PHD OEQ/MEQ

c. Bone marrow biopsy will reveal a blast count of ≥20%. This patient has clinical features most consistent with acute leukemia, which is defined by a bone marrow blast count of ≥20%. They have been ill for a short time only and their clinical symptoms (bruising, bleeding, and malaise) are manifestations of "cytopenias" (thrombocytopenia and anemia). Acute leukemia requires immediate treatment. Don't let the sun set on acute leukemia! Circulating leukemia cells are "immature" rather than "mature" and the disease is curable by chemotherapy.

A 32 yo parent of two (pronouns: they/them) presents to their PCP with a two-week history of fever, malaise, easy bruising and gum bleeding. Their PCP performs a CBC and refers them to a hematologist for further evaluation of abnormal blood counts. Which of the following is most likely to be TRUE? Select one: a. This patient will be initially treated with "observation only". b. CBC revealed a high white blood cell count consisting mainly of mature lymphocytes. c. Bone marrow biopsy will reveal a blast count of ≥20%. d. This disease is not curable by chemotherapy.

d. This patient's disease is curable by chemotherapy. This patient has an aggressive lymphoma: he is symptomatic with fast-growing lymphadenopathy and "B" symptoms, and has been ill only for a short time. These features are consistent with aggressive rather than indolent lymphoma. Diagnosis of aggressive lymphoma is made by excisional lymph node biopsy, not bone marrow biopsy. Translocations between chromosome 9 and 22 (the Philadelphia chromosome) are associated with chronic myeloid leukemia (CML), not lymphoma. Patients with lymphoma do not usually present with symptoms of symptoms of thrombocytopenia (bruising, bleeding) or anemia (fatigue), especially when they exhibit a normal CBC. Aggressive lymphomas are curable by chemotherapy, but they always require treatment and do not undergo spontaneous remission.

A 54 yo man (pronouns: he/his) presents with a two-month history of an enlarging mass under his left arm, night sweats, fever, and a 15 lb weight loss. His CBC was normal, but lactate dehydrogenase (LDH) was abnormally elevated. Which of the following is most likely to be TRUE? Select one: a. Diagnosis will be made by bone marrow biopsy. b. The tumor will have a translocation between chromosome 9 and 22. c. Patients with this disease often present with bruising, bleeding and fatigue. d. This patient's disease is curable by chemotherapy. e. This patient has a chance of spontaneous remission.

d. have a higher growth fraction As the name implies, cytotoxic therapy is very toxic and has little selectivity for tumor cells over normal cells. The main difference is that a greater percentage of tumor cells are actively dividing, or to put that in different words, the growth fraction is higher in tumor cells than in normal cells. This difference is thought to contribute to a small preference by cytotoxic agents for tumor tissue over healthy dividing tissu

A 54-year-old man (pronouns: he/his) is started on cytotoxic chemotherapy for metastatic colon cancer. At his next appointment, a CT scan shows decreased tumor burden. His oncologist explains that the chemotherapy effectively killed many of the patient's cancer cells and left his normal cells relatively unharmed. This selectivity occurs because tumors: Select one: a. are nutrient-starved due to decreased blood flow b. lack cyclin-dependent kinases c. lack the DNA-repair mechanisms of normal cells d. have a higher growth fraction

a. S-phase Drugs such as methotrexate that interfere with the cell's ability to synthesize new DNA will arrest the cell cycle when synthesis occurs, namely the S -phase. Drugs that affect microtubules will affect the M phase, while alkylating agents in general affect all phases equally.

A 55-year-old woman (pronouns: she/hers) presents to her oncologist with newly diagnosed breast cancer. The oncologist prescribes methotrexate as part of the treatment regimen. As a result of this medication, malignant cells within the tumor will most likely arrest in which of the following phases of the cell cycle? Select one: a. S-phase b. M-phase c. G1-phase d. G2-phase e. Malignant cells are equally likely to arrest in any of these phases

c. Deoxyadenosine The correct answer is deoxyadenosine. The child has inherited mutations in the genes for adenosine deaminase (ADA) and cannot convert adenosine to inosine (and deoxyadenosine to deoxyinosine). The deoxy- adenosine is toxic and will accumulate in the blood cells, eventually forming dATP through salvage reactions; this is a form of severe combined immunodeficiency, or SCID. Orotic acid builds up in hereditary orotic aciduria, but immune defects are not associated with that condition. Uric acid accumulation leads to gout without affecting the formation of the immune system. NADPH is required for the ribonucleotide reductase reaction, but its levels are not altered, nor is it secreted into the blood in an adenosine deaminase deficiency. dGTP levels do not increase with an adenosine deaminase deficiency.

A 6-month-old infant presents to the ED with flu symptoms. He was hospitalized 2 weeks after birth and treated for a cold, which resolved, and has had frequent infections since then. Family history indicates that the boy's mother had a brother with similar symptoms, who died at 2 years of age. Workup demonstrates a lack of B and T cells. As part of the diagnostic process various blood metabolites are measured; which of the following is most likely to be elevated? Select one: a. Uric acid b. Orotic acid c. Deoxyadenosine d. NADPH e. dGTP

c. Doxorubicin Doxorubicin is the drug that causes damage to the heart. This is dose-dependent, and the toxicity increases with cumulative lifetime exposure. Patients need to have a record of how much doxorubicin they have received in their lifetime to avoid excess toxicity (e.g., when pediatric cancer survivors require chemotherapy later in life). The dose limiting toxicity (DLT) of cyclophosphamide (Cytoxan) and etoposide is bone marrow suppression, while the DLT of vincristine is peripheral neuropathy.

A 60-year-old man (pronouns: he/him) receiving chemotherapy for non-Hodgkin's lymphoma (NHL) presents to his physician with increasing shortness of breath during physical activity. An echocardiogram of the heart shows that his ejection fraction has declined from a baseline of 65% to current value of 48%, indicating weakening of the heart muscle. Which of the following medications is most likely responsible for this patient's presentation? Select one: a. cyclophosphamide (Cytoxan) b. Vincristine c. Doxorubicin d. Etoposide

d. Patients can become symptomatic from autoimmune anemia and thrombocytopenia This patient has small lymphocytic lymphoma (SLL), which is essentially chronic lymphocytic leukemia (CLL) involving the lymph nodes. This disease behaves like an indolent NHL (non-hodgkin lymphoma), progresses slowly, and is not curable by chemotherapy. Patients often die of other conditions rather than of this disease. The malignant cells are CD20+, so the disease is often treated with rituximab (anti-CD20 antibody) but not with CAR-T cells which are directed against CD19 and used in acute lymphoblastic leukemia and other refractory/aggressive B-cell leukemias/lymphomas. When the disease is progressive, patients can become symptomatic from autoimmune anemia or thrombocytopenia; in a minority of cases, transformation occurs to aggressive 'mature' lymphomas, not acute lymphoblastic leukemia.

A 79 yo man (pronouns: he/his) with a history of hypertension and hyperlipidemia presents to his primary care physician with complaints of a lump in his groin that has been slowly growing for several years. Initially, the mass did not bother him, but recently it has been causing some discomfort when he sits in certain positions. A biopsy of the mass reveals effacement of normal lymph node architecture by ill-defined pseudofollicles that contain small round lymphocytes with clumped "soccer ball" chromatin and minimal cytoplasm. Mitotic activity is very low. Which of the following is TRUE of this disease? Select one: a. This disease is rapidly fatal b.This disease inevitably progresses to acute leukemia. c. This disease is curable by chemotherapy. d. Patients can become symptomatic from autoimmune anemia and thrombocytopenia. e. Patients are often treated with CAR-T cells directed against CD19.

d. The amount of IgG made in the secondary response is greater than the amount made in the primary response. The primary response occurs the first time that antigen is encountered. In the primary response, antibodies are detectable in the serum after a longer lag period than occurs in the secondary response. The lag period of the primary response is typically 5-10 days. The first antibodies to appear in the primary response are IgM, followed by IgG or IgA. When there is a second encounter with the same antigen or a closely related (or cross-reacting) one, months or years after the primary response, there is arapidantibody response (the lag period is typically only3-5 days) tohigherlevels than the primary response.During the secondary response, the amount of IgM produced is similar to that after the first contact with antigen, however, a much larger amount of IgG antibody is produced. Somatic hypermutation occurs (again) in germinal centers of lymph nodes and spleen to produce even higher affinity antibodies

A clinically important concept is that protection afforded by a vaccine the first time it is given is delayed compared with the protection afforded by a booster shot in which a faster secondary response occurs. Regarding the primary and secondary (anamnestic) immune responses, which one of the following is most accurate? Select one: a. The IgM made in the primary response is made primarily by memory B cells. b. The lag phase is shorter in the primary response than in the secondary response. c. In the primary response, memory B cells are produced, but memory T cells are not. d. The amount of IgG made in the secondary response is greater than the amount made in the primary response.

e. IL-10 IL-10 is an important regulatory cytokine that is produced by Tregs to dampen immune responses. Interferon-alpha (IFNa) is important in antiviral defense. Interferon-gamma (IFNg) is produced by Th1 cells, CD8+ T cells, NK cells, and group 1 innate lymphoid cells (ILC1s) and activates macrophages and monocytes as part of cell-mediated immune responses. IL-13 is made by Th2 cells and ILC2s and enhances anti-helminth immunity and allergic inflammation. IL-12 is produced by antigen-presenting cells to promote CD4+ T cell Th1 polarization and activation.

A cytokine that is important for regulatory T (Treg) cell function is: Select one: a. Interferon-alpha b. Interferon-gamma c. IL-13 d. IL-12 e. IL-10

e. C5b,6,7,8,9 Terminal complex (C5b,6, 7,8, 9) deficiency results in predisposition towards severe, recurrent Neisseria infections

A deficiency of which one of the following complement components predisposes to bacteremia caused by members of the genus Neisseria? Select one: a.C1 b. C3b c. C5a d. C5b e. C5b,6,7,8,9

d. Suprapatellar bursa The suprapatellar bursa is located deep to the quadriceps tendon and superficial to the femur. This bursa is continuous with the synovial cavity of the knee joint proper. As this space is continuous with the knee joint, fluid can also build up proximally in the thigh at this location. All other bursas listed are located around the knee, but outside of the joint capsule.

A patient comes to your clinic with a swollen left knee. It is determined that an arthrocentesis is required to analyze the fluid within the joint. In addition to the space directly between the femur and tibia, fluid within the knee joint can also accumulate at the: Select one: a. Deep infrapatellar bursa b. Prepatellar bursa c. Superficial infrapatellar bursa d. Suprapatellar bursa

b. Tolerance to certain self-antigens occurs by negative selection of immature T cells in the thymus. Statement B (Tolerance to certain self-antigens occurs by negative selection of immature T cells in the thymus) is true. A is false because clonal deletion occurs with both T and B cells. C is false because the presence of B7 is important for activation of naïve T cells (priming) but is not essential for establishment of tolerance. D and E are false because tolerance can be lost (it is not permanent): adults can develop immune responses to host antigens due to a mix of genetic and environmental factors that "break" tolerance, resulting in autoimmune disease.

Autoimmune diseases such as lupus (SLE) arise when there is loss of immune tolerance. Which of the following statements regarding immunologic tolerance is TRUE? Select one: a. Clonal deletion occurs with T cells but not with B cells. b. Tolerance to certain self-antigens occurs by negative selection of immature T cells in the thymus. c. The presence of B7 on the surface of the antigen-presenting cell is one of the essential steps required to establish tolerance. d. Tolerance is easier to establish in adults than in newborns because more self-reactive T cells have undergone apoptosis in adults than in newborns. e. Once tolerance is established to an antigen, it is permanent (i.e., that individual cannot react against that antigen even though the antigen is no longer present).

a. Higher rates of inflammatory/autoimmune reactions. CTLA-4 and PD-1/PD-L1 blockade (checkpoint inhibition) lead to tumor regression by removing brakes on the immune response to cancer. However, it may result in inadvertent side effect of increased autoimmunity. IgE mediated hypersensitivity reactions are not increased with cancer immunotherapy.

Blocking the molecules CTLA-4 and/or PD-1 to boost anti-tumor responses will result in: Select one: a. Higher rates of inflammatory/autoimmune reactions. b. Higher rates of allergic/ type 1 hypersensitivity reactions. c. Recurrence in malignancy or tumor progression. d. Immunosuppression caused by a "brake" on the anti-tumor immune response.

a. B cells B cells are an integral component of 'adaptive immunity' and have both memory and specificity. Basophils, macrophages, dendritic cells and neutrophils do not have memory and are part of 'innate immunity'. Specificity is a hallmark of cell mediated and antibody mediated immune response.

Certain components of our immune system are characterized by two attributes: being able (1) to respond specifically to microbes and (2) to exhibit memory of having responded to a particular microbe previously. Which one of the following has BOTH specificity and memory? Select one: a. B cells b. Basophils c. Dendritic cells d.Macrophages e.Neutrophils

e.Is as effective the first time it is exposed to a pathogen as it is subsequent times Adaptive immunity (mediated by B- and T-cells) is highly specific in its response to bacteria and exhibits memory following exposure to bacteria (making choices A and C incorrect). Innate immunity responds to pathoen-associated-molecular patterns, which are present on viruses, fungi and bacteria (making choices B and D incorrect).

Chronic granulomatous disease (CGD) is an example of a disease caused by a defect in innate immunity, which impacts phagocytes (macrophages and neutrophils) and their ability to kill certain microbes. Which one of the following is an attribute of the innate, rather than the adaptive (acquired), arm of our host defenses? Select one: a. Is highly specific in its response to bacteria b.Responds to viruses and fungi, but not bacteria c.Exhibits memory following exposure to bacteria d.Is part of our host defense against bacteria but not against fungi e.Is as effective the first time it is exposed to a pathogen as it is subsequent times

a. T cells bearing antigen receptors that strongly recognize self antigens are deleted, a process known as negative selection. Within the thymus, two very important processes called thymic education occur: CD4-positive, CD8-positive cells bearing antigen receptors for "self" proteins are killed (clonal deletion) by a process of programmed cell death called apoptosis . The removal of these self-reactive cells, a process called negative selection, results in tolerance to our own proteins (i.e., self-tolerance) and prevents autoimmune reactions . CD4-positive, CD8-positive cells bearing antigen receptors that do not recognize self MHC proteins are also killed. This results in a positive selection for T cells that react well with self MHC proteins. This is necessary, as T-cell must interact with MHC molecules presenting peptides (protein bits), and if a T-cell can't recognize MHC it's not very helpful down the road :)

Defects in thymic selection can results in autoimmunity and/or immunodeficiency. Regarding events that occur in the thymus during the maturation of T cells, which one of the following is the most accurate? Select one: a. T cells bearing antigen receptors that strongly recognize self antigens are deleted, a process known as negative selection. b. Superantigens are "super" because they play a selective role in both the positive and the negative selection that occurs in the thymus. c. T cells bearing antigen receptors that recognize antigen in association with foreign MHC proteins survive, a process known as positive selection. d. Most mature T cells have both CD4 and CD8 proteins in their surface that ensures their ability to react with antigen presented by either MHC class I or MHC class II proteins.

b.A hapten cannot induce antibody by itself but can do so when covalently bound to a carrier protein. Haptens are typically small moleculars such as drugs or toxins. A hapten alone cannot induce antibody, because the helper T cells are not activated by the hapten. However, hapten-carrier conjugate induces antibody against the hapten. Although the hapten alone (without the carrier protein) can bind to the IgM receptor on the B-cell surface, the interleukins essential for the B cell to become a plasma cell are not made.

Drug allergy such as penicillin allergy is thought to occur due to the immunogenicity of hapten carrier complexes. Regarding haptens, which one of the following is the most accurate? Select one: a. A hapten is the antigen-binding site in the hypervariable region of IgG. b.A hapten cannot induce antibody by itself but can do so when covalently bound to a carrier protein. c.A hapten can bind to the antigen receptor of CD4-positive T cells without being processed by macrophages. d.A hapten is defined by its ability to bind to the smaller of the two polypeptides that comprise the class I MHC proteins.

c. Ribonucleotide reductase Ribonucleotide reductase is correct - it converts rNDPs to dNDPs (ribonucleoside diphosphates to deoxyribonucleoside diphosphates), and is thus required for synthesis of the building blocks of DNA. Inibition of DHFR would impact the ability to produce dTTP, and is often a chemotherapeutic target, but it would not impact other nucleotides. Inhibition of NDP kinase would reduce the ability to produce ANY nucleoside triphosphate, either ribose-based or deoxyribose-based. Inhibition of thymidylate synthase would decrease ability to produce dTTP, but not other nucleotides. Inhibition of xanthine oxidase would decrease uric acid production but would not affect steady state nucleotide levels.

Hydroxyurea is a drug that can be used as a chemotherapeutic agent, and is often used in early stages of CML to lower white blood cell count prior to treatment with targeted therapy like imatinib. In studies in a laboratory setting, levels of all four deoxyribonucleoside triphosphates decrease in cells to which this drug has been added, but levels of the four ribonucleoside triphosphates stay the same. Which of the following enzymes does hydroxyurea MOST likely target? (Use your metabolic map for reference.) Select one: a. DHFR (dihydrofolate reductase) b. NDP (nucleoside diphosphate) kinase c. Ribonucleotide reductase d. Thymidylate synthase e. Xanthine oxidase

c. X-linked hyper-IgM syndrome Explanation: X-linked hyper-IgM syndrome results from a defect in CD40L; CD40L is required for antibody class switching (switching from IgM to other isotypes), but not for the development or survival of B cells or T cells. In DiGeorge syndrome (i.e. 22q11.2 deletion syndrome), there is defective formation of the thymus (amongst other defects), resulting in minimal development of T cells and consequently a profound decrease in the number of T cells in the blood and secondary lymphoid organs (e.g. lymph nodes and spleen). In X-linked agammaglobulinemia, B cells develop very poorly due to a deficiency in Btk, which participates in signaling by the pre-BCR and by the BCR; as a result, there are very few B cells in the blood or lymph nodes/spleen, along with very low levels of antibodies of all classes. Individuals with X-linked severe combined immunodeficiency (SCID) have normal numbers of B cells, but almost no T cells or NK cells; this form of SCID results from a mutation in the gamma-c cytokine receptor subunit, making it non-functional.

In which of the following immunodeficiency syndromes does the patient have relatively normal numbers of B cells and T cells in the blood? Select one: a. DiGeorge syndrome b. X-linked agammaglobulinemia c. X-linked hyper-IgM syndrome d. X-linked severe combined immunodeficiency

e. IgM IgM is a monomer or pentamer, it is the main immunglobulin produced early in the primary response, it is involved in complement fixation (activation) and has the highest avidity of the immunoglobulins. IgG is a monomer, is the main antibody involved in the secondary response, is the only antibody to cross the placenta and opsonizes (enhances phagocytosis). IgA is a monomer or dimer and is the main immunoglobulin in secretions (colostrum, saliva, tears, and respiratory, intestinal and genital tract secretions) IgE is a monomer, it is medically important in 1) defense against parasites and toxins 2)mediates immediate (anaphylactic) hypersensitivity reactions. IgD is a monomer, has no known antibody function but may function as an antigen receptor. It is present on the surface of early, naïve B-cells.

It's time to play "Who am I?" I am the first class of antibody to appear, so my presence indicates an active infection rather than an infection that occurred in the past. I can fix complement, which is an important defense against many bacterial infections. I am found in plasma as a pentamer (five antibody molecules stuck together). Select one: a. IgA b. IgD c. IgE d.IgG e. IgM

c. Ibuprofen Ibuprofen is a NSAID. NSAIDS inhibit cyclooxygenase, which normally produces prostaglandins (PGs). In the kidney prostaglandins facilitate opening of the afferent arteriole to maintain glomerular filtration. (GFR). In the setting of dehydration (due to the marathon) the GFR depends heavily on prostaglandins to maintain GFR. NSAIDS will inhibit formation of PGs and thus reduce GFR. In the setting of dehydration or any setting of low effective circulating volume this reduction will be severe enough to stop GFR, aka acute renal failure. Tylenol is the brand name for acetaminophen. Acetyl cysteine is the treatment for acetaminophen poisoning.

JT (pronouns: he/his) just completed as marathon and wanted to reduce the muscle pain he was sure he would experience the next day. He took 1200 mg of OTC pain meds and ended up in the hospital where he was diagnosed with acute renal failure. Which of the following drugs did JT take? Select one: a. Acetaminophen b. Acetyl Cysteine c. Ibuprofen d. Tylenol

b. Macrophages and CD4-positive T cells infiltrate the site. In the tuberculin skin test, the indurated skin rash is caused by CD4-positive helper T cells and macrophages that are attracted to the injection site. This is also a classic example of a type IV (delayed-type) hypersensitivity reaction, which takes 1-2 days to develop.

One important test to determine whether your patient has been exposed to M. tuberculosis, the organism that causes tuberculosis, is to do a PPD skin test. In this test, PPD extracted from the organism is injected intradermally. Of the following, which one is most likely to occur at the site of a positive PPD? Select one: a. Cytotoxic T cells kill target cells at the site. b. Macrophages and CD4-positive T cells infiltrate the site. c. Histamine and leukotrienes are liberated from mast cells at the site. d. Immune complexes consisting of PPD and IgG are deposited at the site.

a. Neutralize bacterial toxins The primary function of antibodies is to protect against infectious agents or their products. Antibodies provide protection because they can (1) neutralize toxins and viruses and (2) opsonize microorganisms

Patients with CVID (Common Variable ImmunoDeficiency, a humoral immunodeficiency) can present with recurrent sinopulmonary infections, which can be associated with headaches. Which one of the following is a function of humoral (antibody-mediated) immunity? Select one: a. Neutralize bacterial toxins b. Activate the alternative pathway of complement c. Inhibit the growth of Mycobacterium tuberculosis d. Suppress autoreactive T cells

b.Pneumococcal capsular polysaccharide The capsular polysaccharide can induce IgM via the T-independent response. Adding a carrier protein (such as Diphtheria,toxoid) cause helper T cells to be involved, and large amounts of IgG are produced via the T-dependent response that drives antibody class switching. T cells can only see peptides in association with MHC molecules. T cells cannot see polysaccharides and will not be able to response to a Pneumococcal capsular polysaccharide (sugar). Adding a carrier protein to a polysaccharide based vaccine (so called "conjugate vaccine") allows activation of T cells with a peptide antigen and provides T cell help to the B cell that is specific for the polysaccharide portion of Pneumococcal capsule. Toxic shock syndrome toxin binds to the super antigen region of the T-cell receptor and MHCII on antigen presenting cells (APC).

Patients with defects in cellular immunity (T-cell mediated, a part of adaptive immunity) are unable to mount adequate responses to specific vaccines. Which one of the following is most likely to induce an IgM antibody response without the participation of helper T cells? Select one: a. Diphtheria toxoid b.Pneumococcal capsular polysaccharide c.Pneumococcal polysaccharide conjugated to diphtheria toxoid d.Tetanus toxoid e.Toxic shock syndrome toxin

a. Th-17 cells produce interleukin-17, which stimulates the production of Th-2 cells. CD4 'helper' lymphocytes perform diverse functions, including: (1) they help B cells develop into antibody-producing plasma cells; (2) they help CD8 T cells to become activated cytotoxic T cells; (3) they help macrophages kill ingested microbes; and (4) they help limit or suppress excessive immune responses. These functions are performed by three distinct subpopulations of CD4 cells: -The Th-1 cell subpopulation produces gamma interferon (IFNg) that activates macrophages to become more effective killers of intracellular microbes such as Mycobacterium tuberculosis.The activated macrophages have more lysosomal proteases, more hypochlorite, and more reactive oxygen species such as superoxides, all of which collaborate in the killing of the intracellular microbes including viruses. -The Th-2 cell subpopulation performs the B-cell helper function primarily by producing IL-4 and IL-5 and IL-13 . IL-4 induces class switching of B-cells to produce IgE thereby enhancing the host defense against worms. IL-5 increases the number and activity of eosinophils. IL-13 acts on diverse hematopoietic and non-hematopoietic cells in tissues to mediate the "weep-and-sweep" response characteristic of type 2 immunity, including increased mucous production and smooth muscle contractions that can restrict worm infections but are also responsible for many symptoms associated with allergic disease. -The Th-17 cell subpopulation produces IL-17 that recruits neutrophils to a site of inflammation. Th-17 cells enhance mucosal immunity, especially in the gastrointestinal tract, and protect against extracellular bacteria and fungi. - The Treg cell subpopulation is defined by the transcription factor FoxP3 and produces suppressive cytokines (e.g. IL-10). Tregs act via multiple mechanisms to limit excessive immune responses in both lymph nodes/spleen and within organs.

Regarding Th-1, Th-2, and Th-17 cells, which one of the following is the most accurate? Select one: a. Th-17 cells produce interleukin-17, which stimulates the production of Th-2 cells. b. The production of Th-1 cells is enhanced by interleukin-4, whereas the production of Th-2 cells is enhanced by interleukin-2. c. Th-2 cells synthesize gamma interferon, which is important in controlling infections caused by Staphylococcus aureus and other pyogenic bacteria. d. Th-1 cells are involved with delayed hypersensitivity reactions, such as those that control infections caused by M. tuberculosis (Mtb).

d. Gamma interferon (IFNg) is made by Th-1 cells and activates macrophages to more effectively kill intracellular pathogens. Gamma interferon (IFNg): Stimulates killing by macrophages. Increases class I and II MHC protein expression. Inhibits growth of Th-2 cells. IL-2: T-cell growth factor, stimulates growth of both CD4 and CD8 T cells IL-12: Drives development of Th1 subset of T cells (IFNg producing T cells) IL-4 :Drives development of Th2 subset of T cells, stimulates B cell growth and increases isotype class switching to IgE, which contributes to allergic response

Regarding interleukins, which one of the following is the most accurate? Select one: a. IL-2 is made by B cells and increases class switching from IgM to IgG. b. IL-4 is made by cytotoxic T cells and mediates the killing of virus-infected cells. c. IL-12 is made by eosinophils and enhances the production of cells that mediate immediate hypersensitivity d. Gamma interferon (IFNg) is made by Th-1 cells and activates macrophages to more effectively kill intracellular pathogens.

e. There are receptors for the heavy chain of IgG on the surface of neutrophils and macrophages that mediate a host defense process called opsonization. Neutrophils and macrophages express multiple Fc receptors that can bind IgG and IgG-containing immune complexes. This allows them to recognize microbes (and other structures) that are 'opsonized' and that should be phagocytosed and degraded. IgE is generated during allergic 'type 2' immune responses and its generation is enhanced by IL-4 signaling in lymph nodes. It binds to cells that express the high affinity IgE receptor (FcER1) such as mast cells and basophils, poising these cells to degranulate if free antigen is encountered. It also can directly bind some multicellular parasites (worms) to limit infection and promote expulsion. IgA is an immunoglobulin isotype present as a dimer in body secretions, including tears, GI tract, and breast milk. The primary function of IgA is to opsonize microbes. IgD, along with IgM, are initial isotypes expressed on the surface of naïve but mature B-cells. IgD is not secreted and plays little role in immune responses. IgG can activate complement (via the classical pathway, not the alternative pathway). This results in the generation of C3a and C5a which promote further inflammation, and can result in the deposition of the membrane attack complex (MAC complex) that can degrade bacterial cell walls (C5b-C9).

Regarding the function of the different classes of antibodies, which one of the following statements is the most accurate? Select one: a. IgE blocks the binding of viruses to the gut mucosa. b. IgA acts as an antigen receptor on the surface of B cells. c. IgD is our most important defense against worm parasites, such as hookworms. d. IgG can activate the alternative pathway of complement, resulting in the production of C3a that degrades the bacterial cell wall. e. There are receptors for the heavy chain of IgG on the surface of neutrophils and macrophages that mediate a host defense process called opsonization.

c. The disease most often involves neck lymph nodes. The cell shown in the image is a Reed-Sternberg cell, which is seen in classical Hodgkin lymphoma (CHL). Classical Hodgkin lymphoma most often involves neck lymph nodes. It is not the most common lymphoma (diffuse large B-cell lymphoma is) and does not present with extensive extranodal involvement, but instead presents with localized lymph node involvement and spreads contiguously, more similar to a non-hematopoietic tumor. Unlike malignant cells in non-Hodgkin lymphomas, the Reed-Sternberg cells and Hodgkin cells are a minority (<5%) of the lymphoid cells in the involved tissue. These RS cells are abnormal, neoplastic B-cells and 'recruit' a spectrum of reactive immune and stromal cells to surround them.

Select one: a. The disease is the most common lymphoma. b. The disease presents with extensive extranodal involvement. c. The disease most often involves neck lymph nodes. d. These cells form the majority of lymphoid cells in the tissue involved.

d.Acute myeloid leukemia The pictured cell is a blast (high nuclear/cytoplasmic ratio, fine chromatin, prominent nucleolus) that contains Auer Rods (eosinophilic cytoplasmic tubular aggregates of myeloperoxidase/MPO). The identification of ≥20% blasts in the bone marrow or peripheral blood is diagnostic of acute leukemia. Additionally, the identification of Auer Rods in blasts confirms the myeloid lineage and is diagnostic of acute myeloid leukemia (AML). (Blasts in acute lymphoid leukemia, ALL, do not have Auer Rods.) The neoplastic cells in diffuse large B-cell lymphoma are large, mature lymphoid cells with coarse chromatin; they do not circulate in the blood and usually are generally not found in the bone marrow. Classical Hodgkin lymphoma has Hodgkin/Reed-Sternberg cells that do not resemble blasts, do not circulate in the blood, and are very rarely present in the bone marrow.

Select one: a.Acute lymphoid leukemia b.Diffuse large B-cell lymphoma c.Classical Hodgkin lymphoma d.Acute myeloid leukemia

e. Any of the above The patient's clinical signs and symptoms (joint pain, fatigue, edema, facial rash) and laboratory findings (elevated ANA titer, elevated serum creatinine, moderate proteinuria) all point to SLE with renal involvement (lupus nephritis). In SLE, immune complexes and complement are deposited and/or formed at sites of tissue injury including glomeruli; reflecting this immunologic mechanism, immunofluorescence testing on this biopsy should be positive for all tested immunoglobulin classes and complement components - the so-called "full house" staining pattern of lupus nephritis.

Select one: a.IgG b.IgA c.C3 d.C1q e. Any of the above

Probenecid will prevent reuptake of uric acid in the proximal convoluted tubule by inhibiting the URAT1, the transporter that is responsible for the normal reabsorption of uric acid. Prednisone and high dose colchicine can be used to reduce the inflammation, but will not lower uric acid levels. (Note that high dose colchicine has severe GI toxicity, therefore this this is not a common approach.) Thiazide diuretics will hemoconcentrate uric acid, which can precipitate an attack; low dose aspirin should be avoided as it can inhibit the action of probenecid. Note in the stem that allopurinol is associated with a rash, which has a genetic component and can be life threatening if it represents true allopurinol hypersensitivity syndrome (AHS); screening for HLA-B*5801 is recommended in populations where this allele in elevated.

Select one: a.Low-dose aspirin b.Prednisone c.High-dose colchicine (4.8 mg/6 hrs) d.Hydrochlorothiadize e.Probenecid

d.Type IV The image shows a well-developed non-caseating granuloma; together with described clinical features, this finding is most consistent with systemic sarcoidosis that involves skeletal muscle. Granulomatous inflammation is associated with strong TH1 cell activation and high-level production of cytokines such as IFN-γ; it represents a form of T-cell mediated (type IV, delayed-type) hypersensitivity. Type I hypersensitivity reactions (allergies) are mediated by IgE antibodies and are not associated with granuloma formation. Type II (antibody-mediated) and type III (immune complex-mediated) hypersensitivity reactions lead to tissue inflammation, but are not associated with granuloma formation.

Select one: a.Type 1 b.Type II c.Type III d.Type IV

a.<3,000 WBC/ml Synovial fluid generally has a low number of cells, a few hundred to a thousand in the basal state. In degenerative arthritis there can be more cells but the number is generally <3,000 WBC/ml. This is in contrast with synovial fluid from inflammatory arthritis, which contains 10,000 -50,000 WBC/ml.

Synovial fluid in osteoarthritis generally has: Select one: a.<3,000 WBC/ml b.40,000 WBC/ml c.100,000 WBC/ml d.150,000 WBC/ml

e.Cell-mediated immunity protects against intracellular infections. Antibody mediated immunity may contribute towards graft rejection, anaphylactic shock, and auto-immune disease. Cell-mediated immunity neutralizes intracellular viruses. The only true statement is that cell-mediated immunity protects against intracellular infections.

There are two broad types of adaptive immunity: antibody-mediated immunity (B-cell/plasma cell-dependent) and cell-mediated immunity (T-cell dependent). Given this, which one of the following clinical scenarios is the most accurate? Select one: a. Antibody-mediated immunity helps prevent graft rejection. b.Antibody-mediated immunity protects against anaphylactic shock. c.Antibody-mediated immunity protects against autoimmune diseases. d.Cell-mediated immunity neutralizes extracellular viruses. e.Cell-mediated immunity protects against intracellular infections.

All these features (the types of joints, symptom chronicity, joint symmetry, and presence of erosions) are used to distinguish different types of arthritis. Other features that are used are the presence or absence of inflammatory symptoms such as morning stiffness, timing of joint symptoms (intermittent, constant) and whether pattern of joint involvement is fixed, additive, or migrating.

Types of arthritis can be distinguished by: Select one: a.Types of joints involved b.Acute or chronic onset c.Symmetry of involved joints d.Presence of bony erosions e.All of the above

c.Morning stiffness of the hands lasting 3-4 hours Inflammatory arthritis generally presents with stiffness and pain after periods of inactivity; this is often described as gelling. Symptoms are generally worse in the morning because sleep is a long period of inactivity. (Many older patients feel a bit stiff in the morning for maybe 30 min, but morning stiffness of more than an hour, particularly 3-4 hours, is a sign of inflammatory arthritis along with warmth, erythema, and swelling.) In contrast, degenerative arthritis such as osteoarthritis which is "non-inflammatory" is commonly worse with activity and improves a bit with rest. DIP joints are characteristically involved in OA (osteoarthritis) but not in RA. A photosensitive skin rash is commonly seen in SLE (systemic lupus erythematosus) but is not seen in RA. The inflammatory arthritis of RA can cause swelling of knees, but it is most commonly symmetric and chronic rather than intermittent.

What symptom (s) is (are) most suggestive of an inflammatory arthritis such as Rheumatoid Arthritis (RA)? Select one: a.Pain and joint tenderness of the DIP joints b.An associated complaint of a photosensitive skin rash c.Morning stiffness of the hands lasting 3-4 hours d.Intermittent swelling of the right knee

c.Immune complex- and complement-mediated inflammation Tissue injury in SLE is primarily due to type III (immune complex-mediated) hypersensitivity: complexes of nuclear antigens and antinuclear antibodies (ANA) form either within the circulation or in situ (following antigen planting at tissue sites); immune complex formation/deposition then leads to activation of the complement cascade, leukocyte infiltration, inflammation, and tissue injury. Histamine secretion occurs in type I (allergic) hypersensitivity reactions, while antibody-mediated cell dysfunction is a hallmark of type II (antibody-mediated) hypersensitivity. CD4+ T cell-mediated inflammation and CD8+ T cell-mediated cytotoxicity are both forms of type IV (T cell-mediated) hypersensitivity.

Which immune-mediated mechanism leads to tissue injury in systemic lupus erythematosus (SLE)? Select one: a.Histamine secretion b.Antibody-mediated cell dysfunction c.Immune complex- and complement-mediated inflammation d.CD4+ T cell-mediated inflammation e.CD8+ T cell-mediated cytotoxicity

d. Red blood cell storage Although the spleen can act as a red blood cell reservoir in some mammals, it does not have this function in humans. Removal of damaged RBCs is a very important spleen function (damaged RBCs are captured by the splenic macrophages, while healthy RBCs pass freely). In addition, spleen recycles the RBC iron and mounts immune response to blood-borne foreign antigens. Fetal spleen has a hematopoietic function; while hematopoiesis is completely taken over by the bone marrow in adults, extramedullary hematopoiesis can occur in the adult spleen in pathologic conditions involving the bone marrow.

Which of the following is NOT a known function of the human spleen? Select one: a. Removal of damaged red blood cells b. Immune response c. Hematopoiesis d. Red blood cell storage e. Iron recycling

e. It binds to CD28 and blocks interaction with B7-1 and B7-2 CTLA-4-Ig is a chimeric protein that consists of CTLA-4 attached to an Ig heavy chain to increase its half-life. It is a soluble protein without any signaling properties. By binding to B7-1 and B7-2, CTLA-4-Ig prevents CD28 from binding to these molecules. As a result, T cells cannot get the second signal (costimulation) they require to become fully activated. Both CD28 and CTLA-4-Ig can bind B7-1 and B7-2 on antigen presenting cells, but CTLA-4-Ig does not bind CD28.

Which one of the following is NOT TRUE about mechanism of action of CTLA-4-Ig: Select one: a. It binds with higher affinity to B7-1 (CD80) and B7-2 (CD86) than CD28 does b. It is a soluble form of CTLA-4 and does not have any signaling properties c. It blocks interaction of CD28 with B7-1 and B7-2 d. It prevents T cells from getting the second signal (costimulation), in addition to T cell receptor stimulation that is required for full activation e. It binds to CD28 and blocks interaction with B7-1 and B7-2

Epithelial surfaces such as skin, pulmonary epithelium, gut mucosa , and GU mucosa, are in direct contact with the "outside" world and thus, play an essential barrier role against invading microbes. Disruption of these layers, which can occur in diseases such atopic dermatitis that reduce the skin barrier function can make an individual susceptible to infections. Complement and other soluble factors play an important role in early protection against microbes. Marcophages can ingest invading microbes. NOD-like receptors (NLRs) are part of the pathogen detecting intracellular pathway. IgG antibodies are a product of B cells and a part of the adaptive immune system, even though once they are made in response to an immunization or previous infection, they are always around and ready to go.

Which one of the following is NOT part of the innate immune system that plays an early role in protection against infection: Select one: a. skin and the pulmonary epithelium b. complement c. macrophages d.IgG antibodies e. NOD-like receptors (NLRs)

c. It consists of Toll-like receptors (TLRs) that form a macromolecular complex The inflammasome is an intracellular cytoplasmic macromolecular complex that is part of the innate immune system. As a result of stimulation by a number of intracellular signals, including uric acid (gout) crystals, caspase 1, which is the protease part of the inflammasome becomes activated. Caspase 1 then cleaves pro-IL-1b to generate active IL-1b, which is a pro-inflammatory cytokine that recruits and activates other cells of the immune system such as neutrophils and monocytes. TLRs are either on the surface or inside endosomes of a cell and are NOT in the cytoplasms. Unlike the inflammasome, TLRs do not form large complexes and do not activate IL-1b directly. IL-1b is a generalized "Go-Signal" that activates many immune and non-immune cells, and IL-1b or its receptor (IL-R1) are the target of several blocking agents (e.g. anakinra, canakinumab).

Which one of the following is NOT true about the inflammasome: Select one: a.It's part of the innate immune system b. It's activated by a number of intracellular signals including uric acid (gout) crystals c. It consists of Toll-like receptors (TLRs) that form a macromolecular complex d.A major component of the inflammasome is a protease named caspase 1 e. the major cytokine that is made by the inflammasome is IL-1β

a. B cells and dendritic cells Dendritic cells, macrophages and B-cells can all serve as antigen presenting cells (APCs).

Which one of the following sets of cells can present antigen to helper T cells (CD4+ T cells)? Select one: a. B cells and dendritic cells b. B cells and cytotoxic T cells c. Macrophages and eosinophils d. Neutrophils and cytotoxic T cells e. Neutrophils and plasma cells

c. dendritic cells Dendritic cells (DCs) are highly efficient in antigen processing and delivery to T cells. They pick up antigens that have entered the skin or crossed other mucosal barriers and are activated by PAMPs to express costimulatory molecules (B7-1 and 2) and to migrate through the afferent lymphatics to the tissue draining lymph node. Within the lymph node, the activated antigen presenting dendritic cells activate antigen specific T cells by providing them with antigen and costimulation. An optimal vaccine platform would deliver the antigens and PAMPs to dendritic cells.

You are trying to design a new vaccine delivery system for cancer immunotherapy. Your goal is to inject this vaccine in the arm, just like any other vaccine, so that it can provide the tumor antigens in a way that would activate the T cells to fight off the tumor. You want to direct your delivery system to the immune cell type that is the most efficient in delivering the protein antigens to T cells and be able to activate them. That immune cell is: Select one: a. B cells b. neutrophils c. dendritic cells d. macrophages e. eosinophils

b. The patient's serum was reacted with Borrelia antigens. Then antibody to human mu heavy chain labeled with an enzyme was added. Then the enzyme substrate was added, and a color change was observed.

You have just received a lab report that says your patient is positive for IgM antibody to Borrelia burgdorferi in an enzyme-linked immunosorbent assay (ELISA). This supports your clinical impression that the patient has Lyme disease. Which one of the following best describes how the ELISA was performed? (For brevity, the wash steps have been left out.) Select one: a. The patient's serum was reacted with antibody to human mu heavy chain. Then Borrelia antigens labeled with an enzyme were added. Then the enzyme substrate was added, and a color change was observed. b. The patient's serum was reacted with Borrelia antigens. Then antibody to human mu heavy chain labeled with an enzyme was added. Then the enzyme substrate was added, and a color change was observed. c. Borrelia antigens were reacted with antibody to human mu heavy chain. Then the patient's serum labeled with an enzyme was added. Then the enzyme substrate was added, and a color change was observed. d. Borrelia antigens were reacted with antibody to human mu heavy chain labeled with an enzyme. Then the patient's serum was added. Then the enzyme substrate was added, and a color change was observed.

In this test, the antigen is in solution. The antibody cross-links antigen molecules in variable proportions, and aggregates (precipitates) form. In the zone of equivalence, optimal proportions of antigen and antibody combine; the maximal amount of precipitates forms, and the supernatant contains neither an excess of antibody nor an excess of antigen In the zone of antibody excess, there is too much antibody for efficient lattice formation, and precipitation is less than maximal (resulting in false negative result). In the zone of antigen excess, all antibody has combined, but precipitation is reduced because many antigen-antibody complexes are too small to precipitate (i.e., they are "soluble").

You think your patient has secondary syphilis, and you order a VDRL serological test. The lab reports that the test is negative. If this is a false-negative result due to the "prozone" phenomenon, which one of the following is the most likely explanation? Select one: a. The patient's serum has too much antibody, and the reaction is in the zone of antibody excess. b. The patient's serum has too much antigen, and the reaction is in the zone of antigen-excess phase. c. The patient's serum has too little antibody, and the reaction is in the zone of antibody-deficient phase. d. The patient's serum has too little antigen, and the reaction is in the zone of antigen-deficient phase. e. The patient's serum has an amount of antibody that puts it in the zone of equivalence.

b. Allergen binds to IgE on the surface of mast cells and histamine is released. The wheal and flare reaction is consistent with immediate type (IgE mediated) hypersensitivity. Symptoms associated with IgE mediated hypersensitivity reactions are mediated by histamine release by tissue mast cells and basophils which causes vasodilation, increased capillary permeability, and smooth muscle contraction (also resulting in the wheal and flare reaction noted on the skin test).

Your patient has episodes of eye tearing, "blood-shot" eyes, and runny nose, which you think may be due to an allergy to some plant pollen. You refer the patient to an allergist, who performs skin prick tests with various allergens. A rapid wheal-and-flare reaction is seen on the patient's back at the site where several pollens were injected. What is the most likely sequence of events that produced the wheal-and-flare reaction? Select one: a. Allergen binds to IgE on the surface of B cells and IL-4 is released. b. Allergen binds to IgE on the surface of mast cells and histamine is released. c. Allergen binds to IgE on the surface of mast cells and histamine is released. d. Allergen binds to IgE in the plasma, and the allergen-IgE complex binds to the surface of macrophages and IL-1 is released.

a. She has too little C1 inhibitor. C1 inhibitor deficiency (either quantitative deficiency or functional deficiency) results in a clinical condition called hereditary angioedema. These patients suffer from recurrent episodes of angioedema which can involve various body parts, including larynx. Exams love to ask this question, this is a complement function independent of traditional complement roles in microbial protection.

Your patient is a 20-year-old woman (pronouns: she/hers) who complains of swellings on her arms and legs and a feeling of fullness in her throat that makes it difficult to breath. The swellings are not red, hot, or tender. You suspect she may have angioedema caused by a complement abnormality. Of the following, which one is the most likely explanation? Select one: a. She has too little C1 inhibitor. b. She has too little C3b. c. She has too little factor B. d. She has too much C5a. e. She has too much C9.

c. It is caused by a superantigen that induces an overproduction of cytokines from helper T cells. Toxic shock syndrome is caused by superantigen that induces an overproduction of cytokines from helper T cells. Answer choice (A) results in anaphylaxis, (B) results in hereditary angioedema (D) refers to contact dermatitis which is a delayed hypersensitivity and could account for the rash, but not the fever, myalgias and vomiting and (E) results in combined immunodeficiency

Your patient is a 20-year-old woman (pronouns: she/hers) who experienced the sudden onset of fever, vomiting, myalgias, and diarrhea. This was followed by hypotension and a sunburn-like rash over most of her body. You make a presumptive diagnosis of toxic shock syndrome (TSS). Which one of the following is the most accurate description of the pathogenesis of this disease? Select one: a. It is caused by the release of large amounts of histamine from basophils. b. It is caused by an insufficient amount of inhibitor of the C1 component of complement. c. It is caused by a superantigen that induces an overproduction of cytokines from helper T cells. d. It is caused by a delayed hypersensitivity response to procainamide, which she was taking for her atrial fibrillation. e. It is caused by a mutation in the gene for ZAP-70, one of the signal transduction proteins in T lymphocytes.

a. One of the drugs formed immune complexes with IgG Serum sickness is an immune complex mediated disease (Type III Hypersensitivity, immune complex mediated) in which Antigen-antibody immune complexes are deposited in tissues, complement is activated, and polymorphonuclear cells are attracted to the site. They release lysosomal enzymes, causing tissue damage. (B, One of the drugs activated CD4-positive T cells and macrophages) results in delayed hypersensitivity (Type IV) (C, One of the drugs activated the alternative pathway of complement) results in cytotoxic hypersensitivity (Type II) (D, One of the drugs cross-linked IgE on the mast cells and caused the release of histamine) results in IgE mediated anaphylaxis (Type I)

Your patient is a 77-year-old man (pronouns: he/him) with enterococcal endocarditis who was treated with penicillin G and gentamicin Five days later, fever and a diffuse maculopapular rash developed. There is no urticaria, hypotension, or respiratory compromise. Urinalysis revealed proteinuria and granular casts. You suspect he may have serum sickness. Which one of the following immunopathogenic mechanisms is most likely to be the cause? Select one: a. One of the drugs formed immune complexes with IgG. b. One of the drugs activated CD4-positive T cells and macrophages. c. One of the drugs activated the alternative pathway of complement. d. One of the drugs cross-linked IgE on the mast cells and caused the release of histamine.

c. The serum globulin preparation containing antibodies against the virus is best because it provides immunity in the shortest time. The serum globulin preparation is a form of passive immunity. Passive immunity involves giving preformed antibodies (immune globulins) to provide immediate protection. Immunization could be effective but will take 5-7 days for the patient to form her own antibodies and begin to acquire protection.

Your patient says that she must travel on business 3 days from now to a country where hepatitis A is endemic. She just read in the newspaper that there are two types of protection against this disease: one is a vaccine that contains killed hepatitis A virus, and the other is serum globulin (antibody) preparation that contains antibodies to the virus. She asks which you would recommend and for what reason? Select one: a. The vaccine containing killed hepatitis A virus is best because it induces the most antibody. b. The vaccine containing killed hepatitis A virus is best because it provides the most long-lived immunity. c. The serum globulin preparation containing antibodies against the virus is best because it provides immunity in the shortest time. d. The serum globulin preparation containing antibodies against the virus is best because it provides the most long-lived immunity.