Transcript Host-Microbe Relationships and Disease

1
Host-Microbe Relationships and Disease
• Classical ecological definitions
– Mutualism: organisms live together, both benefit
• E. coli in GI tract; we get Vitamin K, protection from
pathogens, it gets warm wet place to live, lots to eat.
– Commensalism: one organism benefits, the other is not
particularly benefited or harmed; to eat at the same table
• Most GI tract microbes; we provide a warm wet place
to live with food, we don’t get all that much in return.
– Parasitism: one organism benefits at the other’s expense
• Disease-causing bacteria; to them, we’re dinner.
• Classically, a “parasite” lives in or on host.
2
Terms, terms, and more terms
• Contamination: presence of microbes (where they don’t
belong).
• Infection: multiplication of parasitic organisms in/on host.
– Infestation: used to describe larger organisms, e.g. lice.
• Disease: malfunction in or damage to the host.
– Many kinds of “disease”; here we discuss “infectious
disease”.
– Disease is a condition of the host, not an infectious
microbe.
• Pathogen: a parasite capable of causing disease
– Not all pathogens are equal as we will see..
• Pathogenicity: ability of pathogen to cause disease
3
Terms, terms, and more terms-2
• Virulence: relative ability to cause disease.
– Especially variations in pathogenicity w/in specific group
– Can be weakened (attenuation) or increased (animal
passage); Growing pathogens on agar attenuates them.
• Normal microbiota: the microbes normally found on the
body. Since people are not “normally” sick, pathogens are
not normally consider “normal microbiota”.
• “flora” is to be avoided as microbes are NOT plants!
– Resident microbiota: always found on human tissues.
– Transient microbiota: come and go, can include potential
pathogens.
4
Where do they live?
• Microbes live where it is “topologically outside”
– We are a tube within a tube. We have sacs
open to the outside.
• Respiratory tract:
– nasal passages, sinuses, trachea, lungs. Lungs
well protected, other areas more populated.
• GI tract: Crowded!
– Mouth is full, fewer in esophagus and stomach; toward
end of small intestine, numbers increase greatly.
– Feces consist largely of bacteria.
http://www.radiation-scott.org/deposition/respfig2.gif
5
Where do they live?-2
• Skin: largest organ in the body.
– Colonized. Various factors keep the numbers down.
• Genito-urinary tract:
– Female reproductive tract colonized, especially with
Lactobacillus (helpful) and yeast (sometimes harmful)
– Lower portion of urethra contains some bacteria, but
bladder, ureters, and kidneys normally sterile.
• Fluids
– Blood, cerebrospinal fluid should be sterile
• All areas of the body have mechanisms for keeping
us from being lunch; to be discussed soon.
6
What determines whether we get sick?
• Inf Dis: the likelihood of
contracting an infectious
disease.
• N: the numbers of infecting
organisms.
•V: the virulence of the organism.
•HF: host factors, including overall health, nutritional
status, genetic background, age, immune status.
7
How dangerous?
• Pathogen: causes disease.
• Opportunistic pathogen: can cause disease under the
right circumstances
– Dose in high numbers
– Host is in a weakened state, e.g. HIV infection.
– Organism gets where it doesn’t belong
• E. coli and urinary tract infections.
– Lack of microbial antagonism, e.g. superinfection
• competition for space, nutrients; bacteriocins.
• Saprotroph: decompose dead stuff.
Whether an organism will cause disease
is not always a clear cut thing
8
• Not everything in biology can be neatly classified.
There is a gradation from pathogen to opportunist to
non-infectious, and what happens depends on the
balance of these 3 factors.
9
Types of disease
•
•
•
•
Inherited diseases: caused by a faulty gene
Congenital: due to damage during development.
Degenerative diseases, due to age or lifestyle
Nutritional, endocrine, mental, immunological,
neoplastic (cancer), idiopathic; same caveat.
• Iatrogenic: caused by doctor.
– Nosocomial infections: occur in hospital.
• Infectious disease: caused by infectious agents
– Bacteria, viruses, fungi, etc.
– Infectious agents may affect other types of disease
10
Types of infectious diseases
• Communicable: can be spread from one person to
another.
– Example: tuberculosis, HIV
• Contagious: highly communicable, can easily be
spread from one person to another.
– Genital herpes, measles.
• Non-communicable: are not spread from one host to
another.
– Examples: your infected appendix bursts
– You get tetanus from “rusty nail”
How bacteria cause disease
11
• Bacteria can be invasive
– Bacteria spread through tissues, usually using
digestive enzymes which damage tissues, kill cells.
• Bacteria can be toxigenic (produce toxins)
– Bacteria may not spread, but release soluble toxins
which dissolve in body fluids, damaging cells.
– Gram negative contain endotoxin (LPS)
• Host processes
– Host defenses, like inflammation, may overrespond, cause significant tissue damage.
Disease by other microbes
12
• How viruses causes disease
– Viruses multiply inside host cells, using cell
resources, often killing cells.
– Viruses stimulate the immune system to fight back;
infected cells are killed.
– Viruses alter cell cycle regulation to promote their
own replication; may lead to cancer.
• Fungi, Protists, and worms
– Produce enzymes that damage host cells
– Multiply in host cells and kill them
– Cause allergic reactions or inflammation
Steps in an infectious disease-Overview
13
• Entry and attachment
– Microbe needs to approach tissue, then attach to it.
• Deal with host defense
– Successful parasite must infect, persist long enough to
reproduce, then escape. Host defense seeks to kill it.
• Damage: if disease is involved, damage occurs.
• Escape: parasite must escape and spread to others.
– Discussed in “Portals of exit”
Virulence Factors: Things that bacteria have that
improve their abilities to cause disease
– Fimbriae, capsules, enzymes, toxins, all these things.
Typical steps in a bacterial infection
14
• Attachment
– Typical first step is attachment to tissues. Often a
specific interaction takes place between molecules.
– Fimbriae, capsules help in attachment.
– Molecules that aid in attachment = adhesins.
• Deal with host defenses
– A pathogen can defend, attack, or hide.
• Interfere with phagocytosis, have a capsule, etc.
• Produce leukocidins, etc.
• Switch surface antigens, hide inside WBC, etc.
Step 3: Damage
15
• Damage occurs from combination of factors
– Bacteria increase their growth by
• Releasing enzymes that break down host cell
molecules, releasing nutrients or allowing spread.
–Hemolysins release iron; siderophores collect.
• Releasing toxins that kill cells or damage organ
systems, eliminating host resistance.
– Bacteria cause disease by
• Stimulating inflammation, leading to damage and
discomfort
• Over-stimulating host defense, damaging cells
and organ systems.
Virulence factors: enzymes and toxins
16
• Enzymes
– Collagenase, hyaluronidase, coagulase,
streptokinase. Allow spread or hiding of pathogen.
• Toxins
– Exotoxins, produced by G+ and G-, proteins, heat
labile, released and affect different targets
• Enterotoxins, neurotoxins, general cytotoxins.
– Endotoxin: LPS, especially Lipid A part
• Present only on Gram –
• Released when bacterium dies
–Acts as Super antigen
Hijacking host defenses
17
• Inflammation
– A protective mechanism, but can cause local
damage.
• Chronic inflammation results in loss of functional
tissue, disease.
• Super antigens
– Endotoxin, Toxic Shock Syndrome toxin, et al.
• Cause massive over response of WBS
– Followed by decreased responsiveness
• Fever, shock, intravascular coagulation