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
(I) Introduction to Medical Microbiology 1. The science of microbiology
– invade the bodies of hosts
• often causing damage through infection and disease
– 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
– 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 1/6
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 2/6
(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
These communities of organisms will live in/on different areas of the body
– This is the so-called “normal flora” or “microbiota” •
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
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,
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
– 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
– 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) 4/6
(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
Cytokine-producing innate lymphoid cells, and also some T and B lymphocytes with limited antigen receptor diversity. Pentraxins, Collectins, Ficolins 5/6
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
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
Which of the following body sites is sterile? a. The mouth b. The esophagus c. The liver d. The conjunctivae e. The outer ear
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)
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.
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.
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.
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