Which of the following is TRUE regarding ILC2s?
- ILC2s can produce IL-5, a type 2 cytokine with with cytotoxic activity against bacteria
- ILC2s promotes clearance of helminths infection by producing IL-7 and IL-2
- ILC2s cannot produce IL-4 because it is epigenetically repressed
- ILC2 is exclusive in its function against parasites and not known to be involved in other immunological responses.
- IgE can bind to ILC2s to stimulate their activation and promotes inflammatory cytokine production
3
You are designing a mRNA vaccine that targets the matrix protein of Influenza virus. Which of the following factor should you consider to improve your vaccine’s efficacy
1. The vaccine should only encode for a single matrix protein variant to ensure specificity
1. The matrix protein variants should have antigens that are recognized by antigen-presenting cells
1. None are correct
1. The addition of an adjuvant could overstimulate the immune system
1. The mRNA should remain unmodified to avoid detection from the immune system
2
Many of the Toll-like receptors use the adaptor protein MyD88 to relay intracellular signals within immune cells. Based on the concepts we covered in class, which of the following statements regarding MyD88-dependent signaling are TRUE? (More than one answer may be correct):
- This signaling pathway is active in many cell types, including cells of the adaptive immune system such as B cells.
- Only B cells express toll-like receptors.
- MyD88 signaling is only involved in antiviral immunity and does not play a role in bacterial infections.
- MyD88-dependent signaling is most likely always occurring at some level in order to maintain immune homeostasis.
- Activation of this signaling pathway does not necessarily result in acute inflammation.
1,4,5
After spending the past few months studying for MIMM 314 in your basement, you noticed that you have developed an itchy rash on your skin that won’t go away. You went to the doctor and were diagnosed with eczema from your persistent skin allergy. To make it worse, she said you also have severe Vitamin D deficiency! Which of the following is true regarding your condition? (More than one answer may be correct)
1. Your skin condition is associated with an overactive type 2 immune response, including increased IL-4, IL-13, and lgE production.
1. Vitamin D triggers excessive IN-y response that leads to skin allergy
1. Vitamin D deficiency impairs the trafficking of regulatory T cells (Tregs) to the skin
1. Your skin condition is caused by excessive activation of Th1 and cytotoxic T cell responses.
1. It is purely an infectious disease caused by bacterial or viral pathogens
1,3
In differentiating Janeway’s “hidden revelation” from Matzinger’s danger theory, what sets them apart?
1. Janeway’s theory primarily revolves around the discernment between self and non-self.
1. Matzinger argues that the activation of PRRs is independent of adjuvants in immune response initiation.
1. Janeway theorized that PRRs can detect PAMPs and factors secreted by damaged cells.
1. Janeway’s hypothesis delves into the intricacies of bystander activation during inflammation.
1. Matzinger denies the roles of PRRs in innate immunity
1
You are performing an experiment with a virus that induces a strong IN-B response in the lungs of mice. What kind of experiment would you perform to determine if resident lung macrophages are an important source of this cytokine? (More than one answer may be correct)
1. Use flow cytometry with intracellular cytokine staining for IF-B to assess IF-B production in lung macrophages after infection
1. Use IN-B knockout mice to and determine if they are still protected from infection
1. Use Cre-Lox mice to delete IN-B specifically in macrophages and measure lung IN-B levels after infection
1. Knock out IF-B in all immune cells and compare lung IF-B levels before and after drug treatment.
1. Measure serum IN-B levels using ELISA to determine if lung macrophages are the primary IFN-B source.
3 and 1
What happens if mTECs fail to express tissue-restricted antigens (TRAs) adequately?
1. Enhanced positive selection of T cells
1. Promotion of effector T cell differentiation
1. There is virtually no negative effects
1. Impaired negative selection of autoreactive T cells
1. Increased production of regulatory T cells (Tregs)
4
Which of the following statements regarding thymic selection of T cells are TRUE? (More than one answer may be correct:
- Positive selection occurs to ensure that T cells can recognize self-MHC molecules.
- Negative selection eliminates T cells that strongly bind to self-antigens to prevent autoimmunity.
- Negative selection occurs in the cortex, while positive selection occurs in the medulla.
- All developing T cells that survive thymic selection express both CD4 and CD8.
- T cells that fail to recognize MHC molecules undergo apoptosis in the thymus.
1,2,5
Which gene is required for TCRβ chain rearrangement?
- GATA3
- Notch
- RAG
- STAT5
- PSMB11
Answer: 3
Explanation: RAG1 and RAG2 are essential for V(D)J recombination of TCR genes
Dendritic cells (DCs) can detect DNA and RNA and react accordingly, however, as you learned in the class, that they don’t necessarily produce the same types of cytokines or cytokine at all in response to sensing DNA/RNA. What could contribute to this disparity in reaction? (more than one answer might be right)
- DNA coming from “self” don’t trigger a reaction
- The degree of modification of the DNA/RNA varies
- Single- vs. double-stranded RNA can make differences in responses
- The heterogeneity of DCs results in different expressions of TLRs
- DCs can go through epigenetic changes leading to alteration in reaction
Answer: 2, 3, 4, 5
Explanation: Multiple factors affect DC responses: DNA/RNA modifications, RNA structure (ss vs ds), DC subset heterogeneity with different TLR expression, and epigenetic changes from prior exposures
Which statement about antigen presentation to T cells is incorrect?
- Maturation of dendritic cells is important for presenting antigens to T cells, and it is accompanied by reduction in phagocytic activities
- Macrophages mostly do not prime naïve T cells
- Both macrophages and dendritic cells can take in antigens through phagocytosis
- Tissue graft rejection within the same species is due to allelic variants of MHC
- B cells can uptake antigen fragments with Ig and present them to T cells to activate naïve T cells
Answer: 5
Explanation: B cells lack sufficient co-stimulatory molecules to activate naïve T cells. They present antigens to already-activated T helper cells, not naïve ones
What best describes the function of AIRE (more than one answer might be right)?
- mTECs gene expression is heavily influenced by AIRE
- It is a transcription regulator important for central tolerance
- AIRE predominantly express on mTEC low population
- It is expressed in B cells in the thymus
- AIRE is indispensable for tissue restricted antigen expression in thymus
Answer: 1, 2, 4
Explanation: AIRE is expressed in mTEC-high cells and thymic B cells, acts as a transcription regulator promoting expression of tissue-restricted antigens for central tolerance and negative selection
Which below statements are correct regarding innate immune memory? (More than one answer may be correct)
- The “memory” is retained through epigenetic changes in the cells
- Innate immune memory is only exhibited through highlighted secondary responses
- The length of the “memory” varies depending on the ligands receptors involved and cell types
- It is antigen specific
Answer: 1, 3
Explanation: Innate immune memory (trained immunity) is retained through epigenetic modifications, varies in duration based on stimuli and cell types, and is NOT antigen-specific like adaptive immunity
In the experiment where the researchers added double positive OT-I transgenic (Tg) ZAP70-AS thymocytes to thymus slice and then periodically added 3-MB-PP1 into the culture, which statement below best describes the goal of the experiment?
- To study the correlation between the DP speed and their calcium signaling intensity
- To understand the roles of ZAP70 in T cells selection
- To assess the importance of interrupted vs. uninterrupted TCR signaling in all T cells selection
- To investigate the proximal binding signaling duration required for CD8 positive selection
Answer: 4
Explanation: By using inhibitable ZAP70 (ZAP70-AS) with timed addition of inhibitor (3-MB-PP1), researchers can determine the minimum continuous TCR signaling duration required for CD8+ positive selection
When cells go through apoptosis to contain the infection, they release cytokines and chemokines that can be recognized by other cells, including immune cells, which can lead to immune activation. Which innate immune activation pathway this situation best describes?
- Recognition of altered self
- Effector-triggered immunity
- Damage recognition
- PAMP-triggered immunity
Answer: 3
Explanation: Apoptotic cells release damage-associated molecular patterns (DAMPs) including cytokines and chemokines that trigger innate immune responses through damage recognition pathways
The size and function of thymus are affected by many intrinsic and external factors. Which is/are true about these influences? (More than one answer could be correct)
- Decrease in thymocytes numbers in aged thymus can be rescued with non-degenerative stromal cells
- IL-7Rα deficiency can alter the survival and proliferation of thymocytes
- Sex hormones such as testosterone and estrogen are positively correlated with the development of thymic atrophy
- Increasing increment in naïve T cells and reduction in memory T cells are often seen during aging process
Answer: 1, 2, 3
Explanation: Thymic function is affected by stromal cell quality (can be rescued with young stroma), IL-7 signaling (essential for thymocyte survival/proliferation), and sex hormones (accelerate thymic involution at puberty)
Dendritic cells (DCs) are very important during the primary allergen exposure. Which statement below is incorrect when describing the function of dendritic cells during this process? (More than one answer may be correct)
- DCs can only uptake allergens that penetrate through the epithelial cells layer in lung
- The migration of DCs is critical for allergen specific antibodies production
- Present allergen with MHCII to naïve T cells
- Produce cytokines that drive linking of IgE and FcεRI
Answer: 1
Explanation: DCs can extend dendrites through epithelial tight junctions to directly sample allergens from the airway lumen without waiting for penetration - they are active samplers, not passive receivers
Which one of the following is TRUE about MHCII?
- A short peptide is bound to MHCII molecule in endocytic compartments prior to binding to antigen derived peptides
- Presents antigen generated inside the cytosol of CD8+ T cells
- Activation on presenting cells leads to killing of infected cells
- TRiC is important in ensuring the right size of peptide to be loaded to MHCII
Answer: 1
Explanation: The invariant chain’s CLIP peptide acts as a placeholder in the MHC II groove, preventing premature binding until the proper antigenic peptide is available in endosomal compartments. HLA-DM then removes CLIP to allow antigen loading
To understand the process of T cells selection in the Thymus, researchers created bone marrow chimeras where they irradiate the MHC Knockout (KO) mice before introducing wild type bone marrows to them. What is the purpose of this experiment?
- To investigate if non-immune cells play a role in MHC mediated double positive (DP) selection process
- To study whether epithelial cells are equipped with MHC for β selection in the thymus
- To show the dual specificity of T cells receptors (TCR) in double positive (DP) T cells selection
- To test if MHCI and II are dispensable for the self-peptide presentation during positive selection
Answer: 1
Explanation: This chimera has MHC-negative thymic epithelial cells (non-immune, from host) but MHC-positive bone marrow-derived cells (from donor). Results show that thymic epithelial cells are essential for positive selection, proving non-immune cells play a critical role
You are studying a fungi infection that induces significant upregulation of IL-17A in lungs in mice. You want to investigate if the neutrophil population in lungs are a potent producer of these IL-17A, what experiments would you conduct? (More than one answer may be correct)
- Use immunohistochemistry to stain neutrophils and extracellular IL-17A to assess their co-localization in the infected lungs
- Knock out IL17A only in mice lung and see if their survival from the infection increases
- Use Cre-Lox mice to delete IL-17A coding gene in neutrophils and measure the IL-17A production in lung after infection
- Isolate neutrophils from mice lungs and infect them with the fungi of interest in vitro, and measure IL-17A production through ELISA
- Stain for intracellular IL-17A in the cells of infected lungs and evaluate its expression in the neutrophil population via flow cytometry
Answer: 3, 4, 5
Explanation: Three valid approaches: (1) Neutrophil-specific IL-17A knockout shows if neutrophils are the source in vivo, (2) In vitro culture tests neutrophil production capability, (3) Intracellular cytokine staining with flow cytometry identifies which cell types (including neutrophils) are actively producing IL-17A using Brefeldin A to trap newly synthesized cytokine
