Immune checkpoint pathways US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Immune checkpoint pathways. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Immune checkpoint pathways US Medical PG Question 1: A medical student is reading about a specific type of T cells that plays an important role in immunologic tolerance. Most of these cells develop in the thymus, but some of them also develop in peripheral lymphoid organs. Usually, they are CD4+ cells and also express CD25 molecules. The functions of these cells are dependent on forkhead box P3 (Foxp3). Their function is to block the activation of lymphocytes that could react with self-antigens in a potentially harmful manner. Which of the following interleukins is secreted by these cells?
- A. Interleukin-6
- B. Interleukin-10 (Correct Answer)
- C. Interleukin-2
- D. Interleukin-12
- E. Interleukin-17
Immune checkpoint pathways Explanation: ***Interleukin-10***
- The description points to **regulatory T cells (Tregs)**, which are CD4+, CD25+, and Foxp3+. A key function of Tregs in maintaining **immunologic tolerance** is the secretion of **IL-10** and TGF-β.
- **IL-10** is a potent **anti-inflammatory cytokine** that suppresses the activation and proliferation of various immune cells, including T cells, macrophages, and dendritic cells, thereby preventing immune responses against self-antigens.
*Interleukin-6*
- **IL-6** is a **pro-inflammatory cytokine** primarily involved in the acute phase response, hematopoiesis, and differentiation of Th17 cells, which is contrary to the immunosuppressive role of Tregs.
- It promotes inflammation and is secreted by various cells, including macrophages, T cells, and B cells, but not typically by Tregs as part of their suppressive function.
*Interleukin-2*
- **IL-2** is an important **T cell growth factor**, crucial for the proliferation and differentiation of T cells, including Tregs themselves, but it is primarily secreted by activated helper T cells (Th1).
- While Tregs express the **CD25 (IL-2 receptor alpha chain)** and require IL-2 for their survival and function, they do not typically secrete IL-2 as their primary immunomodulatory cytokine.
*Interleukin-12*
- **IL-12** is a cytokine mainly produced by antigen-presenting cells (APCs) like dendritic cells and macrophages, and plays a critical role in promoting **Th1 differentiation** and cell-mediated immunity.
- It is a **pro-inflammatory cytokine** that drives immune responses, which is opposite to the suppressive function described for these cells.
*Interleukin-17*
- **IL-17** is the signature cytokine of **Th17 cells**, which are primarily involved in host defense against extracellular bacteria and fungi, but also play a significant role in mediating autoimmune diseases.
- It is a **pro-inflammatory cytokine** and its production is antagonistic to the immunosuppressive function of regulatory T cells.
Immune checkpoint pathways US Medical PG Question 2: A research team develops a new monoclonal antibody checkpoint inhibitor for advanced melanoma that has shown promise in animal studies as well as high efficacy and low toxicity in early phase human clinical trials. The research team would now like to compare this drug to existing standard of care immunotherapy for advanced melanoma. The research team decides to conduct a non-randomized study where the novel drug will be offered to patients who are deemed to be at risk for toxicity with the current standard of care immunotherapy, while patients without such risk factors will receive the standard treatment. Which of the following best describes the level of evidence that this study can offer?
- A. Level 1
- B. Level 3 (Correct Answer)
- C. Level 5
- D. Level 4
- E. Level 2
Immune checkpoint pathways Explanation: ***Level 3***
- A **non-randomized controlled trial** like the one described, where patient assignment to treatment groups is based on specific characteristics (risk of toxicity), falls into Level 3 evidence.
- This level typically includes **non-randomized controlled trials** and **well-designed cohort studies** with comparison groups, which are prone to selection bias and confounding.
- The study compares two treatments but lacks randomization, making it Level 3 evidence.
*Level 1*
- Level 1 evidence is the **highest level of evidence**, derived from **systematic reviews and meta-analyses** of multiple well-designed randomized controlled trials or large, high-quality randomized controlled trials.
- The described study is explicitly stated as non-randomized, ruling out Level 1.
*Level 2*
- Level 2 evidence involves at least one **well-designed randomized controlled trial** (RCT) or **systematic reviews** of randomized trials.
- The current study is *non-randomized*, which means it cannot be classified as Level 2 evidence, as randomization is a key criterion for this level.
*Level 4*
- Level 4 evidence includes **case series**, **case-control studies**, and **poorly designed cohort or case-control studies**.
- While the study is non-randomized, it is a controlled comparative trial rather than a case series or retrospective case-control study, placing it at Level 3.
*Level 5*
- Level 5 evidence is the **lowest level of evidence**, typically consisting of **expert opinion** without explicit critical appraisal, or based on physiology, bench research, or animal studies.
- While the drug was initially tested in animal studies, the current human comparative study offers a higher level of evidence than expert opinion or preclinical data.
Immune checkpoint pathways US Medical PG Question 3: A researcher is studying the interactions between foreign antigens and human immune cells. She has isolated a line of lymphocytes that is known to bind antigen-presenting cells. From this cell line, she has isolated a cell surface protein that binds to class I major histocompatibility complex molecules. The continued activation, proliferation and survival of this specific cell line requires which of the following signaling molecules?
- A. Interleukin 1
- B. Interleukin 4
- C. Interleukin 2 (Correct Answer)
- D. Interleukin 8
- E. Interleukin 6
Immune checkpoint pathways Explanation: ***Interleukin 2***
- The description of the lymphocyte binding the **constant portion of MHC class I** and requiring a signaling molecule for activation, proliferation, and survival points to a **T cell**.
- **Interleukin-2 (IL-2)** is a crucial cytokine for the proliferation, differentiation, and survival of T lymphocytes, acting in an autocrine or paracrine fashion after T cell activation.
*Interleukin 1*
- **Interleukin-1 (IL-1)** is primarily involved in inflammation and fever, produced by macrophages and other innate immune cells.
- While it can act as a costimulator for T cells, it is not the primary cytokine required for their sustained proliferation and survival after initial activation.
*Interleukin 4*
- **Interleukin-4 (IL-4)** is a key cytokine in humoral immunity, promoting B cell proliferation and differentiation, and inducing IgE class switching.
- It also plays a role in the differentiation of naive T cells into **Th2 cells**, but it is not the main cytokine for general T cell proliferation and survival.
*Interleukin 8*
- **Interleukin-8 (IL-8)**, also known as CXCL8, is a chemokine primarily responsible for attracting and activating neutrophils to sites of infection or inflammation.
- It does not have a direct role in the sustained proliferation and survival of activated lymphocytes.
*Interleukin 6*
- **Interleukin-6 (IL-6)** is a pleiotropic cytokine involved in acute phase reactions, hematopoiesis, and the immune response, particularly B cell differentiation and antibody production.
- Although it can influence T cell responses, it is not the primary growth factor for activated T lymphocytes as IL-2 is.
Immune checkpoint pathways US Medical PG Question 4: A 56-year-old African American presents to the emergency department due to abdominal pain, fatigue, and weight loss over the past 3 months. He has a long-standing history of chronic hepatitis B virus infection complicated by cirrhosis. On examination, he has jaundice, leg edema, and a palpable mass in the right upper abdominal quadrant. Abdominal ultrasound shows a 3-cm liver mass with poorly defined margins and coarse, irregular internal echoes. Blood investigations are shown:
Aspartate aminotransferase (AST) 90 U/L
Alanine aminotransferase (ALT) 50 U/L
Total bilirubin 2 mg/dL
Albumin 3 g/dL
Alkaline phosphatase 100 U/L
Alpha fetoprotein 600 micrograms/L
Which of the following targeted agents is approved for advanced-stage hepatoma?
- A. Ustekinumab
- B. Daclizumab
- C. Sorafenib (Correct Answer)
- D. Abciximab
- E. Palivizumab
Immune checkpoint pathways Explanation: ***Sorafenib***
- This patient's presentation with chronic hepatitis B, cirrhosis, a liver mass, and an **elevated alpha-fetoprotein** is highly suggestive of **hepatocellular carcinoma (HCC)**, also known as hepatoma.
- **Sorafenib** is a **multi-targeted tyrosine kinase inhibitor** that inhibits tumor cell proliferation and angiogenesis by targeting VEGFR, PDGFR, Raf kinases, and other kinases involved in tumor progression.
- It was the **first systemic therapy approved for advanced-stage HCC** and remains an important first-line treatment option for patients with advanced disease who are not candidates for surgical or locoregional therapies.
*Ustekinumab*
- **Ustekinumab** is a monoclonal antibody that targets the **p40 subunit of IL-12 and IL-23**, primarily used in the treatment of **psoriasis** and psoriatic arthritis, not HCC.
- It works by blocking inflammatory pathways involved in autoimmune conditions.
*Daclizumab*
- **Daclizumab** is a humanized monoclonal antibody that targets the **CD25 subunit of the IL-2 receptor**; it was previously used for treating **multiple sclerosis** but has been largely discontinued due to safety concerns.
- It is not indicated for the treatment of any form of cancer.
*Abciximab*
- **Abciximab** is a monoclonal antibody that targets the **glycoprotein IIb/IIIa receptor** on platelets, used as an **antiplatelet agent** in patients undergoing percutaneous coronary intervention.
- Its mechanism of action is related to inhibition of platelet aggregation and thrombosis, not cancer therapy.
*Palivizumab*
- **Palivizumab** is a monoclonal antibody used for the **prevention of serious lower respiratory tract disease** caused by **respiratory syncytial virus (RSV)** in high-risk infants.
- It provides passive immunity against RSV and has no role in cancer treatment.
Immune checkpoint pathways US Medical PG Question 5: A 55-year-old Caucasian male presents for a routine colonoscopy. A polyp is found in the patient's transverse colon and is found to be cancerous on histological evaluation. Upon examination, it is found that these cancerous cells have decreased MHC class I expression on their surface. Which immune system cell is most capable of killing these tumor cells?
- A. Cytotoxic T-cells
- B. B-cells
- C. Macrophages
- D. Natural killer cells (Correct Answer)
- E. Eosinophils
Immune checkpoint pathways Explanation: ***Natural killer cells***
- **Natural killer (NK) cells** are specialized lymphocytes that identify and kill cells with **decreased or absent MHC class I expression**, a common feature of tumor cells and virus-infected cells.
- They provide a rapid, non-specific immune response without prior sensitization.
*Cytotoxic T-cells*
- **Cytotoxic T-cells (CTLs)** recognize and kill target cells by binding to specific **antigens presented by MHC class I molecules**.
- Since these cancer cells have **decreased MHC class I expression**, CTLs would be less effective at recognizing and killing them.
*B-cells*
- **B-cells** are primarily involved in humoral immunity, producing **antibodies** that can neutralize pathogens or mark cells for destruction.
- They do not directly kill target cells, and their activation typically requires specific antigen recognition, often with T-cell help.
*Macrophages*
- **Macrophages** are phagocytic cells that engulf and digest cellular debris, pathogens, and some tumor cells.
- While they can kill tumor cells, their primary mechanism involves **phagocytosis** or antigen presentation, not direct cytotoxicity based on MHC I expression levels.
*Eosinophils*
- **Eosinophils** are granulocytes primarily involved in the defense against **parasitic infections** and in allergic reactions.
- They are not a primary defense mechanism against tumor cells, especially not based on MHC class I expression.
Immune checkpoint pathways US Medical PG Question 6: A researcher is studying the circulating factors that are released when immune cells are exposed to antigens. Specifically, she is studying a population of CD2+ cells that have been activated acutely. In order to determine which factors are secreted by these cells, she cultures the cells in media and collects the used media from these plates after several days. She then purifies a small factor from this media and uses it to stimulate various immune cell types. She finds that this factor primarily seems to increase the growth and prolong the survival of other CD2+ cells. Which of the following is most likely the factor that was purified by this researcher?
- A. Interleukin-2 (Correct Answer)
- B. Interleukin-3
- C. Interleukin-4
- D. Interleukin-5
- E. Interleukin-1
Immune checkpoint pathways Explanation: ***Interleukin-2***
- **Interleukin-2 (IL-2)** is a crucial cytokine for the **growth**, **proliferation**, and **survival** of T lymphocytes, which are CD2+ cells.
- Activated T cells, like the acute CD2+ cells in the scenario, are a primary source of IL-2, and IL-2 acts in an **autocrine** and **paracrine** fashion to stimulate other T cells.
*Interleukin-3*
- **Interleukin-3 (IL-3)** primarily stimulates the growth and differentiation of **hematopoietic stem cells** and progenitors, not specifically mature CD2+ cells.
- It plays a role in the development of various myeloid cell lineages and mast cells, and its main effect is not confined to T cells.
*Interleukin-4*
- **Interleukin-4 (IL-4)** is critical for the differentiation of naive T helper cells into **Th2 cells** and is a key cytokine for **B cell proliferation** and **antibody class switching** to IgE.
- While it has immunomodulatory effects on T cells, its primary role is not in promoting the generalized growth and survival of other CD2+ cells.
*Interleukin-5*
- **Interleukin-5 (IL-5)** is predominantly involved in the growth, differentiation, and activation of **eosinophils**.
- It also plays a role in B cell growth and IgA production, but its effects are not primarily on universal CD2+ cell growth and survival.
*Interleukin-1*
- **Interleukin-1 (IL-1)** is a **pro-inflammatory cytokine** produced by macrophages, monocytes, and other immune cells in response to infection or injury.
- It primarily mediates **acute phase responses**, fever, and activates endothelial cells, but its main function is not to promote the growth and survival of T lymphocytes.
Immune checkpoint pathways US Medical PG Question 7: A 57-year-old man presents to his oncologist to discuss management of small cell lung cancer. The patient is a lifelong smoker and was diagnosed with cancer 1 week ago. The patient states that the cancer was his fault for smoking and that there is "no hope now." He seems disinterested in discussing the treatment options and making a plan for treatment and followup. The patient says "he does not want any treatment" for his condition. Which of the following is the most appropriate response from the physician?
- A. "You seem upset at the news of this diagnosis. I want you to go home and discuss this with your loved ones and come back when you feel ready to make a plan together for your care."
- B. "It must be tough having received this diagnosis; however, new cancer therapies show increased efficacy and excellent outcomes."
- C. "It must be very challenging having received this diagnosis. I want to work with you to create a plan." (Correct Answer)
- D. "We are going to need to treat your lung cancer. I am here to help you throughout the process."
- E. "I respect your decision and we will not administer any treatment. Let me know if I can help in any way."
Immune checkpoint pathways Explanation: ***"It must be very challenging having received this diagnosis. I want to work with you to create a plan."***
- This response **acknowledges the patient's emotional distress** and feelings of guilt and hopelessness, which is crucial for building rapport and trust.
- It also gently **re-engages the patient** by offering a collaborative approach to treatment, demonstrating the physician's commitment to supporting him through the process.
*"You seem upset at the news of this diagnosis. I want you to go home and discuss this with your loved ones and come back when you feel ready to make a plan together for your care."*
- While acknowledging distress, sending the patient home without further engagement **delays urgent care** for small cell lung cancer, which is aggressive.
- This response might be perceived as dismissive of his immediate feelings and can **exacerbate his sense of hopelessness** and isolation.
*"It must be tough having received this diagnosis; however, new cancer therapies show increased efficacy and excellent outcomes."*
- This statement moves too quickly to treatment efficacy without adequately addressing the patient's current **emotional state and fatalism**.
- While factual, it **lacks empathy** for his personal feelings of blame and hopelessness, potentially making him feel unheard.
*"We are going to need to treat your lung cancer. I am here to help you throughout the process."*
- This response is **too directive and authoritarian**, which can alienate a patient who is already feeling guilty and resistant to treatment.
- It fails to acknowledge his stated feelings of "no hope now" or his disinterest in treatment, which are critical to address before discussing the necessity of treatment.
*"I respect your decision and we will not administer any treatment. Let me know if I can help in any way."*
- While respecting patient autonomy is vital, immediately accepting a patient's decision to refuse treatment without exploring the underlying reasons (e.g., guilt, hopelessness, lack of information) is **premature and potentially harmful**.
- The physician has a responsibility to ensure the patient is making an informed decision, especially for a rapidly progressing condition like small cell lung cancer.
Immune checkpoint pathways US Medical PG Question 8: A 12-year-old child is exposed to pollen while playing outside. The allergen stimulates TH2 cells of his immune system to secrete a factor that leads to B-cell class switching to IgE. What factor is secreted by the TH2 cell?
- A. IL-4 (Correct Answer)
- B. IL-22
- C. TGF-beta
- D. IL-17
- E. IFN-gamma
Immune checkpoint pathways Explanation: ***IL-4***
- **Interleukin-4 (IL-4)** is a key cytokine produced by **TH2 cells** that promotes **B-cell class switching to IgE**, central to allergic reactions.
- It also stimulates the differentiation of naive T cells into **TH2 cells**, further amplifying the **allergic response**.
*IL-22*
- **IL-22** is primarily involved in maintaining **epithelial barrier integrity** and promoting **tissue repair**, especially in the gut and skin.
- It does not play a direct role in **IgE class switching** or the pathogenesis of type I hypersensitivity.
*TGF-beta*
- **TGF-beta (Transforming Growth Factor-beta)** is a pleiotropic cytokine involved in **cell growth**, differentiation, apoptosis, and immune regulation, particularly promoting **Treg cell development** and IgA class switching.
- It primarily suppresses rather than promotes **allergic reactions** and IgE production.
*IL-17*
- **IL-17** is a cytokine predominantly produced by **TH17 cells** and is crucial in protection against **extracellular bacteria and fungi**.
- It is associated with **autoimmune diseases** and inflammation but not directly with IgE-mediated allergic responses.
*IFN-gamma*
- **Interferon-gamma (IFN-gamma)** is a critical **TH1 cytokine** that activates macrophages, enhances natural killer cell activity, and promotes the cell-mediated immune response.
- It typically **inhibits TH2 responses** and IgE production, thus working against the development of allergic reactions.
Immune checkpoint pathways US Medical PG Question 9: A 33-year-old woman comes to the emergency department because of a 3-day history of lower abdominal pain and severe burning with urination. Two years ago, she was diagnosed with cervical cancer and was successfully treated with a combination of radiation and chemotherapy. She has systemic lupus erythematosus and finished a course of cyclophosphamide 3 weeks ago. She is sexually active with multiple male and female partners and uses a diaphragm for contraception. She has smoked two packs of cigarettes daily for 12 years. Current medication includes hydroxychloroquine. Her temperature is 36.6°C (97.9°F), pulse is 84/min, and blood pressure is 136/84 mm Hg. The abdomen is soft and there is tenderness to palpation over the pelvic region. Laboratory studies show:
Hemoglobin 13.1 g/dL
Leukocyte count 7,400/mm3
Platelet count 210,000/mm3
Urine
pH 7
WBC 62/hpf
RBC 12/hpf
Protein negative
Nitrites positive
Which of the following is the most likely underlying mechanism of this patient's condition?
- A. Ascending infection (Correct Answer)
- B. Hematogenous spread of infection
- C. Radiation-induced inflammation
- D. Neural hypersensitivity
- E. Sexually transmitted infection
Immune checkpoint pathways Explanation: ***Ascending infection***
- The combination of **dysuria**, **pelvic tenderness**, and specific urine findings (WBCs 62/hpf, RBCs 12/hpf, positive nitrites) are highly indicative of a **urinary tract infection (UTI)**. UTIs typically arise from bacteria ascending the urethra into the bladder.
- Factors like a **diaphragm for contraception** and **sexual activity with multiple partners** increase the risk of UTIs due to bacterial translocation and urethral irritation.
*Hematogenous spread of infection*
- While possible in severely immunocompromised patients, **hematogenous spread** to the urinary tract is less common for typical UTIs and is usually associated with systemic symptoms or a distant primary infection source.
- The patient's symptoms are localized to the urinary tract, and there's no evidence of a widespread systemic infection or a primary source from which bacteria would hematogenously spread to the bladder.
*Radiation-induced inflammation*
- **Radiation cystitis** can cause similar symptoms (dysuria, hematuria) but typically presents as **sterile pyuria** (WBCs without bacteria, though positive nitrites here suggest bacterial presence). It would also be expected to occur closer to the radiation treatment or in chronic cases, not as an acute presentation 2 years post-treatment without other contributing factors.
- The presence of **nitrites** in the urine strongly suggests bacterial infection, which is not characteristic of radiation-induced inflammation alone.
*Neural hypersensitivity*
- **Neural hypersensitivity** can cause chronic pelvic pain and urgency but does not typically present with acute onset dysuria, significant pyuria, and positive nitrites as seen in this patient.
- This mechanism is more associated with conditions like **interstitial cystitis/bladder pain syndrome**, which involves chronic pain rather than acute infection signs.
*Sexually transmitted infection*
- While the patient is sexually active with multiple partners, which increases the risk for STIs, common STIs like **chlamydia** or **gonorrhea** typically cause cervicitis or urethritis and often do not lead to the high WBC count and positive nitrites in the urine characteristic of a bacterial UTI.
- Although STIs can present with dysuria, the full picture of **pyuria**, **hematuria**, and **positive nitrites** points more strongly to a bacterial UTI than an uncomplicated STI.
Immune checkpoint pathways US Medical PG Question 10: A 40-year-old woman with myasthenia gravis on pyridostigmine develops worsening weakness, diplopia, and dysphagia. She recently had URI and received azithromycin. Exam shows bilateral ptosis, ophthalmoplegia, and proximal muscle weakness with preserved reflexes. Her acetylcholinesterase inhibitor dose was increased 3 days ago. Edrophonium test shows no improvement. ABG shows hypercapnia. Evaluate the synthesis of clinical findings and determine the life-threatening complication requiring immediate intervention.
- A. Botulism from contaminated food requiring antitoxin administration
- B. Lambert-Eaton syndrome from paraneoplastic antibodies requiring immunosuppression
- C. Myasthenic crisis from insufficient acetylcholinesterase inhibition requiring increased pyridostigmine
- D. Cholinergic crisis from excessive acetylcholinesterase inhibition requiring drug cessation and atropine (Correct Answer)
- E. Guillain-Barré syndrome from post-infectious autoimmunity requiring plasmapheresis
Immune checkpoint pathways Explanation: ***Cholinergic crisis from excessive acetylcholinesterase inhibition requiring drug cessation and atropine***
- A **negative edrophonium test** and recent increase in **pyridostigmine** dose indicates that nicotinic receptors are overstimulated and desensitized, preventing clinical improvement with further drug administration.
- The presence of life-threatening **respiratory failure (hypercapnia)** due to excessive **cholinergic stimulation** necessitates the cessation of the offending drug and the use of **atropine** to manage muscarinic side effects.
*Botulism from contaminated food requiring antitoxin administration*
- While it causes **descending paralysis**, its onset is typically associated with ingestion of C. botulinum toxin and involves **fixed dilated pupils**, unlike the pinpoint pupils often seen in cholinergic excess.
- It would not explain why a patient already on therapy for **myasthenia gravis** is experiencing a crisis immediately following a medication dose increase.
*Lambert-Eaton syndrome from paraneoplastic antibodies requiring immunosuppression*
- This condition involves **presynaptic** calcium channel antibodies and typically shows **improvement with muscle use**, the opposite of this patient's presentation.
- It is generally associated with **small cell lung cancer** and would not cause an acute respiratory failure triggered by a recent change in pyridostigmine dosing.
*Myasthenic crisis from insufficient acetylcholinesterase inhibition requiring increased pyridostigmine*
- A **myasthenic crisis** would typically show clinical improvement during an **edrophonium (Tensilon) test** as it addresses the lack of acetylcholine at the junction.
- Although triggered by infections or drugs like **azithromycin**, the lack of response to edrophonium after a recent dose increase strongly points toward over-medication rather than under-medication.
*Guillain-Barré syndrome from post-infectious autoimmunity requiring plasmapheresis*
- **Guillain-Barré syndrome** typically presents with **ascending paralysis** and a hallmark feature of **absent deep tendon reflexes**, whereas this patient has preserved reflexes.
- It does not present with **ophthalmoplegia** or ptosis as early or prominent signs compared to the sudden clinical worsening seen in established myasthenia cases.
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