Complement System and Activation Pathways

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Questions and Answers

In a scenario where a patient presents with a deficiency in C3 and C4, leading to recurrent infections, which of the following complement pathway dysfunctions is MOST likely the primary immunological mechanism?

Selective impairment of the terminal lytic pathway, specifically affecting the assembly of the membrane attack complex (MAC) and increasing susceptibility to Neisseria infections.
Impaired opsonization due to the absence of C3b, affecting phagocytosis of encapsulated bacteria primarily targeted by the alternative pathway.
Overactivation of the alternative pathway, leading to consumption of C3 and C4, and subsequent dysregulation of the complement cascade.
A combined defect in both classical and mannan-binding lectin (MBL) pathways, disrupting early steps of complement activation and leading to inefficient C3 convertase generation. (correct)
Defective classical pathway activation due to dysfunctional C1qrs complex formation, preventing downstream cleavage of C2 and C4 and subsequent C3 convertase formation.

A researcher is investigating novel therapeutic targets within the complement system. Targeting which factor would MOST selectively inhibit the alternative pathway while preserving the functionality of the classical and mannan-binding lectin pathways?

MASP-2
C9
C4
Factor B (correct)
C1q

If a patient's serum sample demonstrates normal levels of all complement components (C1-C9, Factor B, Factor D, Properdin) but exhibits severely impaired complement-mediated lysis in vitro. Which of the following genetic defects is MOST likely responsible?

A missense mutation in the C8 gene, resulting in a structurally abnormal C8 protein that is unable to properly insert into the cell membrane. (correct)
A mutation affecting the glycosylation of C3b, preventing its proper interaction with Factor B.
A homozygous deletion of the gene encoding CD59, a membrane protein that inhibits the formation of the membrane attack complex (MAC).
A polymorphism in the promoter region of the C5 gene leading to reduced transcription and synthesis of C5 protein yet without impacting serum C5 levels.
An increased expression of Factor H leading to unchecked inactivation of C3 convertase.

A researcher is investigating the effects of a novel cytokine on T helper cell differentiation. They observe that T helper cells exposed to this cytokine in vitro exhibit increased expression of GATA-3, enhanced IL-4 and IL-5 production, and improved B cell help in antibody production. This cytokine MOST likely shares functional properties with which established cytokine involved in adaptive immunity?

Interleukin-4 (IL-4) (B) Signup and view all the answers

A patient with rheumatoid arthritis is treated with a novel biologic agent that selectively inhibits the signaling of TNF-alpha and IL-1. While the patient experiences significant relief from joint inflammation, they also develop a severe, disseminated Mycobacterium tuberculosis infection, despite having a previously negative tuberculosis skin test. What immunological mechanism BEST explains this increased susceptibility to tuberculosis?

Inhibition of TNF-alpha and IL-1 impairs the activation of macrophages and formation of granulomas, both critical for containing Mycobacterium tuberculosis infection. (B) Signup and view all the answers

A researcher is designing an attenuated vaccine against a novel virus. To enhance the cellular immune response and long-term immunity, they plan to incorporate an adjuvant. Which adjuvant strategy would be MOST effective in stimulating cytotoxic T lymphocyte (CTL) responses and promoting cross-presentation of viral antigens?

Including unmethylated CpG oligonucleotides (TLR9 agonists) to activate plasmacytoid dendritic cells and induce type I interferon production. (D) Signup and view all the answers

A patient undergoing immunosuppressive therapy following a solid organ transplant develops a severe Pneumocystis jirovecii pneumonia (PCP). The patient's immunosuppression regimen includes tacrolimus, azathioprine, and corticosteroids. Which of the following mechanisms LEAST likely contributes to the increased susceptibility to PCP in this patient population?

Azathioprine directly inhibits the production of complement components, reducing opsonization and phagocytosis of Pneumocystis organisms. (C) Signup and view all the answers

A researcher is investigating the sequence of events in a novel immune response to a newly identified pathogen. They observe that antigen-presenting cells (APCs) efficiently capture and process the antigen, but T cell activation is significantly impaired. Further analysis reveals a defect in the interaction between the peptide-MHC complex and the T cell receptor (TCR). Which of the following mechanisms BEST explains this observed impairment in T cell activation?

A polymorphism in the gene encoding CD3, resulting in a structurally abnormal CD3 protein that is unable to properly transduce the activation signal. (D) Signup and view all the answers

In the context of a prototypical immune response, the initiation of B lymphocyte activation requires two crucial signals. If a B cell successfully binds to its cognate antigen via its B cell receptor (BCR), signaling the first activation event, which of the subsequent immunological events is absolutely essential to provide the second signal, particularly if the antigen is a soluble protein?

Uptake and processing of the antigen by the B cell, presentation of the processed peptide via MHC class II to a cognate T helper cell, and subsequent co-stimulation and cytokine secretion by the T helper cell. (C) Signup and view all the answers

Following activation, cytotoxic T lymphocytes (CTLs) employ various mechanisms to eliminate target cells expressing foreign antigens. If a CTL exhibits normal expression of perforin and granzymes, but demonstrates impaired cytotoxic activity against target cells in vivo, what is the MOST plausible explanation for this functional defect?

Increased expression of PD-1 on the CTL surface, leading to inhibitory signaling upon engagement with PD-L1 on target cells. (B) Signup and view all the answers

Flashcards

Complement System

A system of circulating proteins that function in both the innate and adaptive immunity.

Complement Activation

In innate immunity, activated by the alternative and mannan-binding lectin pathways; adaptive immunity uses the classical pathway.