Infection- How microorganisms caused infection in human (Part-2)

ü Spreading factors of microbial infection

Toxins

Specific substance that damages host. Bacteria produce two types of toxins- endotoxins and exotoxins.

Ø  Endotoxins are heat-stable lipopolysaccharides (LPS) which form an integral part of the cell wall of Gram-negative bacteria. Their toxicity depends on the lipid component (lipid A). They are not secreted outside the bacterial cell and are released only by the disintegration of the cell wall. They cannot be toxoided. They are poor antigens and their toxicity is not completely neutralized by the homologous antibodies. They are active only in relatively large doses. They do not exhibit specific pharmacological activities. All endotoxins, whether isolated from pathogenic or non-pathogenic bacteria, produce similar effects.

Causes-

·         Fever

·         Hypoglycemia

LPS forcing the cell to take up more and more glucose. The presence of LPS increases the amount of glycolysis still having the glucose level constant so the glucose from our body is reduced.

Reduce glucose because it metabolizes into pyruvate.

 

·         Hypotension

Blood pressure drops. Vasodilation occurs (the dilatation of blood vessels, which decreases blood pressure). When LPS is injected in our body, arterial and ventricle construction (widening) is going on all over the body so the dilatation (the action of dilating or wider a vessel) of blood vessels falls the blood pressure.

·         Disseminated intravascular coagulation (DIC)

Blood start to clot in our blood vessels.

Ø  Exotoxins produced by bacteria protect themselves and spread infection against host cells on organisms. Exotoxins are heat-labile proteins which are secreted by certain species of bacteria and diffuse readily into the surrounding medium causing an infection on host cell so they can colonize and growing on them. They are highly potent in minute amounts and constitute some of the most poisonous substances known. Exotoxins produced by both gram-positive and gram-negative bacteria, mostly or generally produced by gram-positive bacteria but may also be produced by some gram-negative organisms such as Shiga’s dysentery bacillus, vibrio cholera, and enterotoxigenic E.coli. They are just like a protein component secreted by bacteria outside the bacterial cell. In the exponential phase (log phase) of their life cycle, they secreted a higher amount of toxins.

 

Bacteria produced toxins inside their cells and secreted or released it outside the cells to cause infection.

Exotoxins are mostly synthesized in two components

1.      Receptor binding component called B subunit.

2.      Active component called A subunit.

Ø  Subunit A (acting)- response for toxic effects and acts on the host cell.

Ø  Subunit B (binding)- binds to the target cell.

Exotoxins uptake of the toxin in the host cell by receptor-mediated endocytosis for that they require both Subunit A and Subunit B. Subunit B act as a binding subunit helps the toxin to bind with the host cell membrane. Subunit A act as an acting subunit or active subunit, it is a major part of toxic material it is doing an enzymatic effect and activities which is very much resembling their enzymes but they are no typically toxins, they acting there and causing their particular effects. Depending upon the type of Subunit A and B particularly bacteria have different varieties of toxins depends. Example- A+B toxin – A and B produced separately from different polypeptide chain and acts separately but acting on the same cell.

A-B toxin- A and B produced separately but they are joint by a non-covalent binding or interaction.

A/B  toxin- one single protein, they are generated from one polypeptide chain. One protein folded having two different domains. Some proteins having two different domains.

Both subunits binding is required because if only A subunit is infected it is meaningless, it is not acting directly because the binding is important. Exotoxins inert many dangerous effects in our body toxic shock syndrome, fever, many types of establishing effects in our bodies.

Some amount of toxins are found dangerous life-threatening for our body but some are not dangerous. Example- botulinum toxin secreted by Clostridium botulinum bacteria most the dangerous toxin in the earth till now. 1 mg of botulinum toxin and tetanus toxin (secreted by Clostridium tetani) is sufficient to kill more than one million guinea pigs and it has been estimated that 3 kg of botulinum toxin can kill all the inhabitants of the world. Depending upon active sites of toxins we can also divide them in different varieties. Example- exotoxins act on an intestinal region of our digestive tract in our body called enterotoxins, cholera toxin; act on brain cells and nerve cells called neurotoxins, tetanus toxin and botulinum toxin.: the toxin which kills the host called a lethal toxin, botulinum toxin and tetanus toxin; toxin acts on normal cells called cytotoxins.

Treatment of exotoxins with formaldehyde yields toxoids that are nontoxic but retain the ability to induce antibodies (antitoxins). They exhibit specific tissue affinities and pharmacological activities, each toxin-producing a typical effect which can be made out by characteristic clinical manifestations or autopsy appearances.

Some exotoxins produced by bacteria

Exotoxin	Producing organism	Disease	Effect
Diphtheria toxin	Corynebacterium diphtheria	Diphtheria	Inhibits protein synthesis, affects heart, nerve tissue, liver
Botulinum toxin	Clostridium botulinum	Botulism	Neurotoxin, flaccid, paralysis
Perfringens	Clostridium perfringens	Gas gangrene	Hemolysin, collagenase, phospholipase
Erythrogenic toxin	Streptococcus pyogens	Scarlet fever	Capillary destruction
Pyrogenic toxin	Staphylococcus aureus	Toxic shock syndrome	Fever, shock
Exfoliative toxin	Staphylococcus aureus	Scalded skin	Massive skin peeling
Exotoxin A	Pseudomonas aeruginosa	-	Inhibits protein synthesis
Pertussis toxin	Bordetella pertussis	Whooping cough	Stimulates adenyl cyclase
Anthrax toxin	Bacillus anthracis	Anthrax	Pustules, blood poisoning
Enterotoxin	Escherichia coli	Diarrhea	Water and electrolyte loss
Enterotoxin	Vibrio cholera	Cholera	Water and electrolyte loss
Enterotoxin	Clostridium perfringens	Food poisoning	Permeability of intestinal epithelia
Neurotoxin	Clostridium tetani	Tetanus	Rigid paralysis

 

ü Evading host defense (pathogens overcome host defense mechanisms)

 

Certain factors that are important properties of microorganisms having to evade host immunity because host immune the system is always trying to protect against those harmful pathogens, there are certain ways pathogens have to evade (escape) host immune system or to elude the system. Example- pathogenic Staphylococci produce thrombin-like enzyme coagulase which prevents phagocytosis by forming a fibrin barrier around the bacteria.

Five major types of strategies taken by pathogens to elude our immune system.

 

1.      Antigenic distinguishes- In this process antigen hide inside some self molecules. An antigen can only be detected by an immune system if it is free, if our immune system cells take this antigen up and recognize them as nonself, so they can lead up some action against it. But in this process some antigen try to force themselves inside self molecules and some cells materials, as that they hiding in self molecules, those self molecules cannot recognize by host immune system cells as the results that the cell and pathogen remain healthy cannot recognize that pathogen as antigen because it hiding itself in host self cells components.

 

2.      Immunosuppression- Antigen suppress the activity of immune cells specifically. If antigen presents their and place there for a longer period of time throughout the bloodstream, then the immune system recognizes, catches, and kills them. But in this process pathogen residing and hiding somewhere else for a very long period of time, it just stays their long period of time and then starts to grow and infecting and go against the immunity property.

 

 Example- Salmonella typhi is a bacteria causing typhoid fever. It residing inside host gall bladder for 7 to 8 hours and during that time all our immune system thinks everything is going fine no antigen is there in the bloodstream and then the immune cells just go away once they leave the bloodstream in that case again Salmonella thyphi thrives into the bloodstream and start dividing and infecting other regions start multiplying there. They try to find the situation when the immune system is compromised and suppress, then they start thriving then the infection started spreading.

 

 

3.      Specific immune response- Staying somewhere, where the immune cells (macrophages, killer cells and cytotoxic killer cells) cannot find them. They are hiding in those cells and regions where immune cells would not present, there are some regions where the immune cells patrolling all the time and there are some other regions which are free from immune system cells. Because not all the host tissues or cells are protected by the same amount of immune cells, there are certain regions which are not that much taking care by the immune cells and pathogen stays in those regions for a longer period of time persistently (continuously) and then start to form a infection.

 

4.      Induction of ineffective antibodies- Bacteria itself is an antigen and secret molecules, that molecules act as an antigen. The toxin is on the surface of the bacteria, the bacteria know what is the important infecting part so it itself produces certain molecules which are immunogenic but it is not much harmful to the host cells, so it starts to produce that material which is non-harmful for the host but can generate an immune response.

Trigger the immune system to produce the antibody against those molecules which are non-harmful so that’s why these antibodies called ineffective antibody because they bind to those molecules which are non-harmful and not necessary for causing infection but these molecules induce an immune response against themselves much faster. So the host cell thinks the orange molecules as non-harmful molecule and orange antigen start to act deadly and damaging host cell and tissues.

 

5.      Antigenic variation- Antigenic phase change or shift. Example- Neisseria gonorrhoeae. In this bacteria look at the genome of the pilE protein which is responsible for causing very aggressive infection. If the host cell previously encountered Neisseria gonorrhoeae and with the same type of pilE protein it might have a high amount of antibodies against it. But in this process, when the Neisseria gonorrhoeae encounters second time in host cell it varying this pilE protein.

The different combination of those genes give rise to much new variety of pilE protein as each time it infecting an individual with a new variety of pilE the protein it is very difficult for the host memory cells to overcome with this situation so that kind of situation is deadly for the host cell.

 

Summary