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 dont get all that
  much in return.
• Parasitism one organism benefits at the others
  expense
• Disease-causing bacteria to them, were dinner.
• Classically, a parasite lives in or on host.

2
Terms, terms, and more terms

• Contamination presence of microbes (where they
  dont 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 doesnt belong
• E. coli and urinary tract infections.
• Lack of microbial antagonism, e.g. superinfection
• competition for space, nutrients bacteriocins.
• Saprotroph decompose dead stuff.

8
Whether an organism will cause disease is not
always a clear cut thing

• 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

11
How bacteria cause disease

• 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
  over-respond, cause significant tissue damage.

12
Disease by other microbes

• 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

13
Steps in an infectious disease-Overview

• 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.

14
Typical steps in a bacterial infection

• 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.

15
Step 3 Damage

• 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.

16
Virulence factors enzymes and toxins

• 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

17
Hijacking host defenses

• 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