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Toll like receptors (TLR's) are pattern recognition receptors that recognize specific pathogen-associated molecular patterns (PAMP's) on different pathogens and induce an immune response against the foreign pathogen. Numerous immune cell types express TLR's, including antigen-presenting cells and natural killer cells. TLR's play a critical role in the recognition and induction of the immune response against viruses.
A person that has a decreased inherent ability to detect RNA viruses such as influenza and hepatitis would presumably have a defect in which specific TLR?
TLR7 recognizes single-stranded RNA. TLR9 recognizes DNA, TLR4 recognizes lipopolysaccharide, TLR2 recognizes different bacterial components, TLR5 recognizes flagellin.
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The common precursor for all blood and immune cells, including red blood cells and lymphocytes, is found in what part of the body?
All blood cells, including erythrocytes and lymphocytes, come from the same stem cell precursor in the bone marrow. These hematopoietic stem cells give rise to both the myeloid and lymphoid progenitor cells, which are responsible for all blood cells and immune cells. This common precursor spawns cells that then differentiate into the various components of humoral, cell-mediated, and innate immunity.
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Which types of leukocytes are granular?
The five types of leukocytes are: neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Three of these (neutrophils, eosinophils, and basophils) contain granules, tiny sacs containing enzymes which can lyse microorganisms. The other two leukocytes (lymphocytes and monocytes) do not contain these granules.
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Which is not a function of B cells?
B cells play numerous integral roles in the immune response against foreign pathogens (viruses, bacteria, and fungi), including forming transient microenvironments called germinal centers, where they produce long-lived plasma cells that are high affinity for specific antigen and memory B cells. They also serve as antigen-presenting cells and producers of cytokines and chemokines; However, B cells are not able to produce extracellular traps, which primarily are composed of DNA and work to trap pathogens. Neutrophils produce extracellular traps.
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Which of the following group of cells are of the myeloid lineage?
Cells of myeloid lineage include dendritic cells, monocytes, macrophages, neutrophils, basophils, and eosinophils, while cells of lymphoid lineage include NK cells, B cells and T cells.
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Which of the following statements is true?
Naive B cells (and most other immune cell subtypes) need more than one signal to become activated. They normally need B cell receptor signaling (signal 1), costimulation by other receptors (signal 2), and cytokines/chemokines (signal 3). This system is necessary in order to prevent aberrant activation of lymphocytes (safeguard against autoimmunity).
In regards to the other statements, there are numerous autoreactive B cells at any given time due to the stochastic nature of VDJ recombination and germinal center reactions. Therefore, tolerance mechanisms and checkpoints are incredibly important to keep these cells in check; central and peripheral tolerance are equally important. Self-nuclear reactive B cells and T cells are both necessary and critical in autoimmune pathogenesis. Female sex hormones are definitely believed to contribute greatly to autoimmune disease pathogenesis (e.g. estrogen). Over 75% of autoimmune patients are women.
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Which of the following is NOT an antigen presenting cell?
This question asks which of the following is NOT an antigen presenting cell, therefore, any option that is an antigen presenting cell in the immune system is an INCORRECT answer.
During an immune response, the cells involved in antigen presentation are dendritic cells, macrophages, and B-cells. T-cells, then, must be the answer choice that is NOT an antigen presenting cell, and thus is the correct answer.
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Which of the following is not a true statement regarding germinal centers?
T cells, especially CD4+ follicular helper T cells, are absolutely critical and necessary for the induction and maintenance of germinal centers.
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Which cytokine is typically associated with the T helper 1 (Th1) response?
The following helper T cells are paired with the following cytokines:
Th1 - IFN-gamma
Th2 - IL-4
Th9 - IL-9
Th17 - IL-17
Tfh - IL-21
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What is the group of diseases called when a person's immune system loses its ability to recognize its own MHC proteins?
Autoimmunity arises when one's immune system is unable to recognize its own MHC proteins, which could potentially lead to aberrant activation of the immune response. Furthermore, autoreactive immune cells that are normally induced to undergo apoptosis may be able to escape these tolerance mechanisms and induce tissue damage.
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Which of the following class of immunoglobulins is normally responsible for the promotion of the allergy response?
IgE plays a critical role in induction and promotion of type I hypersensitivity (allergy, asthma, etc.) normally through engagement of Fc receptors on the surface of basophils and mast cells, which primes them to produce large quantities of granules and chemical mediators (including histamines and cytokines).
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Which of the following cell types is considered to be part of the innate immune response?
Natural killer (NK) cells are prominent members of the initial innate immune response against foreign pathogens. They play numerous integral roles in the innate response including cytotoxic killing, cytokine production, and antibody-mediated cell cytotoxicity.
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the loss of tolerance to self antigens leading to the presence of high autoantibody titers. There are several underlying causes behind SLE, one of which is a dysregulation in the clearance of apoptotic cells, which can lead to secondary necrosis. This leads to the leakage of danger signals which contributes to the loss of peripheral tolerance and chronic inflammation.
A deficiency in the clearance of apoptotic cells can be attributed to which immune cell type?
The defect in clearance of apoptotic cells in SLE is mainly attributed to macrophages, which serve integral roles in phagocytosis of dead cells and debris. An inability to clear these apoptotic cells over time leads to secondary necrosis, which results in the production and release of several DAMPS or damage-associated molecular pattern molecules which are potent inducers of the immune response.
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Somatic hypermutation of B cell receptor (BCR) genes in immature, developing B lymphocytes generates numerous specificities that are useful against a specific foreign antigen, however the process generates many more specificities that are either low affinity or reactive against self-antigens. Tolerance mechanisms, which include apoptosis or anergy, are in place in the bone marrow to prevent these "non-useful" or "harmful" B cells from exiting. However, these checkpoints are not 100% accurate and numerous B cells with autoreactive BCR's leave and travel to secondary lymphoid tissues.
Tolerance checkpoints exist in secondary lymphoid tissues to purge the repertoire of low-affinity or autoreactive B cells. What is the tolerance checkpoint mechanism in the secondary lymphoid tissues referred to as?
Peripheral tolerance is the correct term for the tolerance checkpoint mechanisms that are instituted in the secondary lymphoid organs such as spleen and lymph nodes. B cells with BCR specificities that are low affinity or reactive against self-nuclear antigen will be purged from the repertoire.
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Bone marrow chimeric mice are an invaluable tool used by immunologists to elucidate specific mechanisms of the immune response. The generation of these chimeras involve whole body irradiation to eliminate the mouse bone marrow followed by adoptive transfer of bone marrow from a donor mouse (usually transgenic).
One critical step in the successful generation of bone marrow chimeric mice involves the depletion of T cells from the donor bone marrow. Which of the following is reason for this necessary step?
T cells from the donor must be depleted due to the risk of incompatible MHC antigens on the recipient cells. If there is incompatibility, the donor T cells will attack and kill the host cells resulting in a graft versus host response.
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Duchenne Muscular Dystrophy is an X-linked recessive genetic disorder, resulting in the loss of the dystrophin protein. In healthy muscle, dystrophin localizes to the sarcolemma and helps anchor the muscle fiber to the basal lamina. The loss of this protein results in progressive muscle weakness, and eventually death.
In the muscle fibers, the effects of the disease can be exacerbated by auto-immune interference. Weakness of the sarcolemma leads to damage and tears in the membrane. The body’s immune system recognizes the damage and attempts to repair it. However, since the damage exists as a chronic condition, leukocytes begin to present the damaged protein fragments as antigens, stimulating a targeted attack on the damaged parts of the muscle fiber. The attack causes inflammation, fibrosis, and necrosis, further weakening the muscle.
Studies have shown that despite the severe pathology of the muscle fibers, the innervation of the muscle is unaffected.
Which of the following does not play a key role in the adaptive immune response?
The adaptive immune response involves the presentation of antigens, identification of antigens, activation of immune response, and elimination of pathogens. Dendritic cells present the antigen to the helper T-cells, which identify it and activate B-cells and cytotoxic T-cells to eliminate the pathogen.
Natural killer cells play a key role in the innate immune response by eliminating pathogens without the recognition of antigens.
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Sexually transmitted diseases are a common problem among young people in the United States. One of the more common diseases is caused by the bacterium Neisseria gonorrhoeae, which leads to inflammation and purulent discharge in the male and female reproductive tracts.
The bacterium has a number of systems to evade host defenses. Upon infection, it uses pili to adhere to host epithelium. The bacterium also uses an enzyme, gonococcal sialyltransferase, to transfer a sialyic acid residue to a gonococcal surface lipooligosaccharide (LOS). A depiction of this can be seen in Figure 1. The sialyic acid residue mimics the protective capsule found on other bacterial species.
Once infection is established, Neisseria preferentially infects columnar epithelial cells in the female reproductive tract, and leads to a loss of cilia on these cells. Damage to the reproductive tract can result in pelvic inflammatory disease, which can complicate pregnancies later in the life of the woman.
A key immune response to Neisseria in humans is the activity of macrophages. What is true of how macrophages combat infection?
Macrophages are professional phagocytic cells. They ingest pathogens, and often use reactive oxygen species to kill pathogens via a burst of radical activity in specialized cellular compartments.
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Scientists use a process called Flourescent In-Situ Hybridization, or FISH, to study genetic disorders in humans. FISH is a technique that uses spectrographic analysis to determine the presence or absence, as well as the relative abundance, of genetic material in human cells.
To use FISH, scientists apply fluorescently-labeled bits of DNA of a known color, called probes, to samples of test DNA. These probes anneal to the sample DNA, and scientists can read the colors that result using laboratory equipment. One common use of FISH is to determine the presence of extra DNA in conditions of aneuploidy, a state in which a human cell has an abnormal number of chromosomes. Chromosomes are collections of DNA, the totality of which makes up a cell’s genome. Another typical use is in the study of cancer cells, where scientists use FISH labels to ascertain if genes have moved inappropriately in a cell’s genome.
Using red fluorescent tags, scientists label probe DNA for a gene known to be expressed more heavily in cancer cells than normal cells. They then label a probe for an immediately adjacent DNA sequence with a green fluorescent tag. Both probes are then added to three dishes, shown below. In dish 1 human bladder cells are incubated with the probes, in dish 2 human epithelial cells are incubated, and in dish 3 known non-cancerous cells are used. The relative luminescence observed in regions of interest in all dishes is shown below.
When the body recognizes that cells have become cancerous, it responds in part by mobilizing cell-mediated killing of cancer cells. What cells are most likely responsible for this killing?
CD8+ T-cells are also called cytotoxic T-cells. They are the main agents of cell-mediated immune cytotoxicity. This function is critical for the elimination of virally infected or cancerous cells. Macrophages, in contrast, are responsible for eliminating foreign pathogens and do not attack non-foreign cells.
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Where do the T-cells of the immune system mature into functional T-cells?
T-cells are originally formed from stem cells in the bone marrow, however, T-cells, unlike B-cells, mature in the thymus. The thymus is a lymphoid organ located in the upper chest.
In contrast, B-cells are formed and mature in the bone marrow.
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Most scientists subscribe to the theory of endosymbiosis to explain the presence of mitochondria in eukaryotic cells. According to the theory of endosymbiosis, early pre-eukaryotic cells phagocytosed free living prokaryotes, but failed to digest them. As a result, these prokaryotes remained in residence in the pre-eukaryotes, and continued to generate energy. The host cells were able to use this energy to gain a selective advantage over their competitors, and eventually the energy-producing prokaryotes became mitochondria.
In many ways, mitochondria are different from other cellular organelles, and these differences puzzled scientists for many years. The theory of endosymbiosis concisely explains a number of these observations about mitochondria. Perhaps most of all, the theory explains why aerobic metabolism is entirely limited to this one organelle, while other kinds of metabolism are more distributed in the cellular cytosol.
Some version of phagocytosis was likely the initial event that introduced a free-living prokaryote into the host described in the passage. Which of the following cells is most commonly associated with phagocytosis?
Neutrophils are professional phagocytes of the immune system. They prevent infection by phagocytosing potential invaders.
Note, however, that neutrophils could not have been the initial cell type to phagocytose a free-living prokaryote. Neutrophils are eukaryotic, and evolved long after endosymbiosis first occurred. They are, however, still closely linked to phagocytosis in humans.
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