vi sinh trong y học (microbiology in medicine)

Medical microbiology, academic year 2018-2019
Khoa Y, Đại Học Duy Tân
Lecturers: Đặng Thị Mỹ Hà, José Luis Navarro
Last updated: 18.12.2018

Lecture 1
Contents

(I) Introduction to Medical Microbiology
1. The science of microbiology
2. The importance of microorganisms
3. Microorganisms as a cause of disease: Robert Koch: The germ theory of disease
and the Koch’s postulates
4. Early days of Microbiology
5. Taxonomy
6. Evolution
7. Phylogeny. Phylogenetic trees
(II) Host-pathogen interactions
1. Normal flora in the human body
2. Basic concepts for understanding host-pathogen interactions
3. The infectious process.
a. From exposure to infectious disease: The states of infection: colonization,
commensalism, latency and disease
b. Factors that influence the development of host damage
c. Steps of the infectious process
i. Entrance. Portals of entry
ii. Adhesion
iii.
Establishment and damage
1. Microorganism abilities: Invasiveness and toxigenicity
2. Host response

(III) The host response to infection: Basics of immunology (1 of 3)
1. Introduction
2. Types of immunity
a. Innate immune system
b. Adaptive immune system

Time to
read at
home
40 min

Time in
the class

70 min

45 min

70 min

45 min

30 min

(I) Introduction to Medical Microbiology
1. The science of microbiology

•

– invade the bodies of hosts

• often causing damage through infection and
disease

Microbiology is

– a specialized area of biology that studies
• small life forms

•

– that are not observed without
magnification

– Pluricellular organisms: helminths and fungi
– Viruses, which are microscopic but not cellular.

– Microscopic organisms are called

Are they alive?

• microorganisms, microbes, …
• Some people call them “germs”

•

•

•

Microbial cells can be

– Prokaryotic: small, relatively simple, non
nucleated
– Eukaryotic: larger, more complex type that contain
a nucleus and organelles.
Viruses are microorganisms but not made of cells.
– Smaller in size
– They infect a cell (prokaryotic or eukaryotic) hosts
in order to reproduce themselves.
Some microbes are pathogens

Others:

– Prions
2. The importance of microorganisms

•
•
•
•
•

Microbes are involved in nutrient production
Make many chemical reactions that higher organisms
need
All the oxygen we breathe is the result of past
microbial activity
Some microbes recycle nutrients through
decomposition
If microorganisms do not exist, higher life forms
would never have evolved and could not now be

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Lecture 1

maintained

•

Microbes live in most of the world’s habitats:
ubiquitous

•
•

The majority of biomass on Earth (more than 60%)
Most microorganisms are not harmful for humans;

• However, nearly 2 000 microbes are pathogens
that cause infectious diseases

•

Before 16th century nobody knew that
microorganisms can cause diseases

•

16th century: “something” could be transmitted from a
sick person to a healthy person

•

19th century: Robert Koch: “The germ theory of
disease”: Some diseases are caused by
microorganisms

3. Microorganisms can cause disease
Robert Koch (1843 – 1910) and The germ theory of
disease

•

1884, Koch’s postulates: Sequence of four steps for
directly relating a specific microbe to a specific
disease:
(1) The organism that cause the disease must always
be present in animals suffering from the disease but
not in healthy animals.
(2) The organism must be cultivated in a pure culture
(isolated) outside the animal body.
(3) The isolated organism must cause the disease
when inoculated into healthy susceptible animals.
(4)The organism must be isolated from the newly
infected animals and cultured again in the laboratory,
after which it should be seen to be the same as the
original organism.

4. Early days of microbiology
• 1664, Robert Hooke: Discovery of fungi

• 1684, Antoni van Leeuwenhoek: Discovery of bacteria
• He made lenses of excellent quality; some gave
magnifications up to 300X
• 1796, Edward Jenner
– He developed the first vaccine (against
smallpox)
• Mid to late 1800s, Louis Pasteur
– Mechanisms of fermentation, some vaccines.
• Late 1800s, Robert Koch
5. Taxonomy
• Hierarchy
• The order of taxa between the top and bottom levels
is: Domain, Kingdom, Phylum or division, Class, Order,
Family, Genus, Species.
– For microorganisms:
• Type or var (serotype, serovar)
• Strain
• Thus, each domain can be subdivided into a series of
kingdoms,
– each kingdom into several phyla,
– each phylum several classes, and so on.
• Some groups of organisms do not exactly fit into the
eight taxa.

–

In that case, additional levels can be imposed
immediately above (super) or below
• Example: superphylum and subclass

6. Evolution
– Living things change gradually through millions of
years
– Selective process
• Those changes that most favor the survival of a
particular organism or group of organisms
tend to be retained, and
• those that are less beneficial to survival tend to
be lost
– Evolution is founded on:
- All new species originate from preexisting
species
- Closely related organisms have similar features
because they evolved from common ancestral
forms

• Evolution theory is based in a very big amount of
evidence from the fossil record and from the study of
morphology (structure), physiology (function), and
genetics (inheritance)

•

The phylogeny studies the evolutionary relatedness,

– it can be represented by a diagram with a tree
format

• The trunk of the tree represents the main
ancestral lines, and

• the branches show “sons” into specialized
groups of organisms.

•

More ancient groups at the bottom and the more
recent ones at the top

7. Phylogeny
• The first phylogenetic trees:
– Two kingdoms: plants and animals
• But later some organisms did not truly fit either of
those categories, so
– a third kingdom for simpler organisms that lacked
tissue differentiation (protists) was recognized
• Eventually, when significant differences became
evident even among the protists,
– a fourth kingdom was proposed for the bacteria
• Robert Whittaker built on this work and during the
period of 1959 through 1969 added a fifth kingdom
for fungi
– The relationships were based on structural
similarities and differences, such as
• cellular organization and
• type of nutrition
• Molecular biological methods (study of rRNA, mainly
the 16SrRNA subunit) for determining phylogeny have
led to the development of a different tree
• Archaeons (originally archaebacteria) are a separate

“superkingdom”, or domain
• The Woese-Fox three-domains classification
– places all eukaryotes in the Domain Eukarya and
subdivides the prokaryotes into the two Domains
Archaea and Bacteria
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Lecture 1

(II). Host-pathogens interactions
1. Normal flora in the human body

•

The human fetus lives in a protected and sterile
environment

•

When the baby is born

– He/she is exposed to many different

microorganisms
• From the mother, other close contacts, and the
environment

•

•

Toxigenicity

These communities of organisms will live in/on
different areas of the body

– This is the so-called “normal flora” or “microbiota”
•

Virulence
factor

Areas of the body with normal flora
– Skin
– Upper respiratory tract
• Nose and nasopharynx; mouth and
oropharynx
– Eye surface
• Only on the conjunctivae
– Outer ear
– Gastrointestinal tract
– Lower genitourinary tract
• Anterior urethra
• Vagina
Sterile sites of the human body

– Central nervous system (CNS)
– Blood, tissues, organ systems
– Sinuses, inner and middle ear

– Lower respiratory tract
• Larynx (a part), trachea, bronchi, bronchioles,
lungs, alveoli

– Kidneys, ureters, urinary bladder, posterior
urethra

– Uterus
2. Basic concepts for understanding host-pathogen
interactions
Host
Pathogen

Opportunistic
pathogen

Pathogenicity

Virulence

Organism that harbors a pathogen.
The host is the human body
A microbe capable of causing host
damage. It lives on or in the host.
Very few microorganisms are
pathogens
A microorganism that is not harmful in
normal conditions. Some of them may
be normal flora. They can cause
disease only if they are introduced into

unprotected sites or if a host’s immune
system is defective
The capacity of a microbe to cause
damage in a host. This is a 'qualitative'
concept: The microorganism may be
either 'pathogen' or 'non pathogen'.
The relative capacity of a microbe to
cause damage in a host. This is a

Local infection
Systemic
infection
Nosocomial
infection

‘quantitative’ concept. : It is a
measurement of the degree of
pathogenicity of a microorganism. The
'pahogen' is 'more virulent' or 'less
virulent'
A component (molecule, structure) of
a pathogen that harms the host. A
pathogen is more virulent if it contains
more virulence factors.
Ability of a microbe of producing
chemical substances (toxins) that alter
the normal function of host cells with
harmful effects
Infection that is limited to a specific
body area

Infection that has spread to the whole
body
Infection acquired at a health care
facility (hospitals…)

3. The infectious process
a. From exposure to infectious disease: The states of
infection: colonization, commensalism, latency and
disease

•

Damage results from the interaction between host
and microorganism.

Depending on the amount of host damage over
time, we can observe different states (or outcomes)
of infection:
Exposure
The contact of a host with a
microorganism
Incubation
Time between entrance and the
period
beginning of symptoms. Very variable
Infection
Acquisition of a microbe by a host,
usually followed by multiplication
Colonization
A state of infection. There is damage

from none to great. As damage
increases, the host immune system
starts working and it can eliminate or
retain the microbe. Dmage may
progress further.
(Colonization is the same as
commensalism if microbes do not
induce any damage)
Commensalism A state of infection. It results in either
no damage or clinically inapparent
damage to the host, though it can
produce an immune response
Commensal
Microbe that induces either no
damage after primary infection; a
state that is thought to be established
early in life
Latency
A state of infection. The host-microbe
interaction with a microbe that
remains present in a host for an
undetermined period of time can lead
to host damage that is apparent
microbiologically, histopathologically,

•

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Lecture 1

Infectious
disease

radiographically, or serologically
without being associated with clinical
disease
The clinical manifestation of damage
that results from a host-microbe
interaction

c. Steps of the infectious process
(i). Portals of Entry

•

After exposure, A microorganism may enter the
human body to begin an infection
– It enters by a characteristic route, that is the portal
of entry

•

The microorganism can be either
– Exogenous: From a source outside the body
– Endogenous: The microorganism already exists in
the body

(ii). Adhesion: The process by which microbes stick to

the surfaces of host cells. After microbes have entered the
body, adherence is a major initial step in the infection
process. "Adherence", "adhesion", and "attachment"have
almost the same meaning

•

Mediated by special molecules or structures called
adhesins. Adhesins bind specific receptor sites on host
cell surface
• A particular pathogen is limited to only those
cells (and organisms) to which it can bind
– Adhesion is dependent on binding
between specific molecules on both the
host and pathogen

•

Therefore, adhesins are a kind of virulence factor

b. Factors that influence the development of damage

•

The host and the microorganism are in a dynamic
interaction

•

The outcome of this interaction depends upon

– The properties of the microorganism
– The host

•

The microorganism

– How many?
• Number of microorganisms present

(iii). Establishment and damage

•

Finally, host damage is caused by

– Microorganism abilities
• Invasiveness

– How much?
• The virulence of the pathogen that depends on
the number of viruelnce factors

•

The host

– Degree of resistance, the immune system ‘skills’
• Weak

• Normal
• Strong: If host defenses are very strong and

•

– Ability of a pathogen to enter into host
cells or tissues, spread, and cause disease
–
Initiated by adhesins, and caused by lytic
substances (invasins)
– Invasins are also virulence factors
Toxigenicity
–
Ability of producing ‘toxins’
– Toxins are also virulence factors

– Host response

uncontrolled, host damage is also produced

We can fight (or prevent) infectious diseases acting in different sites of the infectious process:
- (1) Treatment ("antimicrobial treatment"): Usually done with antimicrobials, but other measures are sometimes useful
- (2), (3), (4) Prevention: Also called "Prophylaxis":
- "Pre-exposure prophylaxis" (2): Prevention of infection, before the individual is exposed to the pathogen. Usually done
with "active immunization" (vaccination), but other measures are sometimes useful
- "Post-exposure prophylaxis" (3): Prevention of infection, once the individual has been already exposed to the pathogen.
Sometimes done with antimicrobials. Other times, vaccination or "pasive immunization" may be useful
- Prevention of disease (4). For some infectious diseases, we can also prevent the development of disease once the human
is infected. This is usually done with antimicrobials (for example, tuberculosis)
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Lecture 1

(III) The host response to infection: Basics of immunology (1 of 3)
1. Introduction
Its response is the same on repeated exposure to the
same pathogen
Immunity means protection from infectious disease
– Non-reactivity to self (self-tolerance): There is no
Immune response: Collective and coordinated
response against self antigens (in normal conditions):
response to fight against the introduction of foreign
So, response occurs only against foreign antigens
substances into the body
– It is non-specific: It uses a limited number of receptors
Immune system: Collection of all cells and molecules
to recognized pathogens
responsible for immunity
• These receptors are called pattern recognition
• The function of the immune system is defense against
receptors (PRRs)
pathogens: Recognize, Respond and Eliminate them
• They recognized molecular patterns of the
• But it does not usually react against that individual’s
pathogens, called pathogen-associated molecular
own (self) antigens and tissues
patterns (PAMPs)
• However, even non-infectious foreign substances can
– The innate immune response combats microbes by

produce immune responses
two main reactions
• It can also provide a defense against tumors
• Inflammation: By recruiting phagocytes and other
Problems
leukocytes to destroy the microbes
– The immune system recognizes and responds to
• Antiviral response: By blocking viral replication or
tissue grafts Rejection of transplants
killing virus-infected cells
– The immune system can injure self cells and
induce damage
b. The adaptive immune system
– Slower: It needs ~10 days to develop in the first
2. Types of immunity
(primary) response
Defense against microbes is mediated by
–
Mediated
by lymphocytes and their products
– Innate immune response: Early reactions
–
It
is
specific:
They recognize an individual antigen:
– Adaptive immune response: Later reactions
The antigen receptor expressed by a particular
lymphocyte is different from that of all other
lymphocytes

– Non-reactivity to self (self-tolerance)
– It has immunologic memory
- More effective defense: It improves upon repeated
exposure to the same microbe
- This memory is the reason why vaccines work
– There are two types of adaptive responses:
• Cellular immune response: Mediated by T
lymphocytes (T cells)
• Humoral immune response: Mediated by molecules
a. The innate immune system
called antibodies: Antibodies are produced by B
– Quick: It does not require prior exposure to the microbe
lymphocytes (B cells)
– In the early stages of an infection
Both, innate and adaptive responses start at the same
– It can limit the spread of a pathogen
time, but adaptive immune response is slower
– Moderately efficient
Both are complementary and cooperate with each
– No immunologic memory: The innate immune system
other
“does not remember” prior encounters with microbes.

•
•
•

•

•

•
•

Innate immune system
Adaptive immune system
Non-specific:
Specific:
- It recognizes molecules shared by groups of - It recognizes antigens (microbial and non-microbial)
related microbes (PAMPs)
- It recognizes antigens of different microbes of the same class
- It also recognizes molecules produced by
and even different antigens of one microbe
damaged host cells called "damage-associated
molecular patterns" (DAMPs)
Diversity of receptors - Limited: encoded in the germline
- Very large: produced by somatic recombination of genes
~100 different receptors belonging to a few - Only two families of receptors (immunoglobulins and T-Cell
protein families
Receptors), but produce millions of variations so can
recognize millions of antigens
Memory
No
Yes
Non-reactivity to self Yes
Yes
("self-tolerance")
Cellular components - Epithelial barriers, Phagocytes, Dendritic
- Lymphocytes
cells), Mast cells, NK cells

- Other cells1
Humoral (soluble)
- "The complement system"
- Antibodies
components
- Other molecules2
- "The complement system"
- Other molecules: some interleukins (IL)
Specificity

1
2

Cytokine-producing innate lymphoid cells, and also some T and B lymphocytes with limited antigen receptor diversity.
Pentraxins, Collectins, Ficolins
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Lecture 1

Questions
1.

2.

The 'germ theory of disease’ that states that some
microorganisms can produce infectious diseases
was postulated by:
a. Ignaz Semmelweiss.
b. Anton van Leeuwenhoek.

c. Joseph Lister.
d. Louis Pasteur.
e. Robert Koch.
Scientists give names to microorganisms using a
hierarchical system that contains the following
groups: Domain, Kingdom, Phylum, Class, Order,
Family, Genus and Species. In the bacterium
Escherichia coli, what is "Escherichia" and what is
"coli"?
a. Domain: Escherichia. Family: coli
b. Family: Escherichia. Species: coli
c. Family: Escherichia. Genus: coli
d. Genus: Escherichia. Species: coli
e. Kingdom: Escherichia. Genus: coli

3.

Which of the following body sites contains
normal flora?
a. The brain
b. The nose
c. The blood
d. The spleen
e. The bone marrow

4.

Which of the following body sites is sterile?
a. The mouth
b. The esophagus

c. The liver
d. The conjunctivae
e. The outer ear

5.

Which of the following molecules are virulence
factors?
a. Immunoglobulins
b. Toxins
c. The proteins of the "complement"
d. Interferons
e. T-cell-receptors (TCR)

6.

Microorganisms that cause infectious diseases
when the immune system is NOT working
properly are called:
a. Nosocomial pathogens.
b. Opportunistic pathogens.
c. Commensal pathogens.
d. Systemic pathogens.

7.

What is TRUE about the infectious process?
a. Virulence factors are chemical
components produced by leukocytes.
b. Host damage is only produced by the

microorganism itself.
c. A strong immune response may produce
damage.
d. “Infection” has the same meaning as
“disease”.
e. Commensalism produces important host
tissue damage.

8.

What is 'self-tolerance'?
a. The ability of the immune system to fight
foreign antigens.
b. The ability of the immune system to fight
self antigens.
c. The ability of the immune system to
recognize self antigens and not fight
against them.
d. The ability of the adaptive immune
system to remember prior exposures to
foreign antigens.

9.

Which cells of the immune system produce
antibodies?
a. Neutrophils
b. T lymphocytes
c. B lymphocytes
d. Dendritic cells

e. Macrophages

10. An important difference between the innate
immunity and the adaptive immunity is:
a. The innate immune response is slower
b. The innate immune response has
memory
c. Millions of different antigens are
recognized by the adaptive immune
system but not by the innate immune
system
d. Phagocytes produce antibodies in the
innate immune system, and lymphocytes
produce antibodies in the adaptive
immune system
e. The innate immune system may react
against self antigens, but not the
adaptive immune system

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