Lippincott chapter 3 - DONE Flashcards
Pathogenic microorganism def.
it is defined as one that is capable of causing disease
Virulence can be quantified by:
how many organisms are required to cause disease in 50% of those exposed to the pathogen or to kill 50% of test animals
The probability that an infectious disease occurs is influenced by:
both the number and virulence of the infecting organisms and the strength of the host immune response opposing infection
Virulence factors:
are those characteristics of bacterium that enhance its pathogenicity, that is, properties that enable microorganisms to establish itself and replicate on or within a specific host
Some of the most important steps in the infectious process are:
- entry into the host
- adherence to the host cells
- invasiveness
4 iron sequestering - virulence factors that inhibit phagocytosis
- bacterial toxins (exotoxins, and endotoxins)
Ways that an microorganism can enter the host:
- respiratory tract
- GI tracts
- urogenital tract
- through skin that has been cut, punctured, or burned
After the microorganism has entered the host, what is it that the pathogen has to overcome?
it has to overcome diverse host defenses before it can establish itself
Give examples of the things the pathogen must overcome before establishing itself in the host:
- phagocytosis
- acid environments of the stomach and urogenital tract
- hydrolytic and proteolytic enzymes found in saliva, stomach, and small intestine
What gives the bacteria a better chance in surviving the host defence mechanisms?
those who have an outer polysaccharide capsule have a better chance in surviving the hosts primary defenses
Give examples of bacteria that has an outer polysaccharide capsule:
- Streptococcus pneumoniae
- Neisseria meningitidis
What does the bacteria use to adhere to its host?
- Some bacteria (e.g. Escherichia coli) use pili to adhere to the surface of host cells. Group A streptococci have similar structures (fimbrae)
- Other bacteria have cell surface adhesion molecules or particularly hydrophobic cell walls that allow them to adhere to the host cell membrane.
Why does the bacteria adhere to the host?
- to avoid being carried away by mucus or washed by organs with significant fluid flow
- to form a microcolony
What are invasive bacteria?
it is those taht can enter the host cell or penetrate mucosal surfaces, spreading from the initial site of infection
Invasins:
many bacterial pathogens express membrane proteins known as “invasins” that interact with host cell receptors, thereby eliciting signaling cascades that result in bacterial uptake by induced phagocytosis.
Inflammation:
invation is followed by inflammation
What types of inflammations do we have?
- pyogenic (involving pus formation)
- granulomatous (having nodular inflammatory lesions)
What decides the type of inflammation?
if the inflammation is pyogenic or granulomatous depends on the organism
What does the pus of pyogenic inflammations contain?
mostly neutrophils
What does the pus of granulomatous lesions contain?
- fibroblasts
- lymphocytes
- macrophages
What is an essential nutrient in most of the bacteria?
iron
What does the bacteria do to obtain the iron required for growth?
they produce iron-binding compound, called siderophores. These compounds capture iron from the host by chelation, and then ferrated siderophore binds to specific receptors on the bacterial surface.
Siderophores:
is an iron-binding compound that the bacteria produce to obtain the iron required for growth
What can iron be used to in the bacteria?
Iron is actively transported into the bacterium, where it is incorporated into essential compounds such as cytochromes
The pathogenic Neiserria species are exceptions in that they……….
do not produce siderophores but instead utilize host iron-binding proteins, such as transferrin and lactoferrin, as iron sources. They do so by expressing dedicated receptors that binds to these host proteins and remove the iron for internalization
The most important antiphagocytotic……
- structure is the capsule external to the cell wall
- factors are the cell wall proteins of gram-positive cocci, such as protein A for staphylococcus and M protein of group A streptococci
Bacterial toxins:
some bacteria cause disease by producing toxic substances
What are the two categories of substances produced by bacteria?
- exotoxins
- endotoxins
Exotoxins:
- are proteins
- are secreted by both gram- positive and gram-negative bacteria
Endotoxins:
- are synonymous with lipopolysaccharides (LPS), is not secreted by instead is an integral component of the cell walls of the gram-negative bacteria
How are the structures of exotoxins?
they have two polypeptide components. One is responsible for binding the protein to the host cell, and one is responsible for the toxic effect.
Diphtheria toxin (exotoxin):
an enzyme that blocks protein synthesis. It does so by attaching an adenosine diphosphate-ribosyl group to human protein elongation factor EF-2, thereby inactivating it.
Heat stable toxins (ST):
most exotoxins are rapidly inactivated my moderate heating (60 degree celsius), notable exceptions being staphylococcal enterotoxin and E. coli heat stable toxin
What does dilute formaldehyde do to exotoxins?
Treatment with dilute formaldehyde destroys the toxic activity of most exotoxins but does not affect their antigenicity
Toxoids:
formaldehyde-inactivated toxins
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Endotoxins:
- heat-stable
- LPS components of the outer membranes of gram-NEGATIVE bacteria
Where are endotoxins released?
into the host´s circulation following bacterial cell lysis
What does the LPS consist of?
polysaccharide composed of repeating sugar subunits (O antigen), which protrudes from the exterior cell surface; a core polysaccharide; and a lipid component called lipid A that is integrated into the outer leaflet of the outer membrane.
What is the lipid A moiety responsible for?
for the toxicity of LPS
What is the main physiologic effects of LPS endotoxins?
- fever
- shock
- hypotention
- thrombosis
=> collectively referred to as septic shock
How are the effects of LPS produced indirectly?
(septic shock)
they are produced indirectly by macrophage activation, with the release of cytokines, activation of complement, and activation of the coagulation cascade.
What can cause a sudden massive release of endotoxin into the circulation?
elimination of the causative bacteria with antibiotics can initially exacerbate the symptoms causing a sudden massive release of endotoxin into the circulation.
gram-positive and gram-negative shock
- gram-negative bacteria-> shock is more severe.
- gram-positive gram-positive -> do not contain LPS, but they can still elicit a shock
Host-mediated pathogenesis
the tissue damage caused by the host (lymphocytes, macrophages, and polymorphonuclear leukocytes) at the site of infection allows the bacteria to proliferate (?)
Phase variation:
the genetically reversible ability of certain bacteria to turn off and turn on the expression of genes coding for surface antigens.
Antigenic variation:
involves the modification of the gene for an expressed surface antigen by genetic recombination with one of many variable unexpressed DNA squences
Opportunistic pathogen:
is an organism that is unable to cause disease in healthy, immunocompetent individuals but can infect people whose defense have been impaired
Bacterial disease may be communicable from person to person or……..
noncommunicable
Give an example of a bacteria that is communicable:
Vibro cholera
Describe botulism:
botulism is noncommunicable because only those people who ingest botulinum exotoxin are affected
Describe cholera:
- contagious
- occur as localized epidemics in which the disease frequency is higer than normal
Pandemic:
- when an epidemic becomes world wide
- arise because the human population has never been exposed to, and therefore, has no immunity against the specific strain of influenza virus
Cell death caused by virus:
- the virus have specific genes that inhibits the bacteria´s synthesis of DNA, RNA, and proteins -> this leads to cell death
What do we call the viruses that kill their host?
- adenovirus
- poliovirus
What are the types of vital pathogenesis at the cellular level?
- cell death
- transformation of the host cell
- host cell fusion
- cytopathic effect
Transformation:
- is n irreversible genetic process caused by the integration of viral DNA into the host´s DNA
- transform normal cell to maligant cell
- less fastidous growth -> indefinetly extended lifetime
Cell fusion:
- > producing giant, multinucleated cells
- the ability of infected cell to fuse is apparently due to virus-induced changes in the structure of the cell membrane
Cytopathic effect
- refers to any visible change in the appearance of an infected cell
- e.g. cell rounding, patches, stainable viral proteins inside the cell, and cell disintegration
Typical symptoms of disease may occur, often in two temporally distinct forms:
- early symptoms at the primary site of infection
2. delayed symptoms due to dissemination from the primary site, causing infection of secondary site
- some viruses remain localized after entering the body……..
and cause disease that is largely restricted to the primary site of infection
- Other viruses undergo multiplication……
in cells at the primary site, which may be accompanied by symptoms, followed by invasion of the lymphatic system and blood
Viremia:
the presence of virus in the blood
- How is the virus disseminated?
Virus is disseminated throughout the body via the bloodstream and can infect cells at secondary sites characteristic for each specific virus type, thus causing the disease typically associated with that species
- What does viruses exhibit?
Viruses frequently exhibit tropism for specific cell types and tissues. This specificity is usually caused by the presence of specific host cell surface reseptors recognized by particular viruses
Give an example of an especially important site for secondary localization of virus infections:
fetus. Virus from the maternal circulation infects cells of the placenta, thereby gaining access to the fetal circulation an, ultimately, to all tissues to all of the developing fetus. This can result in fetal death or abnormalities. Neonatal infection can also occur during birth the the fetus comes in contact with infected genital secretions of the mother or after birth when the infant ingests infected breast milk.
Give examples of common sites of viral shedding:
- skin
- respiratory tract
- GI tracts
- bodily fluids
How much time does it take for the virus to be totally eliminated in a typical, uncomplicated, acute infection?
2-3 weeks. This outcome is primarily a function of the host´s immune system, with involvment of both cell-mediated and humoral response. The relative importance of these two responses depends on the virus and the nature of the disease.
Cell-mediated responses:
- earliest immune system response to virus infection is a generalized inflammatory response, accompanied by nonspecific killing of infected cells by NK cells.
- enhanced by interferone and other cytokines
- begins before virus-specifc immune response
- SEE MORE PAGE 17
NK cells =
natural killer cells
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Viruses that can be transmitted from the mother to the infant:
- Herpes simplex virus type 1 and 2
- Human cytomegalovirus
- Human immunodeficiency virus
- Rubella virus
Infected mothers can transmit viral infections to their offspring by three routes:
- in utero by transplacental spread
- during delivery through an infected birth canal
- after birth by ingestion of milk
Koch´s postulates
- the microorganism must always be found in similar diseased animals but not in healthy ones
- the microorganism must be isolated from a diseased animal and grown in pure culture
- the isolated microorganism must cause the original disease when inoculated into a susceptible animal
- the microorganism can be reisolated from the experimentally infected animal
Mechanism of infectious process:
- entry into the host, with evasion of host primary defenses
- adhesion of the microorganism to host cells
- invasion of the host
- propagation of the organsim
- damage to host cell by bacterial toxins or immune response of the host
- progression or resolution of the disease
Subclinical:
- an infection with no detectible symptoms
- example: asymptomatic gonorrhea
Latent:
- an infection with the potential to become active at some time
- examples: Treponema pallidum (syphilis) and Mycobacterium tuberculosis (tuberculosis)
Opportunistic:
- an infection due to an organism that generally does not cause disease unlessnormal host defenses are compromised
- example: Pneumocystis pneumonia in patients with HIV
Primary:
- infection by an organism that may become latent and later cause other disease manifestation
- example: Treponema pallidum (syphilis)
Secondary:
a) reactivation of a latent infection
b) the second stage of an infection
- examples:
a) Mycobacterium tuberculosis (tuberculosis)
b) Treponema pallidum (syphilis)
Mixed:
- two or more bacteria infecting the same tissue
- example: pelvic inflammatory disease may be initiated by infection with N. gonorrhoeae or C. trachomatis but other organisms including anaerobes play important roles in progression of the disease
Pyogenic:
- pus formation
- example: staphylococcal and streptococcal infection
Fulminant:
- Infections that occur suddenly and intensely
- example: Necrotizing fasciitis from Streptococcus pyogenes, also called “flesh eating bacteria”