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BMS3031 - Molecular mechanisms of disease - S1 2026

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Long‑lived plasma cells can persist for

years in specialised bone marrow niches, continuing to secrete high‑affinity

antibodies even in the absence of ongoing antigen exposure. Experimental

disruption of stromal cell interactions or cytokines such as APRIL, BAFF and IL‑6

leads to a rapid loss of these plasma cells.

What does this most strongly indicate about the

biology of long‑lived plasma cells?

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Cytokine signals provided by helper T cells influence

antibody isotype production during immune responses. In vitro experiments using

mouse B cells demonstrate that exposure of B cells to IL‑4 biases

class switching toward IgG1 and IgE.

Which mechanism BEST explains how IL‑4 determines this isotype outcome?

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Rituximab is a chimeric monoclonal antibody directed against

CD20 on human B cells. In laboratory studies, rituximab binds CD20 equally well

on human B cells in both human and murine environment (eg mice transplanted with

a human B cell lymphoma). However, effective B‑cell depletion is observed only

when human complement or human Fc receptor–expressing

effector cells are present. Clinically, the degree of B‑cell

depletion correlates with intact complement activity and Fcγ receptor–mediated

effector function rather than with antibody binding alone.

Considering these observations, why is the human

constant (Fc) region functionally essential for rituximab’s therapeutic effect?

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Under normal circumstances, weak interactions between B‑cell

receptors and self‑antigens fail to trigger full activation due to

signalling thresholds that enforce tolerance. In a genetically modified system,

B cells show normal development and receptor diversity but require

significantly less signalling input for activation. Over time, this system

develops circulating autoantibodies and immune complex‑mediated

pathology.

What is the most likely immunological consequence of

lowering this activation threshold?

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Primary immune responses initially generate IgM antibodies

with relatively low intrinsic affinity, while later times in responses reveal higher-affinity

IgG antibodies. Despite this difference, IgM antibodies can efficiently

neutralise pathogens early in infection.

Which explanation BEST accounts for the functional

effectiveness of IgM in this context?

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Both SARS‑CoV and SARS‑CoV‑2

infect human cells by engaging ACE2, yet SARS‑CoV‑2 exhibits more efficient

transmission and cell entry. SARS-CoV-2 has additional features in its spike

protein which influence how efficiently the virus can enter its host cells.

Which molecular feature most clearly contributes to this

difference?

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A hospital microbiology lab identifies a strain of

Acinetobacter

baumannii

with decreased sensitivity to a carbapenem antibiotic. Molecular

testing shows a truncating mutation in a gene encoding an outer‑membrane

channel protein that normally permits passive diffusion of certain antibiotics

into the bacterium.

Which resistance strategy does this mutation most directly

represent?

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A pharmaceutical company has developed a new antimicrobial

that is active against multidrug-resistant organisms. In clinical practice,

these infections are typically treated with existing agents that are effective

but associated with significant toxicity or resistance concerns. When seeking

regulatory approval, the company designs its pivotal trials as non-inferiority

studies rather than superiority trials.

Which rationale best explains this choice?

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The effectiveness of prior immunity against influenza

viruses declines over time, necessitating periodic updates to vaccine

formulations. Thus, seasonal vaccines must be created each year.

What evolutionary process most directly explains

this phenomenon?

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A

patient in intensive care has a bloodstream infection caused by a carbapenem-resistant

Acinetobacter baumannii s

train.  Initial

treatment uses colistin, a polymyxin antibiotic. During treatment, colistin

resistance evolves. What is the most likely mechanism of colistin resistance?

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