Transmission of Microbes Flashcards
1
Q
Routes of Entry of Microbes
A
Microbes can enter the host through breaches in the skin, by inhalation or ingestion, or by sexual transmission
2
Q
Skin
A
Epidermal barrier
Mechanical defects (punctures, burns, ulcers)- Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa
Needle sticks- HIV, hepatitis viruses
Arthropod and animal bites- Yellow fever, plague, Lyme disease, malaria, rabies, Zika virus
Direct penetration Schistosoma
3
Q
Gastrointestinal tract Epithelial barrier
A
Attachment and local proliferation
of microbes- Vibrio chloerae, Giardia
Attachment and local invasion of
microbes- Shigella, Salmonella, Campylobacter
Uptake through M cells- Poliovirus, certain pathogenic bacteria
4
Q
GIT Acidic
A
Acid-resistant cysts and eggs Many protozoa and helminths
5
Q
GIT Bile and pancreatic organism
A
Resistant microbial external coats Hepatitis A, Rotavirus, Norovirus
6
Q
GIT Normal protective flora
A
Broad-spectrum antibiotic use Clostridium difficile
7
Q
Respiratory tract Mucociliary clearance
A
attachment and local proliferation
of microbes- Influenza viruses
Ciliary paralysis by toxins- Haemophilus influenzae, M. pneumoniae, Bordetella pertussis
8
Q
Respiratory tract- Resident alveolar macrophages
A
Resistance to killing by phagocytes M. tuberculosis
9
Q
Urogenital tract Urination
A
obstruction, microbial attachment and local proliferation- E. coli
10
Q
UGT, normal vaginal flora
A
Antibiotic use- candida albicans
11
Q
UGT, Intact epidermal/epithelial barrier
A
Microbial attachment and local proliferation- Neisseria Gonorrhoeae
Direct infection/Local invasion- Herpes, Zika, T. Pallidum
Local Trauma- HPV
12
Q
How do pathogens enter GIT?
A
food, drink, or contaminated water- especially during floods- diarrheal diseases are rampant.
13
Q
What are some of the most important barriers against GIT infections
A
Acidic and Gastric secretions
14
Q
How much dose of V. cholerae is needed for infection to manifest?
A
10^11
15
Q
How many times does stomach acid neutralize the pathogen?
A
10,000 fold for V. cholerae
16
Q
Shigella and Giardiasis
A
resistant to gastric acid, fewer than 100 organisms
17
Q
The other normal defenses in GIT are
A
Viscous mucus layers; Lytic pancreatic enzymes and bile detergents; Mucosal and anti-microbial peptides called defensis; Normal flora; IgA antibodies made by MALT
18
Q
Pathogens that use M cells to enter GIT
A
Polio, E coli, V. Cholerae, Salmonella, Shigella flexneri
19
Q
how are host defenses weakened in GIT
A
Low gastric acidity, antibiotics, obstruction, and cessation of peristalsis
20
Q
TOxins in food
A
S. aureus, Bacillus Cereus
21
Q
How is the vagina protected from pathogens from puberty until menopause?
A
low pH by lactobacilli catabolism, antibiotics kill lactobacillus, causing overgrowth of yeast and result Vaginal candidiasis
22
Q
Spread and Dissemination of Microbes
Within the Body
A
Some microorganisms proliferate locally, at the site of
the initial infection, whereas others penetrate the epithelial
barrier and spread to distant sites by way of the lymphatics, the blood, or nerves
23
Q
Lysis and invasion
A
Some extracellular bacteria, fungi,
and helminths secrete lytic enzymes that destroy tissue and allow direct invasion.
24
Q
S. aureus secretes
A
hyaluronidase, which degrades the extracellular matrix between host cells. Invasive microbes initially follow tissue planes of least resistance and drain
to regional lymphatics. S. aureus may travel from a localized abscess to the draining lymph nodes. This can
sometimes lead to bacteremia and spread to deep organs (heart, bone)
25
Through blood and lymph
. Microorganisms may be spread
either in extracellular fluid or within host cells. Some viruses (e.g., poliovirus, HBV), most bacteria and fungi,
some protozoa (e.g., African trypanosomes), and all helminths are transported in the plasma. Leukocytes can carry herpes viruses, HIV, mycobacteria, Leishmania, and
Toxoplasma.
26
parasites that are found in blood
Plasmodium and Babesia are
| found within red cells
27
Cell-to-cell transmission
Most viruses spread locally from
cell to cell by replication and release of infectious virions,
but others may propagate from cell to cell by causing
fusion of host cells, or by transport within nerves (as with rabies virus and varicella-zoster virus)
28
The consequences of the bloodborne spread of pathogens
| vary widely depending on
virulence of the organism, the magnitude of the infection, the pattern of seeding,
and host factors such as immune status
29
Sporadic bloodstream invasion by low-virulence or nonvirulent microbes
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 poses a serious danger and manifests
as fever, hypotension, and multiple other systemic signs
and symptoms of sepsis
30
Can major manifestations of infectious disease appear at sites distant from the point of microbe entry?
Yes, Eg. V. zoster; Measles
31
Schistosoma mansoni
parasites penetrate
the skin but eventually localize in blood vessels of the portal system and mesentery, damaging the liver and intestine. Schistosoma hematobium also penetrates the skin,
but localizes to the urinary bladder and causes cystitis. The
rabies virus travels from the site of a bite by a rabid animal
to the brain by retrograde transport in sensory neurons,
where it then causes encephalitis and death.
32
Transmission of Microbes
Transmission depends on the hardiness of the microbe. Some microbes can survive for extended periods in dust,
food, or water. Bacterial spores, protozoan cysts, and thick shelled helminth eggs can survive in a cool and dry environment. Less hardy microorganisms must be quickly
passed from person to person, often by direct contact.
33
Skin as a mode of transmission
Skin flora, such as S. aureus and dermatophytes
(fungi), are shed in the desquamated skin. Some sexually transmitted pathogens are transmitted from genital
skin lesions, such as HSV and Treponema pallidum
(causing syphilis).
34
Oral secretions as a mode of secretion
Viruses that replicate in the salivary
glands and are spread in saliva include mumps virus,
CMV, and rabies virus
35
• Respiratory secretions
Viruses and bacteria can be shed
in respiratory secretions during talking, coughing, and
sneezing. Most respiratory pathogens, including influenza viruses, spread in large respiratory droplets, which
travel no more than 3 feet. However, a few organisms,
including M. tuberculosis and varicella-zoster virus, are
spread from the respiratory tract in small respiratory
droplets or within dust particles that can travel long
distances in the air. These properties determine the type
of isolation precautions that are used to prevent the
spread of infection
36
• Stool
Organisms shed in stool include many pathogens
that replicate in the lumen or epithelium of the gut, such
as Shigella, G. lamblia, and rotavirus. Pathogens that replicate in the liver (hepatitis A virus) or gallbladder (S.
enterica serotype Typhi) enter the intestine in bile and
are shed in stool.
37
Blood.
Pathogens spread via blood may be transmitted
by invertebrate vectors, medical practices (blood transfusion, reuse of equipment), or sharing of needles by
intravenous drug abusers. Bloodborne parasites, including Plasmodium spp. and arboviruses, are transmitted by
biting insects
38
Urine
Urine is the usual mode of exodus from the
human host for only a few organisms, including S. haematobium, which grows in the veins of the bladder and
releases eggs that reach the urine
39
Genital tract.
Sexually transmitted infections (STIs)
spread from the urethra, vagina, cervix, rectum, or oral
pharynx. Organisms that cause STIs depend on direct
contact for person-to-person spread because these
pathogens cannot survive in the environment. Transmission of STIs often is by asymptomatic individuals
who do not realize that they are infected. Infection with
one STI increases the risk for additional STIs, mainly
because the risk factors are the same for all STIs
40
Vertical transmission
Transmission of infectious agents
from mother to fetus or newborn child is a common
mode of transmission for some pathogens, and may
occur through several different routes
41
Placental-fetal
transmission is most likely to occur when the mother is
infected with a pathogen during pregnancy. Some of the
resulting infections interfere with fetal development,
and the degree and type of damage depend on the age
of the fetus at the time of infection.
42
rubella
| infection during the first trimester
lead to heart malformations, mental retardation, cataracts, or deafness
43
rubella infection during the third trimester
has little effect.
44
Congenital microcephaly and other CNS
| complications have been associated with
Zika virus
infection during pregnancy. Much is still unknown
about timing of infection relative to the trimester of
pregnancy
45
Transmission during birth
caused by contact with infectious agents during passage through
the birth canal. Examples include gonococcal and chlamydial conjunctivitis. Postnatal transmission in maternal milk can transmit CMV, HIV, and HBV.
46
Infectious agents establish infection and damage tissues by
| any of three mechanism
• They can contact or enter host cells and directly cause death of infected cells.
• They can release toxins that kill cells at a distance, release enzymes that degrade tissue components, or damage
blood vessels and cause ischemic necrosis.
• They can induce host immune responses that, although
directed against the invader, cause additional tissue
damage. Thus, the defensive responses of the host can be a mixed blessing, helping to overcome the infection
but also contributing to tissue damage.
47
Mechanisms of Viral Injury
Viruses can directly damage host cells by entering them and replicating at the host’s expense. The manifestations
of viral infection are largely determined by the tropism ofm the virus for specific tissues and cell types. Tropism is influenced by a number of factors
48
Host receptors for viruses.
Viruses are coated with surface
proteins that bind with high specificity to particular host
cell surface proteins. Entry of many viruses into cells
commences with binding to normal host cell receptors.
For example, HIV glycoprotein gp120 binds to CD4 and CXCR4 and CCR5 on T cells and macrophages. Host proteases may be needed to enable binding of
the virus to host cells; for instance, a host protease cleaves and activates the influenza virus hemagglutinin
49
Specificity of transcription factors
The ability of the virus
to replicate inside particular cell types depends on the
presence of lineage-specific transcription factors that
recognize viral enhancer and promoter elements. For
example, the JC virus, which causes leukoencephalopathy
50
JC virus, which causes leukoencephalopathy
replicates only in oligodendroglia in
the CNS because the promoter and enhancer DNA
sequences regulating viral gene expression are active in
glial cells, but not in neurons or endothelial cells
51
Physical characteristics of tissues
Host environment and temperature can contribute to tissue tropism. For example, enteroviruses replicate in the intestine in part because they can resist inactivation by acids, bile, and digestive enzymes. Rhinoviruses infect cells only within
the upper-respiratory tract because they replicate optimally at the lower temperatures characteristic of this site.
52
Direct cytopathic effects
Viruses can kill cells by preventing the synthesis of critical host macromolecules, by producing degradative enzymes and toxic proteins, or by inducing apoptosis.
53
Anti-viral immune responses
Viral proteins on the surface
of host cells may be recognized by the immune system,
and lymphocytes may attack virus-infected cells. Cytotoxic T lymphocytes (CTLs) are important for the defense
against viral infections, but CTLs also can be responsible
for tissue injury
54
How does Hep-B cause damage to infected hepatocytes
CTL-mediated, normal response
55
Transformation of infected cells
Different oncogenic
viruses (e.g., HPV, EBV) can stimulate cell growth and survival by a variety of mechanisms, including hijacking the control of cell cycle machinery, anti-apoptotic strategies, and insertional mutagenesis (in which the
insertion of viral DNA into the host genome alters the expression of nearby host genes).
56
Bacterial Virulence
Bacterial damage to host tissues depends on the ability
of the bacteria to adhere to host cells, invade cells and
tissues, or deliver toxins
57
pathogenicity islands
Pathogenic bacteria have virulence genes that are frequently found grouped together in clusters
58
Plasmids
replicating circular DNAs) and bacteriophages (viruses) are genetic elements that spread between bacteria and can carry virulence factors, including toxins or enzymes that confer antibiotic
resistance. Exchange of these elements between bacteria can endow the recipient bacteria with a survival advantage and/or the capacity to cause disease
59
How does bacterial acquire Antibiotic resistance
Carbapenemase genes
carried on plasmids have spread among gram-negative
bacilli worldwide, resulting in strains for which there are
no available effective antibiotics, causing the CDC to list
these organisms as an urgent threat.
60
Quorum sensing.
Many species of bacteria coordinately
regulate gene expression within a large population in which specific genes, such as virulence genes, are expressed after bacteria reach high concentrations. This
in turn may allow bacteria growing in discrete host sites, such as an abscess or consolidated pneumonia, to overcome host defenses. S. aureus coordinately regulates virulence factors by secreting autoinducer peptides. As the bacteria grow to increase concentrations, the level of the autoinducer peptide increases, stimulating exotoxin
production
61
Biofilms
Communities of bacteria can live within a
viscous layer of extracellular polysaccharides that
adhere to host tissues or devices such as intravascular
catheters and artificial joints. Biofilms make bacteria
inaccessible to immune effector mechanisms and
increase their resistance to anti-microbial drugs. Biofilm
formation seems to be important in the persistence and
relapse of infections such as bacterial endocarditis, artificial joint infections, and respiratory infections in individuals with cystic fibrosis
62
Bacterial Adherence to Host Cells
Bacterial surface molecules that bind to host cells or extracellular matrix are called adhesins. Diverse surface structures are involved in the adhesion of various bacteria
63
S. pyogenes adhesion to host
has protein F and teichoic acid projecting
from its cell wall that bind to fibronectin on the surface of
host cells and in the extracellular matrix.
64
Stalks of pili are
structurally conserved, whereas amino
acids on the tips of the pili vary and determine the binding specificity of the bacteria. Strains of E. coli that cause urinary tract infections uniquely express a specific P pilus that binds to a Gal(α1–4)Gal moiety expressed on uroepithelial cells. Pili on N. gonorrhoeae
65
Antigenic variation affecting the
| antigens expressed in the pili
an important mechanism
| by which N. gonorrhoeae escapes the immune response
66
Bacterial Toxins
Any bacterial substance that contributes to illness can be
considered a toxin. Toxins are subclassified as endotoxins,
which are components of the bacterial cell, or exotoxins,
which are proteins that are secreted by the bacterium
67
Bacterial endotoxin
```
a lipopolysaccharide (LPS) that is a
component of the outer membrane of gram-negative bacteria
```
LPS is composed of a long-chain fatty acid anchor, termed lipid A, connected to a core sugar chain, both of which are very similar in all gram-negative bacteria. Attached to the core sugar is a variable carbohydrate chain (O antigen), which is used to serotype strains of bacteria to aid in diagnosis
68
LPS activates
protective immunity through induction of important cytokines and
chemoattractants (chemokines), as well as increased expression of costimulatory molecules, which enhance
T-lymphocyte activation.
69
high levels of LPS
play an important role in septic shock disseminated intravascular coagulation, and acute respiratory distress syndrome,
mainly through induction of excessive levels of cytokines such as tumor necrosis factor
70
Exotoxins
secreted proteins that cause cellular injury and disease. They can be classified into broad categories by their mechanism and site of action.
71
Enzymes.
Bacteria secrete enzymes (proteases, hyaluronidases, coagulases, fibrinolysins) that act on their respective substrates in vitro, but their role in disease is
understood in only a few cases. For example, exfoliative
toxins are proteases produced by S. aureus that cleave
proteins known to hold keratinocytes together, causing
the epidermis to detach from the deeper skin
72
A-B toxins:
Toxins that alter intracellular signaling or regulatory pathways. The two-component toxins have an
active (A) component with enzymatic activity and a
binding (B) component that binds cell surface receptors
and delivers the A protein into the cell cytoplasm.
73
The effect of these toxins depends on
binding specificity
of the B domain and the cellular pathways affected by
the A domain.
74
A-B toxins are made by many bacteria
| including
Bacillus anthracis, V. cholerae, and Corynebacterium diphtheriae.
75
Mechanism of anthrax exotoxin action
The B subunit, also called
protective antigen, binds a cell-surface receptor, is cleaved by a host protease,
and forms a heptamer.
76
ThreeA subunits of edema factor (EF) or lethal factor
| (LF) bind to
heptamer, enter the cell, and are released into the cytoplasm. EF binds calcium and calmodulin to form an adenylate cyclase that
increases intracellular cAMP, which causes efflux of water and interstitial
edema
77
. LF
protease that destroys mitogen-activated protein kinase
kinases (MAPKKs), leading to cell death. cAMP, cyclic adenosine monophosphate.Note that each B subunit binds either EF or LF, but not both
78
Injurious Effects of Host Immune Responses
```
Granulomatous inflammation.
T-cell–mediated inflammation
Innate immune inflammation
Humoral immunity
Chronic inflammatory diseases
Cancer
```
79
Granulomatous inflammation
Infection with M. tuberculosis results in a delayed hypersensitivity response and
the formation of granulomas, which sequester the bacilli
and prevent its spread, but also produce tissue damage
(caseous necrosis) and fibrosis.
80
T-cell–mediated inflammation
Damage from HBV and
HCV infection of hepatocytes is due mainly to the
immune response to the infected liver cells and not to
cytopathic effects of the virus.
81
Innate immune inflammation
Pattern recognition receptors bind to pathogen-associated molecular patterns
(PAMPS) and to damage-associated molecular patterns
(DAMPS) released from damaged host cells, activating
the immune system and leading to inflammation
82
Humoral immunity
Poststreptococcal glomerulonephritis can develop after infection with S. pyogenes. It is caused by antibodies that bind to streptococcal antigens
and form immune complexes, which deposit in renal glomeruli and produce nephritis
83
Chronic inflammatory diseases
In the development of inflammatory bowel disease, an important early event may be a compromise of the intestinal epithelial barrier, which enables the entry of both pathogenic and commensal microbes and their interactions with
local immune cells, resulting in inflammation. The cycle of inflammation and epithelial injury may be an important component of the disease, with microbes playing
the central role.
84
Cancer
Viruses, such as HBV and HCV, and bacteria, such as H. pylori, that are not known to carry or to activate oncogenes are associated with cancers, presumably because these microbes trigger chronic inflammation with subsequent tissue regeneration, which provides fertile ground for the development of cancer
85
IMMUNE EVASION BY MICROBES
microorganisms have developed many
means to resist and evade the immune system
These mechanisms of escaping the immune response are important determinants of microbial virulence and
pathogenicity.
86
Antigenic variation.
Neutralizing antibodies against
microbial antigens block the ability of microbes to infect cells and recruit immune cells to kill pathogens. To escape recognition, microbes use many strategies that involve genetic mechanisms for generating antigenic
variation.
87
Borrelia species
switch their surface antigens via gene rearrangement
88
Trypanosoma
species have many genes for their major surface antigen, VSG, and
vary the expression of this surface protein. There are more than 90 different serotypes of S. pneumoniae, each
with a different capsular polysaccharide.
89
Modification of surface proteins
Host cationic antimicrobial peptides, including defensins, cathelicidins, and thrombocidins, provide important initial defenses against invading microbes.
90
```
Bacterial pathogens (Shigella spp., S.
aureus)
```
avoid killing by making surface molecules that
| resist binding of anti-microbial peptides, or that inactivate or downregulate anti-microbial peptides.
91
Overcoming antibodies and complement
Host defense
includes coating of bacteria with antibodies or the complement protein C3b (opsonization) to facilitate phagocytosis by macrophages
92
M. tuberculosis subverts the
| complement response by
activating the alternative complement pathway in the extracellular environment,
and complement products coat the bacteria, resulting in
uptake of the organism by monocytes; by this means,the organism reaches its site of replication
93
```
Many bacteria (such as Shigella, enteroinvasive E. coli, M. tuberculosis, M. leprae, S. enterica serotype Typhi) use the inside
of cells as a
```
“hideout” that allows them to escape from
| antibodies and complement
94
Listeria monocytogenes
can manipulate the cell cytoskeleton to spread directly from
cell to cell, thus allowing the bacteria to evade immune
defenses.
95
Resisting phagocytosis and bacterial killing in phagosomes.
Phagocytosis and killing of bacteria by neutrophils and
macrophages constitute a critical host defense against
extracellular bacteria.
96
S. pneumoniae, Neisseria meningitidis, H. influenzae
makes them more virulent by preventing phagocytosis
of the organisms by neutrophils. Surface proteins that
inhibit phagocytosis include proteins A (S. aureus) and
M (S. pyogenes).
97
Macrophages usually kill bacteria by
fusion of the phagosome with the lysosome to form
| a phagolysosome
98
M. tuberculosis
blocks fusion of the
lysosome with the phagosome, allowing the bacteria to
proliferate unchecked within the macrophage
99
Legionella
produces a pore-forming protein called listeriolysin O and two phospholipases that degrade the phagosome membrane, allowing the bacteria to escape into the cytoplasm and avoid destruction in the macrophage. Legionella also secretes proteins that modulate small GTPases, master regulators of intracellular signaling to modify trafficking
100
Escaping the inflammasome
The activation of the cytosolic
the inflammasome is one pathway of innate immune responses to microbes. It is stimulated by microbial products and culminates in the activation of caspases, which induce the secretion of the pro-inflammatory cytokines IL-1 and IL-18 and induce a form of cell death
called pyroptosis
101
bacteria, such as Yersinia and Salmonella, express
virulence proteins that inhibit the formation of the mature inflammasome, suppress caspase activation, block signaling pathways that are required for inflammasome activation, or limit the access of other bacterial proteins to the inflammasome
102
Disruption of interferon pathways
Viruses have developed a large number of strategies to combat interferons
(IFNs), which are mediators of early antiviral defense.
Some viruses produce soluble homologues of IFN receptors that bind to and block the actions of secreted IFNs,
or produce proteins that inhibit intracellular JAK/STAT
signaling downstream of IFN receptors.
103
RIG-I (RNA
| helicase retinoic acid inducible gene I protein)
host
cytoplasmic pattern recognition receptor for intracellular double-stranded RNA viruses. RIG-I inhibits signaling by this receptor, thus blocking the downstream IFN pathway and overcoming this host defense.
104
Decreased T-cell recognition
```
DNA viruses (e.g., HSV,
CMV, and EBV) can bind to or alter the localization of major histocompatibility complex (MHC) class I proteins, impairing peptide presentation to CD8+ cytotoxic
T cells
```
105
downregulation of MHC class I molecules
```
might cause virus-infected cells to be targets for
NK cells, herpesviruses also express MHC class I homologs that act as decoys that engage inhibitory receptors of NK cells
```
106
Herpesviruses
```
can target MHC class II
molecules for degradation, impairing antigen presentation to CD4+ helper T cells
```
107
Viruses also can infect leukocytes to directly compromise their function
HIV infects CD4+ T cells, macrophages, and dendritic cells
