Medical biology, microbiology, virology, immunology department

by as. O.V. Pokryshko

The interaction of the susceptible human organism and the pathogenic microorganism in certain conditions of the external and social environment which gives rise to an obvious or latent pathological process is called an infectious process.

Pathogenicity. This is the potential capacity of certain species of microbes to cause an infectious process.

Virulence signifies the degree of pathogenicity of the given culture (strain). Virulence, therefore, is an index of the qualitative individual nature of the pathogenic microorganism. Virulence in pathogenic microbes changes under the influence of natural conditions.

Main Features Main Features of Pathogenicof Pathogenic Microorganisms.Microorganisms.

The virulence of pathogenic microorganisms is associated with

adherence, invasiveness, capsule production, toxin production, aggressiveness and other factors.

The adherence

Adherence factorAdherence factor DescriptionDescription Filamentous hemagglutinin

Causes adherence to erythrocytes

Fimbriae Help attach to solid bacteria to solid surfaces

Glycocalyx or capsule Inhibits phagocytosis and aids in adherence

Pili Bind bacteria together for transfer of genetic material

Slime Tenacious bacterial film that is less compact than a capsule

Teichoic and lipoteichoic acid

Cell wall components in gram positive bacteria that aid in adhesion

Adherence bacteria to cell surfacesAdherence bacteria to cell surfaces

Adherence of vibrio cholera on the mucoseAdherence of vibrio cholera on the mucose

Capsule production

Capsule production Capsule production makes the microbes makes the microbes resistant toresistant to phagocytosisphagocytosis and and antibodiesantibodies, and , and increases their invasive increases their invasive properties. properties.

Thus, for example, Thus, for example, capsular capsular anthrax bacillianthrax bacilli are not subject to are not subject to phagocytosis, while phagocytosis, while noncapsular variants are noncapsular variants are easily phagocytized.easily phagocytized.

The role of capsular material The role of capsular material in bacterial virulence.in bacterial virulence.

Some pathogenic microorganisms Some pathogenic microorganisms ((B.B. anthra anthraciscis, C, C.. perfringens, S. pneumo perfringens, S. pneumo--niae,niae, causative agents of causative agents of plague and plague and tularaemiatularaemia)) are capable of producing a are capable of producing a capsule in animal and human bodies. capsule in animal and human bodies. Certain microorganisms produce capsules Certain microorganisms produce capsules in the organism as well as in nutrient media in the organism as well as in nutrient media (causative agents of (causative agents of rhinoscleroma, rhinoscleroma, ozaena, pneumonia).ozaena, pneumonia).

Virulent microbes are characterized by the ability to penetrate tissues of the infected organism (iinvasnvasiveive properties properties).

collagenase and hyaluronidase immunoglobulin A protease leukocidins M-protein protein A

InvasInvasiveive properties properties of pathogenic bacteriaof pathogenic bacteria

Collagenase and hyaluronidase degrade collagen and hyaluronic acid, respectively, thereby allowing the bacteria to spread through subcutaneus tissue (Streptococci, Staphylococci, Clostridium ).

Immunoglobulin A protease degrades IgA, allowing the organism to adhere to mucous membranes, and is produseed chiefly by N. gonorrhoeae, Haemophilus influenzae, and S. pneumoniae.

Leukocidins can destroy both neutrophilic leukocytes and macrophages.

M-protein of S. pyogenes is

antiphagocytic.

Protein A of S. aureus binds to IgG and prevents the activation of complement.

Coagulase, which is produced by S. aureus and accelerate the formation of a fibrin clot from its precursor, fibrinogen (this clot may protect the bacteria from phagocytosis by walling off the infected area and by coating the organisms with a layer of fibrin)

The invasion of cells by bacteria

According to the nature of production, According to the nature of production, microbial toxins are subdivided into microbial toxins are subdivided into exotoxins and endotoxexotoxins and endotoxinsins. .

More than 50 protein exotoxins of bacteria are known to date.

Toxin production

Exotoxins easily diffuse from the cell into the surrounding nutrient medium.

They are characterized by a markedly distinct toxicity, and act on the susceptible organism in very small doses.

Exotoxins have the properties of enzymes hydrolysing vitally important components of the cells of tissues and organs.

Exotoxins exert their effects in a

variety of ways – by inhibition of protein

synthesis, inhibition of nerve synapse

function, disruption of membrane trans-

port, damage to plasma membranes.

ExotoxinsExotoxins may be devided into fifth may be devided into fifth categories on the basis of the site affected:categories on the basis of the site affected:

neurotoxinsneurotoxins (tetanotoxin, botulotoxin) C. tetani, C. botulinum, B. cereus, S. aureus;

cytotoxinscytotoxins (enterotoxins, dermatonecrotoxin)E. coli, Salmonella spp., Klebsiella spp., V. cholerae, C. perfringens;

functional blocatorsfunctional blocators (cholerogen), V. cholerae;

membranotoxinsmembranotoxins (hemolysins, leucocidin), S. aureus;

exfoliatinexfoliatin S. aureus.

Action of the hemolysin on red blood cellsAction of the hemolysin on red blood cells

MICROORGANISM TOXIN DISEASE ACTION

Clostridium botulinum

Several neurotoxins

Botulism Paralysis; blocks neural transmission

Clostridium tetani Neurotoxin Tetanus Spastic paralysis; interferes with motor neurons

Corynebacterium diphtheriae

Cytotoxin Diphtheria 

Blocks protein synthesis

Bordetella pertussis

Pertussis toxin

Whooping cough Blocks G proteins that are involved in regulation of cell pathways

Streptococcus pyogenes

Hemolysin  

Scarlet fever Food Lysis of blood cells

Staphylococcus aureus

Enterotoxin Poisoning Intestinal inflammation

Aspergillus flavus Cytotoxin Aflatoxicosis Blocks transcription of DNA, thereby stopping protein synthesis

Amanita phalloides

Cytotoxin Mushroom food poisoning

Blocks transcription of DNA,thereby stopping protein synthesis

Endotoxinsare more firmly bound with the body of the

bacterial cell, are less toxic and act on the

organism in large doses; their latent period is usually

estimated in hours, the selective action is poorly

expressed.

According to chemical structure, endotoxins are related to glucoside-lipid and polysaccharide compounds or phospholipid-protein complexes.

They are thermostable. Some endotoxins withstand boiling and autoclaving at 120°C for 30 minutes.

Action of the endotoxinAction of the endotoxin

Endotoxin in the bloodstream

Differences between exotoxins and endotoxinsDifferences between exotoxins and endotoxins

exotoxinsexotoxins endotoxinsendotoxinsProteinsProteins LipopolysaccharidesLipopolysaccharides

Heat labileHeat labile Heat stableHeat stable

Actively secreted by cells, Actively secreted by cells, diffuse into surrounding diffuse into surrounding mediummedium

form part of cell wall,do form part of cell wall,do not diffuse into not diffuse into surrounding mediumsurrounding medium

Readily separable from Readily separable from cultures by physical cultures by physical means such as filtrationmeans such as filtration

Obtained only by cell Obtained only by cell lysinglysing

Action often enzymicAction often enzymic No enzymic actionNo enzymic action

Specific pharmacological Specific pharmacological effect for each exotoxineffect for each exotoxin

Non-specific action of all Non-specific action of all endotoxinsendotoxins

Specific tissue affinitiesSpecific tissue affinities No specific tissue affinityNo specific tissue affinity

Active in very minute Active in very minute dosesdoses

Active only in very large Active only in very large dosesdoses

Highly antigenicHighly antigenic Weakly antigenicWeakly antigenic

Stimulate formation of Stimulate formation of antitoxin which neutralizes antitoxin which neutralizes toxintoxin

Do not stimulate formation Do not stimulate formation of antitoxinof antitoxin

Converted into toxoid by Converted into toxoid by formaldehydeformaldehyde

Can not be toxoidedCan not be toxoided

Produced by both gram-Produced by both gram-positive bacteria and positive bacteria and gram-negative bacteriagram-negative bacteria

Produced by gram-Produced by gram-negative bacteria onlynegative bacteria only

Frequently controlled by Frequently controlled by extrachromosomal genes extrachromosomal genes (e.g. plasmids)(e.g. plasmids)

Synthesis directed by Synthesis directed by chromosomal genes chromosomal genes genesgenes

In characterizing pathogenic microbes a unit of virulence has been established.

Dlm (Dosis letalis minima), representing the minimum amount of live microbes which in a certain period of time bring about 95-97 % death of the corresponding laboratory animals.

the absolute lethal dose of pathogenic microbe Dcl (Dosis certa letalis) which will kill 100 % of the experimental animals has been established.

At present LD50 (the dose which is lethal to one

half of the infected animals) is considered to be the most suitable, and may serve as an objective criterion for comparison with other units of virulence.

The term infection (L. infectio to infect) signifies the sum of biological processes which take place in the macroorganism upon the penetration of pathogenic microorganisms into it.

Infectious disease designates one of the extreme degrees of manifestation of the infectious process.

Infectious diseases are considered to be phenomena including biological and social factors.

Infectious diseases differ from other diseases in that

they are caused by live causative agents

of a plant and animal origin and are contagious, the presence of a latent period, specific reactions of the body to the causative agent and production of immunity

For the origination and development of the infectious process three conditions are necessary: 1. the presence of pathogenic microbe,2. its penetration in to a susceptible macroorganism, 3. certain environmental conditions in which the interaction between the microorganism and macroorganism takes place.

Koch’s postulates.

What is an Epidemic?What is an Epidemic?The occurrence of more cases of The occurrence of more cases of

disease than expected in a given area or disease than expected in a given area or among a specific group of people over a among a specific group of people over a particular period of time*.particular period of time*.

The occurrence of more cases of The occurrence of more cases of disease than expected in a given area or disease than expected in a given area or among a specific group of people over a among a specific group of people over a particular period of time*.particular period of time*.

EpidemicEpidemic

What is a Pandemic?What is a Pandemic?

An epidemic occurring over a very wide An epidemic occurring over a very wide area (several countries or continents) area (several countries or continents) and usually affecting a large proportion and usually affecting a large proportion of the population.of the population.

Examples:Examples:– CholeraCholera– AIDSAIDS– Pandemic InfluenzaPandemic Influenza

An epidemic occurring over a very wide An epidemic occurring over a very wide area (several countries or continents) area (several countries or continents) and usually affecting a large proportion and usually affecting a large proportion of the population.of the population.

Examples:Examples:– CholeraCholera– AIDSAIDS– Pandemic InfluenzaPandemic Influenza

PandemicPandemic

Source of infectionSource of infection::Sick menSick animalCarrier

Transmission factorTransmission factor:: infected foodinfected food, , waterwater, , dirtydirty handshands, , fliesflies, , fomitesfomites..

VectorsVectors of pathogenicof pathogenic microorganimsmicroorganims: : ticksticks, , louseslouses, , fleasfleas mosquitosmosquitos..

Routes of diseases transmission

There are various modes which pathogens are transmitted from a source to a susceptible individual.

airborne transmissionfoodborne transmissionsexual transmissiondirect contact transmissionparenteral route

Respiratory tract and airborne transmission.

Airborne transmission occurs when pathogenic microorganisms are transferred from an infected to a susceptible individual via the air. Droplets regularly become airborne during normal breathing, but the coughing and sneezing associated with respiratory tract infections are primarily responsible for the spread of pathogens in aerosols and thus the airborne transmission of disease.

High-speed photograph of an aerosol generated High-speed photograph of an aerosol generated by an unstifled sneeze.by an unstifled sneeze.

Gastrointestinal tract—water and foodborne transmission.

Microorganisms routinely enter the gastrointestinal tract in association with ingested food and water. Waterborne and foodborne pathogens can infect the digestive system and cause gastrointestinal symptoms.

Genitourinary tract – sexual transmission.

The genitourinary tract provides the portal of entry for pathogens that are directly transmitted during sexual intercourse. Such infections are known as venereal or sexu- ally transmitted diseases.

Superficial body tissues – direct contact transmission.

In some cases the deposition of pathogenic microorganisms on the skin surface can lead to an infectious disease. Since they require direct contact between skin and microorganisms for transmission to occur, these diseases are called contact diseases. Some diseases transmitted in this manner are superficial skin infections.

Parenteral route. Punctures, injections, bites, cuts, wounds, surgical incisions, and cracking skin due to swelling or drying establish portals of entry to a host for a potential pathogen. Such access is called the parenteral route (from Greek para [beside] and enterik [intestinal tract]. Microorganisms thus gain entry to the body by being deposited directly into the tissues beneath the skin or into the mucous membrane.

Portals of entry. The routes of entry are the respiratory tract, gastrotestinal tract, genitourinary tract, skin, and wounds.

The invasive properties of specific pathogens permit them to penetrate the body's defense mechanisms through a specific portal of entry. Most pathogenic microorganisms will cause disease only if they enter the body via this specific route.

The dynamics of the development of the infectious process consists of

1. the incubation period 2. prodromal period, 3. the height of the disease 4. period of recovery ( convalescence).

A certain period of time elapses from the moment of penetration of the pathogenic microbe to the onset of the first sings of the disease, which has been named the incubation period of the disease.

The sites at which microorga- nisms leave the body are called portals of exit. Pathogens of the genitourinary and gastrointestinal systems generally exit the body with body fluids or feces. Pathogens of the respiratory sys- tem exit through the nose or mouth in fluids expelled during coughing, sneezing, and speaking. Some pathogens, such as the bacteria that cause tuberculosis, are resistant to desiccation and can remain viable in the air for a long while. These organisms can be transmited via the air, and inhalation of contaminated air can lead to infection.