Transcript Spring 2015-Chapter 14

HOST-MICROBE RELATIONSHIPS
AND DISEASE PROCESSES
CHAPTER 14
Copyright © 2012 John Wiley &
Sons, Inc. All rights reserved.
Host-microbe relationships
Symbiosis- is an association between two (or more) species.
1) mutualism- both members of the relationship
benefit
2) commensalis- two species live together in a
relationship such that one benefits and the other one neither
benefits nor is harmed.
3) parasitism- one organism, the parasite, benefits
from the relationship whereas the other organism, the host is
harmed.
The lines between these different symbiotic
relationships is not always clear- by taking up residence on the
skin and utilizing nutrients microbes that show mutualistic or
commensalistic behavior may prevent colonization of the skin by
other, potentially harmful, disease-causing microbes a
phenomenon known as microbial competition. Also between
parasitism and commensalism- normally harmless organisms can
become parasitic if it gains entrance to certain parts of the body.
Contamination, infection and diseaseContamination-microorganisms are
present.
Infection- multiplication of any parasitic
organism within or upon the host’s body-does
not necessarily result in disease
Disease- disturbance in the state of health
wherein the body cannot carry out all its normal
functions
Pathogens, pathogenicity and virulence
Pathogenicity is the capacity to produce disease.
Pathogenicity depends on the ability of an organism to invade and
avoid the hosts defense mechanisms, and to multiply.
Virulence-refers to the intensity of the disease produced by
pathogens and it varies among different microbial species.
The virulence of a pathogen can be decreased by attenuation,
the weakening of the disease producing ability of the pathogen.
Attenuation can be achieved by repeated subculturing on
laboratory media or by transposal of virulence (e.g,. Passage of
rabies virus through a rabbit until it was no longer virulent in
humans).
The yellow area give examples (not complete by any means) of how these systems may be
Compromised or how they set an environment for infection.
removal of ciliated
cells by influenza vir
antibiotics
burns,
cuts
aeration, macrophage delivery
diseases of the blood or
systemic
bacterial infections
acid loving bacteria- Helicobacter pylori
Rhinovirus cannot survive the rapid
pH change
antibiotics
not sufficient fluids
Natural body defenses against infection
Among the resident and transient microflora are some species of
organisms that do not usually cause disease but can do so under
certain conditions. These organisms are termed opportunists
and conditions that create opportunities for these organisms
include:
1. Failure of the host’s normal defenses, e.g,
immunocompromised (AIDS, Transplant, chemotherapy),
severe burns.
2. Introduction of the organisms in unusual body sites e.g,
E.coli in urinary tract, or S. aureus in the brain.
3. Disturbances in the normal microflora- e.g, caused by
some antibiotics.
Koch’s Postulates:
1. The specific causative agent must be observed in every case
of a disease
2. The agent must be isolated from a diseased host and must be
grown in pure culture.
3. When the agent from the pure culture is inoculated into
healthy, but susceptible, experimental hosts, the agent must
cause the same disease
4. The agent must be re-isolated from the inoculated disease
experimental host an identified as identical t the original
specific causative agent.
Not all infectious diseases can fulfill Koch’s postulates
(bacterial or viral diseases in which the organisms cannot be
cultured, e.g., syphilis, viral diseases), however, the approach to
establishing whether or not an organism is responsible for a
disease uses Koch’s postulates as a guideline.
Kinds of Diseases
Infectious and noninfectious diseasesInfectious diseases are diseases cause by infectious agents such
as bacteria, viruses, fungi, protozoa and helminths (we will not
cover the latter two categories in this course).
Noninfectious diseases are caused by any other agents than
infectious organisms.
Contagious disease-A contagious disease is a subset category of
infectious diseases (or communicable diseases), which are easily
transmitted by physical contact (hence the name-origin) with the
person suffering the disease, or by their secretions or objects
touched by them.[
When diseases are discovered to move from the bottom
category (noninfectious disease) to the top category
(infectious disease) a cure or partial cure is often
accomplished (e.g., ulcers or cervical carcinoma).
Communicable and noncommunicable diseases
Communicable- can be spread from one host to another
Contagious diseases- communicable diseases that are more easily
spread than others-such as, influenza, common cold, rubella
Noncommunicable infectious disease- are not readily spread
from one host to another, e.g., tetanus, botulinum, legionellosis,
The Disease Process- How Microbes Cause Disease
How bacteria cause diseaseVirulence factors- structural or physiological characteristics that help
organisms cause infection and disease,
e.g., pili for adhesion to cells (famous gonorrhea study),
capsules to prevent phagocytosis, enzymes, such as
hyaluronidase that help to digest tissues.
Direct actions of bacteria- Bacteria can enter the body by
penetrating the skin or mucous membranes,
by sexual transmission, `
by being ingested with food,
by being inhaled in aerosols, or
by transmission on a fomite (inanimate object).
If the bacteria are immediately swept out of the body they cannot initiate
infection.
Adherence or attachment, is a critical point in the production of bacterial
disease
Adhesin are proteins or glycoproteins found on attachment pili (fimbrae) and
capsules.
Also organisms such as Shigella appear to attach via their LPS.
Adhesin are proteins or glycoproteins found on attachment pili (fimbrae) and capsules.
Colonization- is another critical point in the production of
disease and it refers to the growth of microorganisms on
epithelial surfaces, such skin or mucous membranes or other
host tissues. Again a question of adherence (adhesins).
Invasiveness- only a few pathogens cause disease by
colonizing surfaces; most have additional virulence factors
that enable the pathogen to invade tissue, i.e.. invasiveness
Invasiveness- only a few pathogens cause disease by colonizing surfaces; most have additional
virulence factors that enable the pathogen to invade tissue, ie.. invasiveness
pathogens
pathogens coagulase
hyaluronidase
blood clot
streptokinase
Some bacteria enter cells and are protected within these cells, such as, rickettsias, chlamydias,
mycobacterium tuberculosis and Neisseria gonorrheae.
Fig. 14.5 Enzymatic virulence factors help bacteria invade tissues and evade host defenses
Bacterial Toxins
Endotoxins
Exotoxins
• Gram negative
• Gram positive
• LPS
• Proteins, usually enzymes
• Fever
• Potent effects
• Shock
• Specialized tissue damage
• Released at cell death
• Secreted
Copyright © 2012 John Wiley &
Sons, Inc. All rights reserved.
Bacterial toxins- A toxin is any substance that is poisonous to other
organisms.
Exotoxins- soluble substances secreted into host tissues-are mostly
polypeptides more powerful and specific than endotoxins, and can be
denatured by heat to form toxoids.
The Gram positive species of Clostridium, Bacillus, Staphylococcus,
Streptococcus and several other bacteria produce exotoxins.
Vibrio cholerae and toxigenic E.coli are Gram negative organisms that
produces a potent exotoxins.
Many exotoxins are of the A-B type (slide 20). The B subunits bind to
the surface membrane of the cell, whereas, the A subunit is the
business end.
Endotoxins- are part of the cell wall (LPS), of gram negative organisms,
that are released into host tissues when the bacteria die or divide.
Endotoxins have nonspecific effects such as fever or a sudden drop in
blood pressure. They also cause tissue damage in diseases such as
typhoid fever and epidemic meningitis.
Adhesins are proteins or glycoproteins found on pili and capsules
se
50%
Fa
l
50%
Tr
ue
A. True
B. False
New, aggressive form of HIV identified in Cuba In Cuba, a variant of HIV that is
much more aggressive than other known forms of the virus has been
documented. Patients infected with this new variant progress to AIDS so
rapidly that they may not even know they are infected, with AIDS symptoms
occurring within 3 years of infection. If a person contracts multiple strains of
HIV - typically by engaging in unprotected sex with multiple infected partners
- then these strains can recombine into a new variant of HIV within the host.
The new Cuban variant of HIV is one such recombinant version of the virus.
HIV anchors itself to co-receptors - proteins on the membranes of cells - before
the virus is able to penetrate the cell. The first co-receptor that HIV anchors to
is known as CCR5. Then, after a number of years of normal health, the virus
switches to the anchor point CXCR4, which results in a faster progression to
AIDS. In the recombinant form of HIV identified in Cuba, HIV makes the
transition to CXCR4 shortly after infection, reducing the healthy phase and
initiating the progression to AIDS. The patients with the recombinant HIV
were found to have abnormally high doses of the virus and defensive
molecules called RANTES. RANTES is part of the human immune response and
binds to CCR5 - the co-receptor that HIV initially anchors onto after infection.
Hope for people with Parkinson’s Scientists at Harvard University say they see
promising signs from their study on an experimental treatment for Parkinson's disease.
The researchers transplanted tissue from fetal dopamine cells into the brains of
patients with Parkinson’s in Canada.
Patients with severe symptoms experienced 50% fewer symptoms in the years after
surgery. People who had been taking medication to control their Parkinson’s but found
that the medicine no longer worked also saw significant improvements after surgery.
Looking at the brains of five patients after they died from non-Parkinson’s related
illnesses, the scientists found that the transplanted cells stayed healthy. Earlier research
led scientists to hypothesize that the cells would become corrupted, but the cells
remained functional for at least 14 years after the patients got them. This is the first
proof that this kind of transplant method could work.
"Though it is encouraging and even exciting to see some PD cells survive over a decade
following a human transplant, we are still humbled by the challenges in developing a
viable therapy," Dr. Michael Okun, national medical director for the National Parkinson
Foundation, cautioned. "All transplants for Parkinson's disease remain hampered by an
inability to constitute a complex multilevel brain circuitry."
Action of endotoxin
a, or active subunit
Action of exotoxin
Action of exo- and endotoxinimportant and not in your text
b, or binding subunit
A-subunit alters cell function
DT= diphtheria toxin
Nicotinamide-adenine-dinucleotide-phosphateribose (NADP)
ADP-ribosylation is a
mechanism used by many
toxins. The target proteins
differ (diphtheria ADPribosylates the EF factor;
cholerae toxin ADP-ribosylates
adenylcyclase).
Figure of ADP ribosylation- the most common mechanism of
Bacterial toxin action- Typical of diphtheria toxin
Clostridium botulinum
Blocks muscle contraction
Clostridium tetanus –blocks
muscle contraction
inhibition
Botulinum toxin blocks the release of neurotransmittor
ADP-ribosylates
the protein that
regulates the synthesis of
of cyclic AMP. The result
is highly elevated levels
of cyclic AMP which in
turn results in a blockage
in movement of Na+ into
the tissues and an outflow
of Cl- ions into the lumen.
The gut has a marked
increase in NaCl.
Action of choleratoxin
How viruses cause disease
In cultured cells viruses cause observable changes termed
cytopathic effect (CPE)
Viral infections can be productive or abortive.
Productive infection occurs when viruses infect a cell and
produce infectious offspring
Abortive infection occurs when viruses enter a cell but are
unable to make offspring (viruses used for gene therapy
are typically engineered to have an abortive infection).
Latent viral infections- a virus that remains inactive
typically for a relatively long period but has the potential to
be reactivated, e.g., varicella/zoster, or HSV,
Persistent viral infection- hepatitis B virus
B
e
Before viral infection
After viral infection
Fig. 14.7 An example of the cytopathic effect (CPE)
Fig. 14.9 Stages in the course of an infectious disease
Infectious Diseases- Past, Present and Future
1918-flu
pandemic
Fig. 14.11 Changes in the
Causes of death in the US
From 1900 to the 1990’s