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1. In 2001, a bioterrorist attack, in which spores were mailed to prominent figures or institutions, resulted in several cases of inhalation anthrax.
(a) What is the name of the organism that causes anthrax? [2 points].
(b) If individuals who develop inhalation anthrax are not treated promptly, what is the likely outcome of the disease? [2 points].
(c) Briefly outline how spores travel from the lung to the mediastinal (draining) lymph nodes, what happens to them when they get there, and how the organism subsequently disseminates. What virulence factors allow this organism to (i)avoid phagocytosis by macrophages and neutrophils, and (ii)cause the outcome in (b), above? [6 points].
2. Primary septicemia, caused by disseminated infection with the Gram-negative bacterium,
Vibrio vulnificus, is reported to have the highest mortality on a per case basis among all types of foodborne illness.
(a) What are the two characteristics that distinguish virulent strains of V. vulnificus from strains of this organism that do not cause primary septicemia? [2 points].
(b) Explain how a lack of either, or both, of the virulence factors identified in (a) might render V. vulnificus unable to cause primary septicemia. [2 points].
(c) Outline the stages of the host–pathogen interaction that occur when a person develops primary septicemia after eating raw shellfish contaminated with V. vulnificus. [6 points].
3. A physician practicing in the United States sees a patient who has fever, chills, headache, body aches, and general malaise. Although these signs and symptoms are non-specific, after taking a patient history, the physician suspects malaria.
(a) What critical piece of information uncovered in the patient history led the physician to suspect malaria? [2 points].
(b) What two characteristics of Plasmodium species would the physician need to consider when designing a treatment regimen for this patient? [2 points].
(c) Briefly outline the roles played by the sporozoite and merozoite forms of the malaria parasites during infection of a naïve human host, and explain how they cause the signs and symptoms of malaria. [6 points].
4. Giardia lamblia causes giardiasis, a human disease that results from localized infection of the gastrointestinal tract.
(a) What kind of microorganism is G. lamblia? [2 points].
(b) What are two other eukaryotic microbes that can cause disease after localized infection of the human gastrointestinal tract? [2 points].
(c) What clinical signs and symptoms are commonly associated with localized infections of the gastrointestinal tract? [6 points].
5. Foodborne illness caused by microorganisms can result from several different pathogenic mechanisms, one of which is direct intoxication.
(a) In the context of foodborne illness, what is meant by ‘direct intoxication’? [2 points].
(b) What type of outbreak, or epidemic, would be associated with disease caused by this mechanism? [2 points].
(c) Give three, named examples of pathogens that can cause foodborne illness by direct intoxication, and for each one indicate whether or not it can also cause disease by localized infection of the GI tract. [6 points].
6. Listeria monocytogenes is a species of Gram-positive bacterium that is found ubiquitously in soil. It also is a facultative intracellular pathogen that escapes from the phagosome after being taken up by macrophages.
(a) What is the reservoir for L. monocytogenes? [2 points].
(b) On which class of major histocompatibility complex will L. monocytogenes antigens be presented by macrophages? [2 points].
(c) Briefly outline the sequence of events in the immune response that begins after L. monocytogenesis first detected in the tissues and which culminates in the clearance of the infection. [6 points].
7. Neisseria meningitidis is one of three organisms that are common causes of bacterial meningitis.
(a) How are N. meningitidis infections acquired? [2 points].
(b) What are the principal virulence factors of N. meningitidis? [2 points].
(c) Briefly outline the sequence of events in the host–pathogen interaction that occurs between entry of N. meningitides bacteria into the body, and the onset of meningitis in an affected person. [6 points].
8. The etiologic agent of plague, Yersinia pestis, is a Gram-negative bacterium that has a non-human animal reservoir.
(a) To what family of bacteria does Y. pestis belong? [2 points].
(b) How is Y. pestis most commonly transmitted to humans from reservoir animals? [2 points].
(c) Briefly outline what happens to the bacteria after they enter a naïve human host by the route identified in part (b), how they travel to the draining lymph node and what happens when they get there, and how subsequently pneumonic plague can develop in the infected person. [6 points].
9. Rabies is a serious disease that is endemic to North Carolina. If a patient potentially has been exposed to rabies virus, the appropriate clinical response is to perform post-exposure prophylaxis (PEP).
(a) What is the reservoir of rabies virus? [2 points].
(b) By what means is rabies virus most commonly transmitted from the reservoir to humans? [2 points].
(c) What is rabies PEP, and how, specifically does it prevent neurological rabies from developing in a person who has been exposed to rabies virus? [6 points].
10. Histoplasmosis and blastomycosis are systemic mycoses, diseases caused by endemic dimorphic fungi that may be encountered in North Carolina.
(a) What is meant by the term ‘endemic’ as it relates to a pathogen? [2 points].
(b) What is a dimorphic fungus? [2 points].
(c) Briefly outline the host–pathogen interactions that lead to a systemic mycosis, and identify the similarities and differences that apply to Histoplasma capsulatum and Blastomyces dermatitidis [6 points].
11. A number of pathogens are transmitted horizontally between humans by sexual activity.
(a) Give two examples of sexually-transmitted pathogens for which routine immunization is available in the United States. [2 points].
(b) Sexual transmission is an example of a horizontal transmission route. What, in contrast, is meant by vertical transmission? [2 points].
(c) For pathogens that are horizontally transmitted by sexual activity, list the potential routes by which vertical transmission might occur, and give one, named example of such a pathogen for each route. [6 points].
12. Severe influenza generally results from an infection of the lower respiratory tract, and yearly vaccination is recommended to prevent, or reduce the severity of, this disease.
(a) What organism is most likely to cause severe influenza? [2 points].
(b) What are the two different types of vaccine used in the U.S. for routine immunization against influenza? [2 points].
(c) Give examples of four characteristic clinical signs or symptoms of influenza, and indicate which among them are constitutional symptoms. [6 points].
13. Chlamydophila psittaci is an intracellular bacterial pathogen belonging to the family Chlamydiaceae.
(a) What is the name of the disease caused by C. psittaci? [2 points].
(b) Why is penicillin (and related antibiotics) ineffective in treating C. psittaci infections? [2 points].
(c) Briefly outline the stages in the interaction between C. psittaci and host cells that leads to the release of newly replicated bacteria. [6 points].
14. Invasive strains of Group A streptococcus (GAS) have virulence factors that allow them to prevent or evade both the innate and adaptive immune responses.
(a) What are two examples of diseases that can be caused by invasive GAS? [2 points].
(b) Explain how highly virulent strains of GAS are able to avoid the humoral adaptive immune response. [2 points].
(c) The innate immune response normally results in infiltration of neutrophils and clearance of bacteria from infected tissues. What two aspects of this process are counteracted by invasive GAS strains, and what are the specific virulence factors involved? [6 points].
15. Wound infections arise when pathogens enter the body at sites where the skin has been damaged.
(a) Skin is an example of a barrier defense against pathogens. What are two other examples of barrier defenses? [2 points].
(b) Most organisms that are normally found in the environment, and might enter a wound, are not pathogenic. Why not? [2 points].
(c) List the three types of pathogenic mechanism by which bacteria can cause disease after entering a wound, and give a specific, named example organism for each one. [6 points].
1. Immune surveillance refers to processes that take place while the human body is in the “ready” state, waiting to encounter pathogens.
(a) Which cells bring antigens to naïve lymphocytes to initiate an adaptive immune response? [2 points]
(b) Where in the body do naïve lymphocytes encounter non-self antigens for the first time? [2 points]
(c) Briefly outline what each of the following cell types do during the “ready” state of immune surveillance: naïve B- and T-lymphocytes, neutrophils, and macrophages [6 points]
1. Legionella pneumonophila is a species of Gram-neagtive bacterium that is found ubiquitously in fresh-water. It also is a faculative intracellular pathogen that blocks phagolysosome fusion after being taken up by macrophages.
(a) What is the reservior for L. pneumophila? [2 points]
(b) On which class of major histocompatibilty complex will L. pneumophilia antigens be presented by macrophages? [2 points]
(c) Briefly outline the sequence of events that begin after macrophages first take up L. pneumophilia in the tissues and culminate in clearance of the infection by an adaptive immune response. [6 points]
1. MCV4 is a conjugate vaccine that can provide protection against meningococcal disease caused by encapsulated Neisseria meningitdis of serotypes A, C, Y, and W-125.
(a) What kind of N. meningitdis antigens are present in MCV4? [2 points]
(b) Does MCV4 protect against infection with N. meningitidis serotype B? Explain your resoning. [2 points]
(c) Briefly outline the steps that lead to activation of a naïve B cell after its B-cell receptor binds to one of the neisseria meningitidis antigens present in MCV4. [6 points]
1. Treatment for infectious diseases can take several forms, which include surgery in certain cases, as well as the widespread application of antimicrobial chemotherapy.
(a) For what types of infection would surgical intervention be appropriate treatment? [2 points]
(b) How is that non-microbicidal drugs (“-statics”) nevertheless can form the basis of a curative treatment for an infectious disease? [2 points]
(c) Briefly outline the four mechanisms used by pathogens to evade or counteract antimicrobial drugs, and indicate to which class(es) of pathogens each mechanism applies. [6 points]
1. Vaccination is intended to generate immunity, via immunological memory and circulating specific antibody, before a person encounters a specific, virulent pathogen for the first time.
(a) During a primary immune response, a process occurs that results in changes to the antigen-binding site of the antibody encoded by an activated B cell. What is the name given to this process? [2 points]
(b) What effect(s) are booster vaccinations inteded to have on immunity? [2 points]
(c) List the different types of vaccine currently used for routine immunization of the general public in the United Sates, and give one specific example vaccine of each type. [6 points]
1. Post-exposure prophylaxis (PEP) refers to a medical intervention that is carried out after exposure, or potential exposure, to a pathogen with the intent to prevent disease.
(a) What factors determine whether PEP is feasible for any given pathogen? [2 points]
(b) Upon which two principles are current PEP protocols based? [2 points]
(c) Give three examples of diseases for which PEP is employed as a public health control measure and describe a specific protocol used for each one. Include at least one example from each kind of protocol indentified in part (b). [6 points]
1. Herd immunity can protect a population against infectious disease even though not all of the individuals in the population are immune.
(a) What pathogen-specific charactersitics determine the proportion of the population that must be immune in order for herd immunity to operate? [2 points]
(b) Against what type of epidemics would herd immmunity be effective? [2 points]
(c) Briefly explain the mechaism through which herd immunity operates. [6 points]
1. Some groups of people are at higher risk than others for contracting certain kinds of diseases. Information gathered by a physician is intended to identify patients in such groups, and will be used to arrive at a differential diagnosis.
(a) What is a differential diagnosis? [2 points]
(b) What is the general name for the type of disease for which veterinarians are at increased risk in comparison to members of the general public? [2 points]
(c) Briefly outline the steps taken by a physician in the process of diagnosing an infectious disease. [6 points]
1. In October 2004 there was an outbreak of infection by Escherichia coli 00147:H7 among people who had attended the North Carolina State Fair. This outbreak was investigated by a team of epidemiologists from the North Carolina Division of Public Health (NCDPH) and the Centers for Dsiease Control and Prevention (CDC).
(a) In general, what is the most common way for people to be exposed to E. coli 0157:H7? [2 points]
(b) The fair already was over before the E. coli 0157:H7 outbreak was recognized. Why did NCDPH decide to investigate the outbreak? [2 points]
(c) List the components of a generic outbreak investivation, and indicate which one of them was not employed by the NCDPH-CDC team during this investigation? [6 points]
1. The disease tuberculosis (TB) is caused by infection with Mycobacterium tuberculosis. Infections with this organism can result in either active TB, in which mycobacteria are shed and can be detected in a patient’s sputum (coughed-up mucus), or in clinically latent TB, which is characterized by a lack of mycobacterial shedding.
(a) What combination of diagonostic tests would allow a clinician to determine whether they have active or latent TB? [2 points]
(b) If the patient is determined to have active TB, what kind of public health control measure would be necessary to prevent them from exposing members of the general public? [2 points]
(c) Name the kind of infection control precautions that would be employed if an active TB patient required hospitalization. List, and briefly describe, each of the applicable precautions. [6 points]
1. Vibrio cholerae O1 and Corynebacterium diphtheriae both are bacterial pathogens that
establish extracellular infections on mucosal surfaces and cause disease through the
action of a secreted exotoxin.
(a) Give two examples of secreted bacterial proteins that act as virulence factors,
but are not exotoxins. [2 points].
(b) What class(es) of antibody would not contribute to protection against disease
caused by C. diphtheriae? Explain your reasoning. [2 points].
(c) Identify the similarities and differences between the exotoxins produced by V.
cholerae O1 and C. diphtheriae, respectively. Consider the structure of the
toxins, their mode of action, and the consequences for affected host cells. [6
2. A delayed-type hypersensitivity (DTH) reaction is an immunopathology caused when T
cells respond to their specific antigen by producing cytokines in peripheral tissues.
(a) Specifically, what kind of T cells are involved in a DTH reaction? [2 points].
(b) Give a named example of a cytokine that is produced by the responding T cells,
and identify its major function. [2 points].
(c) How are antigens processed for presentation to T cells during a DTH reaction? In
what form, and on what type of cell, are the antigens presented to the
responding T cells? [6 points].
3. Pathogenic strains of the Gram-positive bacterium, Streptococcus pneumoniae all have
an anti-phagocytic, polysaccharide capsule that is an essential virulence factor for this
(a) How does the capsule prevent phagocytosis of the bacteria during the immune
system’s early induced response? [2 points].
(b) What effector component(s) unique to the adaptive immune response is/are
required to defeat this virulence factor? [2 points].
(c) Describe two mechanisms by which the effector component(s) identified in (b)
allow encapsulated S. pneumoniae organisms to be recognized by phagocytes
during an adaptive immune response. [6 points].
4. Influenza A virus normally infects mucosal epithelial cells, and infection is confined to
this cell layer (i.e. the virus infection is not invasive).
(a) What is the usual portal of entry for influenza virus in humans? [2 points].
(b) What effector components of the adaptive immune response would be involved
in combating an influenza virus infection? [2 points].
(c) Briefly outline the steps in the host–pathogen interaction that takes place during
influenza A virus infection of humans. [6 points].
5. In some patients, antibiotic therapy can lead to gastrointestinal disease caused by
endogenous infection with the opportunistic, Gram-positive bacterial pathogen,
(a) Among patients who are undergoing the same antibiotic therapy, why are only
some at risk for developing antibiotic-associated gastrointestinal disease? [2
(b) Given two strains of C. difficile, one of which can only colonize people, while the
other can cause gastrointestinal disease, what specific virulence factor would
you expect to be present in the latter but absent from the former? [2 points].
(c) Briefly outline the events that take place in the affected patients, beginning with
the initiation of antibiotic therapy, which culminate in gastrointestinal disease
caused by C. difficile. [6 points].
6. When a macrophage encounters Gram-negative bacteria in the peripheral tissues, a
local inflammatory response typically ensues.
(a) How does a macrophage detect the presence of Gram-negative bacteria? [2
(b) What two kinds of signaling molecules does the macrophage secrete after it
detects the bacteria? [2 points].
(c) Explain what happens during the local inflammatory response that follows.
Indicate which cellular and molecular features of the response account for the
redness, swelling, heat, and pain that are characteristic of inflammation. [6
7. Hantaan virus enters the body via the respiratory tract and then spreads through the
blood. Disseminated infection leads to hemorrhagic fever with renal syndrome. An
adaptive immune response that generates virus-specific cytotoxic T lymphocytes (CTLs)
is required to clear the infection.
(a) What adaptive immune system component would be important for controlling
the viremia? [2 points].
(b) How are naïve CD8+ T-cells activated? [2 points].
(c) After activation, CD8+ T-cells proliferate and differentiate into CTLs. Briefly
outline how virus-specific CTLs recognize and destroy virus-infected host cells. [6
8. In many cases, non-encapsulated, extracellular bacteria can be cleared efficiently from
blood and tissues by phagocytic cells of the innate immune system.
(a) How are these bacteria recognized by phagocytes as things that should be
engulfed? [2 points].
(b) What are two humoral component(s) of the innate immune system that can
directly enhance the process of phagocytosis by individual cells? [2 points].
(c) Briefly outline the sequence of events that takes place after engulfment of a
bacterium, and which culminate in its death inside the phagocyte. In your
description, indicate when during this sequence each of the major classes of
specific mechanisms used by phagocytes to kill bacteria is brought to bear. [6
9. Human immunodeficiency virus (HIV) uses the host cell surface molecule CD4 as a
specific receptor, and it can infect and ultimately kill CD4+ cells.
(a) What is the main cell type in the body which expresses CD4 on its surface? [2
(b) Why is the decline in the number of CD4+ cells in the body only gradual during
the clinically latent stage of HIV infection? [2 points].
(c) Explain the normal functions of CD4+ cells during an adaptive immune response,
and indicate how the loss of these cells can explain the immunodeficiency
characteristic of acquired immune deficiency syndrome (AIDS). [6 points].
10. The availability of a diverse array of lymphocyte antigen receptors to bind specific
antigens is critical for the functioning of the adaptive immune system.
(a) On what cell types are the two kinds of lymphocyte antigen receptor found? [2
(b) Under what conditions are foreign peptides recognized by each kind of antigen
receptor? [2 points].
(c) Explain briefly how diversity is generated in the protein sequences of mature
lymphocyte antigen receptors. [6 points].
11. During infection by certain pathogens, local invasion of host tissues may occur.
(a) Define what is meant by “invasion” in this context. [2 points].
(b) For an opportunistic pathogen, such as Candida albicans, which lacks specific
virulence factors for invasion, what kinds of extrinsic factor(s) (i.e. ones external
to the microbe) could allow invasive disease to be caused? [2 points].
(c) After entry of an obligate-extracellular bacterial pathogen into a host, briefly
outline the sequence of all the events that lead up to invasion: (i) if the
bacterium secretes a cytolytic exotoxin, and (ii) if the bacterium secretes the
enzyme, hyaluronidase. [6 points].
12. The production of antibodies that can recognize pathogen-specific antigens is a critical
aspect of most adaptive immune responses.
(a) What is an antigen? [2 points].
(b) What is an epitope? [2 points].
(c) Briefly outline the steps that occur between the initial binding of antigen to the
B-cell receptor on a naïve B cell, and the accumulation of high levels of IgG in the
serum. Describe activation of the B cell, as well as the subsequent events. [6
13. Infection of humans with Vibrio cholerae serotype O1 typically causes the disease,
(a) What is the usual portal of entry for Vibrio cholerae O1 in humans? [2 points].
(b) Not all serotypes of Vibrio cholerae can cause cholera. What specific kind of
virulence factor would you expect to be common only to the cholera-causing
serotypes of this bacterium? [2 points].
(c) Briefly outline the steps in the host–pathogen interaction that takes place during
infection of humans by Vibrio cholerae. [6 points].
14. Primary, lytic infection of epithelial cells by herpes simplex virus (HSV) is brought under
control by the immune system. However, before it is eliminated, HSV is able to establish
a latent infection in neurons that innervate the tissue.
(a) What cytokine would you expect to be produced by the infected epithelial cells?
(b) For HSV, what distinguishes a lytic infection from a latent infection? [2 points].
(c) Explain how the adaptive immune response brings primary HSV infection under
control, and indicate why this immune response is ineffective against the
latently-infected nerve cells. [6 points].
15. Rickettsia rickettsii is an intracellular pathogenic bacterium that is taken up into host
cells by phagocytosis, but manages to avoid being killed.
(a) What general mechanism is used by R. rickettsii to avoid being killed after
phagocytosis? [2 points].
(b) Give an example of a specific virulence factor that is employed by R. rickettsii
during this process. [2 points].
(c) Considering its location within the infected host cell, what kind of T-cell response
would be required to clear R. rickettsii infections? How are antigens processed
for presentation to T cells during R. rickettsii infection, and in what form are the
antigens presented to the responding T cells? [6 points].
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