Mechanisms of Pathogenicity Flashcards
Presence of bacteria is not always associated with ______________.
infection – in fact most of the bacteria in and on our bodies are beneficial or commensal ( organisms
Commensalism
an association between two organisms in which one benefits and the other derives neither benefit nor harm.
Pathogenicity
Pathogenicity refers to the ability of an organism to cause disease by overcoming host defenses (i.e., harm the host).
How can a microbe cause disease?
- microbe that is part of normal microbiota enters different part of body where normally not found (ex. E. coli in urinary tract)
- exposure to pathogenic strain (ex. E. coli O157:H7)
- microbes introduced into body and get past natural defenses of innate immune system, then either directly damage host tissues or release toxins that damage host
How does the chain of infection work?
An infectious agent present in a reservoir leaves through a portal of exit. It is then transmitted in a number of ways to another host. The host receives an infectious dose of pathogens via the portal of entry. The host must be susceptible ) lowered defenses or overwhelming dose.
Virulence
Degree of pathogenicity.
What must pathogens do before they cause disease?
They must attach or adhere to tissues. Bacteria accomplish this by using adhesins or ligands, viruses utilize receptors on host cells.
Adhesins
surface projections on pathogen, mostly made of glycoproteins or lipoproteins. Adhere to complementaryreceptors on the host cells. Adhesions can be part of:
Glycocalyx: e.g.Streptococcus mutans
Fimbriae (also pili and flagella): e.g.E. coli
Host cell receptors are most commonly sugars (e.g. mannose for E. coli
Preferred Portal of entry
most pathogens have a preferred portal of entry that is required in order for them to gain access to a host and cause disease. If access is gained via another portal disease may not occur.Portal of entry refers to not only how the pathogen enters the body, but how it then survives within the host and causes disease. Pathogens must enter the “right” way in order to cause disease; the “right way” varies for different pathogens.
What are the main portals of entry?
- Mucous membranes
- Skin
- Parenteral route (parent-ter-al)
Elaborate on the portals entry?
- Conjunctiva (membrane on inner eyelid and sclera)
- Respiratory tract; this occurs when contaminated droplets or dust particles are inhaled.
- Gastro-Intestinal tract; via contaminated fingers, food and water.
- Skin; Impenetrable for most microorganisms; some can enter through hair follicles, sweat ducts.
- Parenteral route; Trauma (S. aureus, C. tetani), Arthropods (Y. pestis), Injections, surgery, medical devices
What is the most common portal of entry?
The respiratory tract
ID50
Infectious dose for 50% of the test population
LD50
Lethal dose (of a toxin) for 50% of the test population
Biofilms
Biofilms provide attachment and resistance to antimicrobial agents.
Capsules
inhibition or prevention of phagocytosis
Cell wall proteins
A virulence factor that allows a pathogen to overcome immune defenses. ex. M protein
M Protein
a cell surface and fimbriae protein involved in attachment to epithelial cells in hosts and resistance to phagocytosis, as well as preventing complement-mediated lysis (prevents immune system from depositing proteins on cell surface that promote cell death by lysis)
Antigenic variation
Antigenic variation refers to the mechanism by which an infectious agent such as a protozoan, bacterium or virus alters its gene expression to change its surface proteins in order to evade a host immune response.
How do bacteria penetrate the host cell’s cytoskeleton and move through and between host cells?
some bacteria produce invasins, proteins that cause the actin of the host cell’s cytoskeleton to form a basket that carries the bacteria into the cell. Bacteria also use actin and cadherin to move through and between host cells
name some virulence factors
- Enzymes
- Capsules
- Cell wall proteins
- Antigenic variation
- Penetration into the host cell cytoskeleton
Enzymes that can be considered virulence factors.
- Coagulase
- Kinase
- Hyaluronidase
- Collagenase
- IgA protease
Coagulase
causes the formation of blood clots allowing bacteria to evade phagocytosis.
Kinase
dissolves blood clots
Hyaluronidase
(spreading factor) it hydrolyzes hyaluronic acid, a type of polysaccharide that holds together certain cells of the body, particularly cells in connective tissue. Maybe involved in tissue blackening that allows microbes to spread from the initial site of infection. hyaluronidase may be mixed with a drug to promote the spread of the drug through the body tissue.
Collagenase
causes the hydrolysis of collagen
IgA protease
IgA destruction (IgA are a class of antibodies, important in maintaining mucous membrane barriers intestinal tract, respiratory tract, urogenital tract, and conjunctiva)
How do pathogens damage the host?
- They take nutrients from the host; siderophores bind iron tighter than host cell proteins.
- They directly damage host cells; Bacteria can multiply within host cell causing damage
- They produce toxins; chemical molecules harm host cells
- They induce hypersensitivity reactions
Exotoxins
Produced by the bacteria during growth and metabolism, secreted by the bacteria into the surrounding medium or released following lysis. Exotoxins are proteins, many are enzymes that catalyze certain biochemical reactions. Gram + and Gram - bacteria can both produce exotoxins. Exotoxins do not produce fevers. Antitoxin neutralizes exotoxins. The LD50 of an exotoxin is usually small. They circulate to the site of activity, they affect the body before an immune response they may have specific action sites.
Endotoxins
toxins located inside a bacterial cell. Endotoxins are part of the outer membrane in gram - bacteria only. The Lipid A portion of the LPS is an endotoxin; endotoxins are lipopolysaccharides and exotoxins are proteins. Endotoxins are released during cell multiplication and lysis. Endotoxins stimulate macrophages to release large amounts of cytokines, symptoms are caused by inflammation, patient can experience endotoxic shock. Endotoxins cause fever and are not neutralized by antitoxin. The LD50 of endotoxins is relatively large.
Toxin
Substances that contribute to pathogenicity
Toxigenicity
Ability to produce a toxin.
Toxemia
presence of toxins in the bloodstream
Antitoxin
antibodies produced by host immune system to neutralize toxins
Toxoid
inactivated or altered exotoxins used in vaccines to stimulate antitoxin production (TDAP shot)
hepatotoxin, neurotoxin, enterotoxin
These are exotoxins that affect the liver, nervous system and intestines.
How do A-B toxins work?
A bacteria produces and release an A-B toxin, The binding portion B attaches to a host cell receptor. The plasma membrane of the host cell invaginates at the point where the A-B toxin and plasma receptor makes contact. The exotoxin enters the cell by receptor mediated endocytosis.A-B toxin and receptor are enclosed in a vesicle during pinocytosis. A-B components of the exotoxin separate. The A component alters host cell function, often by inhibiting protein synthesis. The b component is released from the cell and the receptor is reinserted into the plasma membrane for reuse.
A-B toxin
the first toxins studied intensively and are named for the 2 parts they have (A and B). A and B are both polypeptides. Most exotoxins are A-B toxins. A is the active enzyme component and B is the binding component.
What are the types of exotoxins?
- A-B toxins
- Membrane-disrupting toxins
- Superantigens
- Genotoxins
Membrane-disrupting toxins
lyse host cells by making protein channels into the plasma membrane and disrupting phospholipid bilayer. ex. Leukocidin and Hemolysin.
Luekocidin
a type of membrane- disrupting exotoxin that destroys granulocytes and macrophages. They form protein channels
Hemolysin
Cause the lysis of red blood cells to obtain iron when heme is released. They cause the formation of protein channels on the plasma membrane.
Superantigens
A special type of Exotoxin. They nonspecifically stimulate T-cells and cause intense immune response due to release of cytokines from host cells. Symptoms include fever, nausea, vomiting, diarrhea, shock, and death.
Lysogeny
bacteriophage DNA inserted into the host cell genome and remaining in an inert (inactive) state. If activated, virus production may occur and transduction of virulence factor genes may occur when new phages infect other bacteria – thus spreading virulence factors.
How are endotoxins released?
Bacterial cell death, antibiotics, and antibodies may cause the release of endotoxins
How do endotoxins cause fever and shock?
Endotoxins cause fever (by inducing the release of interleukin-1) and shock (because of a TNF-induced decrease in blood pressure).
TNF
Tumor necrosis factors (or the TNF family) refer to a group of cytokines that can cause cell death (apoptosis).TNF release also allows bacteria to cross blood-brain barrier, makes BBB leaky.
Endotoxins can cause DIC, what is DIC?
Disseminated intravascular coagulation is when an endotoxin activates blood clotting proteins and causes clots that block capillaries, which leads to tissue death.
How does an endotoxin cause fever?
a macrophage ingests a gram negative endotoxin producing bacterium, The release of the bacterium’s endotoxin causes the macrophage to release interleukin-1 into blood vessels where it reaches the hypothalamus in the brain. In response to interleukin-1 the hypothalamus releases prostaglandins which cause inflammation and fever.
What are the pathogenic properties of viruses that allow them to infect a host?
Viruses evade the immune system by:
- Growing inside cells away from immune system
- Some have attachment sites which mimic substances which are useful to the cell; spikes on rabies virus mimic acetylcholine.
- Some viruses can hide their attachment sites (like HIV) CD4 is long and slender.
What are the 2 categories of cytopathic (visible) effects of a viral infection.
- cytopathic effects can be cytocidal (cause cell death)
- can also be noncytocidal (causes damage but not death)
What are some cytopathic effects? What type of cytopathic effects are they?
- Lysis of host cell due to copious amounts of viruses building up in the cell from replication, or the release of lysosomal contents which cause cells to be digested from within. (cytocidal)
- Inclusion bodies may be seen (may contain viral components); alteration of cellular activities (non-cytocidal)
What are the pathogenic properties of fungi?
- Fungal waste products may cause symptoms
- Chronic infections provoke allergic responses
- Some fungi produce proteases
ex. Candida, Trichophyton - Some have a capsule which prevents phagocytosis
ex. Cryptococcus
What are some examples of fungal toxins?
- Ergot toxin
Claviceps purpurea - Aflatoxin
Aspergillus flavus
What is ergotism caused by?
Ergotism is caused by the chemicals in the fungus called ergot (pronounced AIR-got) (ergot toxin). Consumption of foods contaminated with ergot and ergot derivatives may cause vomiting, diarrhea, hallucinations, and may lead to gangrene in serious cases. The chemical responsible for the hallucinations is actually LSD! lysergic acid.
Aflatoxin
associated with liver damage, immune system suppression, and even tumorigenesis in infected animals
What are the pathogenic properties of Protozoa?
- Presence of protozoa and protozoan waste products may cause symptoms
- They avoid host defenses by:
Growing in phagocytes and antigenic variation
What are the pathogenic properties of helminths?
- Presence of helminths interferes with host function
- Helminths metabolic waste can cause symptoms
Wuchereria bancrofti
A type of helminth; Infective larvae transmitted via mosquito vector; portal of entry = skin; localizes to lymphatic system and causes elephantiasis
List the portals of exit and how microbes exit through them.
- Respiratory tract: Coughing and sneezing
- Gastrointestinal tract: Feces and saliva
- Genitourinary tract: Urine and vaginal secretions
- Skin
- Blood: Biting arthropods and needles or syringes
- Fomites: inanimate objects (door handles)
Portals of exit are usually the same as the portals of ________________.
entry
Why is lysogenic conversion of medical concern?
Some bacterial pathogenesis is caused by the prophages they contain.
brake down the word Pathogen
Pathos = To harm
-gen = to cause
The skin is ____________ which helps to protect from pathogens.
slightly acidic; stomach acid also kills many bacteria we ingest.
Microbiome
all the microbes in or on humans
Mucus membrane
An epithelial tissue that secretes mucus and that lines many body cavities and tubular organs including the gut and respiratory passages. Protects body from outside environment.
The dose of pathogens ________.
matters when it comes to causing disease.
Are LD50 and ID50 always the same?
No sometimes LD50 may be higher.
What type of bacteria use invasins?
Gram - rods.
Hyaluronic acid is _____________ than collagen.
more common
How does a large release of cytokines cause low bp and shock?
Cytokines cause blood vessels to become leaky, this leads to a loss in fluid. Low fluid in the plasma causes a decrease in blood pressure.
PMN
polymorphonuclear neutrophils (granulocytes)
