Med Micro Case Studies

Why might prior antibiotic treatment increase potential for infection with C. difficile?

Why might prior antibiotic treatment increase potential for infection with C. difficile?

Prior antibiotic treatment might increase the potential for infection with C. difficile by clearing out healthy, normal flora in the body, leaving room for the pathogenic bacteria to grow.

Why are fecal transplants being used for treatment of C difficile?

Fecal transplants can be used to treat C. difficile infections by introducing healthy flora/bacteria present on the stool from a healthy individual back into the body, thus clearing out the disease-causing bacteria and replacing it with normal flora

What role might the thicker mucus observed in CF patients play?

The thicker mucus observed in CF patients prevents cilial movement in the respiratory tract. The cilia are used to push harmful substances out of the body, but if their movement is inhibited, then they are unable to perform their function. This allows a buildup of various different pathogens in the mucus and respiratory tract.

How might differences in Cl- concentrations in the lower respiratory tract be a factor in patients with CF?

Different Cl- concentrations in the lower respiratory tract could either increase or decrease susceptibility by making the environment more or less hospitable, or preventing pathogens from entering the body.

CF patients have higher levels of neutrophils but have more damage to the respiratory tract, what may explain this?

Increased levels of neutrophils in CF patients would seem to correlate to stronger immune responses, but the elevated presence of neutrophils in the blood can both block/inhibit airways and additionally cause immune-mediated damage to the respiratory tract.

P. aeruginosa can be found as normal flora in the GI tract of some individuals but can cause disease if in the lower respiratory tract, explain why this might be? Explain how CF patients acquire P. aeruginosa.

P. aeruginosa may grow as normal flora in the GI tract because that is where it is supposed to be. In this environment, it would be non-pathogenic because it is not an abnormal growth, so the immune system would not attack it. Additionally, it is not producing any virulence factors, so no disease would be caused. However, if it gets somewhere it doesn’t belong - in this case, the respiratory tract - then it would likely shift to a pathogenic form and begin producing virulence factors, and the immune system will recognize it as a pathogen and mount an attack.

What types of infections would you hypothesize to be more common in patients with neutropenia and why?

Neutropenia is characterized by a decreased number of neutrophils in the blood. Neutrophils are a part of the innate immune system. Therefore, a person with fewer neutrophils would be more susceptible to pathogens that reside in the blood (bacteremia, viremia, etc.)

What type of infections are individuals with deficiencies in complement genes most susceptible to?

Again, the complement system is a mechanism of the innate immune system. Someone who has deficient complement genes is more likely to be susceptible to recurrent infections.

Early in the COVID pandemic one common practice that was used to try and identify infected individuals was measuring their body temperature. What is the theory behind this - what are you actually detecting

A fever is a sign that the innate immune system has kicked into gear. Cytokines send signals to immune cells such as neutrophils, macrophages, & dendritic cells, which accumulate at the site of infection. The complement system also assembles, leading to the formation of the membrane attack complex (MAC). This localization of immune cells can cause inflammation. Additionally, and in the case of COVID, the body can regulate its temperature to make the environment inhospitable to invading bacteria. By in- creasing the temperature, there is a chance that the bacteria cells will die off.

Individuals with genetic mutations that result in decreased or non-functional NK cells often have problems with herpes virus infections. Why might this be the case?

The herpes virus is a double stranded DNA virus that is capable of integrating its genetic material into the genome of the host cell. NK cells are typically responsible for detecting infected cells that could potentially be tumorous. If an individual carries the genetic mutation for decreased or non-functional NK cells, then they have a greater disposition to developing tumorous and cancerous cells.

Individuals with genetic mutations that result in decreased or non-functional NK cells often have problems with herpes virus infections. What does this tell us about the role of NK cells in herpes virus infections?

This tells us that NK cells play a critical role in helping to control herpes viruses in infected individuals by eliminating infected cells.

A patient comes in with a systemic bacterial infection. The patient is given an antibiotic which results in cell death by causing bacteria lysis. The bacteremia dramatically decreases but the patient is “sicker.” Why?

While the antibiotic killed off the bacteria, so it is no longer alive and able to reproduce, it did not eliminate the structures inside the body, which has spread to its entirety. The buildup of dead bacteria parts in the body, especially if they are gram negative, can act as an endotoxin, further sickening the patient.

RIG-1 and MDA are pathogen associated molecular pattern (PAMP) receptors that recognize dsRNA and trigger innate immune responses. Influenza viruses, which make dsRNA during replication of the viruses, can still replicate - how?

dsDNA viruses such as influenza utilize eukaryotic cellular machinery to replicate their genetic material. Because they are located within a human cell, the innate immune system will not attack the virus because it recognizes the self. Additionally, many viruses have genes that destroy receptors that recognize pathogen-associated pattern receptors, which allow the virus to replicate without activating the immune system.

There is data suggesting that more men than women may have a genetic defect resulting in worsened very early immune responses to SARS-2. What might explain this?

Women have two X chromosomes, meaning that they have two copies of certain genes which might code for and improve specific immune responses. Twice as many immune genes = strong immune responses.

Explain why individuals who lack a spleen (and thus a specific type of macrophage) are more susceptible to certain bacterial blood infections.

Individuals lacking a spleen are more susceptible to certain bacterial blood infections because they are deficient in specific macrophages, which might play a role in preventing or fighting off different infections.

Explain why patients who have Bare Lymphocyte Syndrome (BLS), which results in the lack of MHC II, are susceptible to chronic infections and rarely make it past age ten.

MHC II is involved with the antigen presenting cells (macrophages and dendritic cells) of the innate immune system, which then serve as the messengers to activate the adaptive immune response. The APCs opsonize exogenous pathogens and present the epitopes/antigens. CD4+ T cells bind to the epitope at receptor sites and can then relay the message on to other CD4+ T cells, allowing an adaptive immune response to develop. If an individual doesn’t have MHC II, then any pathogen that makes its way into the body will never have to face the adaptive immune system. Only the innate immune system is present to fight off the agent, and this usually will allow the infection to become chronic and permeate the body.

The Hmong population in Wisconsin was found to be more susceptible to potentially lethal fungal infections with Blastomycosis dermatitis. Based on genetic testing and experimental models, it was demonstrated that this population probably has decreased production of a certain cytokine. Why might this be the cause of the increased risk to this population?

Decreased production of cytokines may prevent infected cells from sending out signals to attract immune cells to the site of infection. With this lack of initial immune response, neither the nucleated cells nor the antigen presenting cells of the innate immune response are specifically called to the infection site, so there are very few APCs to opsonize the fungus, present the antigens through MHC II, and initiate an adaptive response.

Why might adding a PAMP during vaccination increase the response made to a vaccine?

PAMPs are specifically designed to mimic patterns associated with certain pathogens. Adding them to the vaccine will amplify the pathogenic response, further activating the immune system into forming a response.

HIV targets and kills CD4+ T cells (and other immune cells). Why does this cause susceptibility to other infections that are easily controlled or cleared by HIV-uninfected individuals?

By killing off the CD4+ T cells and other immune cells, a person is left extremely susceptible to infection because they are lacking an adaptive immune response. This means that there is no fighting force for pathogens to go up against, so it is likely the agent will not be controlled or cleared.

HIV targets and kills CD4+ T cells (and other immune cells). Like many other viruses, HIV has developed mechanisms to avoid recognition by the immune system. Besides affecting the immune system itself, how might this virus hide from the body?

HIV is capable of molecular mimicry, coating itself in host-cell-made sugar structures. This means the immune system either doesn’t recognize the virus, or won’t attack it to avoid harming self cells. It is also capable of shifting and/or hiding its epitopes to avoid immune detection.

Individuals with thymic aplasia have functional B cells but not functional CD8+ T cells. When infected with measles viruses they don’t develop the characteristic rash but eventually die from secondary infections and continued viral replication. What is happening?

CD8+ T cells are responsible for detecting epitopes presented on MHC I by the nucleated immune cells. This would pertain to cells infected by the measles virus. Without sufficient adaptive immune cells to eliminate infected cells, the measles virus is able to spread and eventually kill off the host.

Individuals with IgA deficiency can handle most infections but are particularly susceptible to respiratory infections. Why?

IgA antibodies are usually found on the outside surface of various membranes. That means that while other antibodies are able to handle infections on the inside of the body, there is nothing to eliminate pathogens on outside surfaces before they establish an infection. This is especially true in the case of the respiratory tract, where pathogens can live on the outside surface of the throat/esophagus and cause infection.

A patient has their blood tested for antibodies against pathogen X. The sample comes up positive for IgM antibodies against pathogen X but not IgG antibodies. What does this tell you about the infection?

This tells us that the infection is in the early stages, because IgM is the antibody associated with early infections, while IgG is associated with infections in their later stage.

Scientists are creating new proteins in the lab to treat CMV infections. It has the CD8 TCR for a major epitope for the virus fused to the Fc region from IgG. How might this work?

The epitope for CMV viruses fuse to the Fc regions of IgG. NK cells and macrophages are triggered by the Fc regions of antibodies, so the macrophages opsonize the virus and present the epitope on their MHC I to activate the adaptive immune response.

Scientists are creating new proteins in the lab to treat CMV infections. It has the CD8 TCR for a major epitope for the virus fused to the Fc region from IgG. Possible limitation?

Not everyone has the correct MHC I type to recognize specific epitopes.

The basic premise of CART therapy uses genetically engineered CD8+ T cells to attack self epitopes (usually epitopes specific to cancer cells). Limitations?

The therapy might inadvertently attack host cells. Additionally, it is limited to specific epitopes and MHC dependent.

The basic premise of CART therapy uses genetically engineered CD8+ T cells to attack self epitopes (usually epitopes specific to cancer cells). Sources for cells to engineer?

Donor cells, or from the bone marrow.

What is a good indicator of whether a vaccine can be made against a particular pathogen?

Vaccines can only be made if the body is capable of producing a natural immune response. Additionally, they can only be made if the pathogen exists within the blood, and if the body is able to clear the infection on its own.

What are the advantages and disadvantages of developing live-attenuated vaccines?

Live-attenuated vaccines are very strong because they involve a live, albeit weakened, version of the pathogen. This elicits a strong immune response and good memory is formed. The disadvantages of live-attenuated vaccines are that, because it is a live pathogen, there is a risk of infection especially in individuals with weakened immune systems.

Synagis is passive immunization that may be given to children at high risk for bad RSV infections once a month during RSV season. Why once a month?

This is a passive immunization, meaning the response against it lasts only as long as antibodies are present.

Synagis is passive immunization that may be given to children at high risk for bad RSV infections once a month during RSV season. Limitations?

Passive immunity does not build an adaptive immune response, as no self-made antibodies are made.

Consequences of infections with Rhinoviruses (hundreds of serotypes, antigenically distinct)

can get reinfections, especially since there are so many versions of the same virus. Also means that no vaccine can be made because of wide genetic diversity.

Consequences of infections with Coronaviruses (prevent formation of long-term immune memory)

since no long-term memory response is formed, reinfections are possible. Also, it is not likely for a vaccine to be developed.

Consequences of infections with Measles (erase all immune memory)

leads to potential for secondary bacterial infections, cannot develop a vaccine.

After a family reunion potluck, almost everyone who ate the potato salad started vomiting within an hour. Explain what happened.

It is likely some type of bacterial exotoxin in the potato salad, meaning those who ate it were intoxicated with a large dose of the pathogen at once, causing disease.

Why do we put food in the freezer or refrigerator?

Cold is a bacteriostatic agent, meaning it slows but does not eliminate bacterial growth.

Why is heat an important tool in food safety?

Heat is a bactericidal agent, so it kills off the bacteria, helping to decontaminate infected foods.

Staphylococcus aureus is one of the most common bacteria found on our skin, but is extremely dangerous when it gets inside of our bodies. Why?

Again, it is normal flora on the outside of our bodies, but when it gets inside the body, the conditions change and it may begin producing exotoxins, becoming pathogenic.

Identify three ways you might identify whether a person has food poisoning with regular E. coli or E. coli O157H7.

Because these are the same species with only slightly different genes, macroscopic, even microscopic, antigenic, and phenotypic tests will not work, you need to test using RFLP/PCR to distinguish between the two.

Explain how Staphylococcus aureus may acquire resistance to certain antibiotics from the environment

Transduction (bacterial “parasite” deposits genes from other bacteria), transformation (process of picking up genes from the environment), conjugation (acquisition of plasmids and other genes via sex pilus from one bacteria to another).

Explain how Staphylococcus aureus may acquire resistance to certain antibiotics on its own.

Transposition (genes moving within genome changes which genes are expressed.

Explain why certain bacteria that cannot prevent phagocytosis by macrophages (e.g., chlamydia) may still have no problems reproducing.

Chlamydia is an example of an obligate intracellular pathogen meaning it can only replicate inside a host cell. These types of bacteria grow inside of host cells and do so by escaping lysosomes to avoid being broken down.

Patient X is diagnosed with toxic shock. Diagnostics of the infection reveals the pathogen to be a gram-negative organism that lacks any virulence genes. What is causing the disease?

The lipopolysaccharide structures on the surface of all gram negative bacteria serve as endotoxins, so while the bacteria itself is not producing any toxins, the structures with enough accumulation can cause toxic shock and trigger the immune system into action.

What are two things that some bacteria are able to do to make them extremely hard to remove from medical equipment during the sterilization process?

Bacteria are capable of forming spores - stable, non-reproducing but hardy forms that can exist in the environment - and biofilms - multiple layers of the bacteria which makes it extremely difficult for antibiotics to penetrate and reach the original cell.

I. For certain pathogens, instead of making vaccines against the pathogens, we make inactivated vaccines against exotoxins/toxids. Why might it be better to do this?

Ultimately, it is the exotoxin that is causing illness, and due to bacteria’s ability to acquire foreign DNA, other bacteria might be capable of producing an exotoxin associated with a different pathogen.

Why do you think it might be harder in general to identify antifungal compounds than antibacterial compounds that have fewer side effects in humans?

Fungal cells are very similar to our own in size and complexity. This makes it very difficult to develop antifungal drugs that will not end up harming our own cells. Usually, these medications target the cell wall that is found in fungal cells, but not human ones.

Explain how antibiotic usage can result in an increased susceptibility to vaginal yeast infections.

Antibiotic usage may clear out the normal flora that resides in the vagina, leaving room for a yeast to grow and cause an infection.

What are three populations particularly at risk for fungal infections?

The immunocompromised or suppressed, who are unable to fight off fungal infections. Children, because there is less distance the fungus needs to travel to reach particularly vulnerable places and establish a systemic infection.

How might you protect yourself from the inhalation of mold spores?

Wear a mask.

How can some foods make you sick, or give hallucinations or kill you without a fungal infection?

Mycoses can produce exotoxins as a result of their biochemical pathways, which are toxic to humans. If these exotoxins are present in the food, they can make you sick/cause hallucinations/kill you even without the fungus itself being present.

Why might “black mold” under some conditions make people ill but not in others?

Black mold may cause illness under some conditions if the infected person has a compromised or suppressed immune system. Additionally, the amount of dimorphic fungi in the body can cause illness.

Explain why sticks may be an effective mechanism for the transmission of fungus.

Fungi usually grow on sticks in the mold form. Sticks are pointy, which make them ideal objects for breaking the skin barrier and depositing a mold (which becomes a yeast) into the body.

Why might the fungal cells appear different on the stick than in a human host?

Certain fungi are dimorphic, meaning they grow as molds in cold environments, typically outside of the body, but can transform into their yeast form when they are in warmer environments, such as the body.

A 61-year-old man–with a history of home-brewing–stumbled into a Texas emergency room complaining of dizziness. Nurses ran a Breathalyzer test and sure enough, the man’s blood alcohol concentration was a whopping 0.37%, or almost five times the legal limit for driving in Texas.

This man has had years of exposure to yeast spores, which have likely established themselves in his digestive tract. These yeast ferment the sugar found in the food he eats, converting it to ethanol (alcohol) and causing a state of drunkenness.

Explain why size exclusion filters might be better than chemical treatment of stagnant water for backpackers to drink.

Parasites are much larger, so to prevent them from entering the water, using a size filter would do the job. Some parasites are also resistant to chemical treatments.

If you know you are going to an area where a parasite transmitted by an insect vector is endemic, what are two things you could do to try and prevent the parasite from establishing an infection?

Wear clothing, sleep under nets, or, in some cases, take drugs before arriving to help avoid or at least mitigate potential infections.

Why might getting water up your nose result in brain infections, but swallowing it won’t?

Getting contaminated water up the nose places parasites in the nasal cavity, with only a thin membrane separating it from the brain. If the parasite gets into the brain it causes infection there. Swallowing, on the other hand, takes the parasite down the esophagus into the stomach, a much longer distance for the parasite to travel to establish a brain infection.

Explain why treating a schistosome infection with the antiparasitic drug Praziquantel might not work in patients with AIDS.

Schistosomes cause a lot of immune mediated damage due to molecular mimicry. Using Praziquantel will likely end up targeting the few remaining immune cells in AIDS patients in addition to the parasite itself, worsening the current infection and all future infections. Additionally, antiparasitics work to unmask epitopes on parasites (usually are hidden), but once they are unmasked, there is no immune system to eliminate the parasite in AIDS patients.

How do you think certain intestinal worms in animals can cause skin infections in humans (think about sand).

Fecal-oral transmission. Animals such as cats (key carriers of toxoplasma gondii) may be natural reservoirs for certain parasites. If they defecate and humans come into contact with their feces, there is a chance for parasitic infections. Especially with sand, which might break the skin barrier through abrasion.

Explain why, with certain parasitic infections, even with continually generating new, theoretically effective adaptive immune responses, we cannot clear the replicating parasite.

Parasites are capable of many different tactics to avoid immune responses such as antigen shifting or phase variation and masking epitopes to avoid immune detection.

Explain how certain parasitic infections can replicate in “plain sight” of the immune system.

Molecular mimicry.

Why might some potential parasites cause asymptomatic infections in a natural host and symptomatic infections in another, other than differences in immune responses.

The parasite expresses different genes depending on the signals it receives from the environment.

How can insecticides directly or indirectly help prevent certain parasitic infections?

Many parasites rely on insect vectors for transmission. Indirectly, insecticides prevent certain parasitic infections by killing off the insect vector, so there is no way for the parasite to travel from host to host. Directly, some insects are the parasite, so insecticides would kill off the insect itself.

Based on what you have learned about other pathogens, what do you think might occur in terms of replicating and infective forms of many parasites when the acquisition is from other people (e.g., STDs)

likely to be in the replicative form (e.g., trophozoite), cannot survive well in the environment due to poor protection

Based on what you have learned about other pathogens, what do you think might occur in terms of replicating and infective forms of many parasites when the acquisition is from the environment (e.g. water)

cyst, or environmentally stable form.

You work for big pharma. You have been tasked to develop a new line of antiviral drugs what types of infections might you target and why?

Acute and chronic infections to eliminate the virus. Systemic and localized.

You work for big pharma. You have been tasked to develop a new line of antiviral drugs what are the ideal characteristics/properties you hope to have in your new drug?

Fights both chronic and acute infections, high efficacy of eliminating virus without causing harm to human cells. Targets stages of virus lifecycle.

You have been tasked to develop a new drug against a particular viral disease (e.g., hepatitis). You are sort of successful. It works in some patients but not in others. Why might this be the case?

Drugs do not clear viral infections; they are simply static agents designed to suppress viral replication. In patients with healthy immune systems, they might help the immune system control the virus, making it seem as though the drug is successful by minimizing disease. On the other hand, in those with suppressed or compromised immune systems, there is no immune system to control the virus even with the aid of the drug. Additionally, there are many different viruses that can cause the same disease, so there is a possibility that the antiviral drug being used is not the correct one for the virus.

Antiviral drugs work by blocking a step in the virus life cycle. Why does this result in the clearance of one chronic viral infection but not all viral infections?

Each antiviral drug is specific to one virus.

Why might a virus make two versions of the same protein - one version has a transmembrane domain so that it is embedded in the viral envelop and one that is secreted from virally infected cells?

One protein can perform two different functions (Delivery and/or protection) but other viruses must produce two proteins: one to deliver, one to protect.

Why might a virus produce its spike/peplomer proteins last (relative to other viral proteins, like their viral polymerase)?

A virus might produce its spike/peplomer proteins last because these are the elements that go on the outermost surface of the cell. They are delivery proteins, so they need to be on the outside in order to find receptors to attach to.

Assembly of viral particles is not a very efficient process with some viruses making as little as one infectious particle for every 10,000 particles generated. How can viruses be successful with such an inefficient process?

Because they produce so much progeny.

How can we use the production of viral structural proteins, in the absence of potential progeny genomes, for a medical benefit?

The structural proteins can be used for vaccines.

What are some key elements required for the eradication of certain viruses?

They must be limited to humans and acute infections.

Why do you think drug resistance occurs more rapidly with most RNA than DNA viruses?

RNA is more prone to mutations than is DNA. Therefore there is a higher chance that an RNA virus might mutate in a way the codes for drug resistance.

Why must all RNA viruses encode a polymerase but some DNA viruses may not?

Host cells do not have the primers or machinery needed to transcribe and translate viral RNA. With the exception of single stranded positive sense RNA viruses, all RNA viruses need to have RDRP (and for Retroviruses, DDDP) in order to replicate their genetic information.