All questions
Question 1
A 1-year-old boy presents with recurrent bacterial and fungal infections, including Pneumocystis jirovecii pneumonia and chronic diarrhea. Laboratory studies show severe lymphopenia, particularly of CD4+ T cells, and hypogammaglobulinemia. Flow cytometry reveals that his peripheral blood mononuclear cells fail to express HLA-DR, -DP, and -DQ molecules on their surface. This patient's defect most directly impairs which of the following immunologic processes?
This patient's defect most directly impairs which of the following immunologic processes?
- Presentation of endogenous antigens to CD8+ T cells
- Activation of naive CD4+ T helper cells (correct answer)
- NK cell-mediated cytotoxicity
- Phagocytosis of opsonized bacteria
Explanation: The patient has Bare Lymphocyte Syndrome Type II, characterized by a failure to express MHC class II molecules (HLA-DR, -DP, -DQ). MHC class II molecules are required for antigen-presenting cells (APCs) to present exogenous antigens to naive CD4+ T helper cells. Without this presentation, CD4+ T cells cannot be activated, leading to a severe combined immunodeficiency affecting both cell-mediated and humoral immunity (as T cell help is needed for B cell activation).
Question 2
A 35-year-old woman is diagnosed with tuberculoid leprosy. A skin biopsy from a lesion shows numerous granulomas containing activated macrophages and CD4+ T lymphocytes. The containment of Mycobacterium leprae within these granulomas is heavily dependent on the cell-mediated immune response. Which of the following cytokines, produced by activated T helper cells, is most critical for activating the macrophages in this patient's lesions?
Which of the following cytokines, produced by activated T helper cells, is most critical for activating the macrophages in this patient's lesions?
- Interleukin-4 (IL-4)
- Interleukin-5 (IL-5)
- Interferon-gamma (IFN-γ) (correct answer)
- Interleukin-10 (IL-10)
Explanation: Interferon-gamma (IFN-γ) is the principal macrophage-activating cytokine. It is produced by Th1-type CD4+ T cells and NK cells. In infections with intracellular pathogens like Mycobacterium leprae, IFN-γ is critical for enhancing the microbicidal activities of macrophages, a key step in forming effective granulomas and controlling the infection.
Question 3
A 19-year-old male college student presents to the emergency department with a high fever, severe headache, nuchal rigidity, and a petechial rash. A lumbar puncture confirms a diagnosis of meningococcal meningitis caused by Neisseria meningitidis. His medical history is significant for a similar episode one year prior. A deficiency in which of the following would most likely explain his recurrent infections with this specific pathogen?
A deficiency in which of the following would most likely explain his recurrent infections with this specific pathogen?
- C1 esterase inhibitor
- C3
- C5b-C9 components (correct answer)
- Decay-accelerating factor (CD55)
Explanation: Deficiencies in the terminal complement components (C5b, C6, C7, C8, C9), which form the membrane attack complex (MAC), confer a specific susceptibility to recurrent infections with encapsulated bacteria of the Neisseria species (N. meningitidis and N. gonorrhoeae). The MAC is essential for lysing these particular organisms.
Question 4
A 30-year-old woman presents with fatigue and dark-colored urine in the morning. Laboratory studies show normocytic anemia, elevated LDH, and low haptoglobin, consistent with intravascular hemolysis. Flow cytometry of her red blood cells reveals an absence of CD55 and CD59. The lack of these proteins on the cell surface leads to uncontrolled activation of which of the following?
The lack of these proteins on the cell surface leads to uncontrolled activation of which of the following?
- The classical complement pathway
- The alternative complement pathway (correct answer)
- The lectin pathway
- The contact activation system (kinin-kallikrein)
Explanation: This patient has paroxysmal nocturnal hemoglobinuria (PNH), caused by a somatic mutation in the PIGA gene, leading to a deficiency of GPI-anchored proteins like CD55 (decay-accelerating factor) and CD59 (MAC inhibitory protein). These proteins normally protect host cells from complement-mediated damage. The alternative pathway undergoes continuous, low-level spontaneous activation ('tick-over'). Without these regulators, the alternative pathway is amplified on the surface of red blood cells, leading to MAC formation and chronic intravascular hemolysis.
Question 5
A 7-year-old boy with a history of severe allergies and asthma presents with an acute exacerbation after exposure to cat dander. His blood work shows marked eosinophilia. The differentiation of naive T helper cells into the Th2 subtype and the subsequent production of IgE and activation of eosinophils are primarily driven by which cytokine?
The differentiation of naive T helper cells into the Th2 subtype and the subsequent production of IgE and activation of eosinophils are primarily driven by which cytokine?
- Interleukin-12 (IL-12)
- Interferon-gamma (IFN-γ)
- Interleukin-4 (IL-4) (correct answer)
- Tumor necrosis factor-alpha (TNF-α)
Explanation: Interleukin-4 (IL-4) is the key polarizing cytokine for the differentiation of naive CD4+ T cells into the Th2 subtype. Th2 cells are central to allergic reactions. They produce more IL-4, which promotes B cell class switching to IgE, and IL-5, which promotes the growth and activation of eosinophils.
Question 6
A 45-year-old man receives a kidney transplant from an unrelated donor. Despite immunosuppressive therapy, he develops acute cellular rejection 10 days post-transplantation. A biopsy of the allograft shows a dense mononuclear infiltrate. The donor's kidney cells are being targeted by the recipient's CD8+ cytotoxic T lymphocytes. Which of the following molecules must be expressed on the surface of the donor's renal tubular epithelial cells for this recognition to occur?
Which of the following molecules must be expressed on the surface of the donor's renal tubular epithelial cells for this recognition to occur?
- MHC class I (correct answer)
- MHC class II
- B7 (CD80/86)
- CD40
Explanation: CD8+ cytotoxic T lymphocytes recognize antigens presented on MHC class I molecules. All nucleated cells, including renal tubular epithelial cells, express MHC class I. In transplant rejection, the recipient's T cells recognize the donor's MHC molecules (alloantigens) as foreign, leading to an attack on the graft tissue.
Question 7
A scientist is developing a vaccine against a virus that exclusively infects epithelial cells, which are not professional antigen-presenting cells (APCs). For the vaccine to generate a robust CD8+ T cell response, viral antigens must be presented by MHC class I molecules on dendritic cells (DCs). Since the DCs are not directly infected, they must take up exogenous viral particles or debris from infected cells. This process, where exogenous antigens are presented on MHC class I, is known as what?
This process, where exogenous antigens are presented on MHC class I, is known as what?
- Clonal selection
- Affinity maturation
- Isotype switching
- Cross-presentation (correct answer)
Explanation: Cross-presentation (or cross-priming) is a specialized process carried out primarily by dendritic cells. It involves the uptake of exogenous antigens (like viral particles from infected cells) and their diversion from the standard MHC class II pathway into the MHC class I pathway. This allows the DC to prime naive CD8+ T cells against an antigen that the DC itself did not produce, which is crucial for initiating cytotoxic T cell responses against many viruses and tumors.
Question 8
A 28-year-old man returns from a trip to sub-Saharan Africa and is diagnosed with a Schistosoma infection. A complete blood count is ordered. A marked increase in which of the following cell types would be expected, driven primarily by the cytokine IL-5 produced by Th2 cells?
A marked increase in which of the following cell types would be expected, driven primarily by the cytokine IL-5 produced by Th2 cells?
- Neutrophils
- Basophils
- Eosinophils (correct answer)
- Monocytes
Explanation: Infections with helminthic parasites, such as Schistosoma, characteristically induce a strong Th2-type immune response. Th2 cells produce several key cytokines, including Interleukin-5 (IL-5). IL-5 is the primary cytokine responsible for the development, recruitment, and activation of eosinophils. Eosinophils play a crucial role in anti-parasitic defense, particularly against helminths, through mechanisms like antibody-dependent cell-mediated cytotoxicity.
Question 9
A clinical trial is investigating a new biologic agent for the treatment of Crohn's disease, an inflammatory bowel disease characterized by an overactive Th1 response. The agent is a recombinant form of a cytokine known to suppress the activation and proliferation of T cells and macrophages, thereby reducing intestinal inflammation. Which of the following cytokines has these potent immunosuppressive and anti-inflammatory properties?
Which of the following cytokines has these potent immunosuppressive and anti-inflammatory properties?
- Interleukin-6 (IL-6)
- Interferon-alpha (IFN-α)
- Granulocyte-macrophage colony-stimulating factor (GM-CSF)
- Interleukin-10 (IL-10) (correct answer)
Explanation: Interleukin-10 (IL-10) is a key anti-inflammatory cytokine produced by many cell types, including macrophages and regulatory T cells. It functions to suppress immune responses by inhibiting the production of pro-inflammatory cytokines (like IFN-γ from Th1 cells) and downregulating the expression of MHC class II and co-stimulatory molecules on antigen-presenting cells. Its properties make it a therapeutic target for inflammatory conditions.
Question 10
A 40-year-old woman is diagnosed with systemic lupus erythematosus (SLE). Her disease is characterized by the formation of immune complexes containing anti-dsDNA antibodies and nuclear antigens. These complexes deposit in various tissues, like the kidneys, leading to glomerulonephritis. The clearance of these immune complexes is a critical function of the complement system, which is initiated when which of the following molecules binds directly to the Fc portion of the antibodies in the complex?
The clearance of these immune complexes is a critical function of the complement system, which is initiated when which of the following molecules binds directly to the Fc portion of the antibodies in the complex?
- C1q (correct answer)
- C3b
- Factor D
- Mannose-binding lectin
Explanation: The classical complement pathway is the primary mechanism for clearing immune complexes from the circulation. This pathway is initiated by the binding of C1q, the recognition subunit of the C1 complex, to the Fc region of IgM or IgG antibodies that are bound to an antigen. This binding event triggers a cascade of enzymatic activations, leading to opsonization and clearance of the complex.
Question 11
A laboratory is investigating the effects of a novel viral protein that allows infected cells to evade destruction by cytotoxic T lymphocytes (CTLs). They find that cells expressing this viral protein have markedly reduced surface expression of MHC class I molecules, while MHC class II expression is unaffected. Further analysis shows that peptides derived from cytosolic proteins are being generated normally by the proteasome. The viral protein most likely interferes with which of the following cellular components?
The viral protein most likely interferes with which of the following cellular components?
- The invariant chain
- The lysosome
- The TAP transporter (correct answer)
- The phagosome
Explanation: Many viruses have evolved mechanisms to evade the CD8+ T cell response by downregulating MHC class I expression. The scenario describes a block in the MHC I pathway after peptide generation but before surface expression, with the MHC II pathway unaffected. The TAP transporter is a critical step unique to the MHC I pathway, responsible for moving peptides from the cytosol into the ER. Blocking TAP is a common viral strategy (e.g., used by HSV and CMV) that fits the experimental findings perfectly.
Question 12
A 25-year-old woman presents to the emergency department with acute swelling of her lips, tongue, and face that developed over the past few hours. She denies any new food or drug exposures. She reports similar, self-resolving episodes in the past, and her father had similar problems. Physical examination reveals non-pitting, non-pruritic edema. A deficiency in C1 esterase inhibitor is suspected. This deficiency leads to unregulated production of bradykinin due to the uncontrolled activity of which enzyme?
This deficiency leads to unregulated production of bradykinin due to the uncontrolled activity of which enzyme?
- C3 convertase
- Factor XII (Hageman factor)
- Kallikrein (correct answer)
- Thrombin
Explanation: Hereditary angioedema is most commonly caused by a deficiency of C1 esterase inhibitor (C1-INH). C1-INH regulates not only the classical complement pathway but also the contact system. Its deficiency leads to unchecked activation of the contact system, resulting in excessive activity of kallikrein. Kallikrein cleaves high-molecular-weight kininogen to produce bradykinin, a potent vasodilator that increases vascular permeability and causes the characteristic edema.
Question 13
A 55-year-old woman with metastatic renal cell carcinoma is treated with a recombinant cytokine therapy designed to enhance the activity of cytotoxic T lymphocytes and natural killer (NK) cells. This therapy works by promoting the proliferation and differentiation of these effector cells. Which of the following cytokines is most likely being administered?
Which of the following cytokines is most likely being administered?
- Interleukin-1 (IL-1)
- Interleukin-2 (IL-2) (correct answer)
- Interleukin-10 (IL-10)
- Transforming growth factor-beta (TGF-β)
Explanation: Interleukin-2 (IL-2) is a potent growth factor for T cells and also activates NK cells. High-dose recombinant IL-2 (aldesleukin) is a therapy used for metastatic renal cell carcinoma and melanoma due to its ability to stimulate a powerful anti-tumor immune response mediated by T lymphocytes and NK cells.
Question 14
A virology researcher is studying how cytotoxic T lymphocytes (CTLs) recognize and eliminate virally infected cells. He infects a culture of human hepatocytes with a virus. He observes that CTLs from a previously infected patient efficiently lyse these infected hepatocytes. The viral proteins are first degraded in the cytoplasm of the hepatocytes. Which of the following molecules is essential for transporting the resulting peptide fragments into the endoplasmic reticulum for loading onto MHC class I molecules?
Which of the following molecules is essential for transporting the resulting peptide fragments into the endoplasmic reticulum for loading onto MHC class I molecules?
- Invariant chain
- TAP (transporter associated with antigen processing) (correct answer)
- HLA-DM
- Calnexin
Explanation: The presentation of endogenous antigens, such as viral proteins synthesized within a cell, occurs via MHC class I molecules. After degradation by the proteasome in the cytoplasm, the resulting peptide fragments are transported into the endoplasmic reticulum by the TAP (transporter associated with antigen processing) complex. There, they are loaded onto newly synthesized MHC class I molecules before being transported to the cell surface for presentation to CD8+ cytotoxic T lymphocytes.
Question 15
A researcher is studying antigen processing in dendritic cells. She incubates the cells with a soluble, exogenous protein antigen. She uses immunofluorescence to track the pathway of the antigen and the MHC molecules that will present it. After endocytosis, the antigen is degraded in an acidic endolysosomal compartment. Which of the following proteins prevents endogenous peptides in the endoplasmic reticulum from binding to the peptide-binding groove of newly synthesized MHC class II molecules?
Which of the following proteins prevents endogenous peptides in the endoplasmic reticulum from binding to the peptide-binding groove of newly synthesized MHC class II molecules?
- β2-microglobulin
- Invariant chain (Ii) (correct answer)
- TAP-1
- Proteasome activator
Explanation: The invariant chain (Ii) associates with newly synthesized MHC class II molecules in the endoplasmic reticulum. It has two main functions: it physically blocks the peptide-binding groove, preventing it from binding endogenous peptides present in the ER, and it directs the transport of the MHC class II molecule to the endolysosomal compartment where it will encounter peptides from exogenous antigens.
Question 16
A 4-year-old child presents with disseminated mycobacterial infection after receiving the BCG vaccine. Genetic analysis reveals a mutation in the gene encoding the receptor for interferon-gamma (IFN-γ). In a healthy individual, macrophages that have phagocytosed mycobacteria produce IL-12. IL-12 then acts on T cells and NK cells to stimulate their production of IFN-γ. What is the primary function of the IFN-γ that is subsequently produced in this response?
What is the primary function of the IFN-γ that is subsequently produced in this response?
- To induce class switching to IgE in B cells
- To promote the differentiation of Th2 cells
- To strongly activate macrophages to kill intracellular pathogens (correct answer)
- To recruit neutrophils to the site of infection
Explanation: The IL-12/IFN-γ axis is critical for controlling intracellular pathogens like mycobacteria. Macrophages produce IL-12, which drives Th1 differentiation and stimulates T cells/NK cells to secrete IFN-γ. IFN-γ then acts as the principal activating signal for macrophages, binding to its receptor and triggering enhanced microbicidal functions, such as the production of reactive oxygen species and nitric oxide. A defect in the IFN-γ receptor, as in this patient, breaks this feedback loop and leads to severe susceptibility to mycobacterial infections.
Question 17
A 20-year-old woman presents with pharyngitis, fever, and posterior cervical lymphadenopathy. A peripheral blood smear shows atypical lymphocytes. The infection is caused by Epstein-Barr virus (EBV), which infects B lymphocytes. For an effective immune response, viral antigens must be presented to naive CD4+ T helper cells. Which of the following cell types is considered a professional antigen-presenting cell (APC) capable of performing this function?
Which of the following cell types is considered a professional antigen-presenting cell (APC) capable of performing this function?
- Neutrophil
- Natural Killer (NK) cell
- Macrophage (correct answer)
- Basophil
Explanation: Professional antigen-presenting cells (APCs) are defined by their ability to process and present antigens via MHC class II molecules and to provide co-stimulation (via B7 molecules) to activate naive T helper cells. The three main types of professional APCs are dendritic cells, macrophages, and B lymphocytes. Neutrophils, NK cells, and basophils are not considered professional APCs.
Question 18
A 68-year-old man with a history of diabetes mellitus is admitted to the ICU with septic shock secondary to a gram-negative bacillary pneumonia. He is hypotensive (BP 80/40 mm Hg), tachycardic (HR 130/min), and febrile (Temp 39.5°C). The systemic inflammatory response in this patient, characterized by widespread vasodilation and increased vascular permeability, is primarily driven by the massive release of which of the following cytokines from activated macrophages?
The systemic inflammatory response in this patient, characterized by widespread vasodilation and increased vascular permeability, is primarily driven by the massive release of which of the following cytokines from activated macrophages?
- Transforming growth factor-beta (TGF-β)
- Interleukin-2 (IL-2)
- Tumor necrosis factor-alpha (TNF-α) (correct answer)
- Interleukin-4 (IL-4)
Explanation: Septic shock is mediated by a massive, uncontrolled release of pro-inflammatory cytokines in response to components of microorganisms, such as lipopolysaccharide (LPS) from gram-negative bacteria. Tumor necrosis factor-alpha (TNF-α), along with IL-1 and IL-6, is a key mediator released by macrophages that causes fever, hypotension (due to vasodilation and increased vascular permeability), and other systemic effects of sepsis.
Question 19
The human major histocompatibility complex (MHC) is located on chromosome 6 and is also known as the human leukocyte antigen (HLA) system. The genes in this region are highly polymorphic, meaning there are many different alleles in the population. This polymorphism is evolutionarily advantageous because it increases the variety of peptides that can be presented to T cells. Where is the polymorphism of MHC molecules predominantly concentrated?
Where is the polymorphism of MHC molecules predominantly concentrated?
- In the transmembrane domain
- In the immunoglobulin-like domains
- In the peptide-binding groove (correct answer)
- In the cytoplasmic tail
Explanation: The extensive polymorphism of MHC class I and class II genes is concentrated in the exons that encode the amino acid residues lining the peptide-binding groove. This structural diversity directly influences which peptides can bind and be presented to T cells. At a population level, this ensures that there will be individuals capable of presenting peptides from virtually any pathogen, preventing widespread susceptibility to a single infectious agent.
Question 20
A 2-year-old boy is brought to the pediatrician with his third episode of severe pneumonia in the past year, caused by Streptococcus pneumoniae. He has also had multiple ear infections and a skin abscess. Laboratory evaluation reveals a profound deficiency in a key complement component that serves as an opsonin and is central to all three complement pathways. A deficiency in which of the following proteins is the most likely cause of this patient's susceptibility to pyogenic bacterial infections?
A deficiency in which of the following proteins is the most likely cause of this patient's susceptibility to pyogenic bacterial infections?
- C1q
- C3 (correct answer)
- C8
- Mannose-binding lectin
Explanation: C3 is the central component of the complement system, as it is the convergence point for the classical, alternative, and lectin pathways. Its cleavage product, C3b, is a powerful opsonin that coats bacteria, facilitating their phagocytosis. A deficiency in C3 leads to a severe immunodeficiency characterized by recurrent, severe infections with pyogenic, encapsulated bacteria like S. pneumoniae.