Infection- How microorganisms caused infection in human (Part-1)

Keywords

Growth and multiplication of pathogen in or on the tissues of a host is called infection.

Disease resulting from infection is called infectious disease.

Pathogens are microorganisms that are capable of producing disease in the host (from Greek pathos suffering and gen produce, disease-producing).

Pathogenicity is the ability of a microbial species to produce disease.

Sources of infection-

Direct contact-  Humans- coughing, sneezing, body contact.

Vectors- Animals- Example- Cattle- tetanus, anthrax, brucellosis, tuberculosis; Goat- brucellosis; Sheep- tetanus, anthrax;  Dogs- rabies (viral), hydatid (helminthic); Horse- tetanus, glanders; Rats- ratbite fever, Weil's disease (bacterial), plague; Cats- protozoal (toxoplasmosis)

Insects (Biological or mechanical vectors)

Houseflies- typhoid fever, cholera, dysentery; Body lice- typhus, relapsing fever; Mosquitoes- malaria, dengue, yellow fever; Rat flea- plague; Ticks- relapsing fever, spotted fever.; Aedes aegypti mosquito- yellow fever; Anopheles mosquito- malaria

Indirect  contact- Soil- Bacteria- Spores of tetanus bacilli; Fungi- Histoplasma, Capsulatum, Nocardia asteroids; Parasites- roundworm, hookworm

Water- Cholera vibrio, infective hepatitis virus, Cyclops in guinea worm infection

Food- Food poisoning- Staphylococcus; Pre- existent infection in meat or other animal products- Salmonellosis

Transmission of infection by- contact, inhalation, ingestion, inoculation, insects, congenital, iatrogenic and laboratory infections

Determinants of virulence

Virulence- property in a strain of microorganism to produce disease.

Virulence is determined by transmissibility, adhesion with the host cell, invasion, spreading factors (toxins and enzymes), evading host defense by a pathogen.

Measuring virulence-

Lethal Dose 50 (LD₅₀)- number of pathogens that will kill 50% of an experimental group of hosts.

Infectious Dose (ID₅₀)- number of pathogens that will infect 50% of an experimental group of hosts.

Factors (Determinants)

Transmissibility- the ability to transfer infection from one individual to another individual.

Steps of causing infection-

ü Adhesion with the host cell or tissue surfaces

The initial event in the pathogenesis of many infections is the attachment of the bacteria to body surfaces. This attachment is maybe specific adhesion and sometimes maybe non-specific adhesion.

Non-specific adhesion- involves non-specific attractive forces which allow the approach of the bacterium to the host cell surface.

·         Hydrophobic interactions

·         Electrostatic attractions

·         Brownian movement

·         Recruitment and trapping by biofilm polymers

 Specific adhesion- the specific reaction between surface receptors on host cells and adhesive structures (ligands) on the surface of bacteria. These adhesive structures are called adhesins. Adhesins may occur as organized structures, such as fimbriae or fibrillae and pili, or as colonization factors. Fimbriae are a smaller extension of the cytoplasm with the membrane-bound components and these are smaller than pili. Pili also surrounds the microbial cells especially bacteria.

Glycocalyx- layer outside the cell membrane of the microbial cell.

Examples- Pathogenic Escherichia coli- glycocalyx promotes adherence to the brush border of intestinal villi; Streptococcus mutans- deutran glycocalyx promotes binding to tooth surfaces (causes dental plaque).

Adherence proteins- Examples- Streptococcus pyogenes- M protein on the cell binds to receptors on respiratory mucosa; Neisseria gonorrhoeae- Opa protein on the cell binds to receptors on the urogenital epithelium.

Lipoteichoic acid- Examples- Streptococcus pyrogens- facilitates binding to the respiratory mucosal receptor (along with M proteins)

Fimbriae (pili)- Examples- Neisseria gonorrhoeae- pili facilitate binding to urogenital epithelium; Salmonella species- type I fimbriae facilitate binding to the epithelium of small intestine; Pathogenic Escherichia coli- colonization factor antigens (CFAs), which are fimbrial, facilitate binding to the epithelium of small intestine.

This specific adhesion may account for the tissue tropisms, host specificity (species specificity), and genetic specificity exhibited by many pathogens. Adhesins serve as virulence factors, and loss of adhesions is usually often rendering the strain avirulent. Adhesins are usually made of protein and are antigenic in nature.

Tissue specificity- Streptococcus salivarius (adhering to the tongue) Streptococcus mutans (adhering to the teeth causes dental plaque).

Species specificity- E.coli K88- diarrhea in a cow. E.coli K99- diarrhea in calves. Specific immunization with adhesions has been attempted as a method of prophylaxis in some infections, as for instance against E.coli diarrhea in calves and piglets, and gonorrhea in human beings.

Genetic specificity- Red blood cells (Duffy coat glycoprotein is a receptor for malarian parasite) Plasmodium vivax.

ü Invasion

The entry of the pathogen into the host cell or tissue. Two major barriers which cover the whole body or tissue. Natural barriers- Skin, Mucus membrane

Skin (mechanical protection)- majorly two layers- epidermis and dermis.

Microbes that enter the epidermis it scraps out with epidermis because they are dead cells they always scrapping out and go away. The dermis layer is tightly arranged. In the dermis there is a gland one of those is the Sebaceous gland, it is a small gland in the skin which secrets an oily or waxy matter called sebum. Sebum serves to protect the body against microorganisms, it is helping the skin to maintain particular pH. It forms the acid mantle (acidic film) on the surface of the skin. The pH of the skin is between 3 to 5, and acidity that helps to neutralize the alkaline nature of contaminants. So they might be prevented or restrict the growth of the microbes on the surface of the skin or to penetrate the skin. Keratin is a strong protein hold skin cells together very tightly to form a barrier so that intracellular junction is very less in this region if bacteria break to the epidermis and enter the dermis but it is very difficult to bacteria to migrate through the intracellular space.

Mucus membrane- There is a two strategy take up by microbes to invade the mucus membrane.

·         Directed uptake strategy

·         Antigen sampling exploitation strategy

Directed uptake strategy- the pathogen direct the host cell to uptake itself in the host cell.

Pathogen comes in contact with the host cell surface any receptors like glycolipid and glycoproteins. After surface interaction between the host cell and the pathogen, the pathogen weakening up the cell membrane of the host cell and start producing some factors which will alter the structure and shape of the actin filament assembly inside the host cell and that important factor is called invasin. Invasin is a protein factor secreted by a pathogen. Invasin allows the cell to rearrange its cytoskeleton which is actin, it is a very active part of the host cell of the cytoskeleton or eukaryotic cytoskeleton. So actin rearranged inside the host cell, as it rearranging itself it produces a kind of engulfment.

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Example- Salmonella infection take this strategy to invade in the intestinal mucosa.

Antigen sampling exploitation process- It is a routine process inside our intestinal epithelial cells which is covered with mucus in between it.

The role of M cell is, it routinely takes up those foreign materials from the gut lumen which is non-self-cell, cell debris, or any material and passes it from the lumen through the intestinal cell lining into the lymph node. As it is carrying in a lymph node and blood vessel system, there is a macrophage- the scavenging molecule. Scavenging cells of our body are macrophage, T cells, killer cells and many other cells are present which are ready to engulf the foreign material. These cells aggressively killing those antigenic molecules which are dangerous, non-self, bad for our body. After the introduction of foreign material in lymphatic it will easily uptake by macrophage and other killer cells, recognize them as non-self and kill them. That’s how they make the antigen sampling process and everything will be fine in our body. The process of transferring antigen from the gut lumen to the other side of the lumen is called the transcytosis process. While some bacteria invading the mucosa by escaping the M cell pathway, they do not take M cell to go inside by it, they choose other cells to invade the mucosa. Example- Shigella.

ü Spreading factors of microbial infection

It is secreted by microbes or maybe an integral structure of microbes which damage the host cell and tissue. Enzymes and toxins lead to devasting effect to the host cell.

Enzymes

·         Hyaluronidase- It breaks the molecule called hyaluronic acid, hyaluronic acid is providing connectivity of the cells together in connective tissues and other tissues, it act as a intestinal or interacellular cement between the tissues or cells.

Hyaluronidase cleaves or hydrolysis this hyaluronic acid so it disintegrate the tissue and the tissue getting hampered and die. Example- Streptococcus, Staphylococcus, Clostridium perfringens.

·         Collagenase- It breakdown the protein collagen. Collagen is very important protein found in our muscle, it’s a very tight protein attached the muscle cells all together, make the muscle cell or tissue very tighter. Collagenase cleaves all those interaction between the muscle cells, disintegrate the muscle and tissue get hampered. Example- Clostridium perfringens is an anaerobic bacteria and they love to reside in muscles to feed on collagen then breakdown collagen and disintegrate muscle tissue and start producing gases like CO₂, hydrogen peroxide and hydrogen sulphatide gases, they start to swelled up mucles up which is called gas gangrene, very severe disease caused by Clostridium.

·         Neuraminidase- It disintegrate another intercellular cementing material of tissue which is called neuraminic acid. Usually found in our intestinal lining. Neuraminidase breakdown intestinal lining and they get hampered, so the pathogen get entry from the lumen in the endothelial layer of in testine. Example- Vibrio cholera, Salmonella typhi, Shigella dysenteriae.

·         Streptokinase and Staphylokinase- Streptokinase produced by Streptococcus and Staphylokinase produced by Staphylococcus. Kinase enzyme has task of phosphorylating other things or making things activated and inactivated. Streptokinase and Staphylokinase act on plasminogen which is an inactivated part of protein plasminogen, its activate the protein convert into plasmin, plasmin will act on other protein precursor. Active plasmin convert fibrinogen into fibrin, fibrin helps to clot the blood. Now plasmin degrades the fibrin into fibrin split proteins. Due to the no longer functional breakage of fibrin into fibrin split proteins, so the blood cannot clot in our body.

·         Hemolysin and Leukolysin- factors or enzymes breakdown RBCs and WBCs respectively. Both secrete some enzyme factors. Example- Phospholipase and Lecithinase. They act on the cell membrane of RBCs and WBCs, so they start to make pore in the cell membrane and devastated the osmolarity of the cell, and cell eventually die. Phospholipase cleaves the phosphate group of the cell membranes. Cell membrane made up of phospholipid group, phosphate head, and a hydrophobic tail. So, they cleave phosphate head out of it making a kind of hydrophobic as making destabilizing so cell getting ruptured and the cell dies. Lecithinase acts on cell molecules like cholesterol molecules inside the cell and disrupts phosphatidylcholine in membranes. Example- Clostridium, Streptococci (Streptolysin), Staphylococci (Alpha toxin).