A researcher is studying the effects of various substances on mature B-cells. She observes that while most substances are only able to promote the production of antibodies when the B-cells are co-cultured with T-cells, a small subset of substances are able to trigger antibody production even in the absence of T-cells. She decides to test these substances that stimulate B-cells alone by injecting them into model organisms. She then analyzes the characteristics of the response that is triggered by these substances. Which of the following correctly describes how the immune response triggered by the B-cell-alone-substances compares with that triggered by substances that also require T-cells?

Requires MHC class II presentation

A 71-year-old man comes to the physician for routine health maintenance examination. He feels well. He has hypertension and gastroesophageal reflux disease. Current medications include metoprolol and pantoprazole. He does not smoke or drink alcohol. Temperature is 37.3°C (99.1°F), pulse is 75/min, and blood pressure 135/87 mm Hg. Examination shows no abnormalities. Laboratory studies show: Hematocrit 43% Leukocyte count 32,000/mm3 Segmented neutrophils 22% Basophils 1% Eosinophils 2% Lymphocytes 74% Monocytes 1% Platelet count 190,000/mm3 Blood smear shows small, mature lymphocytes and several smudge cells. Immunophenotypic analysis with flow cytometry shows B-cells that express CD19, CD20 and CD23. Which of the following is the most appropriate next step in management?

Fludarabine, cyclophosphamide, and rituximab

A 38-year-old woman comes to the physician for a follow-up examination. Two years ago, she was diagnosed with multiple sclerosis. Three weeks ago, she was admitted and treated for right lower leg weakness with high-dose methylprednisone for 5 days. She has had 4 exacerbations over the past 6 months. Current medications include interferon beta and a multivitamin. Her temperature is 37°C (98.6°F), pulse is 90/min, and blood pressure is 116/74 mm Hg. Examination shows pallor of the right optic disk. Neurologic examination shows no focal findings. She is anxious about the number of exacerbations and repeated hospitalizations. She is counseled about the second-line treatment options available to her. She consents to treatment with natalizumab. However, she has read online about its adverse effects and is concerned. This patient is at increased risk for which of the following complications?

Syndrome of inappropriate antidiuretic hormone

A 28-year-old woman has a follow-up visit with her physician. She was diagnosed with allergic rhinitis and bronchial asthma at 11 years of age. Her regular controller medications include daily high-dose inhaled corticosteroids and montelukast, but she still needs to use a rescue inhaler 3–4 times a week following exercise. She also becomes breathless with moderate exertion. After a thorough evaluation, the physician explains that her medication dosages need to be increased. She declines taking oral corticosteroids daily due to concerns about side effects. The physician prescribes omalizumab, which is administered subcutaneously every 3 weeks. Which of the following best explains the mechanism of action of the new medication that has been added to the controller medications?

Prevention of binding of IgE antibodies to mast cell receptors

Inhibition of synthesis of interleukin-4 (IL-4)

Inhibition of synthesis of IgE antibodies

Selective binding to interleukin-3 (IL-3) and inhibition of its actions

Prevention of binding of interleukin-5 (IL-5) to its receptors

A biology student is studying apoptosis pathways. One of the experiments conducted involves the binding of a ligand to a CD95 receptor. A defect of this pathway will most likely cause which of the conditions listed below?

Autoimmune lymphoproliferative syndrome

A scientist is studying the process of thymus-dependent B cell activation in humans. He observes that, after bacterial infections, the germinal centers of secondary lymphoid organs become highly metabolically active. After subsequent reinfection with the same pathogen, the organism is able to produce immunoglobulins at a much faster pace. Which of the following processes is likely taking place in the germinal centers at the beginning of an infection?

Development of early pro-B cells

Development of immature B cells

B-cell depleting antibodies for USMLE Step 2 CK: High-Yield Pharmacology Lessons

Mechanism of Action - Taking Out the B-Team

Primary Target: CD20 antigen, a protein found on the surface of most B-lymphocytes, from pre-B-cells to mature B-cells.
Antibody Binding: Monoclonal antibodies (e.g., Rituximab) bind specifically to the CD20 molecule.
B-Cell Depletion: This binding triggers the destruction of the B-cell through several immune mechanisms:

Rituximab Mechanisms of Action Against B-Cell Lymphoma

⭐ Exam Favorite: CD20 is NOT expressed on hematopoietic stem cells or mature plasma cells. This means that while mature B-cells are depleted, the body can still regenerate new B-cells and maintain long-term antibody levels from existing plasma cells.

The '-mabs' - Rogues' Gallery & Indications

Rituximab, Ocrelizumab, Ofatumumab
- Target: CD20 on B-cells.
- Mechanism: Triggers complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), leading to B-cell apoptosis.
- Indications:
  - Rituximab: B-cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA).
  - Ocrelizumab: Primary progressive & relapsing multiple sclerosis (MS).
  - Ofatumumab: Relapsing MS.
Belimumab
- Target: B-Lymphocyte Stimulator (BLyS), also known as BAFF.
- Mechanism: Inhibits BLyS, preventing B-cell survival and differentiation into plasma cells.
- Indication: Systemic Lupus Erythematosus (SLE).

B-cell surface markers and therapeutic antibody targets

⭐ High-Yield: Rituximab carries a black box warning for reactivation of the JC virus, potentially leading to Progressive Multifocal Leukoencephalopathy (PML), a severe demyelinating disease of the CNS.

Adverse Effects - When B-Gones Go Bad

Infusion-Related Reactions (IRRs)
- Often cytokine-release syndrome: fever, chills, rigors, hypotension, bronchospasm.
- Occur within 30-120 mins of first infusion.
- Management: Pre-medicate with antihistamines, acetaminophen, and glucocorticoids. Slow or stop infusion.
Infections
- ⚠️ Increased risk due to B-cell depletion and subsequent hypogammaglobulinemia.
- Hepatitis B reactivation: Screen all patients for HBsAg and anti-HBc before starting.
Progressive Multifocal Leukoencephalopathy (PML)
- Rare, severe brain infection caused by JC virus reactivation.
⭐ Exam Favorite: Suspect PML in a patient on B-cell depleting therapy presenting with new, progressive neurological deficits. Diagnosis is confirmed by JC virus DNA in CSF via PCR.

MRI brain: PML non-enhancing white matter lesions

High-Yield Points - ⚡ Biggest Takeaways

Rituximab is the key drug, a chimeric antibody targeting the CD20 antigen on B-lymphocytes.

It works by causing B-cell apoptosis through complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC).

Crucially, it spares plasma cells, so pre-existing antibody levels are maintained.

Used for B-cell lymphomas, CLL, and autoimmune diseases like rheumatoid arthritis.

Watch for infusion reactions and a black box warning for Progressive Multifocal Leukoencephalopathy (PML).

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play