SYTM 5503 Week 2 Practice Questions

[2AB] A 44-year-old woman is referred for fatigue. She has ulcerative colitis and was recently started on sulfasalazine by her gastroenterologist. Her vital signs and physical examination are unremarkable. Hemoglobin and haptoglobin are low. Reticulocytes, MCV, and indirect bilirubin are elevated. Iron, iron saturation, and ferritin are normal. Urine hCG is negative. Direct antiglobulin test is 3+ (positive). Which of the following best explains these findings? A. Drug-induced autoimmune hemolytic anemia B. Systemic lupus erythematosus flare C. Ulcerative colitis flare D. Autoimmune hepatitis

A. Drug-induced autoimmune hemolytic anemia ???

[2J] Which one of the following is NOT a mechanism of T cell tolerance? A. Inhibition of T cell activation by IL-12 from Treg cells. B. Clonal deletion through apoptosis. C. Anergy induced by B7-1 or B7-2 binding to CTLA-4. D. Anergy induced by peptide-MHC binding to TCRs without B7-1 or B7-2 binding to CD28. E. TCR-mediated up-regulation of Bim or similar pro-apoptotic proteins.

A. Inhibition of T cell activation by IL-12 from Treg cells. ???

[2J] Except for the deletion through apoptosis and anergy, what is another mechanism for the generation of central B cell tolerance? A: Receptor editing B: Affinity maturation C: Decreased interaction with Tfh D: Generation of autoantibody E: Increased interaction with FDC

A: Receptor editing ???

[2I] What type of immunity will be established after using convalescent serum to treat people with COVID-19? A. Natural active immunity B. Artificial passive immunity C. Natural passive immunity D. Artificial active immunity

B. Artificial passive immunity ???

[2J] Receptor editing is one of mechanisms to generate central B cell tolerance, which of the following best describes its property? A. Receptor editing occurs only in pathological conditions. B. Regeneration of antibody heavy chain causes the change of effector function of BCR. C. Regeneration of antibody light chain causes the change of specificity of BCR. D. Receptor editing occurs only on IgD but not on IgM.

C. Regeneration of antibody light chain causes the change of specificity of BCR. ???

[2J] An 18-year-old member of a college soccer team is seen by a physician because of chest tightness and dyspnea on exertion. A 15-cm mediastinal mass is detected radiographically. Eighty percent of the white blood cells in the peripheral blood are small, abnormal lymphocytes with lobulated nuclei and scant cytoplasm. Immunophenotyping of the abnormal cells shows them to be CD4+ and CD8+. Where would such cells normally be found in the body? A. Bone marrow B. Peripheral blood C. Thymic cortex D. Thymic medulla E. Splenic periarteriolar lymphoid sheaths

C. Thymic cortex ???

[2I] Which of the following vaccines should not be given to immunocompromised individuals? A. Hepatitis B (HepB) B. Salk Polio vaccine C. Standard flu shot D. Hepatitis A (HepA) E. BCG

E. BCG ???

[2K] What ion is trapped inside Plasmodium digestive vacuoles? A. Chloroquine B. Artemether C. Proguanil D. Lumefantrine

A. Chloroquine

[2DE] A 20-year-old female from Connecticut presents with a 7-day history of fever and chills. In the last 48 hours, she has also developed malaise, anorexia, and muscle pain. Her physical exam is unremarkable except for a few petechiae. She was hiking in the woods recently where there were many ticks. ELISA for IgM is negative, but ELISA for IgG is positive. What is the most likely diagnosis of her condition? A. Malaria B. Lyme disease C. Typhoid D. Dengue E. Babesiosis

???

[2C] In acute viral infections, Cytotoxic T Lymphocytes (CTLs) specific for the virus clonally expand, proliferate, and differentiate into effector and memory lymphocytes, and effectively clear the virus. In contrast, in some chronic viral infections, after initiating a response, CTLs often become unresponsive in a process called CTL exhaustion. What molecule is most likely to be upregulated on a CTL during the process of CTL exhaustion? A: PD-1 B: B7 C: CD80 D: IFN gamma E: PKR

A: PD-1 ???

[2J] Which of the following terms best describes the mechanism by which effector T cells are deleted by repeated stimulation of persistent antigen? A. Activation-induced cell death B. Passive cell death C. Central tolerance D. Peripheral tolerance E. Death by neglect

A. Activation-induced cell death ???

[2K] Artemether and Lumefantrine (Coartem) is a... A. Blood schizonticide B. Tissue schizonticide

A. Blood schizonticide Coartem works against erythrocyte stage only. Lumefantrine inhibits hemozoin formation, thus increasing availability of free Fe2+. Artemether is prodrug that is metabolized to dihydroartemisinin. Dihydroartemisinin interacts w/ Fe2+ to form carbon-centered free radicals. Coartem is administered orally in 1:6 ratio of artemether to lumefantrine. It is used to treat uncomplicated falciparum or non-falciparum malaria; IV artesunate is used to treat complicated falciparum malaria. Take coartem w/ food for increased absorption. Adverse effects include headache, dizziness, nausea, arrhythmias, & palpitations.

[2DE] A 28-year-old man presents with undulating fever and chills for three weeks. He also had one episode of non-bilious vomiting today. He denies any cough, headache, abdominal pain, night sweats, and weight loss. He owns a cattle farm. On examination, his temperature is 101.6°F, his pulse is 108 beats/min, and his blood pressure is 125/80 mm Hg. His fever tends to fluctuate. He has generalized lymphadenopathy. Chest and abdominal examinations are normal. Labs reveal an ESR of 105 mm/hr. Blood culture suggests a Gram negative bacillus. What is the most likely microbial cause of her condition? A. Brucella abortus B. Dengue virus C. Brucella suis D. Yersinia pestis E. Francisella tularensis

A. Brucella abortus Brucella is Gram negative, facultative intracellular bacteria. Their reservoir is farm animals, e.g. cows, sheep, goats, & pigs, so most infected people will have had direct contact w/ such animals or indirect contact by consumption of unpasteurized dairy products. Primary symptoms are nonspecific, e.g. undulant fever, chills, & anorexia. Bacteria travels to multiple organs in reticuloendothelial system & causes their enlargement, e.g. spleen, lymph nodes, liver, etc. Complications include osteomyelitis. Treat w/ tetracyclines, esp. doxy w/ rifampin.

[2J] A 12-year-old child is diagnosed with a T-cell lymphoma. The phenotype of the malignant cell matches that of normal progenitor cells that just leave the bone marrow to enter the thymus. What cell surface markers would you expect to find on the malignant cells? A. CD4-, CD8-, TCR- B. CD4-, CD8-, TCR+ C. CD4-, CD8+, TCR+ D. CD4+, CD8-, TCR+ E. CD4+, CD8+, TCR+

A. CD4-, CD8-, TCR- ???

[2I] When polysaccharides are used for vaccine development, in order to generate high affinity antibodies and memory B cells, which agent is needed to improve the antigenicity? A. Carrier B. Adjuvant C. Nanoparticle D. Directly mixed with antigenic peptide

A. Carrier Protein carriers are conjugated to haptens or peptides esp. polysaccharides, to enhance their immunogenicity & stability. They convert immune response to haptens from T-independent to T-dependent w/ germinal center reaction. As a result, there is higher affinity binding leading to class switching & memory response.

[2H] Which ESA requires the most frequent dosing? A. Epoetin alfa B. Darbepoetin alfa C. MPG Epoetin beta

A. Epoetin alfa There are 3 forms of recombinant EPO: epoetin alfa, darbepoetin alfa, & methoxy-polyethylene glycol (MPG) epoetin beta. They are all administered IV or subQ. Epoetin alfa is EPO + 3 sugar chains, so it has highest affinity to EPO receptors but lowest half-life (4-13 hrs). Therefore, epoetin must be administered 3x per wk. Darbepoetin alfa is EPO + 5 sugar chains, so it has middling affinity & half-life (46 hrs). Therefore, darbepoetin alfa must be administered once every 1-2 wks. MPG epoetin beta is EPO + PEG chain, so it has lowest affinity but longest half-life (124 hrs). Therefore, MPG epoetin beta must be administered once every 2 wks.

[2K] Where can hydroxychloroquine form deposits? A. Eye B. Fingernails C. Hair D. Bone

A. Eye Adverse effects of CQ & HCQ include pruritis (more common w/ CQ), GI upset, nausea, headache, hypoglycemia, psoriasis exacerbation, arrhythmias (QTc prolongation), myopathy, muscle weakness, extrapyramidal (CNS motor) effects, retinal toxicity, hearing loss, & tinnitus.

[2H] Which iron form is more likely to cause GI upset? A. Ferrous (Fe2+) B. Ferric (Fe3+) C. Elemental iron (Fe)

A. Ferrous (Fe2+) Oral iron supplements come in 3 forms. All Fe2+ supplements (ferrous gluconate, ferrous sulfate, dried ferrous sulfate, & ferrous fumarate) must be taken 3 pills daily. All Fe3+ (ferric maltol & polysaccharide iron complex) & Fe (carbonyl iron) supplements must be taken 1 pill daily. They are all used to treat iron-deficiency anemia. However, Fe2+ can be oxidized to Fe3+ in GI tract, thus generating free radicals that irritate GI lining.

[2G] A 28-year-old previously healthy man has experienced increasing fatigue over the past six months and bruises with minimal trauma. Over the past two days, he has developed a cough. On physical examination, his temperature is 38.9°C with diffuse rales in both lungs. He has no hepatosplenomegaly or enlarged lymph nodes. Lab findings show: Hematocrit 21.7% (range 41-50) Hemoglobin 7.2 g/dL (range 14-16) Platelet count 23,400/uL (range 150,000-450,000) WBC count 1310/uL (range 4,500-11,000) The serum bilirubin is normal and anti-nuclear-antibody test is negative. What is the most likely explanation for these findings? A. Hematopoietic stem cell defect B. Hemolysis of antibody coated cells C. Increased susceptibility to lysis by complement D. Metastasis of cancer to bone marrow E. Secondary hypersplenism

A. Hematopoietic stem cell defect Patient has aplastic anemia, i.e. damage to hematopoietic stem cell resulting in pancytopenia & low reticulocyte count. This is one type of anemia due to underproduction. Causes are mostly idiopathic (70%) but can also stem from drugs, chemicals, viral infections, or autoimmune damage. Bone marrow biopsy would show empty, fatty, hypocellular marrow. Most common early symptom is bleeding. Patients usually feel well w/ no signs of anemia. This is different from myelophthisic anemia; in this type of anemia, we would see immature RBCs on blood smear. This is NOT seen in aplastic anemia, since the stem cell defect is so early on that no immature RBCs are produced at all.

[2AB] An infant born at 34 weeks gestation to a 28-year-old woman, gravida 3, para 2. At birth, the infant is jaundiced, swollen, and hydropic. A cord blood sample is taken for fetal red blood cells, and the direct Coombs test is positive. What is the mechanism for the findings in the infant? A. Hemolysis of antibody-coated red blood cells B. Hemopoietic stem cell defect C. Impaired globin synthesis D. Oxidative injury to red blood cells E. Rigid red blood cell membrane

A. Hemolysis of antibody-coated red blood cells Infant has autoimmune hemolytic anemia. Direct Coombs test is used to confirm presence of antibody-coated RBCs (anti-IgG added to patient RBCs causing agglutination of RBCs coated w/ IgG). Indirect Coombs test is used to confirm presence of antibodies in serum (anti-IgG & test RBCs are mixed w/ patient serum so agglutination occurs if serum antibodies are present).

[2K] What is one of the mechanisms of action for chloroquine? A. Hemozoin inhibitor B. ROS generator C. Protein synthesis inhibitor D. Electron transport inhibitor

A. Hemozoin inhibitor CQ & HCQ inhibit formation of hemozoin crystals, thus causing buildup of free heme that is toxic to parasite. In addition, they also accumulate in digestive vacuoles & raise their pH, thus disrupting their function. They are administered orally as prophylaxis (CQ safe for pregnant people) or treatment of CQ-sensitive malaria. Due to its lipophilicity, it has half-life of 20-60 days w/ very high volume of distribution.

[2AB] A 30-year-old man with beta thalassemia major presents with palpitations and dizziness. His BP is 93/65 mm Hg, respiratory rate is 25/min, temperature is 98.9°F. He has an irregular heart rhythm with no murmurs. ECG confirms atrial fibrillation. What is the most likely cause of his atrial fibrillation? A. Iron deposition causing injury B. Extramedullary erythropoiesis C. Hypercoagulable state D. Hypoxia due to anemia E. Hyperthyroidism

A. Iron deposition causing injury ???

[2I] IPV, aka Salk vaccine (approved in 1955), is a formalin-inactivated polio vaccine; OPV, aka Sabin vaccine (approved in 1961), is a live attenuated oral vaccine that plays a key role to stop the polio epidemic. Which one of them can induce stronger mucosal and cellular immunity? A. OPV B. IPV C. Co-administration of IPV and OPV D. Two doses of IPV

A. OPV ???

[2DE] A 42-year-old patient presents to the provider after returning from Brazil. The patient complains of swelling near her eye. The patient's pulse is 71 beats/min, blood pressure 122/70 mm Hg, respirations 12 breaths/min, and temperature 36.7°C (98°F). The physical examination reveals left periorbital edema with minimal erythema. The patient is given nifurtimox and notes resolution at the follow-up examination. What was the most likely vector associated with the transmission of this disease? A. Reduviid bug B. Tsetse fly C. Sandfly D. Body louse E. Aedes mosquito

A. Reduviid bug Patient has trypanosomiasis, most likely due to T. cruzi (Chaga's disease aka American trypanosomiasis). Trypanosomia is hemoflagellate protozoa w/ kinetoplast at base of flagellum. Kinetoplast is extension of single mitochondrion & contains mitochondrial genome. Transmission begins w/ infected triatomine bug, which takes blood meal near patient's mouth & poops trypomastigotes near bite wound. Trypomastigotes enter host thru wound or intact mucosal membranes. Inside, they invade nearby cells where they differentiate into intracellular amastigotes. Amastigotes multiply by binary fission & differentiate into trypomastigotes, which are then released into circulation. Triatomine bug becomes infected by feeding on infected host w/ circulating parasites. Infected trypomastigotes transform into epimastigotes in bug's midgut. Epimastigotes multiply & differentiate into infective trypomastigotes in hindgut. Symptoms of acute phase is acute inflammatory response & secondary organ damage. Amastigotes are found in cardiac, skeletal, & smooth muscle, as well as nervous system, gonads, & phagocyte tissue. During chronic phase 10-30 yrs after acute infection, there is organ involvement, e.g. mega-colon, dilated cardiomyopathy, & mega-esophagus. T. cruzi trypomastigotes are usually C-shaped under microscopy.

[2AB] A six-month-old Asian boy is referred for evaluation of an abnormal HbF only result in newborn hemoglobinopathy screening. The infant appears healthy, and the only abnormality detected on examination is a palpable spleen tip 1-2 cm below the left costal margin. The infant's hemoglobin is 9.5 g/dL. Repeat hemoglobin electrophoresis confirms the presence of HbF only. The mother's electrophoresis reveals HbA with 6.1% HbA2, but the father is unavailable for testing. Which of the following is the most likely diagnosis? A. Thalassemia major B. Thalassemia minor C. Two-gene deletion alpha thalassemia D. Three-gene deletion alpha thalassemia E. Four-gene deletion alpha thalassemia

A. Thalassemia major ???

[2H] What type of cytopenia can heparin cause? A. Thrombocytopenia B. Anemia C. Neutropenia D. Pancytopenia

A. Thrombocytopenia Thrombocytopenia has many different causes, but most prominently, it can be drug-induced. TMP/SMX, Pip/Taz, vanco, linhezolid, phenytoin, carbamazepine, valproate, quinine, quinidine, heparin, & hydrochlorothiazide are some examples. Romiplostim (recombinant thrombopoietin) is administered as subQ injection to increase megakaryocytes. Adverse effects for romiplostim include joint & muscle aches, dizziness, GI upset, insomnia, & possible bone marrow fibrosis.

[2I] Two persons received the same type of COVID-19 vaccine (e.g., Pfizer) with the same dosing. Their antibodies were detached at the same levels 3 months post-vaccination, but one person (X) got breakthrough infection, and the other one (Y) is completely fine. What could be a mechanism in terms of their humoral immune responses to the vaccine? A. X has more non-neutralizing antibodies, the Neutralizing/non-neutralizing antibody ratio is not favorable. B. X doesn't have active effector T cells. C. Y has more balanced IgG, IgM, and IgA antibodies. D. Y has more IgG antibody distributed in the mucosal areas, thereby providing more local protection to prevent virus entry.

A. X has more non-neutralizing antibodies, the Neutralizing/non-neutralizing antibody ratio is not favorable. ???

[2L] A 32 year old male is diagnosed with HIV. Which of the drug regimens below is the preferred first line antiretroviral therapy for this patient? A: Abacavir, Lamivudine and Dolutegravir B: Enfuvirtide and Dolutegravir C: Abacavir, Lamivudine and Darunavir D: Efavirenz, Ibalizumab and Enfuvirtide E: Maraviroc, Fostemsavir and Epzicom

A: Abacavir, Lamivudine and Dolutegravir First-line therapies for naïve patients are centered around dual NRTIs, e.g. abacavir & lamivudine (aka epzicom). Integrase inhibitor like dolutegravir is preferred third drug; however, this is interchangeable w/ NNRTI like efavirenz or protease inhibitor like darunavir. Therapies for treatment-experienced patients include aforementioned drug classes, provided resistance has not developed. Alternatively, CCR5 receptor antagonist like maraviroc or fusion inhibitor like enfuvirtide can be used. Post-attachment (ibalizumab) & attachment (fostemsavir) inhibitors are used as last resort for heavily treatment experienced patients.

[2DE] A mother brings in her 7-year-old girl because the girl has had swollen lymph nodes in her neck for approximately 10 days. the mother says that she likes playing with her 2 cats. On examination, a small papule is noted on the child's forearm. Bilateral cervical lymphadenopathy and tender lymphadenopathy of the right axilla are also noted. The child has a high fever on and off. What is the most likely causative organism of her condition? A. Staphylococcus aureus B. Bartonella henselae C. Streptococcus pyogenes D. Mycobacterium tuberculosis E. Pasteurella multocida

B. Bartonella henselae Patient has cat scratch disease. 3-10 days post-exposure, red spot/macule appears on skin at site of entry, swelling into painless, non-itchy papule. Papule persists for 1-3 wks & is followed by swelling, erythema, & tenderness of regional lymph nodes, esp. axilla, neck, or groin regions. Other symptoms follow, e.g. fatigue, headache, fever, loss of appetite, sore throat, & weight loss. Most patients' disease resolve spontaneously within 2-4 months w/o treatment, though people w/ severe disease or immunosuppressed patients may need antibiotic treatment.

[2AB] A 32-year-old Vietnamese woman gives birth at 34 weeks gestation to a markedly hydropic stillborn male infant. Autopsy findings include hepatosplenomegaly and cardiomegaly. There are serous effusions in many body cavities and generalized hydrops. There is marked extramedullary hematopoiesis in the liver. Which one of the following hemoglobins is most likely to be present in the infant's RBCs? A. A2 B. Barts C. E D. F E. H

B. Barts Infant had Bart's hydrops fetalis syndrome (subtype of alpha thalassemia), where there is no functional alpha globin genes. It is lethal in utero since free gamma chains form Hb Barts tetramers that damage RBCs. Edematous infant is stillborn w/ hepatosplenomegaly.

[2G] A 23-year-old man is evaluated for bleeding gums, fatigue, and his second time for pneumonia. He takes no medications and family history is unremarkable. The patient denies illicit drugs or alcohol. Temperature is 99.4°F, blood pressure is 106/64 mm Hg, pulse rate is 107/min, and respiratory rate is 22/min. Physical examination reveals pallor and blood oozing in the gingival mucosa. Lab findings show: Hemoglobin 7.4 mg/dL Platelets 20000/uL Reticulocyte 0.5% (range 0.7-2.5%) WBC 2300/uL (range 4,500-11,000) with 20% PMNs Peripheral blood smear reveals normocytic red blood cells but negative for schistocytes. Coagulation profile, creatinine, and liver enzymes are within normal limits. Antibodies for hepatitis and HIV are negative. Which one of the following tests is indicated next? A. Chest CT B. Bone marrow biopsy C. Heavy metal toxicology screen D. Serum protein electrophoresis E. Serum ferritin

B. Bone marrow biopsy Patient seems to have pancytopenia, perhaps due to aplastic anemia. 70% of aplastic anemia cases have unknown causes, i.e. idiopathic. Next logical step would be to look at bone marrow to see if it is hypocellular & fatty.

[2C] ICP47 protein in Herpes simplex virus blocks the function of transporter associated with antigen processing (TAP). By doing so, the viruses avoid the recognition by which of the following immune cells? A. CD4 B. CD8 C. B lymphocyte D. Th17 E. NK

B. CD8 Throwback to first block, TAP is used to add intracellular antigen onto MHCI for presentation. Ii, CLIP, & HLA-DM work together to add phagocytosed extracellular antigen onto MHCII for presentation. HSV is known for immune evasion via blocking TAP transporter. Similarly, CMG enacts removal of MHCI from ER.

[2J] Transgenic mouse lines have been very useful for the study of mechanisms of self-tolerance. In one such line, transgenes were introduced encoding a TCR specific for the H-Y antigen, which is a protein expressed by many cell types only in male mice. When these transgenic mice were analyzed, researchers found that T cells expressing the H-Y-specific TCR developed normally in female mice but not in male mice. This finding illustrates which of the following mechanism of self tolerance? A. Peripheral anergy B. Central (thymic) deletion C. Clonal ignorance D. Treg cell-mediated suppression E. Peripheral deletion

B. Central (thymic) deletion ???

[2C] Antigen presentation of extracellular pathogens by antigen presenting cells requires endocytosis of the antigen, followed by the degradation in the acidic environment of the formed phagolysosome. Should the phagolysosome become unable to lower its pH, what is the most likely consequence? A. Deficient NK cell activation B. Deficient presentation of pathogens to CD4 T cells C. Deficient presentation of pathogens to CD8 T cells D. Deficient cell extravasation E. Deficient expression of B7

B. Deficient presentation of pathogens to CD4 T cells Initial immune response to extracellular bacteria involves complement activation & innate immune cells like neutrophils & macrophages. NO is generated via iNOS, which converts Arg to citrulline, & phagocyte oxidase, which converts O2 into ROS. Oxygen-independent killing also takes place w/ antibacterial granules & NETs. Meanwhile, DCs migrate to lymph nodes to present antigens to T cells. MHCII is used to present extracellular antigens to CD4+ helper T cells, while MHCI is used to present intracellular antigens to CD8+ CTLs. DCs would phagocytize extracellular bacteria & use MHCII to present to CD4+. CD8+ CTLs aren't even needed in fighting extracellular bacterial infections.

[2AB] A 48-year-old woman who was being treated for hypertension with alpha methyldopa presented with malaise and generalized weakness. Her hemoglobin is 8 g/dL and hematocrit is 24%. Her reticulocyte count is increased and bilirubin is high. Spherocytes is seen on peripheral smear. Which of the following is the best test to order to help confirm the diagnosis? A. Indirect Coombs test B. Direct Coombs test C. Bone marrow examination D. Hemoglobin electrophoresis E. Protein electrophoresis

B. Direct Coombs test ???

[2K] What is the mechanism for chloroquine resistance? A. Drug-destroying enzyme B. Drug efflux pump C. Antioxidant genes D. Mutated drug target

B. Drug efflux pump Mutation & overexpression of chloroquine resistance transporter (CRT) drug efflux pump in P. vivax & P. falciparum allows parasite to keep CQ levels low inside digestive vacuoles.

[2AB] A 9-month-old infant presents with a gradual onset of decreased appetite, pallor, and poor weight gain. Physical examination reveals hepatosplenomegaly. A CBC shows a severe microcytic, hypochromic anemia with target cells and frequent nucleated red cells on the blood smear. What is the next best test to order? A. Bone marrow biopsy B. Hemoglobin electrophoresis C. Peripheral blood flow cytometery D. Serum erythropoietin level E. Serum ferritin

B. Hemoglobin electrophoresis Infant has thalassemia. Lab findings of beta thalassemia major include microcytic, hypochromic target cells & nucleated RBCs on blood smear. ???

[2I] Why do some people taking injection COVID-19 vaccine (e.g., Moderna) still get breakthrough infection or pass SARS-CoV-2 virus to others? Suppose the vaccine works well to generate detectable serum IgG. A. Injection vaccine only generates humoral immunity, but Not T cell mediated immunity. B. Injection vaccine generates strong systemic IgG response but not mucosal IgA response, therefore having weak mucosal protection. C. Humoral immunity generated by injection vaccine can only last for 3 months. D. Antibodies generated by injection vaccine don't have neutralization function.

B. Injection vaccine generates strong systemic IgG response but not mucosal IgA response, therefore having weak mucosal protection. ???

[2H] Where is endogenous erythropoietin made? A. Liver B. Kidney C. Brain D. Stomach E. Bone marrow

B. Kidney Use erythrocyte-stimulating agents for patients w/ chronic kidney disease, undergoing cancer chemotherapy, undergoing zidovudine therapy for HIV, or undergoing perisurgery (decreases need for transfusions).

[2I] When people receive booster shot for vaccination, their serum antibodies can normally last longer that those who only receive one dose. Which cell is more responsible for the long-lasting antibodies? A. Short-lived plasma cell B. Long-lived plasma cell C. Memory B cells D. Effector helper T cells E. Follicular dendritic cells (FDC)

B. Long-lived plasma cell ???

[2K] What is a prodrug to a DHFR inhibitor? A. Atovaquone B. Progunail C. Hydroxychloroquine D. Mefloquine

B. Progunail Proguanil is prodrug metabolized by CYP2C19 to cycloguanil, which inhibits DHFR. Atovaquone, which is often administered w/ proguanil as malarone, resembles CoQ & disrupts ETC of parasite. Malarone is effective against the erythrocyte stage only. It is administered orally as prophylaxis or treatment of CQ-resistant malaria. It must be taken w/ milk since fat is needed for absorption. Adverse effects include hepatotoxicity, nausea, vomiting, & diarrhea.

[2H] How do some β-Lactam antibiotics (e.g., cefotetan, ceftriaxone) cause hemolytic anemia? A. Causing oxidative damage to erythrocytes B. Provoking the immune system to attack erythrocytes C. Inhibiting enzymes necessary for erythrocyte survival

B. Provoking the immune system to attack erythrocytes Drugs like piperacillin, ceftriaxone, ciprofloxacin, methyldopa, & oxaliplatin can cause immune-mediated hemolytic anemia.

[2K] Overdose of what can cause cinchonism? A. Proguanil B. Quinine C. Artemether D. Tafenoquine

B. Quinine Quinine works against erythrocyte stage only. It inhibits hemozoin formation in Plasmodium digestive vacuoles. It is administered orally as treatment of CQ-resistant malaria, along w/ doxy. Adverse effects (cinchonism) include tinnitus, headache, nausea, vomiting, flushing, & insulin release (hypoglycemia).

[2DE] A 12-year-old male presents with a fever of 102°F, myalgia, periorbital swelling, and generalized maculopapular rash which is more severe in the face, palms, and soles. He recently was on a camping trip to Colorado and was bitten by multiple flies and had a tick removed from his scalp. Which of the following is the most likely organism of this illness? A. Borrelia burgdorferi B. Rickettsia rickettsii C. Leishmania donovani D. Plasmodium falciparum E. Babesia species

B. Rickettsia rickettsii ???

[2DE] A 36-year-old woman returns home to LA after a 3-week-safari to South Africa. She started chloroquine prophylaxis 2 weeks prior to her departure and continued throughout her foreign travel. She stopped taking the pills the day she came back to U.S. Two weeks after her return, she develops paroxysmal fever with chills and rigor, and was quickly hospitalized with jaundice and dark urine. Blood smears reveal red blood cells with delicate ring-like and rare sausage-shaped structures. What is the stage of the parasite that is transmitted by the mosquito? A. Hypnozoite B. Sporozoite C. Liver schizont D. Erythrocytic schizont E. Merozoite

B. Sporozoite Life cycle of Plasmodia is as follows. Once sporozoites enter host, they infect hepatocytes within 3 hrs & transform over next 2-10 days to liver stage (exo-erythrocytic form). P. vivax & P. ovale have hypnozoite form, where they can stay dormant inside hepatocytes. Sporozoites/ hypnozoites convert to merozoites & are released into bloodstream to begin asexual life cycle. Merozoites invade, divide within (ring & trophozoite forms), & lyse RBCs. Schizogony is where proportion of merozoites undergo developmental switch, initiating formation of male & female gametocytes. Gametocytes are ingested during blood meal by FEMALE Anopheles mosquito. Gametocytes mate in mosquito gut & begin cycle of growth & multiplication. Sporozoite form of parasite migrates to mosquito's salivary glands so that it can be injected into another host.

[2H] Colace (sodium docusate) can help to alleviate constipation. How does this drug work? A. Bulk laxative B. Stool softener C. Prokinetic agent D. Stimulant laxative E. Saline laxative

B. Stool softener If patients are unable to tolerate side effects of oral iron supplements, they can take parenteral iron supplements, e.g. sodium ferric gluconate, iron sucrose, ferric carboxymaltose, iron dextran, & ferumoxytol. There is risk of anaphylaxis w/ latter two. In addition to being an alternative treatment for iron-deficiency anemia, parenteral supplements are also used in patients w/ chronic kidney disease anemia.

[2DE] A 27-year-old female immigrant from West Africa presents to her PCP concerned about a sexually transmitted infection exposure. She states her sexual partner is a male survivor of an outbreak that killed over half of his village one month ago. They do not use condoms. She states that during the outbreak he had severe fever, nausea, blood in vomiting, and required a blood transfusion due to bad bruises. Based on her sexual partner's likely recent illness, which of the following best explains her exposure risk? A. Transmission one month after the infection is impossible B. The virus can be isolated from semen, but male to female transmission risk is uncertain C. The virus can be isolated from semen, and male to female transmission is certain D. The virus cannot be isolated from semen but can be transmitted from female to male E. The virus is transmitted by mosquitoes

B. The virus can be isolated from semen, but male to female transmission risk is uncertain Patient likely has Ebola. Phase 1 of disease is incubation for 4-21 days; patients are asymptomatic & not infectious. Phase 2 takes place 8-10 days post-exposure, when patient manifests w/ non-specific symptoms like fever, fatigue, headache, & muscle pain. Phase 3 takes place 5-6 days after onset of symptoms; they worsen, including diarrhea, loss of appetite, chest pain, coughing, & eye inflammation. Phase 4 follows, where body's immune response & damage to vascular system causes blood to leak from veins. There is blood in stool, vomit, cough, & bleeding from gums. Death occurs 7 days after onset of symptoms & 4 days after hospitalization. Survival is dependent on early, strong immune response w/ improvement after first week.

[2DE] A 30-year-old man presents with pain in his throat that started two days ago. He also complains of swelling in his neck. He also has fever with rigors and chills. He came back from a camping trip to North America two days ago. His vital signs show blood pressure 120/85 mm Hg, heart rate 110/min, respiratory rate 20/min, and temperature 102°F. A physical examination performed shows tender cervical lymphadenopathy. An oral examination performed reveals exudative inflammation of the pharynx along with tonsillar ulcers. What is the most likely diagnosis? A. Rickettsia B. Tularemia C. Pasteurellosis D. Plague E. Lyme's disease

B. Tularemia Patient is infected w/ Francisella tularensis: Gram negative, facultative intracellular coccobacilli. Main reservoir is rabbits; infected people may have had direct contact w/ or eaten rabbits, or they had indirect contact thru dermacentor tick. Infection can be spread via aerosol too. Tick bites & painful ulcer forms at site of infection; bacteria enter thru ulcer, travels thru lymph system to reticuloendothelial organs, & causes granulomas w/ caseating necrosis there. Lymph nodes swell & become palpable. Treat w/ aminoglycosides, esp. streptomycin.

[2AB] In California, all newborns with HbH disease are identified through newborn screening, followed by identification of the alpha globin gene deletions or mutations by a Hemoglobin Reference Laboratory. One such laboratory is located at Children's Hospital & Research Center Oakland. Which globin chains combine to make hemoglobin H? A: 2 gamma and 2 alpha chains B: 4 beta chains C: 2 alpha and 2 delta chains D: 4 gamma chains E: 4 alpha chains

B: 4 beta chains There are four alpha-globin genes, two on each chromosome 16. HbH disease (subtype of alpha thalassemia) results when only one globin gene is left standing while other three are knocked out. Upon birth, free beta chains form tetramers (HbH) that damage RBCs. HbH inclusions can be visualized w/ brilliant cresyl blue stain. Treat HbH w/ folic acid.

[2J] A 40-year-old woman is diagnosed with an autoimmune disorder. Autoimmune disorders result from breakdowns in central and peripheral tolerance mechanisms designed to protect host tissues from the immune system. Which one of the following best describes the function of AIRE in promoting tolerance to self-antigens? A: AIRE is secreted by thymic medullary epithelial cells, and then binds and blocks the T cell receptors of potentially autoreactive thymocytes B: AIRE is required for thymic medullary epithelial expression of peripheral tissue antigens C: AIRE stimulates expression of immunosuppressive cytokines in lymph nodes D: AIRE binds to mitochondrial membranes and facilitates the release of Cytochrome C into the cytoplasm E: AIRE suppresses MHC expression in dendritic cells presenting self-antigens

B: AIRE is required for thymic medullary epithelial expression of peripheral tissue antigens ???

[2AB] A 56-year-old high-performing executive decides to take a hiatus from work. He has no addictions. After 6 months in the Himalayas, he returns to his coastal hometown. On arrival, his physical examination and lab parameters are essentially normal, except for a hemoglobin of 18.2 grams/dL (range, 14- 16) and hematocrit of 55% (range, 41- 50). Which one of the following is the likely cause? A: Idiopathic B: Physiological compensation C: Smoking D: Renal tumor secreting erythropoietin E: Hematopoietic stem cell defect

B: Physiological compensation Primary erythrocytosis is aka polycythemia vera (most commonly caused by smoking). It is acquired myeloproliferative disorder where all mature blood cells increase but esp. RBCs. It is assoc. w/ JAK2 mutation. Patient will present w/ headache, dizziness, tinnitus, & blurry vision due to hyperviscous blood. Patient will also have bleeding, easy bruising, epistaxis, pruritis, gout, hypertension, & splenomegaly. They can also have DVT, heart attack, & stroke due to thrombosis. Secondary erythrocytosis can be compensatory (our patient), paraneoplastic, or due to Hb mutants w/ high O2 affinity.

[2AB] A 25-year-old woman has a 3-year-history of arthralgias. Physical examination shows no joint deformity. She appears pale. Laboratory studies show a hemoglobin of 12.5 g/dL (range 14-16). Platelet and WBC counts are normal. The smear shows hypochromic, microcytic anemia. the serum ferritin is normal. Hemoglobin electrophoresis shows 93% HbA, with increased 5.8% HbA2 and HbF 1.2%. Which one of the following is the likely diagnosis? A. Anemia of chronic disease B. Autoimmune hemolytic anemia C. Beta thalassemia minor D. Plasmodium vivax infection E. Iron deficiency anemia

C. Beta thalassemia minor ???

[2K] Which antimalarial drug is a protein biosynthesis inhibitor? A. Proguanil B. Quinine C. Doxycycline D. Primaquine

C. Doxycycline Doxycycline works against erythrocyte stage only. It inhibits expression of apicoplast DNA in malarial parasite, thus inhibiting protein biosynthesis. It is administered orally as prophylaxis or treatment; if for treatment, it is often given w/ quinine. One side effect is photosensitivity.

[2DE] A 26-year-old previously healthy man presents to the hospital with sudden-onset malaise, fever, headache, backache, and myalgias for 5 days. He recently returned from a trip to India. On examination, his temperature is 102.4°F with normal blood pressure and a heart rate of 102/min. He has erythematous blanching diffuse rashes all over the body. Laboratory studies are notable for a platelet count of 72000/uL. This is the second time in the last 2 years he is suffering from similar illness during early winter. The last time, the fever was preceded with a trip to India as well. Which of the following best describes the causative organism? A. Gram positive bacillus with a capsule B. Enveloped virus with dsDNA C. Enveloped virus with ssRNA D. Gram negative, small, intracellular bacillus E. Naked virus with ssRNA

C. Enveloped virus with ssRNA ???

[2I] Which of the following flu vaccines most likely induce IgA antibodies against influenza virus? A. Flucelvax (cell-based) B. FluAd (adjuvanted) C. FluMist (LAIV) D. FluBlok (recombinant subunit) E. FluZone (high dose)

C. FluMist (LAIV) FluMist Quadrivalent is live, attenuated influenza mucosal vaccine administered as spray intranasally for patients older than 2 yrs. Mucosal vaccines are effective in generating immune responses thru MALT for local mucosal & systemic protection against infections. This is done thru presentation They are also important in combatting zoonoses (pathogens originating in animals). Due to its ease of administration & non-invasiveness, there is high patient compliance & high suitability for mass vaccination.

[2H] Sargramostim is a recombinant form of what factor? A. VEGF B. G-CSF C. GM-CSF D. TPO E. EPO

C. GM-CSF Sargramostim is administered subQ or IV (short/continuous infusion) to increase granulocytes, monocytes/macrophages, platelets, & RBCs. It is used to treat neutropenia in patients undergoing chemotherapy, leukapheresis, bone marrow transplant, or radiation. Similarly, filgrastim (daily) & pegfilgrastim (once every 2 wks) are recombinant G-CSF administered subQ or IV (short/continuous infusion) to increase neutrophil production & survival. Adverse effects of recombinant G-CSF include bone pain, fever, & rash.

[2DE] A 13-year-old girl is brought to the emergency department after a cat bite that happened two hours ago. She has immense pain in her hand is constantly crying. She has no past medical history. All her vital signs are within normal limits. On examination, a puncture wound can be visualized on the volar aspect of her right hand with surrounding erythema and tenderness. An X-ray of the hand does not show any signs of fracture. Which of the following organism is the most likely cause of her condition? A. Anaerobic flagellated protozoan parasites B. Gram-positive, rod-shaped, and facultative anaerobic bacterium that does not produce endospores C. Gram-negative, aerobic, pleomorphic, non-sporing bacterium D. Weakly Gram-positive, catalase-positive, rod-shaped bacterium E. Acid-fast, obligatory aerobic rods

C. Gram-negative, aerobic, pleomorphic, non-sporing bacterium Patient has cat-scratch disease, which is covered in more depth in Session 3I. It is caused by Bartonella henselae, which can infect thru scratch/bite from infected cat, exposure to cat saliva thru broken skin or mucosal surfaces, or exposure to cat fleas. Bacteria infects endothelial cells, causing acute inflammatory reaction assoc. w/ activation of pro-inflammatory cascade. It is diagnosed via culture isolation on blood or chocolate agar under 5% CO2 for about 3 weeks or via DNA detection by PCR.

[2H] A 5-year-old boy presents with nausea and diarrhea caused by iron poisoning. IV fluids are given, gastric lavage is performed, and deferoxamine is administered. How does it work? A. Antidiarrheal B. Iron supplement C. Iron chelator D. Antiemetic E. Protoporphyrin IX

C. Iron chelator Deferoxamine is administered IV to chelate iron in cases of iron poisoning & iron overload in patients w/ thalassemia. Chelated iron complex has short half-life & is promptly eliminated renally (pink urine) & fecally.

[2J] Treg is signatured by CD25+. What is the function of CD25? A. It is a transcription factor. B. It is a co-receptor to interact with co-stimulator from APC. C. It is the α chain of the high-affinity IL-2 receptor to sequester IL-2 from activating helper T cells. D. It is an inhibitory receptor functioning like PD-1.

C. It is the α chain of the high-affinity IL-2 receptor to sequester IL-2 from activating helper T cells. ???

[2AB] A 7-month-old infant presents with prominent facial features, failure to thrive, and enlarged spleen on physical exam. His hemoglobin is found to be 5.6 grams/dL. Which of the following laboratory values is also expected? A. Decreased serum ferritin B. Increased red cell distribution width C. Reduced mean corpuscular volume D. Spherocytosis E. Hemoglobin in urine

C. Reduced mean corpuscular volume Infant has thalassemia. ???

[2G] A 17-year-old woman comes to the doctor's office for weakness. She is 5 weeks postpartum from a pregnancy complicated by Rocky Mountain Spotted Fever for which she received chloramphenicol. On physical exam, the patient has pule conjunctivae and petechiae over her extremities. Lab findings show: Hemoglobin 6 g/dL (range 14-16) Platelets 50,000/uL (range 150,000-450,000) WBC 2000/uL (range 4,000-11,000) What is the most common cause of death in a patient with these findings from the following list? A. Stroke B. Myocardial infarction C. Sepsis D. Liver failure E. Hypoxia

C. Sepsis ???

[2H] What type of cytopenia can corticosteroids (e.g., Prednisone) be used to treat? A. Anemia B. Neutropenia C. Thrombocytopenia D. Leukopenia E. Pancytopenia

C. Thrombocytopenia Corticosteroids have general immunosuppressant effect, thus decreasing immune-mediated platelet destruction. High doses of prednisone are given for short time & slowly tapered off if patient responds. Side effects include edema, insomnia, & infection risk, but since drug is taken for very short time, they may not show up. Rituximab is also used to treat antiplatelet antibody (APA) mediated thrombocytopenia by binding to CD20 on B cells & causing their depletion.

[2DE] What is the mechanism by which Ebola spreads in a community? A: Ebola is airborne and spreads quickly in large congregations (e.g. movie theaters, airplanes). B: Ebola is waterborne and can spread through contaminated rivers and lakes. C: Ebola is spread when body fluids (e.g. blood, CSF) from a sick individual enter a healthy individual. D: Ebola is foodborne and can infect individuals that don't thoroughly wash their fruits and vegetables. E: Ebola is transmitted by ticks and mosquitoes but not rodents.

C: Ebola is spread when body fluids (e.g. blood, CSF) from a sick individual enter a healthy individual. Ebolavirus is filovirus: enveloped, non-segmented, negative sense ssRNA virus. It jumps from animals to humans when humans eat bush meat, esp. fruit bats. True reservoir is unknown, but mammals are primary transmission vector, e.g. bats, apes, monkeys, hamsters, mice, guinea pigs, humans, etc. B/w people, ebolavirus is transmitted thru contact w/ urine, stool, saliva, semen, vaginal secretions, breast milk, & rarely sweat of infected person. Patients w/ complete symptomatic recovery may still excrete virus in semen for 6-9 months. Spread can also be indirect thru fomites or contaminated environment.

[2G] A 45-year-old woman has worsening arthritis of her hands and feet since the past 12 years. On examination, she has deformations of her hand and feet. Laboratory studies show an elevated rheumatoid factor. Her laboratory values are as follows: Hemoglobin 11.6 g/dl (range, 14- 16) Hematocrit, 34.8% (range, 41- 50) MCV 87 fL/cell (range, 80-100) Platelet count 268,000 per microliter (range, 150,000 to 450,000) WBC count 6800 per microliter (range, 4,500-11,000) Serum iron 20 micrograms/dL (range, 50 - 170) Total iron binding capacity 195 micrograms/dL (range, 240-400) Serum ferritin of 31.7 ng/mL (range, 12 to 150) Reticulocyte count is 1.1% Serum haptoglobin is normal. What is the most likely mechanism underlying this patient's hematologic abnormalities? A: Auto-antibodies against RBC membranes B: Impaired synthesis of beta-globin chains C: Inadequate usage of stored iron D: RBC sequestering in spleen E: Failure of bone marrow

C: Inadequate usage of stored iron Serum haptoglobin is normal, ruling out (A), which is autoimmune hemolytic anemia. MCV is normal, ruling out (B), which is thalassemia. Patient does not have sickle cell disease, ruling out (D). Since serum iron & TIBC is low, it would seem (C) is the only viable option left.

[2C] A 20-year-old man stands in the elevator right by a person who has a flu and is coughing and sneezing. The influenza viral particles that he inhales attach to respiratory epithelium, and viral infection reduces MHC class I molecules displayed on these epithelium cells. What immune cells are most likely to rapidly destroy the virus infected epithelium cells? A: CD4 positive T cells B: CD8 positive T cells C: Natural killer cells D: B lymphocytes E: Neutrophils

C: Natural killer cells Innate immunity plays large role in blocking & controlling initial infection. Type I IFNs induce anti-viral state in cells by effecting inhibition protein synthesis (phosphorylation of translation initiation factor), degradation of viral RNA thru RNase, & inhibition of viral gene expression & virion assembly. They also activate NK cells, which rapidly eradicate viral-infected cells via IFN-gamma, granzymes, perforin, etc. This is possible b/c viral infection downregulates MHCI, which suppresses NK cell function & sometimes up-regulates NK activating receptors.

[2H] A 71-year-old man with iron-deficiency anemia is advised to take iron sulfate 3 times per day for his condition. How should these pills be taken to ensure the maximal absorption of iron? A: With a full glass of milk B: Before bedtime with water C: On an empty stomach with orange juice D: Immediately after a meal E: Along with a meal

C: On an empty stomach with orange juice Iron is found in red meat, poultry, & seafood. Non-heme iron comes from fortified cereals, wheat germ, broccoli, beans, & potatoes. Absorption of non-heme iron is increased by ascorbic acid (Vit. C). Iron absorption is decreased by food, other multivalent cations, milk protein aka casein, dietary phytates (found in legumes & nuts), tannins (found in coffee & tea), & drugs that decrease gastric pH, e.g. antacids, H2RAs, & PPIs.

[2K] A 51-year-old man returning from Southeast Asia falls ill en-route and is admitted to a hospital with nausea, vomiting, a high fever, and rigors. A blood smear indicates the presence of Plasmodium vivax trophozoites. He is given a 3-day regimen of artemether and lumefantrine, and is discharged with a 14-day course of tissue schizonticide. Which drug is most appropriate to prescribe for this 14 days of treatment? A: Chloroquine B: Doxycycline C: Primaquine D: Atovaquone-Proguanil E: Mefloquine

C: Primaquine Primaquine is prodrug that requires metabolic activation by CYP2D6 to form active hydroxy-primaquine, which can then generate ROS. People who are poor CYP2D6 metabolizers or use CYP2D6 inhibitors may reduce drug efficacy. It works against all stages EXCEPT erythrocyte stage. It is administered orally w/ 7 hr half-life as prophylaxis or treatment of P. vivax/P. ovale liver stage. Adverse effects include pruritis, GI upset, nausea, & headache. Perform genetic test first b/c drug must not be given to patients w/ G6PD deficiency.

[2H] A newborn is diagnosed with sickle cell disease by DNA testing. At 9-months of age, they are started on a daily regimen of oral hydroxyurea. What is the mechanism of this drug in the management of sickle cell disease? A: Reacts with and blocks the polymerization of hemoglobin S B: Increases the production of erythropoietin C: Stimulates the expression of fetal gamma-hemoglobin D: Increases the affinity of hemoglobin for oxygen E: Inhibits the expression of p-selectin

C: Stimulates the expression of fetal gamma-hemoglobin Hydroxyurea is used for patients w/ 2+ vaso-occlusive crises per yr. It activates soluble guanylate cyclase, thus activating signaling pathway in erythroblasts that increases gamma-globin gene expression. It is administered orally 15-35 mg/kg QD. It causes myelosuppression & is teratogenic, so advise patient to use contraception. Other adverse effects include alopecia, hepatotoxicity (monitor LFTs), & increased risk of skin cancer (advise patient to use sunscreen)

[2I] Why can DNA and mRNA vaccines generate effective adaptive immune responses? A: DNA and mRNA are genetic messenger molecules that are more immunogenic than protein antigens. B: DNA and mRNA can replicate when introduced to human bodies, thus generating stronger immune responses. C: These vaccines can synthesize antigens in human somatic cells like myocytes and APCs, thus allowing broad antigen presentation through class I and II MHCs. D: These vaccines can produce more antigens in vivo than live attenuated and recombinant protein vaccines. E: These vaccines can elicit immune responses through nucleic acid and protein antigens.

C: These vaccines can synthesize antigens in human somatic cells like myocytes and APCs, thus allowing broad antigen presentation through class I and II MHCs. ???

[2H] Which of the following is a common side-effect of iron pills? A. Dark stools B. GI upset C. Constipation D. All of the above

D. All of the above GI side effects include nausea, GI cramps, & constipation. Docusate (Colace) and/or fiber are recommended to help w/ constipation. Dark, tarry stools are normal but may mask signs of internal bleeding.

[2H] What is the orally-administered thrombopoietin (TPO) receptor agonist used to treat thrombocytopenia? A. Sargramostim B. Filgrastim C. Romiplostim D. Eltrombopag

D. Eltrombopag Eltrombopag is daily to patients w/ chronic immune thrombocytopenic purpura, HCV-assoc. thrombocytopenia, & aplastic anemia. Adverse effects include hepatotoxicity, nausea, vomiting, diarrhea, myalgia, URIs, & UTIs.

[2DE] A 32-year-old wildlife biologist studying in Uganda is brought to the hospital with a 2-hour history of altered consciousness. He developed fever, chills, and malaise one week after performing a necropsy on a dead chimpanzee. His temperature is 40°C (104°F), pulse is 130/min, and blood pressure is 78/50 mm Hg. Physical examination shows bilateral conjunctival hemorrhages, multiple bruises, and a generalized non-pruritic maculopapular rash. Twenty minutes after a blood sample is obtained, blood continues to ooze from the venipuncture site. An RNA virus is isolated from the patient's blood. An electron micrograph of the virus shows 6-shaped bacilli. The virus most likely belongs to which of the following viral families? A. Arenavirus B. Bunyavirus C. Flavivirus D. Filovirus E. Rhabdovirus

D. Filovirus Patient has Marburgvirus, which is filovirus. It is zoonosis, i.e. virus life cycle is maintained in animal hosts, esp. bats, but spills over accidentally to humans. Initial transmission takes place when patient becomes infected thru contact w/ tissues or body fluids of infected animal; afterward, virus spreads thru infected person's bodily fluids, like Ebolavirus. Incubation period is 3-20 days, though symptoms usually manifest 5-7 days after exposure. It initially infects macrophages, dendritic cells, & fibroblastic stromal cells before disseminating to other areas of body. Systemic viral replication leads to potent, systemic inflammatory response w/ /fever, coagulopathy, vascular leakage, & hypotension. Under microscopy, virus is pleomorphic, appearing as filaments, circles, or No. 6 formation (see figure). Since symptoms are very similar to Ebola, lab tests like ELISA, PCR, electron microscopy, & nucleic acid detection are needed to differentiate them.

[2H] What type of anemia is associated with deficiency in glucose-6-phosphate dehydrogenase (G6PDH)? A. Hypochromic B. Microcytic C. Macrocytic D. Hemolytic

D. Hemolytic When G6P is converted to Ru5P by G6PDH, 2 NADPH is generated. These NADPH are used by glutathione reductase to regenerate GSH, which helps glutathione peroxidase neutralize free radicals. In patients w/ G6PD deficiency, drugs like dapsone, primaquine, metformin, & nitrofurantoin are unsafe since they can cause oxidative RBC damage. Such patients should also be careful w/ acetaminophen, aspirin, phenytoin, probenecid, & sulfa drugs. They should also avoid fava beans due to its vicine content.

[2C] A 27 year old male who works on an organic farm is diagnosed with infection by Necator americanus , a helminthic parasite. What type of antibodies is most likely required to destroy these parasites? A. IgA B. IgG C. IgD D. IgE E. IgM

D. IgE Immune response to parasites depends on their life cycles. Helminthic antigens are presented by DCs to naïve CD4+ T cells, which proliferate & differentiate into Th2 cells. Th2 cells produce IL-4, IL-13, & IL-5. IL-4 & IL-13 induce B cells to produce IgE, which binds to FcεRI & activates mast cells to degranulate. They activate alternative macrophages to enhance fibrosis & tissue repair. Third, they also stimulate intestinal mucus secretion & peristalsis to expel parasite. Meanwhile, IL-5 activates eosinophils, which collaborate w/ mast cells to release cytotoxic mediators to kill parasite.

[2C] A 60 year old woman presents to the ED with nausea, vomiting, and fever for 2 days. Physical exam finds her blood pressure is less than 65 mm Hg and a temperature of 103 103°F. Her mental status is at the baseline. She reveals that she had a hip replacement surgery about 2 weeks ago. The surgery site demonstrates erythema and edema around the wound margins. Blood cultures are negative. The patient is suspected to have a toxic shock syndrome. How does the toxin cause the symptoms in this patient? A. It acts as an IL 1 homologue B. It activates B lymphocytes polyclonally C. It activates complement D. It cross links MHC class II molecules to TCRs polyclonally E. It stimulates neutrophils

D. It cross links MHC class II molecules to TCRs polyclonally Superantigens hyper-stimulate T cell activation by directly binding MHCII outside of peptide groove on APCs and subgroups of Vβ chain of TCR. They also crosslink CD28, activating 2-20% of total T cells & inducing cytokine storm.

[2K] What drug should be avoided in psych patients and can cause weird dreams as a side effect? A. Hydroxychloroquine B. Doxycycline C. Chloroquine D. Mefloquine

D. Mefloquine Mefloquine is effective against erythrocyte stage only. It binds to GTPase center in ribosomes, which mediates ribosomal binding to translation factors & mRNA/tRNA translocation. It is administered orally as prophylaxis (safe in pregnant people) or treatment of CQ-resistant malaria. It is well-absorbed & has half-life of 21 days due to high volume of distribution. Adverse effects include GI upset, nausea, insomnia, abnormal dreams, vertigo, tinnitus, & neuropsychiatric disorders, e.g. anxiety, paranoia, depression, hallucinations, & psychosis. Therefore, do not use in patients w/ major psychiatric disorders.

[2G] An asymptomatic 56-year-old woman has the following laboratory values: Hemoglobin 7.8 g/dl (range, 14- 16) MCV 80 fL (range, 80-100 fL) Serum vitamin B12 488 pg/ml (range, 200 - 600) Serum creatinine 2.2 mg/dl (range, 0.6 - 1.0) Serum iron 18 micrograms/dl (range, 50 - 170) TIBC 220 micrograms/dL (range, 240-400) What is the best working diagnosis for this anemia? A: Iron deficiency anemia B: Macrocytic anemia C: Thalassemia minor D: Anemia of chronic disease E: Hemolytic anemia

D: Anemia of chronic disease Anemia of chronic disease is most common anemia in hospitalized patients, often caused by chronic infections, immune disorders, & malignancies. Lab findings of anemia of chronic disease are decreased Hb, serum iron, & % saturation, since iron is sequestered away. MCH & RDW is normal. MCV & reticulocytes are normal or decreased (similar to iron deficiency anemia). Ferritin is normal or increased (more ferritin may be needed to store away iron), while TIBC is normal or decreased. Bone marrow iron stores are normal but there is reduced iron in RBC precursors. There is also increased free erythrocyte protoporphyrin (FEP) since there is not enough iron available.

[2AB] A 35-year-old woman has had abdominal distention and pain, along with lower extremity edema, over the past 6 months. A physical examination confirms that she has ascites, and ultrasonography demonstrates thrombosis of hepatic veins. A diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) is considered. Which of the following statements regarding the diagnosis of PNH is most accurate? A. She is too young to be diagnosed with PNH B. A normal serum lactate dehydrogenase level reliably excludes PNH C. Pancytopenia is rare in PNH D. Screening for PNH with flow cytometry should be performed E. Coombs test must be positive for diagnosis

D. Screening for PNH with flow cytometry should be performed Paroxysmal nocturnal hemoglobinuria (PNH) is due to acquired defect in myeloid stem cells, resulting in absent GPI. GPI is protein that anchors DAF & MIRL proteins to blood cell membranes; DAF & MIRL protect them from circulating complement destruction. At night, shallow breathing leads to CO2 retention & mild respiratory acidosis, which activates complement. Since these proteins cannot attach to blood cells, they are susceptible to complement. Main cause of death for patients is thrombosis of hepatic, portal, or cerebral veins (destroyed platelets release cytoplasmic contents into circulation). Lab results show hemoglobinemia & hemoglobinuria. There is sometimes hemosiderinuria days after hemolysis. Coombs test is negative. Outdated sucrose test used to screen for PNH by activating complement. Nowadays, acidified serum test (also activates complement) or more commonly flow cytometry to detect lack of CD55 (DAF) is used.

[2C] A 48 year old immigrant from Vietnam presents with fever, weight loss, a persistent cough, and malaise. His symptoms began three months ago and have worsened over time. On exam, he is afebrile with BP 120/80, HR 78/minute, and RR 14/min. Which cell type is responsible for the formation of granulomas in this disease? A. Neutrophils B. TH2 lymphocyte C. CD8 T cell D. TH1 lymphocyte E. Natural killer cells

D. TH1 lymphocyte Granulomas can be produced in response to bacterial & fungal infections, e.g. Tb, leprosy, coccidioidomycosis, histoplasmosis, blastomycosis, etc. It is caused by type IV hypersensitivity immune response. When APC activates CD4+ Th1 cell, Th1 cell secretes TNF & IFN-gamma to stimulate macrophage migration to site of infection & granuloma formation.

[2DE] A 27-year-old woman is admitted to the hospital for fever, with increasing anorexia, headache, weakness, and altered mental status of 4 days' duration. She is an airline attendant, flying between India and the United States. Ten days before admission, she had diarrhea lasting for 36 hours. She has been constipated for 3 days. Her temperature is 102.4°F, heart rate is 60 beats/min, blood pressure is 120/84 mm Hg, and respiration is 18 breaths/min. She has red spots and rash on her chest. Blood cultures grew a non-lactose fermenting, motile Gram-negative rod. What is the most likely microbial cause of her illness? A. Cholera B. Bacillary dysentery C. Food poisoning D. Typhoid E. Traveler's diarrhea

D. Typhoid Salmonella typhi is...???

[2I] Some vaccines can cause adverse effect to promote viral infection through VADE (Vaccine associated disease enhancement), and then what is a mechanism underlying VADE? A. Vaccine-generated IgG can play opsonization function. B. Vaccine-generated IgM can function as BCR to increase B cell activation. C. Vaccine-generated antibodies can function as autoantibody to cause VADE. D. Vaccine-generated antibody can activate classical pathway of complement, therefore causing inflammatory damage to certain tissues and organs.

D. Vaccine-generated antibody can activate classical pathway of complement, therefore causing inflammatory damage to certain tissues and organs. ???

[2I] The quick development and high effectiveness of COVID-19 mRNA vaccine, such Pfizer and Moderna, rely on the following factors, EXCEPT: A. mRNA vaccine is easy to make. B. mRNA can elicit both humoral and cell-mediated immunities since the antigens are synthesized in vivo. C. Efficient delivery of mRNA by lipid nanoparticles. D. mRNA itself can also initiate immune response to generate additional defense.

D. mRNA itself can also initiate immune response to generate additional defense. ???

[2K] A 41-year-old woman returned from a trip to Central America one week ago. She was taking primaquine as an antimalarial prophylactic, and had recently finished her last dose. Her chief complaints include fatigue, dyspnea, and yellowing of the eyes. Results of her blood tests are shown with the reference range in brackets. RBC: 3.2 x10^6/mm3 [4.2 x 10^6 - 5.4 x 10^6] Hgb: 8.9 g/dL [12.0 - 15.5] Indirect bilirubin: 1.6 mg/dL [0.2 - 0.8] Reticulocytes: 3.8% [0.5% - 1.5%] Her doctor explains that she likely has a genetic defect, and her symptoms are caused by an adverse effect of the medication. Which enzyme is most likely deficient? A: Thymidylate synthase B: Thymidine kinase C: Cytochrome P450 3A4 D: Glucose-6-phosphate dehydrogenase E: Ribonucleotide reductase

D: Glucose-6-phosphate dehydrogenase Similar to primaquine, tafenoquine is prodrug requiring metabolic activation by CYP2D6 to form active tafenoquine 5,6-orthoquinone, which can then generate ROS. Tafenoquine is effective against all stages; however, do not use it as monotherapy against erythrocyte stage. It is administered orally w/ 15-day half-life as prophylaxis or treatment of P. vivax/P. ovale liver stage. Perform genetic test first b/c drug must not be given to patients w/ G6PD deficiency.

[2DE] A 33-year-old woman contracts malaria while on a 3-month business trip to a Central American country. She is treated with a full course of chloroquine and recovers uneventfully. Four months after returning to the USA, she has another febrile illness that resembles malaria. A peripheral blood smear shows ring forms in her erythrocytes. Which species of Plasmodium is most likely to have caused the second febrile illness? A: P. falciparum B: P. knowlesi C: P. malariae D: P. vivax E: P. cynomolgi

D: P. vivax Malaria is caused by protozoa Plasmodia. P. falciparum causes malignant tertian malaria (fever every 48 hrs). P. vivax causes benign tertian malaria, while P. ovale causes ovale tertian malaria. P. malariae is only one that causes quartarn malaria (fever every 72 hrs). P. vivax & P. ovale are only two that can remain latent & reappear months later. In terms of differences b/w P. falciparum & P. ovale, vivax forms one ring during ring stage while falciparum forms multiple. Falciparum is sequestered in trophozoite, schizont, & segmenter stages; vivax isn't. Vivax gametocytes are round while falciparum ones are elongated.

[2DE] A 16-year-old girl presents to the emergency department with fever, headache, vomiting, rash, and confusion. She was in her usual state of health approximately two days prior to presentation. She is currently in menses and uses tampons. After examination, she is diagnosed with toxic shock syndrome (TSS) caused by Staphylococcus aureus infection. What best describes the immunological mechanism for TSS? A: Toxins from S. aureus induce hyperglobulinemia B: Superantigens from S. aureus are not recognized by host immune cells C: Toxins from S. aureus suppress cytokine production D: Superantigens from S. aureus induce massive cytokine production E: Superantigens from S. aureus induce massive antibody production

D: Superantigens from S. aureus induce massive cytokine production

[2AB] A 30-year-old Middle Eastern patient visits her family physician. She has a long history of anemia which she was told was inherited. She has never had any blood transfusion or hospitalization. The majority of her family is still in the Middle East, and she is unsure of the name of the condition. A peripheral blood count shows mild microcytic anemia, and her serum ferritin levels are normal. Which one of the following is likely? A. Beta thalssemia B. Hereditary spherocytosis C. Sideroblastic anemia D. Sickle cell anemia E. Alpha thalassemia trait

E. Alpha thalassemia trait Patient has alpha thalassemia trait aka minor, where two alpha globin genes are functional but other two are knocked out. Cis deletion means both genes are knocked out on same chromosome, & this is assoc. w/ increased risk of severe thalassemia in offspring. Thalassemia trait is characterized by mild anemia w/ slightly increased RBC count. Lab values would show normal Hb electrophoresis & target cells on blood smear.

[2C] A 19 year old male is found to have Neisseria gonorrhoeae bacteremia. This bacterium produces an IgA protease capable of cleaving the hinge region of IgA antibodies. What is the most likely physiological consequence of such a protease? A. Membrane attack complex formation is impaired B. Opsonization and phagocytosis of pathogen cannot occur C. Impaired adaptive immune system memory D. Impaired antibody binding to mast cells E. Impaired mucosal immune protection

E. Impaired mucosal immune protection

[2J] Treg play an important function to suppress self-reactive T cells in the peripheral tolerance through the following mechanisms, EXCEPT: A. It inhibits T cells through CTLA4. B. It inhibits T cells through IL-10 and TGF-beta C. It down-regulates DC function by suppressing the expression of co-stimulators. D. It induces apoptosis of T cells and other immune cells. E. It suppresses T cell functions by directly interacting with TCR.

E. It suppresses T cell functions by directly interacting with TCR. ???

[2H] What antidiabetic drug may cause low Vit B12 and folate levels? A. Glyburide B. Rosiglitazone C. Canagliflozin D. Insulin E. Metformin

E. Metformin Macrocytic anemia, i.e. Vit. B12 and/or Vit. B9 deficiency, can have situational causes or be drug-induced. Situational causes include dialysis, liver disease, malabsorption, & tobacco & alcohol use. Anticonvulsants, metformin, methotrexate, trimethoprim, & triamterene can cause folate deficiency. Metformin, H2RAs, & PPIs can cause Vit. B12 deficiency. Treat macrocytic anemia w/ cyanocobalamin (administered IM, deep subQ, sublingual daily, or intranasal weekly) or folic acid (oral daily).

[2C] N. meningitidis, S. pneumoniae are the main cause of meningitis in teens and young adults. What types of immune cells are most likely to be found in the lesion of meningitis? A. Macrophage and TH2 B. Macrophages and Treg C. Neutrophils and Th2 D. NK cell and Th1 E. Neutrophils and Th17

E. Neutrophils and Th17 Neisseria meningitidis are extracellular bacteria that resist phagocytosis by blocking opsonin deposition. Cell-mediated immunity plays minimal role in extracellular bacterial infections. Nonetheless, Th1 & Th17 responses amplify innate immunity. Neutrophils are recruited to cause inflammation, macrophages are activated to kill bacteria, & antibodies are released.

[2I] In 1988 a new childhood vaccine was developed to protect against epidemic meningitis by mixing Haemophilus influenzae type B capsular polysaccharide with whole, killed Bordetella pertussis bacteria which is known to cause whooping cough. What is the function of the whole, killed bacteria in this vaccine? A: Immunogen B: Hapten C: Mitogen D: Carrier E: Adjuvant

E: Adjuvant Adjuvants are substances that increase immunogenicity of antigens by prolonging antigen persistence, enhancing antigen presentation, increasing co-stimulatory signals, etc. ???

[2AB] A routine complete blood count on a patient who is 1-year old shows a mild microcytic anemia. Hemoglobin electrophoresis shows slightly increased hemoglobin A2. What is the most likely reason for this finding? A: Iron deficiency anemia B: Sideroblastic anemia C: Lead toxicity D: Alpha thalassemia E: Beta thalassemia trait

E: Beta thalassemia trait There are two beta-globin genes, one on each chromosome 11. Beta thalassemia trait aka minor results when one gene has reduced functionality while other is normal. People are generally asymptomatic w/ increased RBC count. RBCs are microcytic & hypochromic. Target cells show up on blood smear since Hb abnormality permits bleb to form in central concavity of RBC. Hb builds up within bleb, creating bit of redness in central pallor. HbA is slightly decreased while HbA2 & HbF are slightly increased. RDW & iron levels will be normal (differentiates from iron deficiency).

[2DE] Which feature differentiates the pathogenesis of dengue hemorrhagic shock syndrome from uncomplicated dengue fever? A: Excitotoxic injury of neurons B: Development of dengue virus meningitis C: Neurotropic spread of virus D: Thrombocytosis E: Immune enhancement of infection

E: Immune enhancement of infection Dengue is flavivirus: small, enveloped, positive sense ssRNA viruses. There are 4 serologically distinct viruses, all of which are carried by mosquito Aedea aegypti. Enhancing antibodies are key to pathogenesis of hemorrhagic disease. They are heterotypic, non-neutralizing antibodies from previous dengue infection that bind to infecting virus particle during subsequent heterotypic infection but cannot neutralize virus. Antibody-virus complex attaches to Fcγ receptors on circulating monocytes, thereby facilitating their infection. This leads to increase in overall replication of virus & even more severe disease.

[2C] A 40-year-old woman presents with diarrhea and upon questioning, she discloses that the symptoms began after eating leftovers that had been in the refrigerator for over a week. Infection by Listeria monocytogenes is suspected. What immunological event will contribute most effectively to the eradication of L. monocytogenes infection? A: Dectin recognition of microbial peptides B: IL-13 cytokine production C: IgA antibody production D: M2 macrophage activation E: MHC presentation of microbial peptides

E: MHC presentation of microbial peptides Listeria monocytogenes are intracellular bacteria that disrupt phagosome membrane & escape into cytoplasm of macrophage using hemolysin protein. Since they are inaccessible to antibodies, their eradication is based on cooperation b/w CD4+ & CD8+ T cells.

[2AB] A 29-year-old woman has had fatigue and dizziness for the past 5 months. On examination, she has an erythematous malar rash. The spleen is palpable. She is afebrile. Laboratory studies are as follows: Hemoglobin 8.9 g/dL (range, 14- 16 g/dL) Hematocrit 27.3% (range, 41- 50) MCV 103 fL (range, 80-100 fL) Reticulocyte count 3.3% (range 0.5-2.2%) Serum bilirubin 3.2 mg/dL (range, 0.5-1.2) Serum Haptoglobin is reduced. The peripheral smear shows polychromasia with no schistocytes (fragmented RBCs). Antinuclear antibody and anti-double stranded DNA is positive. Which one of the following laboratory findings will be present? A: D-dimer increase B: Increased RBC osmotic fragility C: Reduced serum vitamin B12(cobalamin) D: Low serum ferritin E: Positive Coombs test

E: Positive Coombs test Patient has autoimmune hemolytic anemia, probably due to IgM. One kind of categorization is primary/secondary; another is IgM/IgG mediated. Primary type (50% of all cases) has unknown cause while secondary type (other 50%) has known cause. IgG-mediated type usually involves extravascular hemolysis; it binds RBCs in warmer central body & RBC membrane is consumed by splenic macrophages, resulting in spherocytes. IgM-mediated type usually involves intravascular hemolysis; it binds RBCs & activates complement against them in colder extremities.

[2DE] A 35-year-old woman presents with fever (on and off, around 101°F), a rash on the back, myalgia, chest pain on exertion, progressive dyspnea and swelling around the eye over the past 2 weeks. He was treated by an allergist, for possible food allergies, with little or no improvement. She had been in the US as a visiting scholar for one month and is originally from Bolivia. On examination her axillary and inguinal nodes were enlarged; the liver was palpable 3 cm below the right costal margin. Blood culture was negative for bacteria and fungi. Blood smear confirmed Leishmaniasis. Which one of the following statements best describes her illness? A: The organism responsible, has 2 nuclei of different sizes B: Its non-human reservoir are domestic and wild rodents C: It is transmitted to humans by a bite of a day dwelling mosquito D: Incubation of the disease is 3 to 8 days E: The infectious form of the pathogen is trypomastigotes

E: The infectious form of the pathogen is trypomastigotes Throwback to last block, Leishmania is unicellular, intracellular protozoan parasite. It is transmitted via phlebotomine sandflies, which inject promastigote while sucking human blood. Promastigote is phagocytized by macrophages, which then transform into intracellular amastigotes within macrophages. Amastigotes multiply in macrophages & infect cells in other tissues. Sandfly sucks blood from human & ingests infected macrophages. Amastigotes bust out of ingested macrophage & transform into promastigote in sandfly midgut. ???

[2H] What drugs chelate iron, reducing its absorption?

Fluoroquinolones, Tetracyclines, HIV integrase inhibitor, Levothyroxine (T4, thyroid hormone), L-Dopa, Ibandronate (Boniva), Methyldopa (for hypertension), Bisphosphonates (for bone mineral density) Since iron is multivalent cation, it decreases absorption of certain drugs by binding to them & forming non-absorbable iron-drug complexes.

[2H] What pathogen does Penicillin VK help prevent in children with Sickle Cell Disease?

Strep pneumo Children w/ sickle cell disease are at increased risk of infections, esp. from S. pneumoniae, H. influenzae, & N. meningitidis. Pen VK is administered twice daily up until 5 yrs of age as prophylaxis against Strep pneumo. Children w/ sickle cell disease are also recommended to receive H. influenzae type B, meningococcal, pneumococcal conjugate (PCV13), & pneumococcal polysaccharide (PPSV23) vaccines. To manage pain from vaso-occlusive crises, NSAIDs or acetaminophen is prescribed for mild to moderate pain. IV opioids are used for severe pain.

[2H] Name a risk associated with the use of erythrocyte-stimulating agents.

Taking erythrocyte-stimulating agents is assoc. w/ increased risk of death from serious CV events like venous thromboembolism, MI, & stroke. Therefore, restrict use to patients w/ Hb < 10 g/dL. Other side effects include hypertension, bone pain, joint aches, fever, headache, rash, nausea, vomiting, dizziness, cough, & dyspnea.

[2K] Artemisinin resistance is a growing threat. True/False

True Mutation in P. falciparum gene Pfk13 protects against protein damage & misfolding caused by artemisinin. It also increases expression of antioxidant proteins to decrease oxidative stress.