechanisms:
- While growing on contaminated food, certain staphylococcal strains release powerful enterotoxins that cause food poisoning without any bacterial multiplication in the gut.
- • V. cholerae and toxigenic E. coli multiply inside the mucous layer overlying the gut epithelium and release exotoxins that cause the gut epithelium to secrete large volumes of fluid, resulting in watery diarrhea.
- • Shigella, Salmonella, and Campylobacter invade and damage the intestinal mucosa and lamina propria and so cause ulceration, inflammation, and hemorrhage that is clinically manifested as dysentery.
- • Salmonella typhi passes from the damaged mucosa through Peyer patches and mesenteric lymph nodes and into the bloodstream, resulting in a systemic infection.
While growing on contaminated food, certain __________release powerful
enterotoxins that cause food poisoning without any bacterial multiplication in the gut.
staphylococcal strains
__________multiply inside the mucous layer overlying the gut epithelium and release exotoxins that cause the gut epithelium to secrete large volumes
of fluid, resulting in watery diarrhea
V. cholerae and toxigenic E. coli
____________ invade and damage the intestinal mucosa and
lamina propria and so cause ulceration, inflammation, and hemorrhage that is clinically
manifested as dysentery.
Shigella, Salmonella, and Campylobacter
_________ passes from the damaged mucosa through Peyer patches and
mesenteric lymph nodes and into the bloodstream, resulting in a systemic infection.
Salmonella typhi
Fungal infection of the gastrointestinal tract occurs mainly in ____________
immunologically compromised
people.
____________ part of the normal gastrointestinal flora, shows a predilection for stratified
squamous epithelium, causing oral thrush or membranous esophagitis, but may also spread to
the stomach, lower gastrointestinal tract, and systemic organs.
Candida
In what form of intestinal protozoa is essential for their transmission? WHY?
The cyst forms of intestinal protozoa are essential for their transmission, because cysts resist
stomach acid
reCYST acid
In the gut, cysts convert to ______________ and attach to sugars on the
intestinal epithelia through surface lectins.
motile trophozoites
What happens next differs among pathogens.
___________attaches to the epithelial brush border
Giardia lamblia
whereas ____________- are taken up by
enterocytes, in which they form gametes and spores.
cryptosporidia
___________ causes contact-mediated
cytolysis through a channel-forming pore protein and thereby ulcerates and invades the colonic
mucosa.
E. histolytica
Intestinal helminths, as a rule, cause disease only when ___________
they are present in large numbers or in ectopic sites, for example, by obstructing the gut or invading and damaging the bile ducts (Ascaris lumbricoides).
_________ may cause iron deficiency anemia by chronic loss
of blood sucked from intestinal villi
Hookworms
the_______________ can deplete its
host of vitamin B12, giving rise to an illness resembling pernicious anemia.
fish tapeworm Diphyllobothrium latum
Finally, the larvae of
several helminths pass through the gut briefly on their way to another organ
__________ larvae preferentially encyst in muscle,
Trichinella spiralis
________ species larvae in the
liver or lung.
Echinococcus
A large number of microorganisms, including viruses, bacteria, and fungi, are inhaled daily by
every city inhabitant.
In many cases, the microbes are inhaled in dust or aerosol particles.
The
distance these particles travel into the respiratory system is inversely proportional to their size.
T or F
True
Large particles are trapped in the ______________
mucociliary blanket that lines the nose and the upper
respiratory tract.
Inhaled microorganisms are trapped in the mucus secreted by goblet cells and
are then transported by ciliary action to the back of the throat, where they are swallowed and cleared.
Particles smaller than _________ travel directly to the alveoli, where they are phagocytosed
by alveolar macrophages or by neutrophils recruited to the lung by cytokines.
5 μm
Microorganisms that invade the normal healthy respiratory tract have developed specific
mechanisms to overcome the mucociliary defenses or to avoid destruction by alveolar
macrophages
T or F
FALSE
Some successful respiratory pathogens evade these defenses by attaching to
epithelial cells in the lower respiratory tract and pharynx. For example are ___________
influenza viruses
How does influenza virus evade the defenses of the epithelial cells of the respiratory tract?
influenza viruses
possess hemagglutinin proteins that project from the surface of the virus and bind to sialic acid
on the surface of epithelial cells.
This attachment induces the host cell to engulf the virus, leading to viral entry and replication within the host cell.
However, sialic acid also interferes with
shedding of newly synthesized viruses from the host cell.
Influenza viruses have another cell
surface protein, neuraminidase, which cleaves sialic acid and allows virus to release from the
host cell.
Neuraminidase also lowers the viscosity of mucus and facilitates viral transit within the
respiratory tract. Interestingly, some anti-influenza drugs are sialic acid analogues that inhibit
neuraminidase and prevent viral release from host cells.
What does hemagglutinin proteins do?
possess hemagglutinin proteins that project from the surface of the virus and bind to sialic acid
on the surface of epithelial cells.
This attachment induces the host cell to engulf the virus,
leading to viral entry and replication within the host cell. However, sialic acid also interferes with
shedding of newly synthesized viruses from the host cell.
What does neuramidase do?
Influenza viruses have another cell
surface protein, neuraminidase, which cleaves sialic acid and allows virus to release from the
host cell.
Neuraminidase also lowers the viscosity of mucus and facilitates viral transit within the
respiratory tract. Interestingly, some anti-influenza drugs are sialic acid analogues that inhibit
neuraminidase and prevent viral release from host cells.
Certain bacterial respiratory pathogens can impair ciliary activity.
- Haemophilus influenzae and
- Bordetella pertussis elaborate
- P. aeruginosa
- M. pneumoniae
- Streptococcus pneumoniae or
- Staphylococcus
___________ elaborate toxins that paralyze mucosal cilia
Haemophilus
influenzae and Bordetella pertussis
____________
a cause of severe respiratory infection in persons with cystic fibrosis
P. aeruginosa
___________-
produce ciliostatic substances
M. pneumoniae
Some bacteria such as ___________- species lack specific adherence factors and often gain access after viral infection causes loss of ciliated epithelium, making individuals with a viral respiratory infection
more susceptible to these secondary bacterial superinfections.
Streptococcus pneumoniae or
Staphylococcus
Chronic damage to mucociliary
defense mechanisms occurs in_______________
smokers and people with cystic fibrosis,
acute injury damage to mucociliary
defense mechanisms occurs
in
___________________
intubated patients and in those who aspirate gastric acid.
Some respiratory pathogens avoid phagocytosis or destruction after phagocytosis.
Give an example.
M.
tuberculosis, for example, gains its foothold in normal alveoli because it is able to escape killing
within the phagolysosomes of macrophages.
Opportunistic fungi infect the lungs when cellular
immunity is depressed or when leukocytes are reduced in number. Give example.
e.g., P. jiroveci in AIDS
patients and Aspergillus species following chemotherapy).
The urinary tract is almost always invaded from the exterior via____________
the urethra .
What is the natural defense of the U?rogenital tract
The regular
flushing of the urinary tractwith urine serves as a defense against invading microorganisms.
Urine in the bladder is normally sterile, and successful pathogens such as___________adhere to the urinary epithelium
- N. gonorrhoeae,
- E. coli
Anatomy plays an important role in infection.
Women
have more than 10 times as many urinary tract infections as men, because _______________
the distance
between the urinary bladder and skin (i.e., the length of the urethra) is 5 cm in women, in
contrast to 20 cm in men.
_______________ can compromise normal
defenses and increase susceptibility to urinary tract infections.
Obstruction of urinary flow and/or reflux
Urinary tract infections can
spread retrogradely from the bladder to the kidney and cause acute and chronic pyelonephritis,
which is the major preventable cause of renal failure.
From puberty until menopause the vagina is protected from pathogens by a _____________
low pH resulting
from catabolism of glycogen in the normal epithelium by lactobacilli.
Antibiotics can kill the
lactobacilli and make the vagina susceptible to infection.
Sexually transmitted pathogens have
developed specific mechanisms for attaching to the vaginal or cervical mucosa, or they enter
via local breaks in the mucosa during sexual intercourse such as:
(HIV, HPV, Treponema pallidum).
Spread and Dissemination of Microbes
Some microorganisms proliferate locally, at the site of infection, whereas others penetrate the
epithelial barrierandspread to distant sites via the lymphatics, the blood, or nerves (
Pathogens that cause superficial infections stay confined to the lumen of hollow viscera ___________
(e.g.,
Vibrio cholera
Pathogens that cause superficial infections adhere to or proliferate exclusively in or on epithelial cells
(e.g., papillomaviruses, dermatophytes).
A variety of pathogenic bacteria, fungi, and helminths are invasive by virtue of their motility or ability to secrete lytic enzymes (e.g., ________________secrete hyaluronidase, which degrades the extracellular matrix between host
cells).
streptococci and
staphylococci
Microbial spread initially follows tissue planes of least resistance and to sites drained by
regional lymphatics.
For example, staphylococcal infections may progress from a localized
abscess or furuncle to regional lymph nodes.
This can sometimes leads to bacteremia and
colonization of distant organs (heart, liver, brain, kidney, bone). Within the blood,
microorganisms may be transported free or within host cells.
What microbes are transported free in the plasma?
Some viruses (**e.g., poliovirus and** **HBV),** most bacteria and fungi, some protozoa **(e.g., African trypanosomes)**, and all helminths are transported free in the plasma
Leukocytes can carry which organisms?
- herpesviruses,
- HIV,
- mycobacteria,
- and Leishmania
- and Toxoplasma organisms.
What viruses and parasites are carried by the RBC?
Certain viruses (e.g., Colorado tick fever virus) and parasites (Plasmodium and Babesia) are carried by red blood cells.
Most viruses spread
from _____________
cell to cell by replication and release of infectious virions,
Give example of virus that may propagate from
cell to cell by fusion or transport within nerves
(e.g., rabies virus).
What are secondary foci?
Infectious foci seeded by
blood are called secondary foci.
They can be single and large (a solitary abscess or
tuberculoma) or multiple and tiny (e.g., miliary tuberculosis or Candida microabscesses in many
tissues) .
Sporadic bloodstream invasion by low-virulence or nonvirulent microbes (e.g., during
brushing of teeth) is common but is quickly controlled by normal host defenses
By contrast,
disseminated viremia, bacteremia, fungemia, or parasitemia by virulent pathogens is a serious
insult and manifests itself by _____________ by bacteria or their endotoxins can rapidly become fatal, even for previously healthy individuals.
fever, low blood pressure, and multiple other systemic signs and
symptoms of sepsis.
FIGURE 8-4
Routes of entry and dissemination of microbes.
To enter the body microbes
penetrate the epithelial or mucosal barriers. Infection may remain localized at the site of
entry or spread to other sites in the body.
Most common microbes (selected examples are
shown) spread through the lymphatics or bloodstream (either freely or within inflammatory
cells) .
However, certain viruses and bacterial toxins may also travel through nerves.
What is the major manifestation of infectious disease?
The major manifestations of infectious disease may appear at sites distant from the point of
microbe entry.
The major manifestations of infectious disease may appear at sites distant from the point of
microbe entry.
For example, ____________viruses enter through the airways but
cause rashes in the skin;
chickenpox and measles
The major manifestations of infectious disease may appear at sites distant from the point of
microbe entry.
For example: __________ enters through the intestine but kills motor neurons.
poliovirus
The major manifestations of infectious disease may appear at sites distant from the point of
microbe entry.
For example:
___________parasites penetrate the skin but eventually localize in blood vessels of
the portal system and mesentery, damaging the liver and intestine.
Schistosoma mansoni
The major manifestations of infectious disease may appear at sites distant from the point of
microbe entry.
For example:
___________-
on the other hand, localizes to the urinary bladder and causes cystitis.
Schistosoma hematobium,
The major manifestations of infectious disease may appear at sites distant from the point of
microbe entry.
For example:
The __________ travels
to the brain in a retrograde fashion within nerves
RABIES
The major manifestations of infectious disease may appear at sites distant from the point of
microbe entry.
For example:
the ____________- hides in dorsal root ganglia, and on reactivation, travels along nerves to cause shingles.
varicella zoster virus (VZV)
The placental-fetal route is an important mode of transmission ( Chapter 10 ). When infectious
organisms reach the pregnant uterus through the cervical orifice or the bloodstream and are
able to traverse the placenta, severe damage to the fetus can result.
Bacterial or mycoplasmal
placentitis can cause premature delivery or stillbirth. Viral infections can cause maldevelopment
of the fetus, with infection early in pregnancy resulting in the most severe disease.
_____________
infection during the first trimester can cause congenital heart disease, mental retardation,
cataracts, or deafness in the infant, while little damage is caused by this during the
third trimester.
Rubella
Transmission of treponemes leads to congenital syphilis only when T. pallidum
infects the mother late in the _________ but then causes severe fetal osteochondritis and
periostitis that leads to multiple bony lesions.
second trimester
Infection also can occur during passage through
the birth canal ___________or through maternal milk (e.g.,
CMV, HBV, human T-cell leukemia virus-1 [HTLV-1]).
(e.g., gonococcal or chlamydial conjunctivitis)
Infection also can occur during passage through maternal milk ___________________
(e. g.,
* *CMV, HBV, human T-cell leukemia virus-1 [HTLV-1]).**
____________ is the major
cause of AIDS in children.
Maternal transmission of HIV
Maternal transmission of HBV can later cause _________________
chronic hepatitis or
liver cancer.
