Question 1

Dendritic cells are tissue resident myeloid cells that are highly phagocytic, like macrophages. However, dendritic cells do not play a major role in large-scale pathogen destruction; instead, they are important in initiating adaptive immune responses of T cells.

Accepted Answer

Dendritic cells are important in initiating adaptive immune responses of T cells, rather than large-scale pathogen destruction like macrophages.

Question 2

All mammalian TLRs have been shown to directly bind to microbial products, leading to TLR signaling.

Accepted Answer

Not all mammalian Toll-like receptors (TLRs) directly bind to microbial products; some TLRs require accessory molecules for ligand recognition and subsequent signaling.

Question 3

An infection in the skin, such as a pimple, often produces pus. The major component of pus is:

Accepted Answer

Pus is primarily composed of dead and dying neutrophils, along with other cellular debris and fluid. Neutrophils are white blood cells that are specialized in fighting infections and are often the first responders to sites of infection in the body. As they fight off pathogens, they release various enzymes that break down the infected tissue and try to contain the infection. However, these enzymes also lead to the death of the neutrophils themselves, which accumulate and form pus. Therefore, choice E is the best answer to this question.

Question 4

Dendritic cells in the skin, known as Langerhans cells, express very high levels of the NOD-like receptor, NLRP3. Previous studies showed that treatment of these cells with the Staphylococcus aureus pore-forming toxin causes K⁺ efflux from the cells. To investigate whether this signal could induce IL-1 (an inflammatory cytokine) secretion by the cells, the following study was performed: The explanation for these results is:

Accepted Answer

The results suggest that live S. aureus bacteria, which can activate a TLR and NLRP3, can induce IL-1 secretion by Langerhans cells. This is indicated by the fact that live S. aureus bacteria induced IL-1 secretion while S. aureus membrane prep (which does not contain a TLR ligand) did not.

Question 5

A key feature of TLR signaling is the ability to induce inflammatory cytokine gene expression extremely rapidly following TLR stimulation. This is accomplished by signaling pathways using several mechanisms to activate transcription factors that are already present in the cell prior to TLR stimulation, but are kept in an inactive state. These signaling pathways use all of the following mechanisms EXCEPT:

Accepted Answer

The correct answer is E because TLR signaling pathways typically do not use induced phosphorylation to prevent protein degradation as a mechanism to activate transcription factors. Instead, they utilize mechanisms such as induced ubiquitination (for protein degradation or inducing protein-protein interactions), and induced phosphorylation (for nuclear translocation or kinase activation) to activate transcription factors that are already present in the cell in an inactive state.

Question 6

NOD1 and NOD2 are cytoplasmic sensors of bacterial products such as muramyl dipeptide (MDP), a constituent in the peptidoglycans of most bacteria. These sensors are highly expressed in epithelial cells that line the body surfaces that pathogens must cross to establish an infection. Interestingly, a subset of patients with an inflammatory bowel disease called 'Crohn's disease' have inactivating mutations in NOD2. Why might this deficiency in NOD2 lead to chronic inflammation in the gut?

Accepted Answer

The answer of NOD1 and NOD2 are cytoplasmic sensors of...

Question 7

In recent years, several new vaccines have been developed that are made from purified viral surface proteins, rather than intact or live viruses. They are referred to as subunit vaccines. In order to generate a protective adaptive immune response to a subunit vaccine, the viral protein(s) must be mixed with an adjuvant. The adjuvant functions to:

Accepted Answer

Adjuvants stimulate dendritic cells to up-regulate co-stimulatory molecules and migrate to the regional lymph node, where they can present the viral protein to T cells and initiate an adaptive immune response.

Question 8

When stimulated by binding to bacterial products, the fMet-Leu-Phe (fMLF) receptor triggers multiple responses by phagocytes, including migration and induction of antimicrobial activities. Most of these responses are activated by small GTPases of the Rac and Rho families that are indirectly activated by fMLF receptor stimulation. The fMLF receptor can initiate multiple downstream signaling pathways because:

Accepted Answer

The fMLF receptor can initiate multiple downstream signaling pathways because it couples to a heterotrimeric G protein, which has alpha (α) and beta-gamma (βγ) subunits with independent activities. This allows the receptor to activate different signaling cascades through the activation of these distinct G protein subunits.

Question 9

Many different NOD-like receptors, including several with pyrin domains and several with HIN domains, can function to trigger inflammasome assembly leading to the activation of caspase-1. The reason for many different sensors in this innate response system is that:

Accepted Answer

The answer of Many different NOD-like receptors, including several with...

Question 10

Mycobacteria are intracellular pathogens that have adapted to life inside phagocytic cells, such as macrophages. These intracellular bacteria are taken up by phagocytosis, similar to other pathogens, but the bacteria are not killed. One possible mechanism that could account for this immune evasion by mycobacteria is their ability to:

Accepted Answer

Mycobacteria are able to prevent fusion of phagosomes with lysosomes, which would otherwise expose them to the acidic and hydrolytic environment of lysosomes. This allows mycobacteria to survive inside the phagosome and continue to replicate.

Question 11

RIG-I like receptors (RLRs) such as RIG-I, MDA-5, and STING are cytoplasmic nucleic acid sensors. Give two examples of how such innate sensors distinguish between the RNA/DNA of the host from that of an infecting pathogen.

Accepted Answer

The answer of RIG-I like receptors (RLRs) such as RIG-I,...

Question 12

Most normal tissues contain resident macrophages, and connective tissue sites in the gastrointestinal tract and the lung contain large numbers of these cells. Yet the blood also contains a high number of circulating 'classical' monocytes that can differentiate into macrophages after entering tissues. These circulating monocytes function to:

Accepted Answer

Circulating monocytes can differentiate into macrophages after entering tissues and amplify the local innate immune response in the infected tissues. This helps in clearing the infection and promoting tissue repair. Option A is incorrect as monocytes don't phagocytose and kill pathogens in the blood, but they help in clearing pathogens in the infected tissues. Option B is incorrect as endothelial cells themselves have intrinsic phagocytic properties, and monocytes do not line endothelial surfaces. Option C is incorrect as lymph nodes have resident immune cells and do not require patrols from circulating monocytes. Option E is incorrect as dendritic cells are differentiated from monocytes but not during an inflammatory response.

Question 13

Stimulation of the nucleic acid sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. In part, this distinction is based on the different adapter proteins used by the nucleic acid sensing TLRs, leading to the activation of IRF factors. The cytokine response following stimulation of nucleic acid-sensing TLRs is characterized by production of:

Accepted Answer

Stimulation of nucleic acid sensing TLRs leads to the production of type I interferon, which has antiviral activity. This cytokine response is specific to the nucleic acid sensing TLRs and is not produced by stimulation of plasma membrane TLRs.

Question 14

Signaling through the Drosophila Toll pathway is initiated when pathogen recognition receptors (PRRs) bind to microbial products, such as bacterial peptidoglycan. Aspects of this pathway share similarity to the mammalian complement cascade as well as to the innate recognition system based on TLRs. One feature of Toll signaling that resembles the complement pathway is:

Accepted Answer

The activation of an extracellular proteolytic cascade involving cleavage of self-proteins is a feature of both the Toll pathway in Drosophila and the complement cascade in mammals. In both cases, the initial recognition of pathogens leads to the activation of an enzymatic cascade that culminates in the deposition of proteins on the microbial surface to mark them for elimination.

Question 15

As a family, TLRs can recognize PAMPs associated with a broad array of different pathogens, including bacteria, viruses, and fungi. Patients with a specific susceptibility to herpesvirus infections have a defect in their ability to respond to viral nucleic acids using TLR-3, TLR-7, or TLR-9, even though these proteins are expressed in the patients' cells. Analysis of the TLRs in macrophages and dendritic cells from these patients would likely show which of the arrangements in Figure?

Accepted Answer

The answer of As a family, TLRs can recognize PAMPs...

Question 16

The NBT (Nitro Blue Tetrazolium) test is used to diagnose the genetic disorder Chronic Granulomatous Disease (CGD). To perform this test, peripheral blood cells from the patient are stimulated with bacterial extracts, and then incubated with the NBT compound. Normal neutrophils turn blue in this test due to cleavage of the compound, while patient neutrophils remain uncolored, as shown in Figure.  
Name a neutrophil receptor that is likely to be stimulated by the bacterial extract in this assay, and describe how this receptor regulates the activity of the enzyme that cleaves NBT.

Accepted Answer

The answer of The NBT (Nitro Blue Tetrazolium) test is...

Question 17

The first pattern recognition receptor (PRR) important in innate immune responses was discovered in the fruit fly Drosophila melanogaster. Stimulation of this receptor, called Toll, induces:

Accepted Answer

Stimulation of Toll receptor in Drosophila melanogaster induces the production of antimicrobial peptides. These peptides are an important part of their innate immune response and act as a first line of defense against infections.

Question 18

Many of the inflammatory mediators produced by tissue macrophages at sites of infection act on the endothelial cells lining the blood vessel walls. An exception to this is (are) the:

Accepted Answer

The answer of Many of the inflammatory mediators produced by...

Question 19

The inflammatory response is characterized by four classic symptoms: heat, redness, pain, and swelling. In some instances, this response can be triggered by stimuli that are non-infectious such as asbestos, a process known as 'sterile inflammation.' When exposure to the stimulating trigger is persistent, a state of chronic inflammation can result. This process is likely to be detrimental to the health of the host.

Accepted Answer

Chronic inflammation can lead to tissue damage and contribute to the development of many chronic diseases such as arthritis, diabetes, and cancer.

Question 20

Macrophages express multiple types of receptors on their surface that stimulate phagocytosis of microbes, leading to pathogen internalization and destruction. Many of these receptors, such as Dectin-1, rely on direct recognition of a PAMP on the pathogen surface. However, some receptors that stimulate phagocytosis rely on soluble factors (not associated with the phagocyte membrane) to identify and mark the pathogen for uptake by the phagocyte. One such receptor is:

Accepted Answer

The complement receptor on macrophages relies on soluble factors, specifically components of the complement system, to identify and mark pathogens for phagocytosis. This process, known as opsonization, involves the coating of pathogens with complement proteins, which are then recognized by complement receptors on phagocytes, facilitating pathogen uptake and destruction.

Quiz 3: The Induced Responses of Innate Immunity