Microbiology

Explanation: 👍 The correct answer is B. This boy most likely has Bruton agammaglobulinemia, which results from an X-linked defect in a tyrosine kinase required for the production of mature B lymphocytes. This disease is most often seen in boys (X linked) and is characterized by low levels of immunoglobulin of all isotypes (no mature B lymphocytes to produce the immunoglobulin). T lymphocyte number (CD4+ and CD8+ counts) is unaffected. The condition presents with recurrent bacterial infections after the age of 6 months, when the levels of maternal antibodies decrease.
👎 A is not correct. Ataxia-telangiectasia is a multisystem disorder caused by a defect in DNA repair enzymes. It manifests as neurologic impairment, ataxia, IgA deficiency, and telangiectasias of the eye and skin. CD4+ and CD8+ counts are not typically affected by this disease.
👎 C is not correct. Chronic granulomatous disease (CGD) results from a defect in the phagocytic ability of neutrophils. Therefore patients with CGD are more susceptible to infections by catalase-positive organisms such as Staphylococcus aureus and fungi. This disease does not affect immunoglobulin or T-lymphocyte levels. A rapid screening test for this disorder is a negative nitroblue tetrazolium dye reduction test. Further confirmatory testing for CGD involves immunoblotting and genetic testing.
👎 D is not correct. Job syndrome (hyper-IgE syndrome) is associated with the failure of helper T lymphocytes to produce interferon-y. Affected patients are FATED: coarse Facies, "cold," or noninflamed, skin lesions; Abscesses, retained primary Teeth, high IgE level, and Dermatologic problems (eczema). CD4+ and CD8+ counts are normally unaffected, but a decrease in CD8+ may also be seen.
👎 E is not correct. This answer is incorrect because all immunoglobulin classes are at low levels in this patient. Selective Ig deficiency is due to a defect in isotype switching. The most common selective immunoglobulin deficiency is IgA deficiency, which can lead to sinus and lung infections, diarrhea, and anaphylaxis on exposure to blood products with IgA. T-lymphocyte numbers are normal. 👎 F is not correct. Severe combined immunodeficiency (SCID) may result from a defective interleukin-2 receptor; adenosine deaminase deficiency, or failure to synthesize MHC class II antigens. SCID causes low levels of all immunoglobulin isotypes. It also profoundly reduces T-lymphocytes counts, which is in conflict with the results of flow cytometry in this case.

🔖Practice question #69

A 9-month-old boy is brought to his pediatrician because of fever and a cough. His parents are concerned because he has required antibiotics for several respiratory and ear infections over the past few months.

Serum analysis shows:
IgG: 90 mg/ dL (Normal range: 700-1600 mg/dL)
IgA: 2 mg/ dL (Normal range: 70-400 mg/dL)
IgM: 5 mg/ dL (Normal range: 40-230 mg/ dL)
IgE: Undetectable (Normal range: 0.002-0.2 mg/ dL)

Flow cytometry reveals normal numbers of CD4+ and CD8+ cells.
This patient is most likely suffering from which of the following conditions?

A) Ataxia-telangiectasia
B) Bruton agammaglobulinemia
C) Chronic granulomatous disease
D) Job syndrome
E) Selective immunoglobulin deficiency
F) Severe combined immunodeficiency

Source: usmle_rx_qbank #2017 #immunology

Explanation: 👍 The correct answer is A. This patient has Graves' disease, an autoimmune disorder resulting from IgG-type autoantibodies to the thyroid-stimulating hormone receptor. The three classic findings associated with Graves' disease are hyperthyroidism, ophthalmopathy, and dermopathy/pretibial myxedema. 👎 B is not correct. Hashimoto's thyroiditis is an autoimmune disorder characterized by antibodies attacking thyroglobulin or thyroid peroxidase (the two most common autoantibodies in these patients) or antibodies against another part of the thyroid or thyroid hormone synthesis pathway. Although some cases of Hashimoto's thyroiditis may present as a transient hyperthyroidism (with symptoms including palpitations and increased metabolic rate) from an initial disruption of thyroid follicles, the majority of cases present with signs and symptoms of hypothyroidism, such as intolerance to cold weather, weight gain, and mental and physical slowness.
👎C is not correct. Plummer's disease is characterized by a nodular goiter that has a hyperfunctioning nodule, causing hyperthyroidism. As opposed to Graves' disease, Plummer's disease is not accompanied by ophthalmopathy or dermopathy/ pretibial myxedema.
👎D is not correct. Iodine deficiency causes hypothyroidism, manifested with signs and symptoms that include intolerance to cold weather, weight gain, and mental and physical slowness.
👎E is not correct. Papillary carcinoma of the thyroid, the most common form of thyroid cancer, usually presents as an asymptomatic thyroid nodule with signs of obstruction from the tumor such as hoarseness, cough, dysphagia, or dyspnea or a cervical lymph node mass (as opposed to symptoms of hyper- or hypothyroidism). Radiation is a common cause of thyroid cancer.

🔖Practice question #68

A 34-year-old woman goes to her primary care physician complaining of visual changes and a recent feeling that "her heart was racing." During the interview, the physician notices that the patient is clearly anxious. During the review of systems, the patient reveals a recent unintentional 4 kg (8.8 lb) weight loss. On physical examination, the physician notes that the patient is tachycardic and has 2+ nonpitting edema in her lower extremities. Which of the following is the most likely etiology of this disease?

A) Autoantibodies to the thyroid-stimulating hormone receptor
B) Circulating antibodies to thyroid peroxidase and thyroglobulin
C) Hyperfunctioning thyroid nodule
D) Iodine deficiency
E) Reaction to radiation

Source: usmle_rx_qbank #2017 #immunology

Explanation: 👍 The correct answer is E. The vignette describes a child who is suffering from small bowel intussusception after a recent GI infection. GI infections cause reactive hyperplasia of Peyer's patches which can then serve as lead point for intussusception. Peyer patches are small masses of lymphatic tissue whose function is to survey intestinal bacterial populations and arm the body against overgrowth of pathogenic bacteria. M cells contained within Peyer patches take up antigens and present them to B cells. B cells then form germinal centers and, following CD40L stimulation from T cells, class switch to IgA and differentiate into plasma cells.
👎 A is not correct. Active immunity refers to the immunity that develops in the host due to production of antibodies by "memory" B and T cells in response to a foreign antigen following infection.
👎 B is not correct. Cell-mediated immunity involves phagocytes, cytotoxic T cells and cytokines produced in response to a foreign antigen following infection. Peyer's patches primarily provide defense mechanism against GI luminal bacteria via antibody-mediated rather than cell-mediated immunity.
👎 C is not correct. Activation of the complement cascade in response to the presence of bacteria is an arm of the innate immune response. Peyer's patches do not primarily act by activation of complement.
👎 D is not correct. This describes an autoimmune response, in which the body is unable to discern between self-antigens and foreign antigens. Though it is an important immune function in the body as a whole, it is not the primary function of Peyer's patches.

🔖Practice question #67

A 2-year-old boy presents with his parents to the emergency room with an episode of acute abdominal pain. According to the patient's dad, this is the second such episode today, and the first episode self-resolved within 15 minutes and was accompanied by some bloody stools. Other than a recent stomach bug, the boy is otherwise very healthy. Using abdominal ultrasound, the boy is diagnosed with small bowel intussusception. What is the defense mechanism provided by the tissue that served as lead point for the development of intussusception in this child?

A) Ability to acquire active immunity to transient infections
B) Ability to activate cytotoxic T cells
C) Ability to activate the complement cascade to identify pathogenic bacteria
D) Ability to distinguish between self-antigens and foreign antigens
E) Ability to present antigens to B cells

Source: usmle_rx_qbank #2017 #immunology

Explanation: 👍🏻The correct answer is D. Natural killer (NK) cells possess a variety of genome-encoded receptors, some activating and others inhibitory. Activating receptors signal for NK effector functions, including killing of the target cell. One mechanism that NK cells use to kill target cells is through release of preformed granules (such as perforin and granzymes). This mechanism is identical to that of the CD8+ cytotoxic T-lymphocytes. Both types of cells target virus-infected and neoplastic cells.

👎🏻A is not correct. CD4+ T-lymphocytes (T-helper cells) are a subgroup of lymphocytes that "help" other components of the immune system establish and maximize their killing abilities. By themselves, helper T-cells do not have any cytotoxic or phagocytic activity, but have the unique ability to prime other immune cells to become activated following exposure to antigens.

👎🏻B is not correct. Dendritic cells are professional antigen-presenting cells that are similar to macrophages. They do not kill via the release of preformed granules that trigger apoptosis in target cells.

👎🏻C is not correct. Macrophages are important phagocytic innate immune cells. Additionally, they are professional antigen-presenting cells. Through the respiratory burst and the production of reactive oxygen/nitrogen intermediates, macrophages are capable of killing bacteria. However, they do not kill via the release of preformed granules to trigger apoptosis in target cells.

👎🏻E is not correct. Plasma cells are a mature form of B lymphocytes that do not have any cytotoxic activity. Plasma cells are derived from activated B lymphocytes that undergo class switching and maturation into memory cells (which retain the ability to produce a particular antibody) and plasma cells (which produce immunoglobulins).

🔖Practice question #66

A 67-year-old man with a history of colon cancer presents for follow-up. He states that he is doing well. In addition to the surgical intervention and chemotherapy that the patient has already undergone, the physician explains, his own CD8+ cytotoxic T-lymphocytes are capable of attacking tumors cells. Which of the following cell types possesses a similar killing mechanism as CD8+ cytotoxic T-lymphocytes?

A) CD4+ T-lymphocytes
B) Dendritic cells
C) Macrophages
D) Natural killer cells
E) Plasma cells

Source: usmle_rx_qbank #2017 #immunology

Explanation: 👍🏻The correct answer is B. Anti-IgG autoantibodies, also known as rheumatoid factor; are present in 80% of patients with rheumatoid arthritis (RA). RA is an autoimmune disease leading to inflammation and degeneration of joint spaces. This patient has a classic presentation of RA, with complaints of morning stiffness, bilateral joint pain, and improvement with use. Many patients also have a family history of RA.
👎🏻A is not correct. Anti-double stranded DNA (dsDNA), along with anti-Smith antibodies, are specific for systemic lupus erythematosus. In this autoimmune disorder; patients often develop malar or discoid rashes, photosensitivity, and renal dysfunction. They can also develop arthritis.
👎🏻C is not correct. In patients with rheumatoid arthritis, rheumatoid factor is an IgM against the Fc portion of IgG.
👎🏻D is not correct. Antineutrophil antibodies are implicated in vasculitides such as microscopic polyangiitis and granulomatosis with polyangiitis (formerly called Wegener).
👎🏻E is not correct. Antinuclear antibodies (ANAs) are implicated in a number of autoimmune disorders and are most strongly associated with systemic lupus erythematosus. About 41% of patients with rheumatoid arthritis (RA) are ANA positive. However, the presence of these antibodies does not confirm the diagnosis of RA. Both of these present with renal pathology (hematuria, proteinuria, rapidly progressive glomerulonephritis, renal failure). Granulomatosis with polyangiitis also has respiratory pathology (hemoptysis, perforation of nasal septum, chronic sinusitis, cough, dyspnea).

🔖Practice question #65

A 42-year-old woman presents to her physician with complaints of fatigue and chronic joint pain. The pain is most severe in her hands and knees bilaterally. She has taken acetaminophen without relief. Further questioning reveals she experiences intense joint stiffness in the mornings, but the stiffness improves with use. A positive test for which of the following autoantibodies would confirm the most likely diagnosis?

A) Anti-dsDNA
B) Anti-lgG
C) Anti-lgM
D) Antineutrophil
E) Antinuclear

Source: usmle_rx_qbank #2017 #immunology

Explanation: 👍🏻The correct answer is D. This is a phenomenon known as peripheral tolerance. It is an important factor because deletion of self-reactive T lymphocytes within the thymus ("central tolerance") is not completely efficient at removing all self-reactive T lymphocytes. Thus, one mechanism of peripheral tolerance is that of anergy: When a T lymphocyte receives the first signal (peptide-major histocompatibility complex) but no second signal (costimulation, such as CD28 -B7 ligation), that T lymphocyte undergoes a reprogramming known as anergy, wherein it is subsequently made refractory to any future stimulation. Note that an anergic T lymphocyte cannot be activated later even if costimulation is present.
👎🏻A is not correct. For a T lymphocyte to become activated and fully able to perform its effector functions, it must receive a second or costimulatory signal. Without a costimulatory signal, the T lymphocyte cannot be activated and instead becomes anergic.
👎🏻B is not correct. A T lymphocyte that becomes anergic does not undergo activation.
👎🏻C is not correct. Causing cells to undergo apoptosis is a function of an activated T-cytotoxic lympocyte.
👎🏻E is not correct. The T lymphocyte will not clonally expand. Clonal expansion is more typical of B lymphocytes and requires a costimulatory signal to first activate the lymphocyte.

🔖Practice question #64

A peripheral T-helper lymphocyte engages peptide-bound class II MHC molecules on the surface of an antigen-presenting cell (APC). The only signal received is from the MHC II complex. No other contact is made between cell surface molecules present on the T lymphocyte and the APC. Which of the following can be concluded about this peripheral T lymphocyte?

A) The T lymphocyte will be activated and fully able to perform effector functions
B) The T lymphocyte will be activated but unable to perform effector functions
C) The T lymphocyte will cause the APC to undergo apoptosis
D) The T lymphocyte will undergo anergy
E) The T lymphocyte will undergo clonal expansion

Source: usmle _rx_qbank #2017 #immunology

Explanation: 👍The correct answer is A. CD3 is a cell surface molecule that is expressed by all T-cell subtypes, including both CD4+ and CD8+ T lymphocytes. Although CD8+ T lymphocytes are the main effectors mediating acute allograft rejection and are capable of directly activating graft rejection, CD4+ T lymphocytes also play a role in allograft rejection. CD4+ T lymphocytes recognize alloantigens through an indirect pathway that results in secretion of IL-2. Several studies have shown that collaboration between helper and effector T-cell subsets is required to ensure rejection. Many antirejection drugs target CD3 because it is common to all T-cell types. Anti-CD3 antibodies that bind to CD3 and trigger destruction of both subsets of T lymphocytes (via phagocytosis or complement-mediated lysis) would be most useful in this scenario. Note that monoclonal antibodies may be triggering, depleting, or blocking, and therefore it is absolutely necessary to characterize which of these effector functions they elicit, as those three scenarios would have three very different therapeutic applications.
👎B is not correct. Cytotoxic T lymphocytes express CD8, and helper T lymphocytes express CD4. Although targeting CD4 T lymphocytes may be partially effective, it would be more useful to deplete all T lymphocytes with an anti-CD3 monoclonal antibody.
👎C is not correct. CD14 is a common macrophage cell surface marker. It is used as a receptor to detect lipopolysaccharide on bacteria in order to facilitate an immune response.
👎D is not correct. CD16 is a common natural killer cell surface marker. It is responsible for initiating antibody-dependent, cell-mediated immunity via the CD16 binding to the Fc region of IgG.
👎E is not correct. CD19 is a common B-lymphocyte surface marker along with CD20.

🔖Practice question #63

Acute allograft rejection is mediated by T lymphocytes that recognize and are activated by the major histocompatibility complex proteins expressed by the donated organ. A researcher wants to design a monoclonal antibody that would destroy the cells implicated in immune-mediated graft reaction. Which of the following cell surface molecules should her antibody target?

A) CD3
B) CD4
C) CD14
D) CD16
E) CD19

Source: usmle_rx_qbank #2017 #immunology

👎🏻A is not correct. A dimeric compound held together by a J chain is an IgA antibody. These secretory molecules are found in mucosal surfaces such as the gastrointestinal tract and the oropharynx. Although this patient most likely fought the original Streptococcus infection with these antibodies, they do not participate in the presentation of antigens to the immune system.
👎🏻C is not correct. The complex described here is the major histocompatibility class (MHC) I, a presenting compound of intracellular pathogens. They are present on all nucleated cells in the body and constantly display to the outside world what proteins they are currently producing. In case of viral infection or a malignant process, CD8+ cells are activated by the unknown peptide now displayed on the MHC I molecules and proceed to kill the cell. MHC I compounds play no role in the processing of extracellular pathogens, as is the case in this patient.
👎🏻D is not correct. Two heavy (H) and 2 light (L) chains are the basic structure of all monomeric antibodies. In the sequelae of a streptococcal throat infection, these antibodies, which originally were formed to bind to streptococcal proteins (specifically M protein), now damage tissues in the body with similar surface molecules. Antibodies are produced as a consequence of antigen presentation but do not participate in it.
👎🏻E is not correct. The molecule described here is the CD4 surface marker. The CD4 surface marker is crucial for recognition of the major histocompatibility class II complex by the T-cell receptor. Although it is important in the process of antigen presentation, the CD4 molecule is not the compound actually displaying the fragment of the pathogen.

Explanation: 👍🏻The correct answer is B. This patient has rheumatic fever; the sequela of an infection with Streptococcus pyogenes, also known as "strep throat." This extracellular pathogen is taken up by phagocytosing cells and killed. The bacterial debris is then displayed on the phagocyte's surface to cells of the immune system. Extracellular pathogens are presented on major histocompatibility class (MHC) II, a compound made up of 2a and 2b homogenous peptides. The short peptide displayed on the MHCII is recognized by CD4+ T cells, allowing for a targeted immune response. People with rheumatic fever have developed an immune response to a streptococcal antigen that is similar to human antigens (molecular mimicry), resulting in cross-reactivity and damage to their own tissues. Rheumatic fever is diagnosed when the Jones criteria are met. Patients must have evidence of prior S. pyogenes infection and either 2 major criteria or 1 major and 2 minor criteria. Major criteria are carditis, polyarthritis, chorea (involuntary and irregular movements of the limbs), erythema marginatum, and subcutaneous nodules. Minor criteria are arthralgia, fever; elevated ESR or CRP, and prolonged PR interval on ECG. Patients with rheumatic fever should have long-term treatment with penicillin to prevent reinfection and worsening disease.

🔖Practice question #62

A 17-year-old girl with a recent history of untreated sore throat presents to the physician with acute-onset fatigue, migratory joint pain, and subcutaneous nodules. She recalls a recent bout of sore throat for which she did not see a physician. A new heart murmur is heard on exam. The creation of the high-affinity targeted antibodies that are the culprit in this patient's condition requires T-cell mediated class-switching of B-cells. What is the structure of the molecule that presents the pathogenic antigen to T-cell in order to activate them?

A) A dimeric molecule held together by a J chain
B) A molecule composed of 2a and 2b homogenous peptides
C) A molecule composed of 3a chains and 1b-globulin
D) A molecule with 2H and 2L chains
E) A transmembrane molecule with a short cytoplasmic tail and 4 linearly arranged extracellular domains

Source: usmle_rx_qbank #2017 #immunology

Explanation: 👍🏻The correct answer is E. DiGeorge syndrome results from a failure of the third and fourth pharyngeal pouches to descend and is caused by deletion on chromosome 22 (22q11.2). Failure of the parathyroid glands to develop leads to hypocalcemia, resulting in tetany. The thymus also fails to develop, leading to an immune deficiency of T lymphocytes. The paracortex is the region of the lymph node where T lymphocytes are located. It is atrophied in patients with DiGeorge syndrome. Because of their T-lymphocyte deficiency people with DiGeorge syndrome commonly suffer from viral or fungal infections, such as oral thrush.
👎🏻A is not correct. The capsule encloses the lymph node and is composed of dense irregular connective tissue. The capsule has trabeculae which form outward processes of connective tissue. The capsule is unaffected in DiGeorge syndrome.
👎🏻B is not correct. The follicle of the cortex houses mainly B lymphocytes and is involved in different immune mediated processes. The follicile is unaffected in DIGeorge
syndrome.
👎🏻C is not correct. The medullary cords contain plasma cells and macrophages. As DiGeorge syndrome involves poor T cell functioning, the medullary cords would therefore be unaffected.
👎🏻D is not correct. The medullary sinus are vessels which seperate the medullary cords. The sinuses receive lymph from the cortical sinuses and drains to the efferent lymph vessels. The medullary sinuses are not affected in DiGeorge syndrome.

🔖Practice question #61

A 3-year-old boy presents to the ER with involuntary, sustained muscle contractions in his arms and legs. Serum analysis reveals a calcium level of 3.8mg/dl and decreased immune function. White plaques with surrounding erythema are noted in the patient's oropharynx. The physician is able to scrape the plaques off with a tongue depressor. What region of this patient's lymph node will be atrophied?

A) Capsule
B) Follicle of the cortex
С) Medullary cords
D) Medullary sinus
E) Paracortex

Source: Usmle_rx_qbank #2017 #immunology