Pathogenesis PDF

Pathogenesis Pathogen: A disease-causing microorganism Pathogens can be viruses, bacteria, or eukaryotic microbes such as protozoans Pathogenic: The ability of a microorganism to cause disease (+ or -). Pathogenesis: The steps (mechanisms) ? involved in the...

Pathogenesis Pathogen: A disease-causing microorganism Pathogens can be viruses, bacteria, or eukaryotic microbes such as protozoans Pathogenic: The ability of a microorganism to cause disease (+ or -). Pathogenesis: The steps (mechanisms) ? involved in the development of disease The “how” a disease develops Term applies to non-infectious diseases too. Pathways for causing disease An infection can cause disease in three, non-mutually exclusive ways: 1. Pathogen directly damages cells/tissue while multiplying (e.g., lysing cells). 2. Pathogen produces toxins that directly damage cells/tissues 3. Pathogen induces an inflammatory response that damages cells/tissues of host (inflammation occurs in response to pathogen itself or its toxin).  Four stages of pathogenesis Exposure: Pathogen encounters cell Adhesion: Pathogen attaches to the cell of host tissue Invasion: The pathogen invades the host’s tissue. Colonization: The pathogen reproduces and establishes a population within the host.  Exposure We are constantly exposed to pathogens, through the food we eat, water we drink, objects we handle, people and animals we contact, insects that bite us, etc. Portal of entry is the anatomic site through which pathogens enter the host organism. Nearly all pathogens require a portal of entry because our skin is an extremely effective barrier.  Adhesion Adhesion is the process of a pathogen attaching to a host cell. Adhesins are proteins that enhance adhesion. These proteins facilitate the binding of the pathogen to protein receptors on host cells. Adhesins are typically found on the fimbriae and cell walls of bacteria, on the cilia of protozoans, and on the capsids or outer membranes of viruses. Example: E. coli bacterium adhering to colon cell using adhesins on fimbriae (adhesins themselves are not visible).  Invasion After adhering, the pathogen invades the host’s bodily tissues. This can occur through direct penetration of the host cells (intracellular pathogens) or through openings between cells (extracellular pathogen). Illustration of extracellular tissue invasion.  Colonization Once a pathogen has entered tissue(s)/cells, it reproduces and multiplies. As with invasion, depending on the pathogen, growth and reproduction can Example: Intracellular replication of malaria pathogen take place inside or outside of host cells (but still within the tissue). Example: Extracellular replication of sleeping  Virulence factors Virulence factors are structures or molecules that enhance pathogen adhesion, invasion, colonization, and/or help evade immune clearance. In other words, virulence factors increase the likelihood that a pathogen makes it through the stages of pathogenesis and successfully colonizes the host. Because your tissues are damaged during pathogenesis, virulence factors therefore increase disease severity in the host. This is why they are called “virulence” factors.  Virulence factors Main categories of virulence factors: Adhesins (help with adhesion stage) Exoenzymes (help with invasion and evading immune responses) Toxins (help primarily with invasion stage) Capsules (help to evade immune responses)  SOME BACTERIAL ADHESINS AND THEIR HOST ATTACHMENT SITES Pathogen Disease Adhesin Attachment Site Streptococcus Respiratory Strep throat Protein F pyogenes epithelial cells Streptococcus Dental caries Adhesin P1 Teeth mutans Neisseria Urethral epithelial Gonorrhea Type IV pili gonorrhoeae cells Enterotoxigenic E. Intestinal epithelial Traveler’s diarrhea Type 1 fimbriae coli (ETEC) cells N- Intestinal epithelial Vibrio cholerae Cholera methylphenylalani cells ne pili Responsible for knowing these five pathogens, the listed diseases, adhesins, and attachment sites. Do not need to know how to spell anything. Bacterial exoenzymes are enzymes secreted outside the cell, which enhance tissue invasion and/or protect from the immune system. Example: Hyaluronan cements host cells together, minimizing space between them. Hyaluronidase-S, an exoenzyme secreted by S. aureus, degrades hyaluronan and creates space to promote invasion.  Coagulase and Staphylokinase S. aureus produces the virulence factor coagulase, which forms a blood clot around the bacteria. This clot acts as a physical barrier, protecting the bacteria from the immune system while they grow. S. aureus then produces the virulence factor staphylokinase, which dissolves the clot and releases a large load of the bacteria into the blood.  Toxins Toxins are biological molecules that cause disease at low concentrations. Toxigenic refers to the ability of a microorganism to produce toxins. Some microbial toxins are virulence factors because they help with the invasion stage of pathogenesis. Other toxins have no role in pathogenesis, but nonetheless cause disease.  Two types of bacterial toxins 1) Exotoxins are proteins that are secreted outside the bacterial cell to perform a specific function, usually targeting certain host cell types. Exotoxins are produced mostly (but not exclusively) by gram-positive bacteria Primary function related to pathogenesis: Kill or damage cells of a tissue, thereby making tissue more permeable to invasion.  A-B exotoxins A-B toxins are exotoxins secreted by bacteria species that cause the diseases cholera, botulinum, and tetanus. After being secreted, toxins need to get inside host cells. How? A-B toxins are made up of two subunits: A and B B binds to host cell, causing it to engulf the toxin (A and B) A breaks apart, escapes vacuole, and is then free to harm cell (mechanism of harm depends on type of A-B toxin) COMMON A-B EXOTOXINS AND ASSOCIATED BACTERIAL PATHOGENS Category Example Pathogen Disease manifestation Cholera toxin Vibrio cholerae Diarrhea Intracellular- targeting Tetanus toxin Clostridium tetani Spastic exotoxins that use paralysis A-B subunit structure to enter cell Botulinum toxin Clostridium Flaccid paralysis botulinum Diphtheria toxin Corynebacterium Necrosis Responsible for knowing everything in diphtheriae table but will not be asked to spell  Just how potent are bacterial exotoxins? Number of grams Substance needed to kill adult human Venom of the Brazilian Between 1,000 – wandering spider (most 0.0134 100,000 x more poisonous spider in world) deadly than any Venom of the Inland Taipan spider poison or (most venomous snake in 0.0025 snake venom on world) earth Diphtheria 0.000001 toxin (from Corynebacterium) Do not need to Shiga know anything 0.0000002 toxin (from Shigella bacteria) in this table. Tetanus toxin (from Clostridium 0.0000002 tetani)  Two types of bacterial toxins 2) Endotoxins: Molecules located in the cell walls of bacteria that induce damaging immune responses. Endotoxins serve little if any role in tissue invasion (i.e., probably do not serve an adaptive function in pathogenesis). The most common bacterial endotoxins are liposaccharides found on outer membrane of gram-negative bacteria. Accumulation of lipid A causes overreactive and damaging immune response Lipid A is the toxigenic component of liposaccharide  Capsules Capsules are polysaccharide structures that cover the outer layer of the cell wall. Capsules can be found on gram-positive and negative bacteria, but only select species have them. Primary function of capsule is to avoid death from the immune system! The capsule's composition makes it difficult for immune cells to recognize the pathogen, hindering their ability to perform phagocytosis.