MEDICINE GROUP: INFECTIOUS
DISEASES AND ONCOLOGY
LECTURE 1 – INTRODUCTION
The human body can be exposed to various factors causing disease. However, from the
inside the body itself can form tumors due to pathogens or viruses, like the Rous Sarcoma
virus, which is an oncovirus.
The Src Protein Kinase has been found as an oncogene in tumor cells. Most kinases are
found as regulators, so if there is a mistake in the gene, they can form proto-oncogenes.
This leads to regulation of embryonic development and cell growth. The V-SRC is
constitutionally active leading to uncontrolled growth. The Human papillomavirus causes
infections on the skin or mucous membranes. In 90% of the cases nothing happens.
However, warts can be formed (benign papilloma) and in rare cases it can cause cancer.
This was more the case for woman, which developed cervical cancer. Helicobacter pylori
implicated in stomach cancer (1%).
The Miasma theory said that people got sick because of bad air. John Snow studied
epidemiology and he identified a water pump as a source of the disease. The Haussmann
Renovation was a change in the architecture so that all the bad air left, however, the
population density decreased and increased hygiene.
Koch postulates
1. The microorganism must be found in abundance in
all organisms suffering from the disease, but should
not be found in healthy organisms
2. The microorganism must be isolated from a diseased
organism and grown in pure culture
3. The cultured microorganism should cause disease
when introduced into a healthy organism
4. The microorganism must be reisolated from the
inoculated, diseased experimental host and
identified as being identical to the original specific
causative agent
What is part of life: organization, homeostasis, metabolism, growth, response,
reproduction, and adaption.
LINES OF DEFENSE
There are different cohabitation models (symbiosis). There is mutualism (both organisms
profit from each other), commensalism (both organisms do not harm each other),
parasitism (one organism suffers from the other). Bacteria can induce disease, but most of
them are helpful to organisms and ecosystems.
In the intestine the bacteria have different functions:
- Protective functions: pathogen displacement, nutrient and receptor competition,
production of anti-microbial factors
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, - Structural functions: barrier fortification, induction of IgA, apical tightening of
tight junctions
- Metabolic functions: control IEC differentiation and proliferation, metabolize
dietary carcinogens, synthesize vitamins, ion absorption, salvage of energy
The lower in the body, the more bacteria are found, because the pH is more favorable for
the bacteria to live in.
The bacteria on the skin differ based on sex, age, site, environment, immune system, etc.
The main first line of defense is the skin. Inside the body the immune system consists of
hundreds of tiny organs (lymph nodes) and two large organs (thymus and spleen), which
are connected by lymph vessels. When bacteria enter the body, the first stage of the
immune system response occurs. The first cells that show up are macrophages. They kill
bacteria by digesting them. The second line are the neutrophils, which are suicide
warriors, which vomit deadly chemicals. They damage even your own cells. In the
meantime, inflammation occurs. Complement proteins are getting to the site of
infections.
The dendritic cells from the battlefield gets to the lymph nodes, where it activated T-
cells. A helper T-cells recognizes the specific T-cells and activates it. This goes very
slowly, but they are active. The helper T-cells start to duplicate. The helper T-cells
activates macrophages again. B-cells are also activated, which make antibodies. When the
bacteria is removed and killed, the cells kill themselves and some helper T-cells form
memory cells, resulting in immunity.
Lysozymes are little antimicrobial peptides, which
are present in tears, the liver, and intestine. They
consists of charged and hydrophobic parts. They can
distinguish between bacterial cell wall and
eukaryotic membranes. Bacteria do not discriminate
between inside and outside of the cell wall, leading
to charged residues on the outside, which can
interact with the charged parts of the lysozymes.
They attach to the membrane and tear apart the
head groups. This leads to more migration of
antimicrobial peptides into the cell leading to
death.
FIGHTING INFECTIOUS DISEASES
Prevention is better than curing, so nutrition, personal hygiene, and resistance are
important. Moreover, vaccination is nowadays also an important factor which prevents
development of diseases. Sterilants or disinfectants are alcohols, phenols, chlorhexidine,
ammonia, and aldehydes. However, they do not distinguish bad and good. A hospital
hygiene machine releases ozone, which lyses the bacterial cell.
THE ENEMIES
Zoonosis are diseases that come from an animal. There is direct zoonosis via air, saliva,
or a bite and indirect zoonosis via a vector.
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, - Viral diseases: rabies, ebola, corona virus
Ebola has a case fatality around 50%, but this has varied from 25% to 90% in past
outbreaks. This has to do with mutation of the virus.
- Bacterial diseases: Q-fever, anthrax, typhus, pest, MRSA
Q-fever is a disease in which the person has fever-like symptoms. The bacterium is
called Coxiella Burnetti. It is a small, gram negative, and obligate intracellular
bacterium. This was caused by aerosol transmission and ingestion by dairy.
- Protozoan diseases: toxoplasmosis
- Helminthiases: trichinosis
- Mycoses: ringworm
- Arthropoda: mites
A drug is circulating through the
body. Beneficial bacteria might also
be harmed by antibacterial drugs.
Therefore, bacteria which are
resistant to this specific drug,
might overgrow leading to another
infection.
This situation is called
opportunistic infection. Here,
bacteria become only pathogenic in cased of weakened immune system. An example is the
Pseudomonas aeruginosa, which is omnipresent and grows easily. It is resistant against
many antibiotics and causes 11% of all hospital infections.
Bacteria attach to a surface and form a
colony there. On that surface they form a
biofilm, which is a bacterial environment
in which they can live. Biofilm-forming
communities cause refractory chronic
infections. 60% of all the infections treated by physicians are related to bacteria organized
in biofilms. Due to the environment and protective layer there is high tolerance against
antibiotics. Biofilm infections can occur due to device-related infections, like contact
lenses, catheters, implants, etc. Bacteria biofilms formation is tightly regulated, as
bacteria decide whether to form a biofilm, which depends on the population density. This
is done by quorum sensing. A bacterial cell is sending out a signal, which reaches another
cell, and this causes a reaction. In low population density there are few virulence factors,
whereas in high population density there are many factors.
ANTIBIOTICS
There are multiple targets on the bacterial
cell for antibiotics. One of the targets is the
ribosome. The difference between bacterial
and eukaryotic ribosome is that bacteria
have a 70S ribosome and eukaryotes have an
80S ribosome, which 50S+30S and 60S+40S
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, subunits respectively. Therefore, specific drugs are
made for only bacteria and eukaryotes or
combined.
- Only bacteria: tetracycline, streptomycin,
chloramphenicol, erythromycin, rifamycin
- Only eukaryotes: cycloheximide,
azinomycin, α-amanitin
- Both: puromycin, actinomycin D
Another target is the bacterial cell wall. There are two types: gram negative and gram
positive. Gram-positive bacteria have a thick peptidoglycan layer and a membrane layer.
Gram-negative bacteria have an outer membrane, thin peptidoglycan layer, and a
membrane layer.
Bactericidal drugs kill the bacterium, whereas
bacteriostatic drugs keep the bacterium in a certain
growth state. For bacteriostatic drugs a functional
immune system is required, so that the immune system
can kill the bacterium.
The status of the patient is very important for administering a drug. Points to check are
allergy, age, kidney function, liver function, pregnancy/lactation, genetic factors, and
immunological response. When administering a
drug pharmacodynamic and -kinetics should be
controlled. The major infections treated by the
general practitioner are airway infections,
urinary tract infections, skin infections, STDs,
and intestinal infections.
Infections in the hospital are more dangerous because the patients with immunity
disorders. Therefore, there are so-called “hospital antibiotics” because there is a low
defense. Moreover, they have special pathogens and problem of resistance.
USAGE OF ANTIBIOTICS AND OCCURRENCE OF RESISTANCE
Simply using antibiotics creates resistance, which is why these drugs should only be used to
treat infections. The resistant bacteria can come from fertilizer or water containing animal
feces, which is used on food crops. Also in healthcare facilities resistant bacteria are
present.
The WHO stated a list with bacteria, for which novel antibiotics are needed due to
resistance. The ESKAPE groups are a group of bacteria which cause severe diseases and are
resistant to a lot of antibiotics. Bacteria part of this ESKAPE groups are:
- Enterococcus faecium
- Staphylococcus aureus
- Klebsiella pneumoniae
- Acinetobacter baumanni
- Pseudomonas aeruginosa
- Enterobacter species
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