Questions for Immunology Exam

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A 10-year-old child developed a sore throat and fever over 24 hours. Physical examination shows pharyngeal erythema and swelling. Laboratory findings include leukocytosis. The child is given acetylsalicylic acid (aspirin). Which of the following features of the inflammatory response is most affected by this drug? □ (A) Vasodilation □ (B) Chemotaxis □ (C) Phagocytosis □ (D) Emigration of leukocytes □ (E) Release of leukocytes from bone marrow

(A) Aspirin (acetylsalicylic acid) blocks the cyclooxygenase pathway of arachidonic acid metabolism, which leads to reduced prostaglandin generation. Prostaglandins promote vasodilation at sites of inflammation. Chemotaxis is a function of various chemokines, and complement C3b may promote phagocytosis, but neither is affected by aspirin. Leukocyte emigration is aided by various adhesion molecules. Leukocyte release from the marrow can be driven by the cytokines interleukin-1 and tumor necrosis factor.

A 63-year-old man develops worsening congestive heart failure 2 weeks after an acute myocardial infarction. An echocardiogram shows a markedly decreased ejection fraction. He dies 1 day later. At autopsy, a section of the infarct shows that the necrotic myocardium has largely been replaced by capillaries, fibroblasts, and collagen. Various inflammatory cells are present. Which of the following inflammatory cell types in this lesion plays the most important role in the healing process? □ (A) Macrophages □ (B) Plasma cells □ (C) Neutrophils □ (D) Eosinophils □ (E) Epithelioid cells

(A) Macrophages, present in such lesions, play a prominent role in the healing process. Activated macrophages can secrete various cytokines that promote angiogenesis and fibrosis, including platelet-derived growth factor, fibroblast growth factor, interleukin-1, and tumor necrosis factor. Plasma cells can secrete immunoglobulins and are not instrumental to healing of an area of tissue injury. Neutrophils are most numerous within the initial 48 hours after infarction, but are not numerous after the first week. Eosinophils are most prominent in allergic inflammations and in parasitic infections. Epithelioid cells, which are aggregations of activated macrophages, are typically seen with granulomatous inflammation. The healing of acute inflammatory processes does not involve granulomatous inflammation.

A 78-year-old woman experiences a sudden loss of consciousness, with loss of movement on the right side of the body. Cerebral angiography shows an occlusion of the left middle cerebral artery. To prevent further ischemic injury to the cerebral cortex, which of the following mediators would be most beneficial? (A) Thromboxane A2 (B) Nitric oxide (C) Leukotriene E4

(B) Endothelial cells can release nitric oxide to produce vasodilation. Nitric oxide also can be administered to patients to promote vasodilation in areas of ischemic injury. Thromboxane A2, platelet-activating factor, and leukotriene E4 have vasoconstrictive properties.

A 19-year-old woman with chronic renal failure received a cadaver renal transplantation. One month later, she experienced increasing serum creatinine and urea nitrogen levels, and a renal biopsy was performed. She was treated with corticosteroids, and her renal function improved. Which of the following changes was most likely seen in the biopsy specimen before corticosteroid therapy was initiated? □ (A) Interstitial infiltration by CD3+ lymphocytes and tubular epithelial damage □ (B) Extensive fibrosis of the interstitium and glomeruli with markedly thickened blood vessels □ (C) Fibrinoid necrosis of renal arterioles with thrombotic occlusion □ (D) Interstitial infiltration by eosinophils with tubular epithelial damage □ (E) Glomerular deposition of serum amyloid-associated protein

(A) Acute rejection of kidney transplants occurs weeks, months, or years after transplantation. It is characterized by infiltration with CD3+ T cells that include the CD4+ and CD8+ subsets. These cells damage tubular epithelium by direct cytotoxicity and by release of cytokines, such as interferon-γ, which activate macrophages. The reaction is called acute cellular rejection, and it can be readily treated with corticosteroids. Interstitial and glomerular fibrosis and blood vessel thickening occur in chronic rejection. Fibrinoid necrosis and thrombosis are more typical of hyperacute rejection, which occurs within minutes of placement of the transplant into the recipient. Eosinophils accumulate in acute interstitial nephritis owing to drug reactions. Amyloid derived from serum amyloid-associated protein can occur in chronic infections and inflammation.

A 43-year-old woman has had a chronic cough with fever and weight loss for the past month. A chest radiograph reveals multiple nodules from 1 to 4 cm in size, some of which demonstrate cavitation in the upper lobes. A sputum sample reveals the presence of acid fast bacilli. Which of the following cells is the most important in the development her lung lesions? A Macrophage B Fibroblast C Neutrophil D Mast cell E Platelet

(A) CORRECT. Epithelioid cells and giant cells are derived from activated macrophages. Tissue macrophages are derived from blood monocytes. These cells are important in the development of granulomatous inflammation in the adaptive immune response to tuberculosis. (B) Incorrect. Although collagen is laid down around a granuloma as part of the response, it is not the major component involved in granuloma formation. (C) Incorrect. Although some neutrophils may be present in a granuloma, they are not the major contributors to granuloma formation. (D) Incorrect. Mast cells are few in number. They are involved in release of mediators primarily in acute inflammatory responses. (E) Incorrect. Platelets are mainly involved in coagulation.

A clinical study is performed of patients with pharyngeal infections. The most typical clinical course averages 3 days from the time of onset until the patient sees the physician. Most of these patients experience fever and chills. On physical examination, the most common findings include swelling, erythema, and pharyngeal purulent exudate. Which of the following types of inflammation did these patients most likely have? A Granulomatous B Acute C Gangrenous D Resolving E Chronic

(A) Incorrect. Granulomatous inflammation typically pursues a course over months to years, and the most important inflammatory cell is an activated macrophage. (B) CORRECT. The short course of days and the purulent exudate are typical features of acute inflammation with a neutrophilic response, most often caused by a bacterial organisms such as group A Streptococcus. Lacking evidence for an acute bacterial infection, avoid use of antibiotics. (C) Incorrect. Gangrene refers to extensive inflammation with necrosis involving a whole organ or body part. (D) Incorrect. With complete resolution, the purulent exudate should be removed, and the course to this point would probably be longer. The process may resolve to an abscess, become more chronic, or lead to scarring (E) Incorrect. Chronic inflammation generally pursues a course of weeks. Purulent exudate is not typical for chronic inflammation, where the predominant cell types are mononuclears: lymphocytes, monocyte-macrophages, plasma cells.

A 20-year-old man has experienced painful urination for 4 days. A urethritis is suspected, and Neisseria gonorrheae is cultured. Numerous neutrophils are present in a smear of the exudate from the penile urethra. These neutrophils undergo diapedesis to reach the organisms. Release of which of the following chemical mediators is most likely to drive neutrophil exudation? A Histamine B Prostaglandin C Hageman factor D Bradykinin E Complement

(A) Incorrect. Histamine increases vascular permeability and promotes vasodilation. (B) Incorrect. Prostaglandin is more important as a mediator of inflammation in producing pain, vascular permeability, and vasodilation (C) Incorrect. Hageman factor is Factor XII of the coagulation sequence and is activated by contact with collagen and basement membrane in damaged tissues. (D) Incorrect. Bradykinin, a product of the kinin system and derived from high molecular weight kininogen, causes pain and promotes vasodilation and vascular permeability. (E) CORRECT. The C5a component of complement, along with chemokines, leukotrienes, and bacterial products, is chemotactic for neutrophils.

A 45-year-old man with chronic renal failure received a kidney transplant from his brother 36 months ago. For the next 30 months, he had only minor episodes of rejection that were controlled with immunosuppressive therapy. In the past 6 months, he has had increasing serum creatinine and urea nitrogen levels. On physical examination, he is afebrile. Microscopic examination of a urinalysis specimen shows no WBCs. CT scan of the pelvis shows that the allograft is reduced in size. Which of the following immunological processes most likely accounts for these findings? A. Vascular intimal fibrosis B. Granulomatous vasculitis C. Release of leukotriene C4 from mast cells D. Complement-mediated cell lysis

(A) These findings represent chronic rejection. The progressive renal failure results from ischemic changes with vascular narrowing. Granulomatous inflammation is not typical of transplant rejection. Release of leukotriene C4 from mast cells is a feature of type I hypersensitivity. Complement-mediated cell lysis can occur when antidonor antibodies are preformed in the host, as occurs in hyperacute rejection.

An experiment introduces bacteria into a perfused tissue preparation. Leukocytes leave the vasculature and migrate to the site of bacterial inoculation. The movement of these leukocytes is most likely to be mediated by which of the following substances? □ (A) Bradykinin □ (B) Chemokines □ (C) Histamine □ (D) Prostaglandins □ (E) Complement C3a

(B) Chemokines include many molecules that are chemotactic for neutrophils, eosinophils, lymphocytes, monocytes,and basophils. Bradykinin causes pain and increased vascular permeability. Histamine causes vascular leakage, and prostaglandins have multiple actions, but do not cause chemotaxis. Complement C3a causes increased vascular permeability by releasing histamine from mast cells.

A 53-year-old woman has had a high fever and cough productive of yellowish sputum for the past 2 days. Her vital signs include temperature of 37.8°C, pulse of 83/min, respirations of 17/min, and blood pressure of 100/60 mm Hg. On auscultation of the chest, crackles are audible in both lung bases. A chest radiograph shows bilateral patchy pulmonary infiltrates and fluid in the right pleural cavity. Thoracentesis yields 500 mL of cloudy yellow fluid. Which of the following inflammatory cell types is most likely to be seen in greatly increased numbers in a sputum specimen? □ (A) Macrophages □ (B) Neutrophils □ (C) Mast cells □ (D) Small lymphocytes □ (E) Langhans giant cells

(B) The patient's signs and symptoms suggest acute bacterial pneumonia. Such infections induce an acute inflammation dominated by neutrophils, which gives the sputum its yellowish, purulent appearance. Macrophages become more numerous after acute events, cleaning up tissue and bacterial debris through phagocytosis. Mast cells are better known as participants in allergic and anaphylactic responses. Lymphocytes are a feature of chronic inflammation. Langhans giant cells are seen with granulomatous inflammatory responses.

A 43-year-old man has had a cough and fever for the past 2 days. On examination, he has a temperature of 37.6°C. A blood culture grows Streptococcus, viridans group. His erythrocyte sedimentation rate (ESR) is increased. Microbial cells are opsonized and cleared. Which of the following would be increased and is involved in opsonization? □ (A) Bradykinin □ (B) C-reactive protein □ (C) Interferon-γ □ (D) Nitric oxide □ (E) Prostaglandin

(B) This acute inflammatory process leads to production of acute-phase reactants, such as C-reactive protein (CRP), fibrinogen, and serum amyloid A (SAA) protein. These proteins, particularly fibrinogen, and immunoglobulins increase red blood cell rouleaux formation to increase sedimentation, which is a nonspecific indicator of inflammation. CRP productionis up-regulated by interleukin-6, whereas fibrinogen and SAA are up-regulated mainly by tumor necrosis factor and interleukin-1. Interferon-γ is a potent stimulator of macrophages. Nitric oxide can induce vasodilation or can assist in microbial killing within macrophages. Prostaglandins are vasodilators.

A 60-year-old woman who undergoes a routine health screening examination has a blood pressure of 155/95 mm Hg. She receives antihypertensive therapy that includes hydralazine. Four months later, she develops arthralgias, myalgias, and a malar erythematous rash. Laboratory findings include an ANA titer of 1 : 2560. Anti-doublestranded DNA antibodies are not present. Her physician suspects the drug may be involved in her disease. Which of the following autoantibodies has the greatest specificity for her condition? □ (A) Anti-Sm □ (B) Antihistone □ (C) Anticentromere □ (D) Anti-SS-A

(B) This patient has a drug-induced systemic lupus erythematosus (SLE)-like condition. Drugs such as procainamide, hydralazine, and isoniazid can cause this condition. Test results for ANA are often positive, but test results for anti-doublestranded DNA are negative. Antihistone antibodies are present in many cases. Characteristic signs and symptoms of SLE are often lacking, and renal involvement is uncommon. Remission occurs when the patient stops taking the drug. Anti-Sm antibody shows specificity for SLE. Anticentromeric antibody is most likely to be present with limited scleroderma (CREST syndrome). Anti-SS-A antibody is most characteristic of Sjögren syndrome

A 25-year-old woman has had increasing malaise, a skin rash of her face exacerbated by sunlight exposure, and arthralgias and myalgias for the past month. On auscultation, a friction rub is audible over the chest. Laboratory findings include pancytopenia and elevated serum creatinine 3 mg/dL. Urinalysis shows hematuria and proteinuria. Which of the following mechanisms is most likely involved in the pathogenesis of her disease? (A) Activation of TH17 cells (B) Defective clearance of apoptotic nuclei (C) Decreased production of IFN-γ (D) Molecular mimicry (E) Superantigen activation of T cells

(B) This young woman has a classic picture of systemic lupus erythematosus (SLE)—facial skin rash that is worsened by sunlight and renal failure with proteinuria and hematuria from immune complex deposition in the glomeruli. Defective clearance and hence increased burden of nuclear apoptotic bodies is considered a fundamental mechanism that underlies SLE. This along with loss of self-tolerance to nuclear antigens gives rise to the pathogenic DNA-anti DNA immune complexes. Activation of TH17 cells occurs in many other immunologic disorders such as inflammatory bowel disease. IFNγ is a product of CD4+ T cells and NK cells. There is no evidence of delayed hypersensitivity or NK cell dysfunction in SLE. Molecular mimicry occurs when a microbial antigen cross-reacts with a normal tissue as in rheumatic fever. Widespread and non-specific activation of T cells by superantigens occurs in toxic shock syndrome

A 35-year-old man has had increasing dyspnea for the past 24 hours. A chest radiograph shows large, bilateral pleural effusions. Thoracentesis yields 500 mL of slightly cloudy yellow fluid from the right pleural cavity. Cytologic examination of the fluid shows many neutrophils, but no lymphocytes or RBCs. Which of the following mechanisms contributes most to the accumulation of the fluid in the pleural space? □ (A) Arteriolar vasoconstriction □ (B) Neutrophil release of lysosomes □ (C) Endothelial contraction □ (D) Inhibition of platelet adherence □ (E) Lymphatic obstruction

(C) Exudation of fluid from venules and capillaries is a key component of the acute inflammatory process. Several mechanisms of increased vascular permeability have been proposed, including formation of interendothelial gaps by contraction of endothelium. This is caused by mediators, such as histamine and leukotrienes. The vessels then become more "leaky," and the fluid leaves the intravascular space to accumulate extravascularly, forming effusions in body cavities or edema in tissues. Arteriolar vasoconstriction is a transient response to injury that diminishes blood loss. After neutrophils reach the site of tissue injury outside of the vascular space, they release lysosomal enzymes. Platelets adhere to damaged endothelium and promote hemostasis. Lymphatic obstruction results in the accumulation of protein-rich lymph and lymphocytes, producing a chylous effusion.

A 5-year-old child reaches up to the stove and touches a pot of boiling soup. Within several hours, there is marked erythema of the skin of the fingers on the child's right hand, and small blisters appear on the finger pads. Which of the following terms best describes this process? □ (A) Fibrinous inflammation □ (B) Purulent inflammation □ (C) Serous inflammation □ (D) Ulceration □ (E) Granulomatous inflammation

(C) Serous inflammation is the mildest form of acute inflammation. A blister is a good example of serous inflammation. It is associated primarily with exudation of fluid into the subcorneal or subepidermal space. Because the injury is mild, the fluid is relatively protein-poor. *A protein-rich exudate results in fibrin accumulation.* Acute inflammatory cells, mainly neutrophils, exuded into a body cavity or space form a purulent (suppurative) exudate, typically associated with liquefactive necrosis. Loss of the epithelium leads to ulceration. Granulomatous inflammation is characterized by collections of transformed macrophages called epithelioid cells.

A 20-year-old, sexually active woman experiences lower abdominal pain of 24 hours' duration. She has no previous history of this type of pain. Her temperature is 37.9°C, and on palpation, the left lower abdomen is markedly tender. Laboratory findings include a total WBC count of 29,000/mm3 with 75% segmented neutrophils, 6% bands, 14% lymphocytes, and 5% monocytes. Laparotomy reveals a distended, fluid-filled, reddened left fallopian tube that is about to rupture. A left salpingectomy is performed. Which of the following is most likely to be seen on microscopic examination of the excised fallopian tube? □ (A) Fibroblastic proliferation □ (B) Langhans giant cells □ (C) Liquefactive necrosis □ (D) Mononuclear infiltrates □ (E) Squamous metaplasia

(C) This patient is experiencing an acute inflammatory response, with edema, erythema, and pain of short duration. Neutrophils form an exudate and release various proteases, which can produce liquefactive necrosis, starting at the mucosa and extending through the wall of the tube. This mechanism results in perforation. Fibroblasts are more likely participants in chronic inflammatory responses and in healing responses, generally appearing more than 1 week after the initial event. Langhans giant cells are a feature of granulomatous inflammation. Mononuclear infiltrates are more typical of chronic inflammation of the fallopian tube, in which rupture is less likely. Epithelial metaplasia is most likely to occur in the setting of chronic irritation with inflammation.

A 34-year-old woman has experienced increasing muscular weakness over the past 5 months. This weakness is most pronounced in muscles that are used extensively, such as the levator palpebrae of the eyelids, causing her to have difficulty with vision by the end of the day. After a night's sleep, her symptoms have lessened. On physical examination, she is afebrile. No skin rashes are noted. Muscle strength is 5/5 initially, but diminishes with repetitive movement. Which of the following is the most likely mechanism for muscle weakness in this patient? □ (A) Secretion of cytokines by activated macrophages □ (B) Lysis of muscle cells by CD8+ lymphocytes □(C) Antibody-mediated dysfunction of neuromuscular junction □ (D) Immune complex deposition in muscle capillaries □ (E) Delayed hypersensitivity reaction against muscle antigens

(C) This patient has features of myasthenia gravis, a form of type II hypersensitivity reaction in which antibody is directed against cell surface receptors. Antibodies to acetylcholine receptors impair the function of skeletal muscle motor end plates. Antibodies are produced by B cells, and macrophages are not a significant part of this hypersensitivity reaction; there is little or no inflammation of the muscle in myasthenia gravis.

A 35-year-old woman who has been in the hospital receiving treatment for leukemia has developed an extensive, scaling rash over the past week. A skin biopsy specimen shows keratinocyte apoptosis along the dermal-epidermal junction, with upper dermal lymphocytic infiltrates. She also has jaundice. This patient has most likely recently undergone which of the following procedures? □ (A) Tuberculin skin testing □ (B) Chemotherapy for malignant lymphoma □ (C) Allogeneic bone marrow transplantation □ (D) Penicillin therapy for pneumonia □ (E) Patch testing for allergen detection

(C) This patient has graft-versus-host disease. The engrafted marrow contains immunocompetent cells that can proliferate and attack host tissues, usually skin, liver, and gastrointestinal epithelium. Tuberculin skin testing is a form of delayed-type hypersensitivity. Some chemotherapy agents can produce a drug reaction with more acute inflammation than was described in this case. Urticaria with type I hypersensitivity is a typical reaction to penicillin therapy. Patch testing is done to determine the type of allergens to which atopic individuals may react

A 31-year-old woman notices that when she is outside in the sun for more than 1 hour, she develops a rash on her face. Laboratory studies show hemoglobin, 10.9 g/dL; hematocrit, 32.9%; platelet count, 156,800/mm3 ; and WBC count, 4211/mm3 . Urinalysis shows no blood or glucose; there is 3+ proteinuria. The ANA test result is positive with a titer of 1 : 2048 and a diffuse homogeneous immunofluorescent staining pattern. Which of the following complications is most characteristic of her illness? □ (A) Bronchoconstriction □ (B) Cerebral lymphoma □ (C) Hemolytic anemia □ (D) Keratoconjunctivitis □ (E) Sacroiliitis □ (F) Sclerodactyly

(C) This woman has systemic lupus erythematosus (SLE). Patients with SLE can develop anti-RBC antibodies, which can cause hemolytic anemia. Cytopenias, including leukopenia, thrombocytopenia, and anemia, also are common. Bronchoconstriction is a feature of bronchial asthma and can occur in allergies as a predominantly type I hypersensitivity reaction. Cerebral lymphomas are rare, but may occur in immunodeficient patients, particularly patients with AIDS. Keratoconjunctivitis can be seen in Sjögren syndrome as a result of decreased tear production from lacrimal gland inflammation. Sacroiliitis is a feature of many of the spondyloarthropathies, such as ankylosing spondylitis. Sclerodactyly is seen in scleroderma. When extensive, it is usually part of the spectrum of findings associated with diffuse scleroderma; when it involves only a few areas of the skin (e.g., just the hands), it is more likely to indicate limited scleroderma (CREST syndrome)

A 9-year-old boy has had a chronic cough and fever for the past month. A chest radiograph shows enlargement of hilar lymph nodes and bilateral pulmonary nodular interstitial infiltrates. A sputum sample contains acid-fast bacilli. A transbronchial biopsy specimen shows granulomatous inflammation within the lung, marked by the presence of Langhans giant cells. Which of the following mediators is most likely to contribute to giant cell formation? □ (A) Tumor necrosis factor □ (B) Complement C3b □ (C) Leukotriene B4 □ (D) Interferon-γ □ (E) Interleukin-1

(D) Interferon-γ is secreted by activated T cells and is an important mediator of granulomatous inflammation. It causes activation of macrophages and their transformation into epithelioid cells and then giant cells. Tumor necrosis factor can be secreted by activated macrophages and induces activation of lymphocytes and proliferation of fibroblasts, which are other elements of a granuloma. Complement C3b acts as an opsonin in acute inflammatory reactions. Leukotriene B4 induces chemotaxis in acute inflammatory processes. Interleukin-1 can be secreted by macrophages to produce various effects, including fever, leukocyte adherence, fibroblast proliferation, and cytokine secretion.

A 36-year-old man has had midepigastric abdominal pain for the past 3 months. An upper gastrointestinal endoscopy shows a 2-cm, sharply demarcated, shallow ulceration of the gastric antrum. A biopsy specimen of the ulcer base shows angiogenesis, fibrosis, and mononuclear cell infiltrates with lymphocytes, macrophages, and plasma cells. Which of the following terms best describes this pathologic process? □ (A) Acute inflammation □ (B) Serous inflammation □ (C) Granulomatous inflammation □ (D) Fibrinous inflammation □ (E) Chronic inflammation.

(E) One outcome of acute inflammation with ulceration is chronic inflammation. This is particularly true when the inflammatory process continues for weeks to months. Chronic inflammation is characterized by tissue destruction, mononuclear cell infiltration, and repair. In acute inflammation, the healing process of fibrosis and angiogenesis has not begun. Serous inflammation is an inflammatory process involving a mesothelial surface (e.g., lining of the pericardial cavity), with an outpouring of fluid having little protein or cellular content. Granulomatous inflammation is a form of chronic inflammation in which epithelioid macrophages form aggregates. In fibrinous inflammation, typically involving a mesothelial surface, there is an outpouring of protein-rich fluid that results in precipitation of fibrin.

In an experiment, neutrophils collected from peripheral blood are analyzed for a "burst" of oxygen consumption. This respiratory burst is an essential step for which of the following events in an acute inflammatory response? □ (A) Increased production in bone marrow □ (B) Attachment to endothelial cells □ (C) Opsonization of bacteria □ (D) Phagocytosis of bacteria □ (E) Generation of microbicidal activity

(E) The respiratory, or oxidative, burst generates reactive oxygen species (i.e., superoxide anion) that are important in destruction of engulfed bacteria. Myelopoiesis does not depend on generation of superoxide. Endothelial attachment of neutrophils is aided by adhesion molecules on the endothelium and the neutrophil surface. These molecules include selectins and integrins. Bacteria are opsonized by complement C3b and IgG, allowing the bacteria to be more readily phagocytosed.

A 45-year-old woman has experienced difficulty in swallowing that has increased in severity over the past year. She also has experienced malabsorption, shown by a 5-kg weight loss in the past 6 months. She reports increasing dyspnea during this time. On physical examination, her temperature is 36.9°C, pulse is 66/min, respirations are 18/min, and blood pressure is 145/90 mm Hg. Echocardiography shows a large pericardial effusion. The ANA test result is positive at 1 : 512.Which of the following serious complications of the patient's underlying autoimmune disease is most likely to occur? □ (A) Meningitis □ (B) Glomerulonephritis □ (C) Perforated duodenal ulcer □ (D) Adrenal failure □ (E) Malignant hypertension

(E) This patient has diffuse systemic sclerosis (scleroderma). The small arteries of the kidney are damaged by a hyperplastic arteriolosclerosis that can be complicated by very high blood pressure and renal failure. Meningitis and adrenal failure are not typical features of autoimmune diseases. Glomerulonephritis is a more typical complication of systemic lupus erythematosus. With scleroderma, the gastrointestinal tract undergoes fibrosis, without any tendency to perforation or ulceration.

Which factors require Vitamin K for synthesis?

-Factors II (prothrombin), VII, IX and X. Anticoagulation proteins: proteins C, S -Vitamin K facilitates the calcium binding function of factors II, VII, IX, and X via carboxylation. -If the newborn is not administered Vitamin K after the birth, newborn with Lack of Vitamin K develops severe tendency to bleeding. -Coumarins (Warfarin) inhibits production of Active Vit K.

KNOW THIS:

1) Antigen binding to B cells is most effective at sending an activation signal to the B cell if it causes BCR clustering. 2) CD3 are the signal transduction molecules associated with TCR

KNOW THIS:

1) IgE on mast cells and eosinophils allows those cells to kill helminth parasites.

Match the following anticoagulant factors with the correct mechanisms 1- Tissue factor pathway inhibitor (TFPI) 2- Antithrombin III (AT III) 3- Thrombomodulin 4- Sodium Citrate 5- Protein C a) binds to the trimolecular complex [Tissue factor + factor VIIa + Ca++] in the extrinsic pathway and blocks the protease activity of factor VIIa. b) enhances the binding of Antithrombin III (ATIII) to factor Xa or to thrombin c) forms a complex with thrombin and removes thrombin from the circulation. d) cleaves the cofactors Va and VIIIa. e) chelates calcium ions in the circulation

1-a, 2-b, 3-c, 4-e, 5-d

________ is a derived of aggregated platelets and is involved in the intrinsic and extrinsic mechanisms of blood clotting. A) Prostaglandin I2 B) Platelet Factor 3 C) Thrombin D) Fibrinogen

The anti-rejection drugs cyclosporin A and FK506 block rejection of transplanted organs by interfering with a. activation of a T cell transcription factor (NFAT) required for T cell activation. b. antibody synthesis required for ADCC of transplanted cells. c. CD3 expression. d. MHC Class I expression. e. processing of graft peptides and presentation on Class I MHC.

The most important receptor through which lymphocytes receive life and death signals is a. antigen receptor. b. bcl-2 receptor. c. Fas receptor. d. FcR. e. growth factor receptor.

Which sequence is correct for the following events? 1. fibrinogen → fibrin 2. clot retraction 3. formation of thromboplastin 4. prothrombin → thrombin A) 3, 4, 1, 2 B) 1, 2, 3, 4 C) 4, 3, 1, 2 D) 3, 2, 1, 4

___ are universal recipients who can receive blood from any donor, but can donate only to individuals with their blood type AB RhD+ AB RhD- O RhD+ O RhD- A RhD+

Gamma-delta T cells a. are made before ab T cells during fetal development. b. are more diverse than ab T cells. c. are precursors of ab T cells. d. outnumber ab T cells 19:1 in the spleen. e. probably bind common pathogen peptides on Class II MHC.

A. The earliest T cells seen during fetal life are gamma/delta T cells.

KNOW THIS:

A mature lymphocyte which has specific antigen receptors but cannot respond to that antigen is called anergic

The amount of diversity in TCR generated within one individual by somatic recombination a. is higher than BCR diversity. b. is about the same as for BCR diversity. c. is lower than BCR diversity. d. is lower than Class I MHC diversity. e. is lower than Class II MHC diversity.

Amino acid sequences in lymphocyte signal transduction complexes which are phosphorylated following antigen binding are called a. ITAMs. b. ITIMs. c. MAPs. d. PTKs. e. syks.

FcgRI on binds with highest affinity to a. antigen-bound IgG1 and IgG3. b. complement-activated IgG1 and IgG3. c. free IgE. d. free IgG1 and IgG3. e. None of the above.

In order for NK cells to do ADCC, they must bind a. antibodies to virus proteins expressed on infected cell membranes b. B7. c. CD16. d. toxic oxygen radicals. e. virus peptides expressed on infected cell membrane MHC.

Platelets ________. A) form the initial plug and involved in primary hemostasis B) have a life span of about 120 days C) are the precursors of leukocytes D) have multiple nuclei

Macrophages normally have low levels of B7 and MHC, but express more after they phagocytose a. bacterial antigens. b. peptide antigens. c. Tc cytokines. d. Th cytokines. e. viral antigens.

A. Bacterial antigens are particularly effective in inducing expression of MHC and B7 in all APC. Peptide antigens do not induce MHC and B7 expression.

The antigen-binding region of TCR is formed by the folding of a. Va and Vb chains. b. Va, Vb, and CD3 chains. c. Va and Vb2-microglobulin chains. d. Vg and Va chains. e. VL and VH chains.

A. Beta2-microglobulin is part of Class I MHC and does not bind antigen. CD3 is a signal transducer and does not bind antigen.

A 94-year-old woman has developed a fever and cough over the past 2 days. Staphylococcus aureus is cultured from her sputum. She receives a course of antibiotic therapy. Two weeks later she no longer has a productive cough, but she still has a fever. A chest radiograph reveals a 3 cm rounded density in the right lower lobe whose liquefied contents form a central air-fluid level. There are no surrounding infiltrates. Which of the following is the best description for this outcome of her pneumonia? A. Abscess formation B. Resolution C. Bronchogenic carcinoma D. Granulomatous cavitation

A. CORRECT. The formation of a fluid filled cavity following an infection with S. aureus suggests that liquefactive necrosis has occurred. The cavity is filled with tissue debris and viable and dead neutrophils (pus). Localized, pus filled cavities are called abscesses. The liquified contents seek a level (air-fluid level). B. Incorrect. The inflammation continues, she still has fever and an abnormal chest x-ray C. Incorrect. Neoplasia is not a consequence of acute inflammatory processes. D. Incorrect. Granulomas can become large and cavitate from central caseous necrosis. However, this process takes months. In this case, acute inflammation was complicated by abscess formation with liquefactive necrosis. The most common organism causing pulmonary granulomas is Mycobacterim tuberculosis.

The effector molecules of cytotoxic T cells do NOT include a. Fas. b. granzymes. c. IFNg. d. perforin. e. TNFb.

A. CTL have FasL to allow them to kill Fas+ targets. If CTL have Fas ()which they may), they can themselves become targets.

Macrophage activation by Th1 cells is an important immune mechanism for eliminating a. bacteria which can resist lysosomal degradation. b. bacteria whose capsule makes them resistant to phagocytosis. c. enveloped viruses. d. parasites that infect T cells. e. viruses that infect macrophages.

A. CTL would be required to eliminate parasites.

B cell co-receptor complex CD19, CD22, and CD81 a. allows B cells to be activated with 1,000-fold less complement-coated antigen. b. allows B cells to be activated with 1,000-fold more complement-coated antigen. c. decreases B cell expression of BCR. d. increases B cell expression of BCR. e. prevents B cell activation by self antigen.

A. Cross-linking of CD21 and BCR increases the sensitivity of the B cell to antigen by 1,000 to 10,000 fold.

If IgaIgb cannot be made, B cells a. cannot express BCR. b. cannot express Class II MHC. c. express 1,000-fold less BCR than usual d. synthesize CD3 and become T cells. e. require 1,000-fold more antigen to be activated.

A. Signal transduction molecules must be made for the receptor to be expressed on the membrane. (The same is true for TCR and CD3)

Which of the following properties are NOT shared by TCR and BCR? a. Antigen-binding avidity is increased by the presence of two antigen binding regions on each receptor. b. Antigen-binding diversity is generated through gene rearrangement. c. Folding of protein domains is maintained by intrachain disulfide bonds. d. Membrane expression and lymphocyte activation by antigen require receptors to be associated with signal transduction molecules. e. Receptor antigen-binding sites are formed from two polypeptide chains.

A. TCR has only one antigen-binding region per molecule, while Ig has two.

Th1 cells secrete cytokines which a. activate macrophages. b. increase susceptibility to allergic reaction c. inhibit macrophage secretion of inflammatory cytokines d. stimulate B cells to secrete neutralizing antibodies e. stimulate proliferation of Th2 cells

A. Th1 cytokines stimulate B cells to produce opsonizing antibodies. Th1 cytokines inhibit Th2 cell proliferation.

A T cell which binds antigen without undergoing a co-stimulatory signal from an APC a. becomes inactivated. b. can become a helper cell but not a killer cell. c. can get a co-stimulatory signal from a different APC d. dies. e. divides but doesn't make effector molecules.

A. The technical term is anergy; anergic cells can bind antigen but are not activated by it. A T cell is pre-selected in the thymus to become a Th or a Tc; both of these cells require co-stimulation for activation. Choice C would risk the induction of autoimmunity. For Choice D some probably do die, but not all. Co-stimulation is required to induce proliferation as well as differentiation.

A tyrosine kinase which is activated by antigen binding is found in the __________ of the BCr or TCR complex. a. cytoplasmic domain b. extracellular domain. c. Ig superfamily domain. d. transmembrane domain. e. variable domain.

A. Tryosine kinases are inside the lymphocyte.

A 61-year-old-male underwent deceased donor liver transplantation 3 weeks ago. During his follow up visit he complains of nausea and abdominal pain. He has been taking all of his medications as prescribed. He has a history of alcohol abuse and his last drink was one year ago. He does not smoke cigarettes and lives at home with his wife. On physical examination temperature is 98.6°F (37°C), blood pressure is 115/80 mmHg, pulse is 90/min, respirations are 18/min, and pulse oximetry is 99% on room air. He has scleral icterus and a positive fluid wave. Liver function tests are elevated/abnormal. Liver biopsy shows mixed dense interstitial lymphocytic infiltrates in the portal triad. What is the mechanism of this reaction? A. CD8+ T lymphocytes reacting against donor MHCs B. Pre-existing recipient antibodies C. Acute viral infection D. Grafted T lymphocytes reacting against host

A: This transplant recipient with nausea, abdominal pain, jaundice, and ascites is presenting with acute rejection due to cytotoxic CD 8+ T and CD4 lymphocytes reacting against the foreign MHCs. Acute rejection occurs several weeks to months following transplantation. It is mediated by CD8+ and CD4 T lymphocytes. Patients present with symptoms of fever, jaundice, abdominal pain, and in some cases, worsening ascites. The gold standard for diagnosis is liver biopsy which shows damage to the parenchymal cells and blood vessels with interstitial lymphocytic infiltrates. Incorrect Answers: Answer b: Pre-existing recipient antibodies are responsible for hyperacute rejection which occurs within minutes of the surgery. Answer c: Transplant recipients are particularly at risk for infections due to their immunosuppressive therapies; however, a viral infection would not present with these biopsy findings. Answer d: Grafted T lymphocytes reacting against host are responsible for graft-versus-host disease. While graft-versus-host disease may occur in individuals with liver transplants you would expect to see a maculopapular rash and would not see these biopsy findings. Acute rejection occurs several weeks to months after transplantation and is due to cytotoxic T lymphocytes reacting against donor MHCs.

Which of the following is not a cause of bleeding disorders? A) thrombocytopenia, a condition of decreased circulating platelets B) excess secretion of platelet-derived growth factor (PDGF) C) a defect in the clotting cascade D) vitamin K deficiency

The final common pathway of coagulation involves: A. The degradation of a transglutaminase (Factor XIII). B. Formation of the prothrombinase complex. C. Formation of prothrombin. D. Formation of fibrinogen. E. N-acetylation by Vitamin A.

B- At final common pathway Factor Xa + Platelet Factor 3 (platelet phospholipids) + Factor Va +Ca++ forms the complex called prothrombin activator (prothrombinase complex) that converts prothrombin to thrombin. Factor Va is the coenzyme in this reaction

2) Thromboembolic disorders ________. A) result in uncontrolled bleeding B) include thrombus formation, a clot in a blood vessel C) include embolus formation, a clot moving within the circulatory system D) are caused by vitamin K deficiency

A germinal center is where B cells a. become mature. b. divide in response to antigen. c. first bind antigen. d. secrete antibody. e. undergo somatic recombination.

Answer this Question:

B cells which express Iga with a truncated cytoplasmic domain (lacking the ITAMS) a. become "stuck" in the immature B cell stage of development. b. can express pre-B cell receptor but not proceed to divide and then recombine light chain genes. c. develop normally since Igb has its ITAM sequences. d. express both IgM and IgD but cannot be activated by antigen. e. require more antigen for activation.

IFNg does all of the following EXCEPT a. activate macrophages. b. cut DNA in target cells into 200bp fragments. c. directly inhibit viral replication in infected cells. d. induce macrophages to express higher levels of MHC on their membranes. e. starve intracellular parasites of tryptophan.

One important test to determine whether your patient has been exposed to M. tuberculosis, the organism that causes tuberculosis, is to do a PPD skin test. In this test, PPD extracted from the organism is injected intradermally. Of the following, which one is most likely to occur at the site of a positive PPD? (A) Cytotoxic T cells kill target cells at the site. (B) Macrophages and CD4-positive T cells infiltrate the site. (C) Histamine and leukotrienes are liberated from mast cells at the site. (D) Immune complexes consisting of PPD and IgG are deposited at the site.

Th1 cells promote cellular immunity by secreting primarily a. IL-1 and IL-6. b. IL-2 and IFNg. c. IL-4 and IL-5. d. IL-10 and IL-12. e. TNFa and FasL

The signal transduction molecules associated with BCR are a. CD21 and CD81. b. Ig-alpha and Ig-beta c. IgD and IgM. d. ITAMs and ITIMs. e. RAG-1 and RAG-2

What converts fibrinogen to fibrin? A) prothrombin B) thrombin C) calcium D) thromboplastin

Of the following diseases, which one is most likely to be caused by a delayed hypersensitivity reaction? (A) Autoimmune hemolytic anemia (B) Contact dermatitis, such as poison oak (C) Hemolytic disease of the newborn (D) Poststreptococcal glomerulonephritis (E) Systemic lupus erythematosus

B. D- for dermatitis and delayed hypersensitivity (type IV)

Membrane events required for Th activation include all of the following EXCEPT binding of T cell a. CD4 to APC Class II MHC. b. CTLA-4 to APC B7. c. high affinity IL-2 receptor to IL-2. d. LFA-1 to APC ICAM. e. TCR to peptide on APC Class II MHC.

B. CTLA-4 is expressed by activated T cells.

Different Ig isotypes are found in different body locations because they a. are secreted in different tissues. b. bind to different FcR that allow them to cross tissue barriers. c. have different addressins. d. have different affinities for antigen. e. None of the above is true.

B. Choice A is incorrect because all are secreted in the secondary lymphoid organs, although more IgA is secreted in the MALT.

T cells differ from B cells by expressing a. antigen receptor of only one idiotype. b. antigen receptor of only one isotype. c. RAG-1 and RAG-2 during somatic recombination. d. a surrogate chain before somatic recombination of the second receptor chain is complete. e. signal transduction molecules with their antigen receptor.

B. Mature B cells have both IgM and IgD BCR, while mature T cells have (usually) alpha/beta or (sometimes) gamma/delta TCR.

Armed effector T cells differ from naïve T cells in that effector cells a. are not antigen-specific. b. do not need to bind co-stimulatory molecules. c. do not need to bind peptide plus MHC. d. do not use CAMs to bind other cells. e. have CD28 instead of CTLA-4 to bind B7.

B. No co-stimulation is needed for the effectors to act on target cells. Effectors have CTLA-4 along with CD28.

The humoral immune response to T-independent antigens includes production of a. IgA. b. IgM. c. memory B cells. d. memory T cells. e. all of the above.

B. Only IgM can be made without T cell cytokine signals. Choice C is incorrect because differentiation into memory cells requires T cell help.

T-independent antigens are often a. components of self cell membranes. b. polyclonal B cell activators. c. repeating peptide epitopes d. too small to be phagocytosed and presented. e. none of the above

B. T independent antigens are repeating but are not peptides.

A monoclonal T cell tumor which developed from a normal T cell would NOT express the normal T cell's a. cell surface markers. b. division rate. c. organ location. d. TCR gene rearrangement. e. All of the above would resemble the normal parent cell.

B. The other choices are correct.

T independent antigens do NOT a. bind to BCR. b. get presented on MHC Class II. c. have repeating epitopes. d. induce B cell proliferation. e. provide co-stimulatory signals to B cells

B. They are T independent because they do not activate T cells via presentation on MHC.

The thymic equivalent of the bone marrow stromal cells are the thymic a. dendritic cells. b. epithelial cells. c. hormones. d. macrophages. e. thymocytes.

B. Thymic DC are important for negative selection of T cells.

Light chain rescue a. allows self-specific B cells to repeat somatic recombination of light chain gene segments. b. is a signal received through binding to the surrogate light chain that rescues the developing B cell from death. c. results from multiple V-J joining events on a single chromosome until productive rearrangement of light chain occurs or all J segments have been recombined. d. signals the developing B cell through Ig-alphaIg-beta to begin recombination of light chain gene segments. e. None of the above is true.

C. Choice A represents receptor editing.

Which ONE of the following acts as a cofactor in the coagulation cascade? A. Factor Xa. B. Factor VIIa. C. Factor Va. D. Factor XIIIa. E. Factor VIa.

C- Factor V is a cofactor for the conversion of prothrombin to thrombin by factor Xa

Which one of the following conditions is an X-linked recessive disease that presents with uncontrolled bleeding and lack of Factor VIII? a. Bernard-Soulier syndrome b. Glanzmann thrombasthenia c. Hemophilia A d. Hemophilia B e. von Willebrand disease

C- Hemophilia A is an inherited, X-linked, recessive disorder caused by deficiency of functional plasma clotting factor VIII (FVIII) and is the most common cause of hemophilia. Morbidity and death are primarily the result of hemorrhage. History of hemorrhage disproportionate to trauma, spontaneous hemorrhage, bleeding disorders in the family. Easy bruising, prolonged bleeding. Usually, the activated partial thromboplastin time (aPTT) is prolonged.

Answer this Question:

Cells receive a death signal through a. bcl-2 receptor. b. death receptor. c. Fas. d. Fas ligand. e. STAT ligand.

Cellular immunity includes all of the following except a. activated macrophages killing phagocytosed bacteria. b. CD8 T cells inducing apoptosis using Fas-FasL binding. c. complement-mediated lysis of bacterial cells. d. MHC-restricted cytotoxic T cells killing virus-infected cells. e. NK cells performing natural killing of tumor cells.

Macrophages kill pathogens using all of the following EXCEPT a. nitric oxide. b. oxygen radicals. c. perforins. d. peroxides. e. proteolytic enzymes.

TCR most closely resembles a. Class I MHC. b. Class II MHC. c. Fab region of immunoglobulin. d. Fc region of immunoglobulin. e. light chain of immunoglobulin.

Which chemical initiates the extrinsic phase of clotting? A) fibrin B) fibrinogen C) thromboplastin D) prothrombin

Which statement about B cell development is FALSE? a. Cells which fail to synthesize and express m chains usually die. b. Each DNA joining event in Ig genes has a 67% probability of resulting in a nonproductive rearrangement. c. The earliest developing B cell which could be stained with FITC-anti-meu chain would be a pro B cell. d. The earliest developing B cell which could be stained with FITC-anti- k chain would be an immature B cell. e. The enzyme which can add nucleotides not encoded in the DNA to Ig genes during recombination is TdT.

Atopic individuals (i.e., those with a hereditary predisposition to immediate hypersensitivity reactions) produce an increased amount of IgE. Of the following, which one is the most likely explanation for the increased production of IgE? (A) Large amounts of IL-1 are produced by dendritic cells. (B) Large amounts of IL-2 are produced by macrophages. (C) Large amounts of IL-4 are produced by Th-2 cells. (D) Large amounts of gamma interferon are produced by Th-1 cells. (E) Large amounts of C3a are produced by the alternative pathway of complement.

C. Th2 helper cells lead to a humoral immune response, typically against extracellular parasites including helminths. They are triggered by IL-4 and IL-2, and their effector cytokines are IL-4 etc. The main effector cells are eosinophils, basophils, and mast cells. *If you are double (2) minded then you will go to hell where there are worms/helminths*

Which of the following statements is TRUE? a. Isotypic exclusion on individual B cells pertains to expression of a single heavy chain isotype on each mature naive B cell. b. Pre-B cells must receive a signal from specific antigen binding to pre-B receptor before they can proceed to the next stage in development. c. Membrane meu chain is always expressed with Iga and Igb d. Membrane m chain is always expressed with VpreB and l5. e. Transgenic mice for recombined H and L immunoglobulin genes have germline H and L genes in non-B cells.

C. A cell that cannot make the signal transduction molecules cannot express H chain on its membrane.

T cells are activated to armed effector cells when they encounter antigen on a. blood-borne pathogens. b. bone marrow stromal cells. c. professional APC. d. virus-infected tissues. e. all of the above.

C. APC supply co-stimulatory signals as well as peptides presented on MHC.

B cells differ from the other professional APC because B cells a. activate T cells in the secondary lymphoid organs. b. present exogenous antigen to T cells on Class II MHC. c. present only peptides from antigens they bind with their membrane Ig. d. use B7 as their co-stimulatory molecule. e. None of the above is true.

C. Macrophages and DC present any antigens they engulf; B cells express only the antigens for which their BCR is specific.

Dendritic cells are the best APCs for activating a. CTL. b. helper T cells. c. naïve T cells. d. Th1 cells. e. Th2 cells.

C. Naïve T cells need more co-stimulation than memory T cells, and DC are best for initiating the immune response. CTL are already activated cytotoxic cells.

Successful immune responses to bacteria which adhere to mucosal surfaces in order to initiate infection depends on the production of a. active complement. b. armed effector CTL. c. neutralizing antibodies. d. opsonizing antibodies. e. oxidative burst.

C. Neutralizing antibodies block attachment of pathogens to mucosal surfaces. Successful immune responses to bacterial toxins depend on the production of neutralizing antibodies also.

The a chain of the IL-2 receptor a. causes the receptor to associate with TCR in the T cell membrane. b. changes the specificity of the receptor to bind IFNg. c. increases the affinity of the receptor for IL-2. d. increases the signal transduction ITAMs of the receptor. e. All of the above are true.

C. Resting T cells have low affinity beta/gamma IL-2R.

CD25 is a. a CAM. b. a co-receptor for TCR. c. part of the receptor for IL-2. d. a signal for positive selection. e. a signal transduction molecule for TCR.

C. TCR co-receptors would be CD4 and CD8. CD25 is the high-affinity IL-2 binding part of IL-2R. TCR signal transduction molecules are CD3.

CD8 is a co-receptor on T cells that binds a. CD3. b. endogenous antigen peptide. c. the constant region of Class I MHC. d. the constant region of TCR. e. the variable region of Class I MHC.

C. This binding stabilizes and increased the avidity of the TCR-antigen-MHC interaction.

KNOW THIS:

Chronically infected macrophages may become resistant to activation. Granulomas, giant cells consisting of fused macrophages surrounded by activated T cells, form when intracellular pathogens cannot be eliminated. As cells in the center of the granuloma die, the dead tissue resembles cheese and is called caseous necrosis. The local inflammatory response resulting from activated Th1 cells and macrophages is called Delayed Type or Type 4 Hypersensitivity (DTH). If macrophages express Fas, they can be killed by FasL-expressing Th1 cells.

CD40 on macrophages binding to CD40L on Th1 cells signals the macrophages to a. die. b. kill cytoplasmic viruses. c. phagocytose the Th1 cells. d. respond to IFNg by expressing more membrane MHC. e. secrete IL-2.

How are monoclonal antibodies produced? A. A mouse is injected with an antigen and then antibodies are harvested from its serum. B. They are produced by the human immune system as a natural response to an infection. C. They are produced by a mouse's immune system as a natural response to an infection. D. Antibody-producing B cells from a mouse are fused with myeloma cells and then the cells are grown in tissue culture.

In the problem below dealing with linked T and B cell immune responses to haptens, the investigators chose to look at production of IgG rather than IgM because a. IgG antibodies are easier to detect than IgM. b. IgG is made before IgM in an immune response. c. no IgM antibody can be produced to a hapten. d. production of IgG requires T cell help but production of IgM does not. e. None of the above is true.

NK cells kill their targets in ADCC using a. complement-mediated lysis. b. Fas and FasL. c. oxidative burst. d. perforins and granzymes. e. all of the above.

Which clotting factor is released from damaged tissue, and initiates a chain of clotting events? A) prothrombin B) thrombin C) fibrin D) tissue thromboplastin

D- tissue thromboplastin= factor III = Tissue Factor --> extrinsic factor--> extrinsic pathway

Answer this Question:

Because individual T cells can rearrange more than one a chain, each cell a. can bind multiple antigens. b. can bind both Class I and Class II MHC. c. can participate in both cellular and humoral immunity. d. is not allelically excluded for a chain. e. is not isotypically excluded for a chain

Proliferation of large pre-B cells a. is part of clonal selection. b. makes the pre-B cells more susceptible to apoptosis following self antigen binding c. results in production of many B cells with the same antigen specificity. d. results in the production of many B cells with the same VH chain but different antigen specificities due to different VL regions. e. requires the presence of RAG-1 and RAG-2

Th1 cells make IL-3 and GM-CSF, which a. activate macrophages. b. induce apoptosis in old macrophages. c. stimulate macrophages to kill vesicular pathogens. d. stimulate macrophage production in the bone marrow. e. None of the above is a function of IL-3 and GM-CSF.

The ability of a cytokine to change gene expression in the target cell is influenced by all of the following EXCEPT a. presence of high-affinity receptors on the target cell. b. presence of soluble cytokine receptors. c. proximity of the producing and target cells. d. rate of transport of cytokine-receptor complexes into the cytoplasm. e. simultaneous production of another cytokine whose receptor uses the same signal transducing subunit.

The term "MHC restriction" refers to the a. ability of MHC genes to regulate TCR rearrangement. b. inheritance of a limited number of MHC antigens. c. problems associated with allograft rejection. d. requirement for antigen to be recognized in association with MHC molecules. e. requirement for MHC molecules in order to reject grafts

Double positive T cells express a. both ab and gd TCR. b. both CD3 and CD4. c. both CD3 and CD8. d. both CD4 and CD8. e. TCR of more than one antigen specificity.

D. "Double positive" T cell refers to CD4 and CD8 co-receptor expression.

Cell adhesion molecules (CAMs) a. are found only on bone marrow stromal cells. b. are specific receptors for cytokines that promote cell-cell binding. c. function primarily to hold developing B cells in one location until they are fully developed. d. signal developing B cells to divide and differentiate. e. signal developing B cells to die because they have bound self.

D. Binding of some CAMs on stromal cells and developing B cells, for example SCF and kit, signal the B cell to survive and continue development.

All of the following are true for antigen receptors on both B cells and T cells EXCEPT a. associated with signal transduction molecules in the membrane. b. generated by somatic recombination during lymphocyte development. c. members of the Ig gene superfamily. d. MHC-restricted in their ability to bind antigen. e. specific for a single antigen epitope.

D. Delta segments are within the alpha segment region of TCR genes.

Which of the following statements is FALSE? a. TCR is allelically excluded on individual T cells. b. CD4 and CD8 co-receptors are also signal transducing molecules for T cell activation. c. The arrangement of a chain gene segments most closely resembles that of k chain. d. The gene segments for the d chain are interspersed with those for the g chain. e. The T cells that are most likely to react against allogeneic kidney cells are CD8+ cytotoxic T cells.

D. Delta segments are within the alpha segment region of TCR genes.

An antigen binding signal at the membrane results in the mature B lymphocyte changing its a. antigen-binding specificity. b. color. c. Ig V-D-J gene rearrangement. d. gene expression. e. signal transduction molecules.

D. Genes will be expressed which allow the B cell to divide and differentiate into an antibody-secreting plasma cell. Somatic recombination does not occur after the lymphocyte matures. B cells undergoing somatic mutation in response to antigen MAY change their antigen-binding specificity.

It takes ___________________ after antigen contact before T cells are armed effector cells. a. 5 minutes. b. 30 minutes. c. 24 hours. d. 4-5 days. e. 7-10 days.

D. It takes 5 minutes for armed effector CTL to program targets to commit apoptosis. This includes activation, clonal proliferation, and differentiation into effector cells.

LFA-1 is a(n) a. co-receptor on T cells. b. co-stimulatory molecule on APC. c. cytokine receptor on APC. d. integrin on T cells. e. vascular addressin on HEV.

D. LFA is used by the T cell to bind ICAM-1 on APCs and sample peptides on MHC.

Most of the cells that enter the thymus a. become MHC-restricted ab TCR cells. b. become MHC-restricted gd TCR cells. c. become monoclonal T cell tumors at various stages of development. d. die because they cannot make a self-MHC binding TCR. e. die because they bind self peptide

D. Most T cells fail positive selection.

Successful immune responses to bacteria which resist phagocytosis because of a polysaccharide capsule depends on the production of a. active complement anaphylatoxins. b. armed effector CTL. c. neutralizing antibodies. d. opsonizing antibodies. e. oxidative burst.

D. Opsonizing IgG antibodies allow macrophages to ingest and destroy encapsulated bacteria.

Cytoplasmic signals generated in response to antigen binding and co-stimulatory signals to Tc cells include all of the following EXCEPT a. activation of transcription factors that upregulate synthesis of IL-2. b. aggregation of TCR and CD8 in the T cell membrane. c. increased free intracellular Ca++. d. induction of RAG synthesis. e. tyrosine kinase binding to the cytoplasmic domains of CD3 and CD8.

D. RAG is expressed only during T cell and B cell development.

The step that commits a cell to becoming a gd T cell is a. development outside the thymus. b. expression of more gd than ab receptors on its surface. c. migration out of the thymus to the skin. d. somatic recombination of d chain before a chain. e. somatic recombination of g chain before b chain.

D. Since the gene segments for the two are intermixed on one chromosome, recombination of one blocks recombination of the other.

D. TCR is MHC restricted; BCR is not.

Once H chain genes have been productively rearranged and expressed on the pre-B cell membrane, the next event to occur in the cell is a. death of cells binding self antigen. b. expression of membrane IgD. c. expression of membrane of IgM. d. proliferation of the pre-B cells. e. somatic recombination of light chain genes.

D. The B cell makes a clone of B cells that can use this successfully recombined mu chain with whatever L chain they recombine next.

The step that commits a cell to becoming a T cell is a. expression of CD4 and CD8. b. expression of CD3. c. migration to the thymus. d. somatic recombination of beta chain. e. somatic recombination of alpha chain.

D. The equivalent step in B cells is recombination of H chain.

Antibody-dependent cell-mediated cytotoxicity (ADCC) is a process in which antibody-coated cells are killed by a. the antibodies. b. complement. c. cytotoxic T cells. d. cells with Fc receptors for IgG3. e. cells with Fc receptors for IgE.

D. This includes NK cells, macrophages, and neutrophils.

Once T cells have received antigen plus co-stimulatory signals, they divide in response to IL-2 secreted by a. B cells. b. dendritic cells. c. macrophages. d. themselves. e. whichever APC activated them.

D. This is called autocrine cytokine action. B cells respond to IL-2 rather than synthesize it.

Cells that have just successfully expressed both a and b chains a. are called single positive thymocytes because they have a single specificity of TCR on each cell. b. are all committed to becoming either Th or Tc. c. divide rapidly before undergoing positive selection. d. have lower amounts of membrane TCR than mature T cells. e. have only ab receptors, while mature T cells express ab and gd receptors.

D. This may be important for binding affinity during positive selection.

Alpha chains are rearranged a. after the T cell binds self antigen. b. before g chains. c. before T cells become CD3+. d. in double negative T cells. e. in double positive T cells.

Antigen-binding B cells entering the secondary lymphoid organs initially go to the a. B cell areas where they can bind antigen presented by follicular dendritic cells. b. B cell areas where they can process and present antigen to T cells. c. plasma cell areas where they can secrete antibody. d. T cell areas where they can be the predominant activator of naïve T cells. e. T cell areas where they can find specific helper T cells.

B cell differentiation begins with the expression of a. membrane m chain + surrogate L chain. b. membrane IgD. c. Membrane IgM. d. germline IgM. e. RAG-1, RAG-2 and TdT.

Epithelial cells which secrete IgA to block pathogen entry are NOT found in the a. digestive tract. b. mammary glands. c. respiratory tract. d. salivary glands. e. skin.

Humoral immunity involves all of the following EXCEPT a. antibody-dependent cell-mediated cytotoxicity. b. antibody secretion by plasma cells. c. B cell activation by antigen plus cytokines. d. immunoglobulin isotype switching. e. macrophage activation by Th1 cells

Isotype switching by B cells occurs in response to T cell a. IFNg. b. IL-4. c. IL-5. d. IL-6. e. all of the above.

Of the cells that enter the thymus, ___% become mature naive T cells. a. 100 b. 75 c. 50 d. 33 e. 3

The developmental step that commits a cell to the B lineage is a. expression of both membrane IgM and IgD. b. expression of membrane m chain. c. expression of recombinase enzymes. d. joining of a VH gene segment to a DH gene segment. e. joining of a DH gene segment to a JH gene segment

The surrogate light chain that is expressed with newly rearranged b chain a. binds self MHC. b. can signal the T cell without CD3. c. is CD44. d. is unique for each developing T cell. e. is pTa chain.

Which of the following is the mechanism for citrate's anticoagulative action? a. Activating plasminogen b. Binding factor XII c. Binding vitamin K d. Blocking thrombin e. Chelating calcium

Which one of the following statements about the platelet phase of hemostasis is FALSE? A. Platelets secrete factors that promote primary hemostasis. B. Most clotting factors circulate as inactive precursors. C. Platelets can adhere to collagen via the Von Willebrand Factor. D. ADP, thrombin, and thromboxane A2 can cause platelets to aggregate. E. Platelet GP1b binds fibrinogen

T cells use all of the following for generating antigen-recognition diversity on the TCR, except a. combinatorial association of chains. b. combinatorial association of segments. c. large germline pool of gene sequences. d. N region addition of nucleotides. e. somatic hypermutation.

E. Don't confuse this with somatic recombination.

Affinity maturation of the humoral immune response is due to a. continued stimulation of B cells by high levels of antigen on the FDC. b. DNA recombination by products of the RAG genes. c. isotype switching. d. negative selection of T cells with the lowest helper potential. e. positive selection of B cells with the highest affinity for antigen.

E. Affinity maturation usually occurs as antigen concentrations fall.

Adaptive cell-mediated immunity involves the generation of activated antigen-specific effector. a. antibodies. b. B cells. c. cytokines. d. macrophages e. T cells

E. Although Th2 cells are important for developing humoral immune memory and isotype switching to IgG and IgA, humoral immunity can be transferred with antibodies while effector T cells must be transferred to transfer cellular immunity.

Before a B cell can receive T cell help, the B cell must a. express membrane B7. b. express membrane CD40L. c. express membrane IFNg receptors. d. go to the site of infection. e. process and present peptide on Class II MHC.

E. B is incorrect because B cells express CD40; T cells express the ligand. Interferon gamma is used by Th1 to activate macrophages and so choice C is incorrect. B cells receive T cell help in secondary lymphoid organs. HELP!

Immature B cells which bind soluble self antigen a. become apoptotic. b. escape clonal deletion and can potentially cause autoimmune disease in adults. c. go on to express normal levels of IgM and IgD but cannot respond to self antigen. d. undergo clonal deletion in the bone marrow. e. usually cannot enter the primary lymphoid follicles and soon die in the periphery.

E. B is incorrect because they do escape clonal deletion but have no T cell help to make a strong autoimmune response.

The antigen specificity of Th activation by macrophages is enhanced by the a. ability of each macrophage to present only specific epitopes to T cells. b. binding of T cell adhesion molecules only to macrophages presenting the antigen recognized by the T cell. c. specificity of CD4 binding to Class II MHC on the macrophage. d. upregulation of CD4 or CD8 co-receptors following antigen binding. e. upregulation of co-stimulatory molecules only on macrophages which have contacted foreign antigen

E. CD4 binds to all class II MHC regardless of the peptide presented. CAMS (Cell adhesion molecules) are the same on all macrophages. Macrophages present epitopes of any antigen they engulf. CD4 and CD8 expression is required for effective antigen binding. Co-stimulation in the absence of foreign antigen is low to prevent induction of autoimmunity.

Plasma cells a. are all very long-lived. b. divide and differentiate into memory B cells. c. produce most of their antibody at the site of infection. d. secrete antibodies as long as antigen binds their membrane Ig receptors. e. None of the above are true.

E. Choice C is incorrect because most plasma cells are in the lymph nodes, spleen, and bone marrow.

Interferons a. activate B cells to make virus-specific antibodies. b. are Th2 cytokines. c. are virus proteins that interfere with activation of cytotoxic T cells. d. interfere with virus entry into host cells. e. inhibit virus replication by infected cells.

E. Interferons are made by host cells. For choice D neutralizing antibodies do this.

Isotype switching resembles somatic recombination because both processes a. are catalyzed by the products of RAG-1 and RAG-2. b. are regulated by helper T cell cytokines. c. can result in stop codons in coding sequences. d. occur in developing B cells in the bone marrow. e. result in the irreversible loss of DNA from the B cell.

E. Isotype switching is not catalyzed by the products of RAG-1 and RAG-2. Somatic recombination is not regulated by helper T cell cytokines.

T cells which activate macrophages do all of the following EXCEPT a. activate macrophages at the site of infection. b. activate only macrophages presenting specific antigen on MHC. c. become activated effector cells in response to antigen plus co-stimulation. d. have membrane CD4. e. provide granzymes that the macrophages use to kill vesicular pathogens.

E. Macrophages don't use granzymes but have their own digestive enzymes to kill pathogens.

The immune system of a person who had a mutation in CD3 could NOT fight a viral hepatitis A infection by a. blocking Hepatitis A virus from infecting liver cells with neutralizing IgG antibodies. b. generating cytotoxic T cells to lyse infected liver cells c. lysing virus-infected cells with NK cells. d. phagocytosing complement-opsonized Hepatitis A virus. e. Both 1 and 2 are correct.

E. T cell help is required for B cells to switch to IgG synthesis, and both helper and cytotoxic T cells have CD3.

Which of the following is NOT a similarity between the cellular and humoral immune responses? a. Antigen-specific lymphocytes undergo clonal selection and expansion. b. Cytokine signals promote effector cell differentiation. c. Memory cells are generated. d. Macrophage cytotoxicity is increased. e. Receptor isotype switching occurs.

E. T cells do not change their receptor isotype.

Rearrangement of both TCR and BCR gene segments does NOT a. generate diversity of antigen binding by recombination of a large pool of germline V, D, and J segments. b. lead to CDR3 being the most hypervariable region in the receptor chains. c. require RAG-1, RAG-2, and TdT expression. d. result in allelic exclusion of membrane receptors. e. result in isotype switching after antigen stimulation of the mature lymphocytes.

E. T cells do not undergo isotype switching.

A 37-year-old man has had nausea and vomiting for 5 weeks. He experienced an episode of hematemesis yesterday. On physical examination he has no abnormal findings. Upper GI endoscopy is performed, and there is a 1.5 cm diameter lesion in the gastric antrum with loss of the epithelial surface. These findings are most typical for which of the following pathologic processes? A Abscess B Serositis C Granuloma D Gangrene E Ulcer

E. Ulcer

T cells move from the circulation into the peripheral lymphoid tissues when they bind a. antigen. b. APC. c. B7. d. homing molecules. e. vascular addressins.

E. Vascular addressins on secondary lymphoid tissue HEV signal T cells to leave the circulation. T cells bind antigen, APC, and B7 in the secondary lymphoid tissue. The homing molecules are on the T cells.

Which ONE of the following does NOT contribute to clot formation? A. Calcium. B. Phospholipids. C. Thrombin. D. Tissue factor. E. Heparin.

E: Heparin is an anticoagulant that enhances the binding of Antithrombin III (ATIII) to factor Xa or to thrombin and inhibits the coagulation.

What is the mechanism of action of Heparin?

Enhances the binding of Antithrombin III (ATIII) to factor Xa or to thrombin and inhibits the coagulation.

A polyclonal response to an infection occurs because most antigens have multiple ________.

Epitopes

Which factors will be absent due to lack of the carboxylation reactions in the liver?

FACTOR II, VII, IX, X will not be produced due to lack of Vitamin K which is an important cofactor of carboxylation reactions.

Which of the factors does Coumarin - warfarin work on?

Factor 2, 7, 9, and 10

Which factor is activated by both the intrinsic and extrinsic pathways?

Factor X

For the past 2 days, a 41-year-old man has had a severe headache, and he now has a temperature of 39.2°C. A lumbar puncture is performed, and the cerebrospinal fluid obtained has a very high WBC count with 94% neutrophils and 6% lymphocytes. Which of the following substances is the most likely mediator for the fever observed in this patient? □ (A) Bradykinin □ (B) Leukotriene B4 □ (C) Histamine □ (D) Myeloperoxidase □ (E) Nitric oxide □ (F) Phospholipase C □ (G) Tumor necrosis factor

G) Fever is produced by various inflammatory mediators, but the major cytokines that produce fever are interleukin-1 (IL-1) and tumor necrosis factor (TNF), which are produced by macrophages and other cell types. They mediate the acute phase responses, such as fever, nausea, and neutrophil release from marrow. Bradykinin, generated from the kinin system on surface contact of Hageman factor with collagen and basement membrane from vascular injury, promotes vascular permeability, smooth muscle contraction, and pain. Leukotriene B4, generated in the lipoxygenase pathway of arachidonic acid metabolism, is a potent neutrophil chemotactic factor. Histamine released from mast cells is a potent vasodilator, increasing vascular permeability. Myeloperoxidase is contained within the azurophilic granules of neutrophils and in the presence of halide converts hydrogen peroxide to HOCl−, which destroys phagocytized organisms by halogenation. Nitric oxide generated by macrophages aids in destruction of microorganisms; nitric oxide released from endothelium mediates vasodilation

What is the main platelet receptor that binds Von Willebrand Factor?

GP1b (GP Ib-IX-V) binds vWf during platelet adhesion

What is the main platelet receptor that binds Fibrinogen during platelet aggregation?

GpIIb/IIIa

What are the common names for the following factors. Factor II, VIII, X?

II = prothrombin and prethrombin VIII = antihemophilic factor and platelet cofactor I X = Stuart-Prower factor, Stuart factor, autoprothrombin III

What is the physiologic function of protein C, S, and antithrombin?

Protein C = inactivates Va and VIIIa Protein S = increases rate at which Protein C inactivates Va Antithrombin = inactivates thrombin (IIa) •anti coagulation

For many uses in the laboratory, polyclonal antibodies work well, but for some types of assays, they lack sufficient ________ because they cross-react with inappropriate antigens. • Sensitivity • specificity • accuracy • reactivity

Specificity

In a 6-month randomized trial of a pharmacologic agent, one group of patients receives a cyclooxygenase-2 (COX-2) inhibitor, and a control group does not. Laboratory measurements during the trial show no significant differences between the groups in WBC count, platelet count, hemoglobin, and creatinine. The group receiving the drug reports subjective findings different from those of the control group, however. Which of the following findings was most likely reported by the group receiving the drug? □ (A) Ankle swelling □ (B) Increased bouts of asthma □ (C) Easy bruisability □ (D) Reduced urticaria □ (E) Increased febrile episodes □ *(F) Reduced arthritis pain*

The COX-2 enzyme is inducible with acute inflammatory reactions. The cyclooxygenase pathway of arachidonic acid metabolism generates prostaglandins, which mediate pain, fever, and vasodilation. Ankle swelling is most likely to result from peripheral edema secondary to congestive heart failure. Asthma results from bronchoconstriction mediated by leukotrienes that are generated by the lipoxygenase pathway of arachidonic acid metabolism. Easy bruisability results from prolonged glucocorticoid administration, which also causes leukopenia. Inhibition of histamine released from mast cells helps reduce urticaria. Fever can be mediated by prostaglandin release, not inhibition.

KNOW THIS:

The thymus is a multi-lobed organ composed of cortical and medullary areas surrounded by a capsule. T cell precursors enter the subcapsular cortical areas, where they encounter networks of cortical epithelial calls (the thymic stroma) and undergo a period of proliferation. As they differentiate, they move from the cortex towards the medulla of the thymus

A 26-year-old female undergoes a stem cell transplant for the treatment of non-Hodgkin's lymphoma after several rounds of failed chemotherapy and radiation. One month after undergoing the transplantation, she develops voluminous diarrhea and reports abdominal pain. She describes the stool as green, mucoid, and watery. The patient also complains of recent development of a painful and itchy rash on her forearms. Physical examination is significant for jaundice and hepatosplenomegaly on abdominal palpation. Which of the following best describes the pathogenesis of her current complication? A) ABO blood group incompatibility B) Preformed antidonor antibodies react against the transplanted tissue C) Donor immunocompetent T cells spread in the host and attack 'foreign' proteins on host cells D) Inhibition of calcineurin production, leading to inhibition of secretion of IL-2 E) T-cell mediated vascular damage, leading to obliterative fibrosis

This patient's presentation is suggestive of graft versus host disease. Graft versus host disease is mediated by T cells in the donor tissue that are sensitized to the MHC antigens of the recipient, leading to attack by T cells of 'foreign' proteins on host cells in the irradiated, immunocompromised host. Acute graft versus host disease occurs between the time of the transplant through 100 days post-engraftment. Symptoms include maculopapular rash, jaundice, hepatosplenomegaly, and diarrhea (skin, gut, and liver are predominantly affected). Chronic graft versus host disease, occurring 100 days or more after engraftment, can present with ocular, oral, GI, pulmonary, and/or neuromuscular symptoms. Graft versus host disease affects 40-60% of allogeneic stem cell transplant recipients and is a major cause of morbidity/mortality. Chemotherapy and radiation cause tissue damage, leading to release of inflammatory cytokines. In turn, those cytokines activate T cells that travel to target organs, where they cause organ damage and dysfunction. Incorrect Answers: Answer 1: Although ABO incompatibility may be a risk factor for development of graft versus host disease and increased morbidity/mortality; the pathophysiology behind the condition is better explained as donor T cells attacking cells in the immunosuppressed recipient. Answer 2: Preformed antidonor antibodies react against the transplanted tissue in hyperacute transplant rejection. Answer 4: Inhibition of calcineurin production, leading to inhibition of secretion of IL-2 describes the mechanism of action of the immunosuppresive agent tacrolimus. Answer 5: T-cell mediated vascular damage, leading to obliterative fibrosis describes the mechanism of chronic transplant rejection.

Tissue plasminogen activator (tPA) tPA is produced by the vascular endothelium...what is its function?

Tissue plasminogen activator (tPA) is an extrinsic fibrinolytic enzyme involved in the breakdown of blood clots via catalysis of plasminogen into plasmin

Some factors have a lower case (a) after them in the coagulation cascade, what is denoted by this (a)?

a = activated factor

Which mineral is essential for coagulation to occur? A) Mg2+ B) Ca2+ C) Na+ D) Fe2+

b- Except for the first two steps in the intrinsic pathway, calcium ions are required for promotion or acceleration of all the blood-clotting reactions.

What happens in excess aldosterone?

• Hold on to Sodium ( Na+)=hypernatremia • Low Potassium ( K+)=hypokalemia • High pH (Low H+) loss of H+=metabolic alkalosis

What activates the intrinsic as compared to the extrinsic pathway?

• Intrinsic = Factor XII (Hageman Factor) becomes activated when exposed to collagen in damaged vascular subendothelium or exposed to charged surfaces like glass • Extrinsic = tissue thromboplastin is released from damaged cells and then activates factor VII in the presence of calcium

What stimulates aldosterone secretion?

• Low Na+ in Plasma ( Hyponatremia) • High K+ (Hyperkalemia) • Low blood Pressure • High Angiotensin II, High Renin • Sympathetic nervous system activation

What happens in the absence of aldosterone?

• Na+ Sodium Loss, Hyponatremia • K+ Potassium Retention, Hyperpotassemia=Hyperkalemia • H+ Retention (Metabolic Acidosis)

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