USMLE Step 1 Immunology Practice Questions

Which type of hypersensitivity reaction is mediated by IgE antibodies binding to mast cells and basophils, leading to the release of histamine and other mediators upon subsequent exposure to the allergen?

• (A) Type I Hypersensitivity (Immediate/Anaphylactic)
• (B) Type II Hypersensitivity (Cytotoxic)
• (C) Type III Hypersensitivity (Immune Complex)
• (D) Type IV Hypersensitivity (Delayed-Type)

What is the primary function of Major Histocompatibility Complex (MHC) Class I molecules?

• (A) Present endogenous antigens (e.g., viral proteins, tumor antigens) to CD8+ cytotoxic T lymphocytes
• (B) Present exogenous antigens (e.g., bacterial proteins) to CD4+ helper T lymphocytes
• (C) Bind to antibodies
• (D) Activate complement

Which cytokine, produced primarily by helper T cells (Th1 subset), is crucial for activating macrophages and promoting cell-mediated immunity?

• (A) Interferon-gamma (IFN-γ)
• (B) Interleukin-4 (IL-4)
• (C) Interleukin-10 (IL-10)
• (D) Transforming growth factor-beta (TGF-β)

Which antibody isotype is the first to be produced during a primary immune response and exists primarily as a pentamer?

• (A) IgM
• (B) IgG
• (C) IgA
• (D) IgE

What is the underlying defect in Severe Combined Immunodeficiency (SCID)?

• (A) Severe defect in both B-cell and T-cell lymphocyte development/function
• (B) Isolated B-cell deficiency
• (C) Isolated T-cell deficiency
• (D) Phagocyte dysfunction

Which process involves the coating of a pathogen with antibodies or complement proteins to enhance its phagocytosis by macrophages and neutrophils?

• (A) Opsonization
• (B) Neutralization
• (C) Antibody-dependent cell-mediated cytotoxicity (ADCC)
• (D) Complement fixation

What is the primary function of Major Histocompatibility Complex (MHC) Class II molecules?

• (A) Present exogenous antigens (phagocytosed material) to CD4+ helper T lymphocytes
• (B) Present endogenous antigens to CD8+ cytotoxic T lymphocytes
• (C) Bind to natural killer (NK) cells
• (D) Mediate antibody class switching

Which autoimmune disease is characterized by antibodies against the acetylcholine receptor (AChR) at the neuromuscular junction, leading to muscle weakness?

• (A) Myasthenia Gravis
• (B) Systemic Lupus Erythematosus (SLE)
• (C) Rheumatoid Arthritis
• (D) Multiple Sclerosis

Which complement pathway is activated by the binding of C1q to antigen-antibody complexes (typically involving IgM or IgG)?

• (A) Classical pathway
• (B) Alternative pathway
• (C) Lectin pathway
• (D) Membrane attack pathway

What is the main function of Regulatory T cells (Tregs), often characterized by expression of CD4, CD25, and FOXP3?

• (A) Suppressing immune responses and maintaining self-tolerance
• (B) Activating macrophages
• (C) Killing virus-infected cells
• (D) Providing help to B cells

DiGeorge syndrome is caused by a developmental failure of the 3rd and 4th pharyngeal pouches, leading to absence or hypoplasia of which immune organ(s)?

• (A) Thymus and Parathyroid glands
• (B) Spleen
• (C) Bone marrow
• (D) Lymph nodes

Which antibody isotype is primarily found in mucosal secretions (e.g., tears, saliva, breast milk, GI tract) and plays a key role in mucosal immunity?

• (A) IgA
• (B) IgG
• (C) IgM
• (D) IgD

Type IV hypersensitivity reactions, such as the tuberculin skin test (PPD) reaction or contact dermatitis (e.g., poison ivy), are mediated primarily by:

• (A) Antigen-specific T lymphocytes (Th1 cells, CTLs) and macrophages
• (B) IgE antibodies and mast cells
• (C) IgG/IgM antibodies and complement
• (D) Immune complexes depositing in tissues

What is the process by which developing T lymphocytes that strongly recognize self-antigens presented by MHC molecules in the thymus are eliminated?

• (A) Negative selection (central tolerance)
• (B) Positive selection (central tolerance)
• (C) Affinity maturation
• (D) Isotype switching

Which cytokine is the major growth factor for T lymphocytes and is crucial for their proliferation and differentiation?

• (A) Interleukin-2 (IL-2)
• (B) Interleukin-4 (IL-4)
• (C) Interferon-gamma (IFN-γ)
• (D) Tumor Necrosis Factor-alpha (TNF-α)

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies against various nuclear components. Which autoantibody is highly specific for SLE, although not the most sensitive?

• (A) Anti-double-stranded DNA (anti-dsDNA) and Anti-Smith (anti-Sm) antibodies
• (B) Antinuclear antibody (ANA)
• (C) Rheumatoid factor (RF)
• (D) Anti-histone antibodies

What is the function of the Membrane Attack Complex (MAC), the end product of the complement cascade?

• (A) Forms pores in the membranes of target pathogens, leading to lysis
• (B) Opsonizes pathogens for phagocytosis
• (C) Recruits inflammatory cells
• (D) Cleaves C3 and C5

Which primary immunodeficiency is characterized by recurrent bacterial infections, absent B cells, and very low levels of all immunoglobulin isotypes, typically presenting in male infants after maternal IgG wanes?

• (A) X-linked Agammaglobulinemia (Bruton's Agammaglobulinemia)
• (B) Common Variable Immunodeficiency (CVID)
• (C) Selective IgA Deficiency
• (D) Hyper-IgM Syndrome

What process occurs in the germinal centers of lymph nodes and spleen, leading to the selection of B cells producing antibodies with higher affinity for the antigen?

• (A) Affinity maturation (somatic hypermutation and clonal selection)
• (B) Isotype switching
• (C) Negative selection
• (D) Clonal anergy

Which type of hypersensitivity reaction involves the deposition of antigen-antibody (immune) complexes in tissues, followed by complement activation and neutrophil recruitment, leading to inflammation and tissue damage?

• (A) Type III Hypersensitivity (Immune Complex)
• (B) Type I Hypersensitivity (Immediate/Anaphylactic)
• (C) Type II Hypersensitivity (Cytotoxic)
• (D) Type IV Hypersensitivity (Delayed-Type)

Natural Killer (NK) cells are lymphocytes of the innate immune system that can kill certain target cells without prior sensitization. How do they primarily recognize target cells?

• (A) Detecting the absence of 'self' MHC Class I molecules on target cells (missing self hypothesis)
• (B) Recognizing specific antigens via T-cell receptors
• (C) Binding to IgE antibodies on target cells
• (D) Phagocytosing opsonized cells

Which cytokine is primarily responsible for inducing immunoglobulin class switching to IgE in B cells?

• (A) Interleukin-4 (IL-4)
• (B) Interferon-gamma (IFN-γ)
• (C) Interleukin-12 (IL-12)
• (D) Transforming growth factor-beta (TGF-β)

Chronic Granulomatous Disease (CGD) is caused by defects in which enzyme complex, leading to impaired ability of phagocytes to kill certain ingested bacteria and fungi?

• (A) NADPH oxidase
• (B) Myeloperoxidase
• (C) Superoxide dismutase
• (D) Catalase

What is the mechanism by which superantigens (e.g., toxic shock syndrome toxin-1) cause excessive T-cell activation and cytokine release?

• (A) Cross-linking MHC Class II molecules on APCs with T-cell receptors (TCRs) outside the normal peptide-binding groove
• (B) Mimicking peptide antigens bound to MHC
• (C) Activating B cells directly
• (D) Blocking co-stimulatory signals

Which process ensures that T cells recognize self-MHC molecules, allowing them to interact effectively with antigen-presenting cells?

• (A) Positive selection (central tolerance)
• (B) Negative selection (central tolerance)
• (C) Peripheral tolerance
• (D) Somatic hypermutation

Which cell type is the most potent professional antigen-presenting cell (APC) for initiating primary T-cell responses?

• (A) Dendritic cells
• (B) Macrophages
• (C) B lymphocytes
• (D) Neutrophils

Hyperacute transplant rejection, occurring within minutes to hours after transplantation, is mediated by:

• (A) Pre-existing recipient antibodies against donor antigens (e.g., ABO blood group or HLA antigens)
• (B) Recipient T cells recognizing donor MHC molecules
• (C) Recipient NK cells attacking donor cells
• (D) Deposition of immune complexes in the graft

Which interleukin, produced by macrophages and other cells in response to infection or injury, acts as an endogenous pyrogen and stimulates acute phase protein synthesis by the liver?

• (A) Interleukin-1 (IL-1) and Tumor Necrosis Factor-alpha (TNF-α)
• (B) Interleukin-2 (IL-2)
• (C) Interleukin-4 (IL-4)
• (D) Interleukin-10 (IL-10)

Wiskott-Aldrich syndrome is an X-linked disorder characterized by the triad of Thrombocytopenia, Eczema, and Recurrent infections (TIE). It is caused by mutations in the WAS gene, which affects:

• (A) Actin cytoskeleton rearrangement in hematopoietic cells
• (B) B-cell development
• (C) T-cell receptor signaling
• (D) Complement activation

Which antibody isotype is most efficient at activating the classical complement pathway?

• (A) IgM
• (B) IgG
• (C) IgA
• (D) IgE

What is the role of the CD40 ligand (CD40L or CD154) on activated helper T cells and CD40 on B cells?

• (A) Provides essential co-stimulation for B cell activation, isotype switching, and germinal center formation
• (B) Inhibits B cell activation
• (C) Mediates T cell killing of B cells
• (D) Facilitates antigen presentation by B cells

Selective IgA deficiency is the most common primary immunodeficiency. Patients are often asymptomatic but may present with:

• (A) Recurrent sinopulmonary and gastrointestinal infections; increased risk of autoimmune diseases and anaphylaxis to IgA-containing blood products
• (B) Severe T-cell dysfunction
• (C) Recurrent fungal infections
• (D) Impaired phagocytosis

What is the function of the Fas ligand (FasL) / Fas (CD95) interaction in the immune system?

• (A) Induction of apoptosis (programmed cell death)
• (B) Co-stimulation of T cells
• (C) Activation of macrophages
• (D) Chemotaxis of neutrophils

Which type of hypersensitivity reaction underlies autoimmune hemolytic anemia (AIHA) and Goodpasture syndrome?

• (A) Type II Hypersensitivity (Cytotoxic)
• (B) Type I Hypersensitivity (Immediate/Anaphylactic)
• (C) Type III Hypersensitivity (Immune Complex)
• (D) Type IV Hypersensitivity (Delayed-Type)

What is the role of Toll-Like Receptors (TLRs) in the innate immune system?

• (A) Recognize pathogen-associated molecular patterns (PAMPs) on microbes, triggering intracellular signaling pathways that lead to inflammation and immune activation
• (B) Present antigens to T cells
• (C) Mediate phagocytosis directly
• (D) Induce apoptosis in infected cells

Which immune cell is primarily responsible for fighting helminth (parasitic worm) infections and is involved in allergic reactions, characterized by bilobed nuclei and large eosinophilic granules?

• (A) Eosinophil
• (B) Neutrophil
• (C) Basophil
• (D) Mast cell

Hyper-IgM syndrome is typically caused by a defect in:

• (A) CD40 ligand (CD40L) on T cells or CD40 on B cells, preventing class switching
• (B) B-cell tyrosine kinase (BTK)
• (C) RAG genes
• (D) Adenosine deaminase (ADA)

What is the function of C3b complement component?

• (A) Acts as an opsonin (enhancing phagocytosis) and participates in formation of the C5 convertase
• (B) Initiates the membrane attack complex
• (C) Chemoattractant for neutrophils
• (D) Stabilizes the C3 convertase

Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow or stem cell transplantation. It occurs when:

• (A) Donor T lymphocytes recognize recipient tissues as foreign and attack them
• (B) Recipient T lymphocytes recognize donor cells as foreign and reject the graft
• (C) Pre-formed recipient antibodies attack the donor cells
• (D) NK cells from the donor attack recipient cells

What is the mechanism of action of cyclosporine and tacrolimus, widely used immunosuppressive drugs in transplantation?

• (A) Inhibit calcineurin, preventing the activation of NFAT and subsequent IL-2 production by T cells
• (B) Block cytokine receptors (e.g., IL-2 receptor)
• (C) Inhibit purine synthesis, preventing lymphocyte proliferation
• (D) Deplete lymphocytes via antibodies

Bare Lymphocyte Syndrome Type II is caused by defects in genes encoding transcription factors required for the expression of which molecules?

• (A) MHC Class II molecules
• (B) MHC Class I molecules
• (C) T-cell receptor (TCR)
• (D) Immunoglobulins