MB 411 Final Exam (all questions and short answer)

Which of the following act as barrier defenses against the entry of pathogens into the body?

1. Eyes: tears, lysozymes 2. Respiratory Tract: mucous, ciliated epithelium, alveolar macrophages 3. GI tract: Washing of urine, acidity of urine, lysozyme, vaginal lactic acid 4. Skin: anatomical barrier, antimicrobial secretion 5. Digestive tract: stomach acidity, normal microbiota, bile

What class of microbial pathogens cause most endogenous infections of humans?

Bacteria

Which of the following characteristics of Clostridium Botulinum is primarily responsible for botulism being a relatively uncommon food-borne disease?

Strict anaerobic growth. Spores

In the context of medical MB, "parasite" refers specifically to which of the following?

Any eukaryotic that is not a fungus

When present in a bacterium, which of the following could be virulence factors?

Anything that helps to overcome barrier defenses against entry. -enzymes to break down extracellular matrix, toxins to kill epithelial cells, proteins to induce transcytosis, bacterial capsules, and ability to survive phagocytosis

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 adaptive immune response that begins after L. monocytogenes is first detected in the tissues and which culminates in the clearance of the infection. [6 points].

(GI PoE, disseminated intracellularly via "Trojan horse") A) Environment, animals, and humans B) MHC I C) - Pathogen phagocytosed by macrophage; bacteria escapes phagosome - Macrophages migrate to lymph node and activate CD8+ via presentation of antigen on MHC I Pathogen antigens presented on MHC I. - CTLs can kill infected host cells. (Extracellular effectors ineffective.)

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? (b) Explain how highly virulent strains of GAS are able to avoid the humoral adaptive immune response. (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?

(Think S.pyogenes) A) Necrotizing fasciitis, pharyngitis, scarlet fever B) The hyaluronic acid capsule prevents the host from raising an antibody response bc hyaluronic acid is a self-antigen C) **Neutrophil and chemokine functions inhibited** - The hyaluronic acid capsule allows the bacteria to evade phagocytosis by neutrophils, macrophages, etc. - S. pyogenes strains may also possess anti-complement protein which prevents opsonization by complement (*C3b and C5a*) and subsequent phagocytosis. *Streptococcal chemokine proteases* produced by the bacteria can work in concert w/ the anti-complement C5a virulence factor to inhibit signaling of neutrophils to the infection site. * Streptokinase also prevents coagulation, so the bacteria may not remain localized and instead can disseminate throughout the body.

For which of the following types of infectious disease would supportive care alone be an appropriate treatment?

*diseases where there is no curative treatment, or treatment doesn't effect outcome* ex. ebola, E. coli

Against which of the following vaccine-preventable diseases is/are the U.S. general public immunized routinely?

*if the option doesn't sound ordinary it's not right*

Which of the following are diseases caused by tick-borne bacteria?

- Rocky mountain spotted fever - Lyme disease/ borreliosis - Relapsing fever - Helvetica spotted fever - Tularemia - Human monocytic enrlichiosis - Human granulocytic enrlichiosis anaplasmosis (HGE)?

Which of the following strategies is/are used by Ehrlichia chaffeensis, the causative agent of human monocytic ehrlichiosis, to prevent it from being killed after uptake into host cells by phagocytosis?

- Block phagosome fusion - Grow within phagosome (intracellular vesicular pathogen)

Which of the following are virulence factors of Staphylococcus aureus?

- Capsule - Protein A (counteract specific antibodies and prevent opsonization) - Exotoxins (cytolytic or membrane damaging toxins, exfoliative toxins, enterotoxins, and toxic shock syndrome toxin-1) - Secreted enzymes: Hyaluronidase, lipase

Which of the following arboviruses is/are endemic to North Carolina?

- La Cross Virus (enveloped and (-)ssRNA) - Eastern Equine Encephalitis Virus (EEEV)- (enveloped and (+)ssRNA) - West Nile Virus (Enveloped and (+)ssRNA)

For which of the following vector-borne pathogens are humans not a dead-end host?

- Malaria - Rocky mountain spotted fever - Human monocytic enrlichiosis - Human granulocytic anaplasmosis - arboviral infections (La Crosse, Eastern Equine, West Nile)- P. knowlesi?????

Which of the following pathogens can give rise to pus-filled vesicles when they infect breaks in the skin?

- Staphylococcus aureus - Streptococcus pyogenes

Which of the following diseases are caused by spirochetes?

- Syphilis - Leptospirosis (Weil's disease and febrile illness) - Lyme disease

Which of the following diseases result from systemic intoxication following localized infection of the skin?

- Tetanus - Wound botulism - Cutaneous anthrax - Cutaneous diphtheria - Toxic shock syndrome (TTS) - Scalded skin syndrome - Scarlet fever

What pathogenic mechanism is responsible for infant pneumonia caused by Chlamydia trachomatis?

- Vertical transmission vs Maternal Parturition - localized infection - Host cell lysis and inflammatory response - inoculation of bacteria into oropharynx

Which of the following statements is/are true of both human papilloma virus and herpes simplex virus?

- both are viral STI's - localized infection (not reportable in NC) - both have dsDNA - Use skin or mucous membrane as PoE

Which of the following cell types are infected by Plasmodium spp. that cause malaria?

- hepatocytes (primary) - red blood cells (secondary)

Which of the following statements is/are true of chlamydiae?

- most common localized bacterial STI in U.S. - Can be treated with antibiotics - Not vaccine-preventable - Gram-negative rod - no peptidoglycan in cell wall - can be horizontally/vertically transmitted

Which of the following diseases may be caused by localized infection with Streptococcus pyogenes?

- pharyngitis (Strep throat) - Rheumatic fever (inflammation of joints, blood vessels, and subcutaneous tissues) - Pyoderma - Skin infection (pus filled vesicles) - Erysipelas - Cellulitis (deep skin infection and produce enough cytokines to cause for fever and chills)

By what pathogenic mechanism does Staphylococcus aureus cause toxic shock syndrome?

- systemic intoxication of localized infection - the exotoxin TSST-1 is produced by the bacteria and disseminated in the blood

Which of the following diseases may be caused by disseminated infection with Staphylococcus aureus?

-bacteremia/endocarditis -hematogenous, hecrotizing pneumonia (PVL) -osteomyelitis -septic arthritis

Which of the following routes of transmission might be associated with pathogens that cause common source outbreaks of disease?

--> linked by common source of exposure; food-borne transmission and vector borne transmission

Which of the following are virulence factors of Streptococcus pyogenes?

-antiphagocytic- hyaluronic acid capsule -proteins with anti-complement (C3b, C5a) functions -exotoxins: pyrogenic toxins, membrane damaging toxins -secreted enzymes: hyaluronidase, streptokinase, streptococcal chemokine protease

Over what distance does droplet transmission occur most efficiently?

3 ft or less

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].

A) Animals (terrestrial mammals; bats) B) Animal Bites C) Rabies post-exposure prophylaxis (PEP) can prevent the virus from disseminating through the nerves to the CNS and causing neurological rabies. *Immune globulin + inactivated viral vaccine* are used for PEP to treat the localized infection before it has time to disseminate. After dissemination, there is not treatment for rabies, and encephalitis, myelitis, and death occurs.

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].

A) Bacillus anthracis B) Shock and Death C) -B. anthracis spores are inhaled - Spores are taken up by phagocytic cells in lungs and transported to draining lymph nodes - Spores germinate within the phagocytic cells giving rise to vegetative bacteria - Vegetative bacteria cause lysis of phagocyte and are released to the extracellular medium - Vegetative bacteria resistant to phagocytosis becuase of polypeptide capsule - They grow within the lymph node and then infect the blood (bacteremia) - They also produce *exotoxins* that can lead to shock and death

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].

A) Disease regularly maintained within a particular population B) Two different shapes/forms associated w/ two respective growth habits (hyphal/mycelial and yeast forms). C) - Inhalation of spores - The warmer temperature of the body then causes spores to germinate into their pathogenic yeast form. - H. capsulatum is a intracellular pathogen so it will disseminates through blood after being phagocytosed w/in cells; bc liver and spleen have a lot of macrophage-like cells, H.capsulatum disseminated infection affects the liver, spleen, and sometimes even CNS and heart valves. By contrast, B. dermatitidis is an extrac. pathogen, so dissemination alternatively affects the skin and bones rather than macrophage-dense organs. - Both pathogens cause chronic inflammatory condition bc fungus not being cleared; this presents as flu-like symptoms - Both pathogens may be treated for disseminated infection with antifungals.

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].

A) Enterobacteriaceae B) infected fleas C) -Flea bites human and bacteria infiltrate host - in human, bacteria phagocytosed, block phagolysosome fusion - carried w/in phagocytes to draining lymph node, grow inside vacuole - *Express antiphagosome factors* (injectable toxins and capsule), released into lymph node - Travel to blood where rapid onset of *bacteremia can cause endotoxic shock and death* **If the bacteria spreads to the lungs, it can become incorporated into respiratory droplets that may be transmitted to other humans (secondary pneumonic plague)

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 upon localized infection of the GI tract. [6 points].

A) Exotoxins are made by bacteria that grow in food prior to its consumption. Disease is caused by exotoxin rather than infection with bacteria B) Common source C) o Clostridium botulinum; yes, can cause localized infection in GI tract of infants or otherwise immunocompromised individuals o Staphylcoccus aureus; no o Bacillus cereus; yes, causing diarrheal disease

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].

A) Human Hepatitis B Virus (HBV), Human Papillomavirus (HPV) B) When an infection is transmitted from a mother to an infant/newborn C) - placental-fetal. (*Treponema pallidum*) (Syphillis) - maternal-parturition. (Chalmydia trachomatis, Neisseria gonorrhoeae, herpes simplex virus) - maternal-neonatal (hepatitis B virus, human immunodeficiency virus)

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 for each one indicate whether it is, or is not, a constitutional symptom. [6 points].

A) Influenza A virus B) Inactivated virus vaccine [IIV] and live-attenuated virus vaccine [LAIV] C) (1) fever/chills - constitutional (2) severe myalgia (muscle aches) - constitutional (3) non-productive cough (4) loss of appetite - constitutional

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 microorganisms 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 different, named example bacterial species for each one. [6 points].

A) Mucous Stomach acidity B) Most organisms do not have the necessary virulence factors to overcome the body's immune system C)Localized infection- *S. aureus* causes impetigo (pus-filled vesicles, skin infection) Disseminated infection- *Leptospira spp.* causes leprosy, *rabies virus* causes rabies Systemic Intoxication from localized infection- *C.botulinum* (wound botulism) , *Bacillus anthracis* (cutaneous anthrax)

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].

A) Parrot fever B) No peptidoglycan in cell wall (which penicillin targets) C) - Disseminated via the "Trojan Horse" (infect phagocytic cells) - Bc they are non-encapsulated they are able to be phagocytosed; however, they avoid being killed by blocking phagolysosome fusion once inside host cell - Innate IR therefore unable to control spread of bacteria; spread systemically inside host cells - Accumulate in organs that contain a large number of macrophages (GI, CNS, liver, kidney) - *Endotoxin* released by pathogen, exacerbates a strong inflammatory response

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 upon 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].

A) Protozoan parasite B) Cryptosporidium parvum (causes cryptosporidiosis), Cyclospora cayetanensis (cyclosporiasis) C) - Loss of Appetite - Nausea - Abdominal pain/cramps - Vomiting - Diarrhea (watery, or blood) - May, or may not, be accompanied by fever

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. meningitidis bacteria into the body, and the onset of meningitis in an affected person. [6 points].

A) respiratory transmission (coughing, kissing, talking) B) Polysaccharide capsule, *endotoxin* (stimulates inflammatory response) C) - N. meningitides enter the body via the respiratory route. - *Adhere to host cells, extracellular growth*, cell and tissue damage (encapsulation inhibits phagocytoses, and endotoxin release stimulates inflammatory response) - systemic invasion and onset of bacteremia - Infection of CSF, inflammatory cytokines cross BBB causing token swelling of meninges

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 where in the body each of the following cell types are found during the "ready" state of immune surveillance: naïve B- and T-lymphocytes, neutrophils, and macrophages. [6 points].

A. Dendritic cells B. in lymphnodes c. Naive B and T-lymphocytes: circulate in blood and efferent lymphatic system Neutrophils cirulate in blood macrophages are located in tissues

3. A physician practising 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].

A. Recent travel to Africa, Indian sub-continent, or particular parts of South America where malaria is endemic and/or a known mosquito bite B. Drug resistance and capacity for persistent liver infection C. 1. Sporozoite are the initial form of Plasmodium spp. transferred to humans during the bite of an infected mosquito, and their target organ is the liver. 2. When they reach it they infect hepatocytes and begin to grow. Hepatocytes will then break open, releasing *merozoites* into the blood. (Primary infection of liver is asymptomatic.) 3. Merozoites infect RBCs and multiply inside of them, causing eventual lysis and release of more merozoites which may go on to repeat the cycle of infection

MenACWY is a conjugate vaccine that can provide protection against meningococcal disease caused by encapsulated Neisseria meningitidis of serogroups A, C, Y, and W-135. (a) What kind of N. meningitidis antigens are present in MenACWY? [2 points]. (b) Does MenACWY protect against infection with N. meningitidis serogroup B? Explain your reasoning. [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 MenACWY. [6 points].

A. capsular/polysaccharides B. No, serotype B not included in vaccine C. 1. antibody (B-cell receptor) recognizes polysaccharide 2. Th2 CD4+ T-cells recognize peptides from carrier protein presented by MHC II on B-cell (after degrades protein into peptides which are loaded onto MHC II) 3. Th2 cells co-stimulate B-cells to produce antibody and undergo isotype switching

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].

A. encapsulated, fast-growing B. - encapsulation protects it from phagocytosis and complement-mediated killing - bc it is fast-growing, a toxic amt of endotoxin could be released before adaptive IR has time to kick in and bring disease under control Removing either/both of these elements would render the IS more able to control/eliminate the infection (c) 1. V. vulnificus enters the body, via food, estuarine water, or wound contamination. -Causes gastroenteritis when ingested by healthy immunocomptent persons when ingested -Dissemination in blood stream (immunosuppressed individuals), releases endotoxin, - Primary septicemia --> septic shock, death Innate IR cannot clear the bacteria bc its encapsulated. *Growth of bacteria is so rapid, endotoxin reaches lethal amount before adaptive IR can take effect.

Which of the following are among the microbial cell killing mechanisms used by phagocytes?

Acidification, toxic oxygen-derived products, toxic nitrogen oxides, antimicrobial peptides, enzymes, competitors

which of the following molecules can act as opsonins?

Acute phase proteins and specific antibody

People with liver damage have reduced capacity to control infection by a number of bacteria and fungi. Which of the following immune system components would you expect to be affected directly by liver damage?

Acute phase response proteins, and macrophages and NK cells

Which of the following statements is/are true of the adaptive immune system in humans?

Adapt to microbes/pathogens that have been exposed to the individual in the past and it can recognize a very large number of molecules and structures

Which of the following are virulence factors commonly found among protozoan parasites?

Adhesins, phosospholipases, secreted proteases

Gram + bacteria. C. dif., an obligate anaerobe, can give rise to endogenous infections that result in antibiotic-associated GI disease. Which of the following statements about C. dff. is/are correct?

Always associated with overt disease, does not need oxygen, colonizes host

The gram + spore forming bacterium Bacillus anthracis is an obligate pathogen of humans. What is an obligate pathogen?

Always result in overt disease

Which of the following are effector functions of complement small fragments?

Attract neutrophils

Which of the following is/are characteristics of an inapparent infection?

Aymptomatic, overt disease is not cuased, causes a carrier state (colonization occurs), and fever, inflammation, flu-like symptoms

Which of the following cell types is/are involved only in antigen-specific immune responses?

B and T cells

Which of the following myeloid cell types are granulocytes?

Basophil, Eosinophil, Neutrophil, Polymorphonuclear leukocyte

Which of the following types of clinical specimens would not normally contain microorganisms?

Blood or cerebrospinal fluid

Which characteristics are common to Cryptosporidium parvum and Cyclospora cayetanensis? Select one: A. they have human reservoirs B. they are apicomplexan parasites C. they always cause disseminated infections D. their oocysts are resistant to common water purification chemicals E. both B and D

Both protozoan parasites. oocytes are resistant to common water purification chemicals. animals reservoirs. Cause ONLY localized infection of the GI tract They are apicomplexan parasites, their oocysts are resistant to common water purification chemicals (both B and D)

For which food borne illness is/are pathogen specific treatments available? Select one: A. staphylococcal food poisoning B. rotavirus gastroenteritis C. botulism D. norovirus gastroenteritis E. both B and D

Botulism

Which of the following pathogens that enter via the Gi tract disseminate inside infected host cells? Select one: A. Clostridium botulinum B. Brucella spp. C. Trichinella spiralis D. Vibrio vulnificus E. both A and D

Brucella spp. Salmonella spp. Listeria monocytogenes

Mycobacterium tuberculosis is an intracellular pathogen that infects macrophages. Which of the following humoral and/or cellular effectors of the immune system would be most important for combating infection by M. tuberculosis?

CTL and NK cells

Which of the following are effector functions of complement large fragments?

Can act as opsonins, get cross-linked onto target cell membranes

Which of the following are characteristics of a facultative intracellular pathogen?

Can reproduce inside or outside of the host cell

Which of the following sexually-transmitted pathogens also can be transmitted

Chlamydia trachomatis human immunodeficiency virus herpes simplex virus Treponema pallidum all of the above

Which of the following bacteria that cause localized infection of the genitourinary tract are found commonly in the U.S.?

Chlamydia trachomatis Neisseria gonorrhoeae

Which of the following pathogens, when transmitted by the respiratory-aerosol route, can be acquired directly from animals?

Chlamydophila psittaci influenza A virus, serotype H5N1

Which of the following are possible outcomes of infection with HepB virus?

Cirrhosis of the liver, hepatocellular carcinoma (chronic HepB), convalescence, and death

Which of the following important molecules of the innate immune system can attract leukocytes to sites of infection?

Chemokines

What two types of signaling molecule are secreted by macrophages when they detect bacteria?

Chemokines and pro-inflammatory cytokines

Which of the following pathogens can cause fast-acting food poisoning that results from toxins produced when the pathogen grows in contaminated food? Select one: A. Salmonella enterica (serotypes other than Typhi) B. Escherichia coli O157:H7 C. Bacillus cereus D. Clostridium perfringens E. both B and D

Clostridium Botulinum (food borne botulism) Staphylococcus aureus (food poisoning) Bacillus cereus (food poisoning)**

Which of the following bacterial pathogens of the GI tract can form spores? Select one: A. Clostridium botulinum B. Staphylococcus aureus C. Bacillus cereus D. Listeria monocytogenes E. both A and C

Clostridium botulinum Bacillus cereus (both A and C)

which of the following are humoral effectors of the innate immune system?

Complement

Which of the following humoral and/or cellular effectors of the innate immune system contribute most to the control of infections caused by extracellular bacteria?

Complement and Neutrophils

Which of the following may be consequences of a failure by the immune system to resolve an infection?

Death, persistent infection, latent infection, reactivated latent infection

Which of the following cell types can present antigens to naive CD8+ T-cells?

Dendritic cells (MHC 1)

Which of the following pathogenic mechanisms can apply to food borne illness caused by Bacillus cereus?

Direct intoxication Localized GI infection Disseminated Infection

What are the characteristics of Salmonella typhi

Disseminated infections asymptomatic carrier state in host Human Reservoir Low infective dose Opportunistic

What is the purpose of clonal deletion during lymphocyte development?

Done in order to rid of potentially self-reactive immature lymphocytes

Which of the following are characteristics of highly virulent strains of Vibrio vulnificus? Select one: A. they are fast-growing B. they produce botulinum neurotoxin C. they are encapsulated D. they disseminate inside infected host cells E. both A and C

Encapsulated Grow quickly Extracellular bacterium Exotoxins Correct: both A and C

Which organisms that cause localized infection in the GI tract are obligate pathogens? Select one: A. Bacillus cereus B. Clostridium perfringens C. Salmonella Saintpaul D. Clostridium difficile E. both B and D

Enterobacteriaceae- including enterohemorrhagic E.coli (EHEC and STEC) and salmonella enterica Campylobacter jejuni salmonella saintpaul

Which of the following pathogens can cause systemic intoxication after infection of the GI tract?

Shiga-toxin producing strains of E. coli Clostridium botulinum

Which of the following is/are clinical signs of disease?

Fever

Which pathogenic mechanisms can apply to food borne illness caused by Staph. aureus? Select one: A. direct intoxication B. localized infection in the GI tract C. systemic intoxication from localized infection in the GI tract D. disseminated infection E. both B and C

GI disease by direct intoxication

Which of the following vaccines are intended to protect against disease caused by sexually- transmitted pathogens?

HPV HepB

Among the following pathogens that enter via the respiratory tract and then disseminate, which has a human reservoir?

Haemophilus influenzae

Which of the following signs and symptoms of localized inflammmation are caused by vasodilation?

Heat and redness

Which of the following vaccines, identified by their abbreviations, are polysaccharideconjugates?

Hib and MenACWY

Which of the following is the reservoir of most sexually-transmitted pathogens of humans?

Human

Which of the following mechanisms for local invasion of tissues potentially could be employed by an obligate extracellular pathogen?

Hyaluronidase is produced by the invading pathogen and cytolytic exotoxins are produced by the invading pathogen

C. Tetani is an extracellular pathogen that can cause systemic disease, even though the bacteria do not disseminate. What class of antibody directed against this or its exotoxin would be important for preventing tetani?

IgG

If a person is exposed to rabies virus via a bite wound, what class of antibody directed against the virus would be most likely to prevent systemic spread of the infection?

IgG and IgA

V. Cholerae O1 causes disease without invading tissues. What class of antibody directed against this or its exotoxin would be able to protect against disease caused by this bacterium?

IgG and IgA

Unlike Vibrio cholerae, the related extracellular bacterium Vibrio vulnificus can cause invasive disease (septicemia). What isotype(s) of antibody generated in response to infection would contribute to the control of V. vulnificus invasive disease, but not to the control of V. cholerae infection?

IgM and IgG

What class(es) of antibody can be produced without T-cell help?

IgM only

Which of the following are factors that might predispose an affected person to Chromobacterium violaceum infection?

Immune deficiency and large inoculum size

Which of the following are beneficial effects of local, short-term inflammation?

Immune system effector molecules and cells are delivered to the sites of infection, increased drainage of tissue fluid into lymph, and generates physical barrier to spread of infection (clots will do this)

Which of the following clinical presentations would be consistent with Listeria Monocytogenes infection in a new born?

In early onset- disseminated abscesses/granulomas affecting multiple organs In late onset- meningitis, or meningo-encephalitis with septicemia

Which of the following are possible outcomes of viral interactions with a cell?

Infection without cell death (persistent infection), failed infection (abortive infection), latent infection and cell death (lytic infection)

Gram- campylobacter jejuni is generally considered to have a low infective dose in humans. What does it mean to have a low infective dose?

Infective dose: number of organisms required on average to cause disease

Which of the following strategies is/ are used by Mycobacterium tuberculosis, the causative agent of tuberculosis, to prevent it from being killed after uptake into host cells by phagocytosis?

Inhibits fusion between the phagosome and lysosomes

Tumor necrosis factor a has which of the following functions?

It activates endothelial cells and causes increased vascular permeability

Which of the following statements is/are true of the innate immune system in humans?

It can respond immediately when a pathogen is encountered and it has both humoral and cell-mediated components

By which of the following pathogenic mechanisms can disease cause during E.coli infections?

Localized infection of the GI tract

The gram - v. cholerae generally is considered to have a high infective dose in humans. What does high infective dose mean?

Lots of microbes must enter the host to cause overt disease

Which of the following cell types can present antigens to CD8 T cells?

MHC I on DC's

Following vaccination with MMR, which of these humoral and/or cellular effectors of the immune system would be most important for clearing the virus infections?

Memory B-cells, Antibodies (neutralize virus) and CTLs (kill infected host cells) *all intracellular cytoplasmic pathogens*

Which of the following are predisposing factors that would make an opportunistic pathogen more likely to cause disease?

Microbe has virulence factors, large inoculum size, microbe has access to normally sterile sites, weakened host immune system

Macrophages are a differentiated form of which of the following types of cells?

Monocytes

which of the following cells types are leukocytes?

Monocytes, lymphocytes, neutrophils, and eosinophils

Which of the following is/are characteristics of organisms that establish endogenous infections in humans?

Must have virulence factors, large population size, weakened host immune system, microbes normally just colonize host

Which of the following organisms is the etiologic (causative) agent of scarlet fever?

Streptococcus pyogenes (Group A Streptococcus)

Which of the following are symptoms/clinical signs of GI disease Select one: A. nausea B. vomiting C. abdominal pain D. diarrhea E. all of the above

Nausea vomiting abdominal pain diarrhea (correct: all of the above)

Human immunodeficiency virus (HIV) infects CD4+ T-cells and ultimately kills them. Untreated HIV infection results in the acquired immune deficiency syndrome (AIDS). Which of the following immune system defects in AIDS patients is/are directly caused by the loss of CD4+ Tcells?

Need Th1 to activate macrophages and Th2 cells needed to activate B-cells and subsequent antibody production

Which of the following types of leukocytes may undergo extravasation at a site of local inflammation?

Neutrophils and macrophages

Which of the following archaea are opportunistic pathogens of humans?

None: there are no archaea pathogens

What kind of relationship does a commensal microbe have with its host?

One partner benefits while the other partner is unaffected

Which of the following are examples of immediate actions that might be taken by public health authorities in response to a case of a reportable disease?

PEP, isolation, restriction/exclusion, potential bioterrorism, emerging pathogen surveillance, contact tracing and follow up

Which of the following signs and symptoms of localized inflammation are caused by increased vascular permeability?

Pain and swelling

What happens when a pathogen infects a dead-end host?

Pathogen is not shed or is shed in insufficient quantities to infect a new host

Certain organisms are able to establish a state of chronic carriage in some individuals. What does chronic carriage mean?

Pathogen will stay with the infected individual for life

Which of the following cell types of the lymphoid lineage is phagocytic?

Plasmacytoid dendritic cells

Which of the following are bacterial pathogens that can cause pharyngitis?

Streptococcus pyogenes (Group A Streptococcus) Neisseria gonorrhoeae

Which of the following vaccines, identified by their abbreviations, are recommended only for infants?

RV and Hib (protects against infant diseases)

Which of the following events occur during a local inflammatory response?

Release of cytokines, production of chemokines, cellular adherence to the blood vessel wall (extravasation of neutrophils), and inflammation

Which of the following strategies is/are used by coxiella burnetti to prevent it from being killed after uptake into host cells by phagocytosis?

Resist toxic products and enzymes within the phagolysosome

Which of the following strategies may be used by intracellular pathogens to avoid being killed following phagocytosis into macrophages?

Resists toxic products and enzymes within the phagolysosome, inhibits fusion between the phagosome and lysosome, secretes phospholipase to degrade the phagosome membrane before it can fuse with lysosomes

Which of the following strategies is/are used by Rickettsia rickettsii, to precent it from being killed after uptake into host cells by phagocytosis?

Secretes phospholipase to degrade the phagosome membrane before it can fuse with lysosomes

Which of the following are bacteria that cause localized infection in the GI tract and have human reservoirs? Select one: A. Escherichia coli O157:H7 B. Campylobacter jejuni C. Bacillus cereus D. Shigella sonnei E. both B and C

Shigella sonnei (shigellosis) or salmonella typhi

Which of the following are characteristics of a PAMP?

Soluble molecules, on pathogen surface, detected by binding to host cell receptors or to secreted molecules, receptors are invariant

Which of the following bacterial pathogens is/are a common cause of otitis media and sinusitis?

Streptococcus pneumoniae

Which of the following pathogens that enter via the respiratory tract are common causes bacterial meningitis?

Streptococcus pneumoniae Haemophilus influenzae

Which of the following pathogenic mechanisms is responsible for scarlet fever caused by Streptococcus pyogenes?

Systemic intoxication from localized Infection Pyrogenic exotoxin Extracellular bacteria adheres to pharyngeal epithelium

Which of the following are routes by which pathogens potentially can disseminate within the body?

Systemic spread of microbe after local invasion at/near PoE and localized infection

Why are conjugate vaccines needed in infants to confer immunity to encapsulated bacteria?

T-independent antibody responses are not fully developed in infants

Which of the following humoral and/or cellular effectors of the adaptive immune system is responsible for the diagnostic rash of measles?

TH1 cells specific for measles virus antigens

Which of the following adaptive immune system effectors specific for Mycobacterium leprae antigens is/are predominant in patients with multibacillary Hansen's disease?

TH2-biased production will create antibody

Which of the following vaccines are intended to protect against disease caused by respiratory tract pathogens?

TIV DTaP

Routine immunizations recommended in the US are intended to protect against disease caused by which of the following members of the genus clostridium? Select one: A. Clostridium difficile B. Clostridium botulinum C. Clostridium tetani D. Clostridium perfringens E. none of the above

Tetanus (C.tetani)

Which of the following cell types can activate macrophages?

Th1 CD4 T cells

Which of the following are cell-mediated effectors of the adaptive immune system?

Th1 T-cells and cytotoxic T lymphocytes

Which of the following cell types can activate B cells?

Th2 cells

What distinguishes Hepatitis A from Poliovirus

The Hepatitis A secondary organ is the liver The Polio virus secondary organ is the neurons Signs for Hepatitis A include jaundice Signs for Poliovirus include asymmetric flaccid paralysis

which of the following do the mechanisms of cell killing used by phagocytes and cytotoxic T-lymphocytes have in common?

They employ enzymes contained within lysosomal granules

a/B necrosis factor a has which of the following functions?

They have antiviral effects

Which statements apply to all pathogens that enter via the GI tract, but then cause disseminated infection? Select one: A. they are extracellular pathogens B. they are intracellular pathogens C. they spread via the blood circulation D. they are Gram-negative bacteria E. both B and D

They spread via the blood circulation

What is the purpose of clonal expansion during an adaptive immune response?

To proliferate and differentiate activated specific lymphocytes to form clones of effector cells

Which of the following types of bactericidal molecules are made from scratch in the phagolysosome of macrophages?

Toxic oxygen species and toxic nitrogen oxides

Excessive cytokine production causes which of the following immunopathologies?

Toxic shock syndrome, delayed-type hypersensitivity, and chronic inflammation

Cholera toxin is an example of a cytotonic enterotoxin. What is a cytotonic enterotoxin?

Toxin that acts in the GI tract and a toxin that alters host cells without killing them

Diphtheria toxin is an example of a cytolytic toxin. What is a cytolytic toxin?

Toxin that causes cell death

Which of the following pathogens that enter via the GI tract can be transmitted vertically? Select one: A. Clostridium botulinum B. Escherichia coli O157:H7 C. Toxoplasma gondii D. Trichinella spiralis E. both B and D

Toxoplasma gondii Listeria Monocytogenes

Which parasites can ONLY be acquired through contaminated food? Select one: A. Cryptosporidium parvum B. Cyclospora cayetanensis C. Toxoplasma gondii D. Trichinella spiralis E. both A and B

Trichinosis spiralis (Trichinosis)

Which of the following parasites infect via the genitourinary tract and are transmitted from person to person by sexual activity?

Trichomonas vaginalis

Which of the following sexually-transmitted pathogens causes asymptomatic infections more frequently in men than in women?

Trichomonas vaginalis

Which of the following vaccines, identified by their abbreviations, contain infectious (live) viruses?

Varicella, MMR

Which of the following factors contribute to pathogenesis for all types of microbial pathogens?

Virulence factors, infective dose, adherence mechanisms

What distinguishes rotavirus from norovirus? Select one: A. low, or very low, infective dose B. disease is acute and self-limiting C. non-enveloped virus particles D. disease is preventable by vaccination E. human reservoir

Viruses belong to different families Rotavirus is common in adults while norovirus is common in infants and children rotavirus infantile diarrhea is vaccine-preventaable disease (no prophylaxis for norovirus) -disease is preventable by vaccination: correct

Against which of the following vector-borne diseases can humans be protected by vaccination?

Yellow fever

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 points].

a) Antibody isotype, IgG, will help contain the amount of virus in the blood by aggregating virus particles so that they can be phagocytosed. b) Activated by dendritic cells in the lymph nodes c) Upon activation, CD8+ T-cells divide, undergoing clonal expansion and will become cytotoxic Tlymphocytes. As the CTLs mature, they enter circulation and encounter antigen attached to MHC I, on host cells. This signal expressed on the outside of the host cell alerts the CTL that it is an infected cell and needs to be killed.

Pathogenic strains of the Gram-positive bacterium, Streptococcus pneumoniae all have an anti-phagocytic, polysaccharide capsule that is an essential virulence factor for this bacterial species. (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].

a) Antigens are hidden by the capsule therefore not recognized by the innate immune system b) Antibody is what you need c) At the beginning IgM is made which will bind to the capsule and fix complement. Once complement is bound macrophages and neutrophils recognize complement large fragments and will be able to act as an opsonin. A different mechanism is Antibody directly acting as an opsonin indicating pathogen needs to be engulfed.

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 points]. (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].

a) CD4+ T cells. b) -The number of CD4 cells in the blood begins a gradual decline, starting from around 1,000 cells per milliliter (mL) of blood to around 500 cells per mL. The relatively stable viral load reflects both a constant rate of new infection and death of the infected cells c) CD4+ cells send signals to CD8 cells to kill infections or viruses. CD4+ T cells are activated by dendritic cells and differentiate into TH1 or TH2 cells. TH1 cells recognize the antigens that are presented on the MHC II receptor and activate macrophages

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].

a) Degrades the phagosome membrane before it can fuse with lysosomes and the bacterium escapes into the cytoplasm of the host cell. b) Phospholipases c) Within the cytoplasm of the host cell. Exogenous MHC_ production and presentation

In some patients, antibiotic therapy can lead to gastrointestinal disease caused by endogenous infection with the opportunistic, Gram-positive bacterial pathogen, Clostridium difficile. (a) Among patients who are undergoing the same antibiotic therapy, why are only some at risk for developing antibiotic-associated gastrointestinal disease? [2 points]. (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].

a) Endogenous infections can be caused in patients who already are colonized with C. difficile before they begin antibiotic therapy b) Exotoxins are required to cause GI disease c) 1) colonizing C. difficile survived antibiotics that kill many GI organisms 2) death of normal flora leaves uncolonized mucosal surface available to be occupied by growth of C. difficile 3) as numbers of C. difficile increase, so does concentration of their exotoxin, which can exceed threshold necessary for overt disease to be caused or 1. The normal enteric flora is disrupted by medication and causes the bacteria to overgrow. (The gut becomes overrun with C. difficile. 2. Bacterial adhesion allows it to attach to colonic cells and grow 3. The cells produce enterotoxin which can lead to ctyokine release as well as bloating and diarrhea

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) Bacterial exotoxins are divided into two categories based on the effect that they have on host cells. What are the names given to these categories? [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 points].

a) Hyaluronidase, proteases, or phospholipases. b) Cytolytic exotoxins and cytotonic exotoxins. [Bacterial exotoxins that kill affected host cells are called cytolytic exotoxins, or "cytotoxins", while those that affect the function of host cells without killing them are called cytotonic exotoxins.] c) Toxin structure: both have A and B protein subunits (B subunits bind to host cell; A subunits enter cell). Cholera toxin (CT) in 1A:5B family; diphtheria toxin (DT) in 1A:1B family. Mode of action: CT activates adenylate cyclase; DT inhibits protein translation. Consequence for affected cell: CT causes hypersecretion of water and electrolytes (cytotonic); DT causes cell death (cytolytic).

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].

a) Inhalation or Ingestion of infected pathogenic particles b) Some effector T cells directly kill cells infected with intracellular pathogens such as viruses, while others participate in responses against extracellular pathogens by interacting with B cells to help them make antibody. The antibody can also specifically target a foreign invader for innate killing systems such as complement, macrophages, neutrophils, and natural killer cells. Effectors of the adaptive immune system also have the ability to neutralize and block binding of extracellular toxins and virus particles. They can also aggregate virus particles allowing the pathogen to be phagocytosed. c) 1. Cells enter the host through droplets and adhere to the respiratory epithelium. 2. The cells penetration the host cell and go through intracellular growth and reproduction leading to more virus cells being formed. 3. Cell damage and tissue damage occur and the influenza virus is released from infected cells and into the airway space to begin another round of infection or be aerosolized and shed from the host in respiratory droplets

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 points]. (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 points].

a) It has cell surface receptors that bind to lipopolysaccharide (LPS, "endotoxin") from the outer membrane of Gram-negative bacteria. b) Cytokines and chemokines c) 1. pro-inflamatory cytokines cause activation of endothelilia cells in local capilaries (vasodilation and increased vascular permeability) 2. Vasodilation causes redness and heat 3. increased VP casues extravastation of effector cells from blood to tissues (swelling and pain can result)

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].

a) Pathogen is no longer confined to outer layer of cells and gets deeper into tissue b) Environment within the host could allow the growth of the pathogen. For example, Candida albicans is naturally found in the body. Invasive disease is caused by the overgrowth of this pathogen. If the population size of the resident organisms increases due to the death of other types of endogenous organisms, allows for the space for Candida albicans to grow and cause disease. c) Once infected, the obligate bacteria can secrete a cytolytic exotoxin that can can kill the infected cell, allowing the pathogen to gain access to the underlying tissue Extracellular pathogens secretes hyaluronidase which degrades the extracellular matrix, once the matrix is degraded, pathogens can move between the epithelial cells and the barrier is breached.

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. [6points].

a) Specific pattern-recognition receptors on phagocyte bind directly to pathogen-associated molecular pattern on bacterium, or bind to opsonins that coat the bacteium b) Complement large fragments and Acute Phase Proteins (act as opsonins) c) respiratory burst activated by formation of phagolysosome (toxic oxygen and nitrogen species are made from scratch within the phagolysosome which encloses the bacterium)

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].

a) Th1 T cells are involved in a DTH reaction. They release the proinflammatory cytokines that give rise to the reaction. b) TNF-alpha is an example of a cytokine produced by the Th1 cells. Its major function is to promote inflammation by promoting the vascular effects that induce vascular permeability and vasodilation, bringing more immune cells and molecules to the site. Among these cells are macrophages, which are activated by the Th1 cells to strengthen their killing power, and thereby the response to the pathogen. c) During the reaction, macrophages are the antigen presenting cells which present the antigen to MHC II receptors that are recognized by TH1 CD4+ cells and are triggered to activate macrophages.

Infection of humans with Vibrio cholerae serotype O1 typically causes the disease, cholera. (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]

a) The portal of entry, POE, is usually by ingestion of human fecal waste found in drinking water. It takes a relatively large dosage of vibrio cholerae to cause disease in humans. Usually drinking water contaminated by feces or consuming contaminated fresh water is the main way we see humans being exposed to this pathogen. b) Vibrio cholerae bacteria that can cause cholera will have a type of cell adhesion protein. This protein allows the bacteria to attach itself to the surface of the intestines and reproduce. Instead of being continually pushed down the digestive tract like the other Vibrio cholerae that do not cause disease, Disease causing serotypes have a way to stay in one place and colonize the intestines. c) When vibrio cholerae infects the host, the first step is always that the pathogen enters the host through consumpsion of water contaminated with raw sewage. The cholerae then adheres to a host cell. It grows on the outside of the host cell in the lumen. This process is dynamic: as bacteria are growing some bacteria are being shed. While the pathogen is growing, vibrio cholerae produces exotoxin. This causes a rush of electrolytes into the lumen which dehydrates the cell causing severe watery diarrhea and cell damage through dehydration. The immune response can intercept the damage produced by the exotoxin, in that, it can use IgA immunoglobulin to bind to the exotoxin thereby deactivating it.

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 points]. (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].

a) They are found on B-cells (which secrete the antigens BCR) and T cells (its antigen, TCR is always bound to the cell membrane) b) B-cell receptors can recognize soluble peptides. T-cell receptors can recognize only peptides that are bound to MHC molecules c) antigen receptor (AgR) genes are composed of protein-coding DNA cassettes (V, J, C for light chains; V, J, D, C for heavy chains). Each cassette is present in multiple copies, all of which differ slightly in sequence. Pseudo random DNA recombination occurs during development of each individual lymphocyte. Randomly-chosen copies of each type of cassette (V, J, and C) are joined together to encode the AgR light chain, and the AgR heavy chain (V, J, D, and C)

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. points].

a) any molecule that can be recognized by a specific receptor on a B cell, or a T-cell. b) the specific piece of antigen that the anitbodies bind to

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? [2 points]. (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].

a) proinflamatory cytokines (TNF alpha) b) latent--> no protein products are deleted (LAT)/ lytic--> protein products are deleted (ICP4) c) Cytotoxic T-lymphocytes and antibodies. The immune response is effective only against epithelial cells since they are the only ones that can present the viral peptide antigens to the CTL through the MHC I receptor

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 diagnostic tests would allow a clinician to determine whether a patient is infected with M. tuberculosis, and distinguish 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) List, and briefly describe, each of the infection control precautions that should be employed if an active TB patient requires hospitalization. Include the elements of standard precautions as well as those of the appropriate transmission-based precautions. [6 points].

a. PPD skin test (latent) and chest x-ray (active) b. Isolation c. standard precautions: hang hygiene, ppe, safe injection practices, safe handling of equipment and items, cough etiquette Airborne precautions: negative-pressure isolation room (AIIR), fit tested N95 respirator for healthcare worker

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].

a. a shortlist of diseases that fit the clinical presentation of patient and their history b. zoonoses: diseases with animal reservoirs c. 1. take history, symptoms, identify possible exposures 2. perform clinical examination 3. establish differential diagnosis 4. order tests to refine diagnosis and begin treatment 5. review results of test and patient response to treatment

In October 2004 there was an outbreak of infection by Escherichia coli O157: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 Disease Control and Prevention (CDC). (a) In general, what is the most common way for people to be exposed to E. coli O157:H7? [2 points]. (b) The fair already was over before the E. coli O157:H7 outbreak was recognized. Why did NCDPH decide to investigate the outbreak? [2 points]. (c) List the components of a generic outbreak investigation, and indicate which one of them was not employed by the NCDPH-CDC team during this investigation? [6 points].

a. contaminated food b. there was a large number of people potentially exposed, and to prevent future outbreaks c. 1. verify diagnosis 2. define a case and conduct case finding 3. tabulate and orient data 4. take immediate control measures 5. formulate and test hypothesis 6. plan and execute additional studies 7. evaluate control measures and implement additional (or different) control measures 8. communicate findings

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 an appropriate treatment? [2 points]. (b) How is it that non-microbicidal drugs ("-statics") nevertheless can form the basis of a curative treatment for an infectious disease? [2 points]. (c) List 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].

a. draining abscesses, wound debridement b. they inhibit microbial growth c. 1. target alteration- B,V,F,P 2. reduced access to drug targets- B, F, P 3. multidrug efflux pumps- B, F, P 4. inactivation of drug- B

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 what 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 identified in part (b). [6 points].

a. long incubation period and whether protocols are available b. Immunization (active/passive) and chemotherapy (antibacterial or antiviral) c. Hep A: immunization after exposure to contaminated food/water rabies: immunization after exposure to an animal with confirmed or unknown rabies status Meningiococcal meningitis- if a family member has meningitis the family that lives with them/exposed are given antibiotics to prevent invasive infection

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 intended 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 States, and give one specific example vaccine of each type. [6 points].

a. somatic hypermutation b. to increase or maintain immune response c. Live attenuated virus: MMR inactivated virus: Hep A polysaccharide: PPSV polysaccharide conjugate: Hib toxoid: Tdap subunit: Hep B

Legionella pneumophila is a species of Gram-negative bacterium that is found ubiquitously in fresh-water. It also is a facultative intracellular pathogen that blocks phagolysosome fusion after being taken up by macrophages. (a) What is the reservoir for L. pneumophila? [2 points]. (b) On which class of major histocompatibility complex will L. pneumophila antigens be presented by macrophages? [2 points]. (c) Briefly outline the sequence of events that begin after macrophages first take up L. pneumophila in the tissues and culminate in clearance of the infection by an adaptive immune response. [6 points].

a. the environment, in this case fresh water b. MHC II (presents to Th1 cells) c. 1. Dendritic Cells take up antigens and present them to naive CD4+ cells in the lymphnodes. 2. CD4+ cells differentiate into Th1 cells 3. Th1 cells can recognize antigen presented on MHC II cells on macrophage and activates the macrophage. 4. macrophage then kills intracellular pathogen

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 characteristics 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 immunity be effective? [2 points]. (c) Briefly explain the mechanism through which herd immunity operates. [6 points].

a. the infective dose, and pathogen shedding b. propagated epidemic c. herd immunity depends on the number of vaccinated members of a population. If enough people are vaccinated, it's unlikely that an a susceptible person will encounter someone that is infected and thus it's unlikely disease will spread.

Which of the following humoral and/or cellular effectors of the innate immune system contribute most to the control of infections caused by viruses?

a/B interferons and NK cells

Which of the following constitute active surveillance for disease outbreaks?

actively looking for cases of disease, monitoring and analyzing hospital admission data

Staphylococcus aureus is an encapsulated, extracellular bacterial pathogen that can cause a variety of diseases. Which of the following humoral and/or cellular effectors of the immune system would be most important for clearing S. aureus infections?

antibody (opsonization) and neutrophils (phagocytes)

Which of the following diseases and conditions should be reported immediately to the local health department if they are reasonably suspected by a physician practicing in North Carolina?

anthrax, botulism, hemorrhagic fever, novel influenza, plague, smallpox

Human papillomavirus type 18 (HPV-18) is sexually transmitted and can establish persistent infections of mucosal epithelia. Following vaccination, which of the following humoral and/or cellular effectors of the immune system would be most important for protecting against future HPV-18 infection?

antibody (IgA for epithelia)

In which of the following classes of pathogen does antimicrobial drug resistance occur by enzymatic inactivation of the drug?

bacteria

Which of the following classes of pathogens cause typical pneumonia?

bacteria

Which of the following types of intracellular pathogens would be expected to enter cells by phagocytosis?

bacteria, fungi, parasites

In which of the following classes of pathogen does antimicrobial drug resistance occur through mutations in target enzymes that prevent drug binding?

bacteria, viruses, fungi, parasites

Which of the following are effector functions of natural killer cells?

bind abnormal host cells and kill them by releasing cytotoxic granules

In which of the following places in the body would monocytes be found?

blood

In which of the following places in the body would naïve lymphocytes be found?

blood, efferent lymphatic system

Results from which of the following types of tests might help a clinician to refine a differential diagnosis?

bloodwork, microscopy, pathogen antigen (ELISA), culture, PCR, serology, radiology, skin test

Which of the following are among the clinical manifestations of E.coli O157:H7 infection? A. bloody diarrhea B. death C. kidney damage D. all of the above E. none of the above

bloody diarrhea. In infants and kids, kidney damage and death. (all of the above)

By which of the following pathogenic mechanisms can disease be caused during Escherichia coli O157:H7 infections? Select one: A. direct intoxication B. localized infection in the GI tract C. systemic intoxication from localized infection of the GI tract D. disseminated infection E. both B and C

both B and C localized infection in the GI tract systemic intoxication from localized infection of the GI tract

A positive PPD skin test for tuberculosis involves which of the following humoral and/or cellular effectors of the adaptive immune system?

cytokines

Which of the following potentially could be a curative treatment for an infectious disease?

chemotherapy

Which of the following are components of subunit vaccines?

composed of purified pathogen proteins mixed with adjuvant to produce a danger signal

Which of the following viral pathogens are etiologic (causative) agents of mild upper respiratory tract disease ("common cold")?

coronaviruses

Which of the following are components of the standard precautions used in infection control practice?

cough etiquette, PPE, safe handling of equipment, hand hygiene

Which of the following are components of cough etiquette (respiratory hygiene)?

cover nose/mouth when sneezing, cough into tissue/sleeve, throw tissues in trash, wash/sanitize hands

Which of the following mechanisms can lead to disease after entry of a sexually-transmitted pathogen into the genitourinary tract?

disseminated infection

By what pathogenic mechanism does Streptococcus pyogenes cause toxic shock syndrome?

disseminated infection (invasive disease)- bacteremia with toxigenic GAS strains

Which of the following may serve as reservoirs for exogenous pathogens of humans?

environment, infected humans, infected animals

Which of the following transmission routes generally involve indirect contact?

fecal-oral route *droplet transmisison considered direct*

Which of the following clinical signs and symptoms are characteristic of influenza?

fever/chills

Which of the following may be vectors for human pathogens?

fleas, ticks, mosquitos

Which of the following are effector functions of terminal complement components?

generate MAC (membrane attack complex) *forms pores in target cell membranes

Which of the following are examples of personal protective equipment?

gloves, gown, mask, N95 respirator

Which of the following are potential targets of antimicrobial drugs?

growth, and the microbe itself

For which of the following diseases is post-exposure prophylaxis a standard public health response?

hep A, rabies, meningitis, HIV

Against which of the following blood-borne pathogens are protective vaccines currently available?

hepatitis B virus

Against which of the following diseases could herd immunity help to protect a human population?

horizontally transmitted (communicable diseases) ex. whooping cough

Which of the following statements is/are true of exposure, as the term is used to describe pathogen transmission?

host comes in contact with source of pathogen; exposure is a prerequisite for infection, but may not always end in infection

Which of the following statements is/are true of zoonotic infections?

humans not always dead end hosts (plague), transmitted to humans from animal reservoirs

In public health practice, which of the following constitute components of an outbreak investigation?

identification of people sick from outbreak

Which of the following characteristics would enable a pathogen to be transmitted efficiently to naïve hosts?

if it can become airborne (low infective dose)

Which of the following drug-resistance mechanisms is/are found only in bacteria?

inactivation of drug

If they are involved in transferring pathogens from one host to another, which of the following would best be described as fomites?

inanimate objects that transfer pathogen

Which of the following is/are characteristics of most pathogens that are maintained in humans?

infect only humans -> largely horizontally transferred (by contact)

Among viruses that commonly cause human disease, which of the following virus-host interactions result in active replication and production of new virus particles?

infection without cell death (persistent infection)

Why does the number of microbes present in the body keep increasing during the early phase of a typical adaptive immune response?

innate immune system failed to control infection, and time is required for clonal expansion to take place

In public health, which of the following is/are routine control measures?

isolation orders for active TB, vaccination of household pets

Among the following diseases, caused by pathogens that enter via the respiratory tract, which include a rash as part of their clinical presentation?

measles rubella

. Which of the following pathogens are transmitted by the airborne route?

measles, TB

Which of the following statements is/are true of immunological memory?

it is conferred in part by pools antigen specific memory t-cells, and memory B-cells (can be T-independent)

Which of the following cell types contribute to the maintenance of serum antibody levels after resolution of an infection?

long term producer B-cells (type of plasma cell)

In which of the following places in the body would naïve lymphocytes encounter their antigen for the first time?

lymphnodes

Where in the body would activated dendritic cells most commonly be found?

lymphnodes

Which of the following is/are characteristics of organisms that establish exogenous infections in humans?

microbes that come from outside the host

Which of the following applications of epidemiology typically would be used to monitor an ongoing immunization program?

monitor adverse effects (type and frequency), changes in disease incidence

How are diseases caused by arboviruses transmitted to humans?

mosquitos

Which of the following are considered to be vertical routes of pathogen transmission?

mother to baby -> 1. cross-placenta 2. during birth (partuition) 3. after birth (maternal-neonatal)

Which of the following statements is/are true of active tuberculosis?

mycobacteria are being shed from the body isolation orders are issued to prevent transmission

Which of the following cell types can secrete antibody?

only plasma cells

Which of the following kinds of antigens can be recognized by T-cell receptors?

peptides (presented on MHCs)

Legionella pneumophila is a pathogenic bacterium that is taken up into macrophages by phagocytosis. L. pneumophila blocks phagolysosome fusion and grows within the phagosome. Which of the following humoral and/or cellular effectors of the immune system would be most important for clearing L. pneumophila infections?

peptides from the phagocytosed bacteria would be presented on MHC II to Th1 cells and macrophage would be stimulated to lyse bacteria

What types of infections is combination therapy with antimicrobial agents intended to treat?

persistent infection, ex. HIV; intent to slow development of drug resistance

After encountering a pathogen in peripheral tissues, myeloid dendritic cells do which of the following?

phagocytose antigen, and migrate to lymphatic system and present antigen to CD4+ in the nearest lymphnode

Which of the following are effector functions of neutrophils?

phagocytosis and digestion of cellular pathogens and debris

Which of the following diseases may be caused by localized infection with Neisseria gonorrhoeae?

pharyngitis

Which of the following diseases may be caused by localized infection withNeisseria meningitidis?

pneumonia

Among the following diseases that result from sexually-transmitted infection, which include genital ulcers among their clinical signs and symptoms?

primary syphilis granuloma inguinale

Which of the following test results would allow pathogens isolated from individual patients to be definitively linked to a common source when they occur during an outbreak?

progeny are clones-> PFGE pattern DNA finger print -> different isolates should belong to the same clone

Which of the following classes of antibiotics would be expected to have activity against chlamydiae?

protein synthesis inhibitors (e.g. doxycycline) nucleic acid synthesis inhibitors (e.g. ciprofloxacin)

Which of the following kinds of antigens can be recognized by B-cell receptors?

proteins, peptides, polysaccharides, haptens (small molecule that elicits immune response when bound to larger carrier molecule)

In public health, which of the following is/are control measures that would be implemented only in response to an outbreak of disease?

recall of contaminated food, post-exposure anaphylaxis (PEP)

Use of disinfectant would be appropriate for which of the following?

reducing microbes on inanimate surfaces

Which of the following are similarities between the cell killing mechanism utilized by the complement system and that of natural killer cells?

release granules that result in cell death

Which of the following viral pathogens are etiologic (causative) agents of lower respiratory tract disease in infants?

respiratory syncytial virus influenza A virus

Routine immunization in the US are intended to protect gastroenteritis caused by which of the following types of virus? Select one: A. polioviruses B. hepatitis A virus C. rotaviruses D. noroviruses E. all of the above

rotavirus

Which of the following diseases is caused by systemic intoxication following a localized bacterial infection of the oropharynx?

scarlet fever

After encountering a pathogen in peripheral tissues, plasmocytoid dendritic cells do which of the following?

secrete antiviral a/B interferons

Which of the following behaviors may be induced in innate immune system cells upon detection of pathogen-specific molecules or structures?

secretion of cytokines, chemotaxis, secretion of chemokines, and phagocytosis

Which of the following are effector functions of macrophages?

secretion of pro-inflammatory cytokines and phagocytosis and digestion of cellular pathogens, presentation of antigens to Th1 cells

Which of the following are features of the immune response to a secondary antigenic challenge?

stimulation of memory B-cells -> IgG production-> reactivate antigen specific memory T-cells ->(these lead to faster response to secondary exposure)

Which of the following are reasons why public health agencies may investigate an outbreak of disease?

stop ongoing outbreaks, to prevent future outbreaks

Which of the following mechanisms can lead to drug resistance in viruses?

target alteration

Which of the following diseases is the Tdap vaccine intended to prevent?

tetanus, diptheria, whooping cough

Which of the following vaccines, identified by their abbreviations, is/are contraindicated for pregnant women?

those containing live attenuated virus (zoster, varicella, MMR)

For individuals with which of the following types of immune system deficiencies is vaccination against Neisseria meningitidis (meningococcal disease) recommended?

those with immune deficiency that don't compromise the humoral response (i.e. hereditary immune deficiency, and no spleen)

In which of the following places in the body would macrophages be found?

tissues

Which of the following types of pathogens are most likely to be transmitted vertically by the maternal-parturition route?

transmitted horizontally (urogenital-sex route)

Which of the following statements is/are true of herd immunity?

transmitted horizontally, it it can protect a population against population against pathogens when not every individual is immune

Among the following classes of pathogen, which commonly cause aseptic meningitis?

virus

Which of the following types of intracellular pathogens would be expected to enter cells by endocytosis?

viruses

Which of the following are considered to be blood-borne pathogens?

viruses that can establish persistent infections: HIV, HBV (Hep b), HCV (Hep c)