UWorld 3/9

Leukotriene B4 stimulates neutrophil migration to sites of inflammation. Other important chemotactic agents include _______

5-HETE (leukotriene precursor), complement component C5a, and IL-8.`

She is admitted to the hospital for severe left leg cellulitis and is started on intravenous cefazolin. Several minutes after the infusion is started, she experiences shortness of breath, diffuse itching, and dizziness. Her blood pressure is 64/38 mm Hg and heart rate is 130/min. On examination, there is a diffuse erythematous skin rash and bilateral wheezing is heard on lung auscultation. Item 1 of 2 Which of the following is most likely to be elevated in this patient's serum as a result of her medication reaction? A. 5-hydroxyindoleacetic acid B. Alkaline phosphatase C. Calcitonin D. Myeloperoxidase E. Tryptase

Anaphylaxis is the result of widespread mast cell and basophil degranulation and the release of preformed inflammatory mediators, including histamine and tryptase. Tryptase is relatively specific to mast cells and can be used as a marker for mast cell activation.

Fluticasone is prescribed. This medication acts primarily by which of the following mechanisms of action? A. Antagonism of leukotriene receptors B. Apoptosis of tissue eosinophils C. Elimination of circulating IgE D. Induction of CD4+ regulatory T cells

B. Apoptosis of tissue eosinophils Glucocorticoids inhibit transcription of proinflammatory mediators and promote apoptosis of eosinophils, T cells, and monocytes. This patient with allergic rhinitis has been prescribed fluticasone, an intranasal glucocorticoid. Glucocorticoids bind to cytoplasmic receptors and translocate to the nucleus where they inhibit transcription of genes that encode inflammatory mediators and decrease immune cell survival and propagation. This results in wide-ranging effects that suppress the function of all leukocyte cell lines, including the following: Decreased tissue production of proinflammatory prostaglandins and leukotrienes through the inhibition of phospholipase A2 Decreased synthesis of almost all proinflammatory cytokines, with increased anti-inflammatory cytokine (eg, IL-10) production Impaired macrophage activation and neutrophil emigration Increased apoptosis of eosinophils, T cells, and monocytes, perhaps by decreasing Bcl-2 expression Glucocorticoids also act on nonimmune cells in the nose (including epithelial cells, goblet cells, and vascular endothelial cells) to decrease uptake of allergen particles, decrease mucus production, and decrease vascular permeability.

After a confirmatory biopsy, treatment with rituximab infusion is planned. This medication is most likely to improve this patient's condition via which of the following mechanisms? A. Blockade of T-cell costimulation B. Depletion of B cells C. Disruption of leukocyte migration D. Inhibition of cytoplasmic kinase E. Interruption of cytokine function

B. Depletion of B cells Rituximab is an IgG monoclonal antibody against CD20, a surface molecule present on developing and mature B cells. Binding of rituximab to CD20 results in Fc receptor-mediated B-cell cytotoxicity and antibody-dependent B-cell phagocytosis, which significantly reduces the B-cell population. Although existing plasma cells are unaffected (they do not express CD20), the reduction in total B-cell population significantly improves inflammatory symptoms. However, depletion of B cells also increases the risk for severe and recurrent bacterial infections, a major adverse effect of therapy.

The patient's anaphylactic reaction is determined to be mediated by antigen-specific IgE antibodies attached to high-affinity receptors on the surface of mast cells and basophils. Which of the following mechanisms is most likely to trigger vasoactive substance release by these cells? A. Antibody-receptor covalent binding B. Antibody-receptor dissociation C. Receptor aggregation D. Receptor detachment from the cell surface E. Receptor internalization

C. Receptor aggregation The high-affinity IgE receptor (FcεRI) is found on mast cells and basophils and plays a primary role in mediating the allergic response. The receptor normally binds the Fc portion of circulating IgE, coating the cell with various antigen-specific IgE molecules. When a multivalent antigen comes in contact with the cell, multiple IgE antibodies become cross-linked, resulting in aggregation of the FcεRI receptors on the mast cell surface. This clumping of receptors leads to the activation of non-receptor tyrosine kinases, triggering an intracellular cascade that ultimately results in mast cell and basophil degranulation.

Steroid hormones, thyroid hormone, and vitamin____ act by binding to intracellular receptors with DNA-binding domains that interact with the regulatory DNA sequences of target genes.

D

A 55-year-old man with end-stage hepatitis C virus infection undergoes orthotopic liver transplantation from a deceased donor. The patient has no perioperative complications and is discharged from the hospital on appropriate immunosuppressant medications. One week after the surgery, he develops nausea, vomiting, abdominal pain, and bloody diarrhea. Physical examination shows a painful maculopapular rash over his neck, back, and extremities that extends to the palms and soles. Endoscopic evaluation reveals multiple ulcerations of the intestinal mucosa. Which of the following is the most likely cause of this patient's current condition?

Graft T cell sensitization against host MHC antigens This patient most likely has graft-versus-host disease (GVHD), a condition that usually occurs after allogeneic bone marrow transplantation. However, GVHD can also occur following transplantation of organs rich in lymphocytes (eg, liver) or transfusion of non-irradiated blood. Patients affected by GVHD are generally severely immunodeficient due to the primary disease process or as a result of immunosuppressive medications. This allows immunocompetent donor T cells from the graft to survive and migrate into host tissues, where they recognize host MHC antigens as foreign and become sensitized. On activation, donor CD4+ and CD8+ T cells (not B cells) participate in host cell destructi

The lepromin skin test will be positive in patients with tuberculoid leprosy as they exhibit a strong CD4+ TH1 cell-mediated immune response to Mycobacterium leprae. Patients with lepromatous leprosy will test negative due to their weak TH1 cell-mediated immune response. Patients with tuberculoid leprosy develop a strong TH1-mediated response (interleukin ______, ______, _____) in affected tissues, leading to the activation of macrophages that kill M leprae organisms, thereby limiting disease extent. However, this localized inflammation damages the skin and cutaneous nerves, leading to the development of a small number of hypopigmented, well-demarcated plaques with decreased sensation

IL-2, IFN-γ, and IL-12)

Lepromatous leprosy is a more disseminated form of the disease characterized by an innate inability to recognize and mount a cellular immune response against M leprae antigens. Affected tissues show extensive accumulation of acid-fast bacilli within macrophages and often a TH2 cytokine profile (IL _____,_____,_____). Patients with lepromatous leprosy develop more numerous, poorly demarcated plaques that are widespread across the body. Over time, the bacterial load increases and the nodular lesions coalesce, causing the development of leonine facies and degeneration and loss of the nose and digits.

IL-4, IL-5, and IL-10

Which of the following hormones binds to an intracellular receptor to help maintain this patient's laboratory findings (blood glucose) within the normal range? A. Cortisol B. Epinephrine C. Glucagon D. Growth hormone E. Insulin F. Norepinephrine

In a fasting state, glucagon and epinephrine bind to transmembrane receptors and prevent hypoglycemia by increasing hepatic glycogenolysis and gluconeogenesis. Prolonged fasting increases the secretion of cortisol, a steroid hormone that binds to an intracellular receptor and acts to increase transcription of enzymes involved in gluconeogenesis, lipolysis, and proteolysis. (Choices B, C, and F) Catecholamines (eg, epinephrine, norepinephrine) and glucagon attenuate hypoglycemia. However, they exert their metabolic effects via extracellular, transmembrane, G protein-coupled receptors that activate adenyl cyclase and increase cyclic AMP production. (Choice D) Growth hormone acts via an extracellular, transmembrane receptor that activates a JAK-STAT pathway. Growth hormone antagonizes insulin action, increases gluconeogenesis, and promotes lipolysis (provides gluconeogenic substrates). (Choice E) In addition to the production of counterregulatory hormones, the inhibition of insulin release from pancreatic beta cells plays a primary role in preventing hypoglycemia during fasting. However, insulin acts on a extracellular transmembrane receptor with intrinsic tyrosine kinase activity.

Acute phase reactants (APRs) are proteins whose serum concentrations change by ≥25% during periods of inflammation. Several APRs have diagnostic and prognostic utility and can be interpreted on the basis of serum concentrations: Negative APRs (serum levels fall in acute inflammatory states) include

Negative APRs (serum levels fall in acute inflammatory states) include albumin, transferrin, and transthyretin (prealbumin).

Bacterial invasion of the intestinal mucosa by (3) causes...

Salmonella, enteroinvasive E coli (EIEC), and Campylobacter jejuni causes inflammatory/bloody diarrhea

_____ is a life-threatening immunodeficiency syndrome that presents in infancy. It is caused by a variety of mutations in different genes that result in impaired T and B cell development and function. This leads to compromised cell-mediated and humoral immunity with the eventual development of severe viral and bacterial infections as maternal immunity wanes. Other common features include mucocutaneous candidiasis, persistent diarrhea, and failure to thrive. Laboratory studies show very low or absent CD3+ T cells and hypogammaglobulinemia. Thymic hypoplasia or aplasia is another common finding in infants with ____ due to severe T cell deficiency.

Severe combined immune deficiency (SCID)

The majority of patients with DH exhibit the small-bowel histologic findings of celiac disease, which include: (3)

Small bowel intraepithelial lymphocytosis Crypt hyperplasia (elongation) Progressive villous atrophy (height shrinkage)

IL-4 is a cytokine produced by _____that

TH2 cells activates B cells, induces IgE isotype switching, and promotes TH2 cell differentiation.

The tapeworm Echinococcus granulosus is the most common cause of hydatid cysts. What do they look like? When infection occurs, echinococcal larvae implant within the capillaries, triggering an inflammatory reaction involving monocytes and eosinophils. Some larvae encyst. Microscopic examination demonstrates an encapsulated and calcified cyst ("eggshell calcification") containing fluid and budding cells that will eventually become daughter cysts. The outer wall is composed of gelatinous sheets surrounded by a thick fibrous capsule. Imaging (ultrasound, CT, MRI) and serology testing can be used for diagnosis.

The tapeworm Echinococcus granulosus is the most common cause of hydatid cysts. Most cases occur in individuals from endemic regions (eg, eastern Mediterranean, Middle East, South America, sub-Saharan Africa, former Soviet Union, western China) or those residing in the southwestern United States with sheep and dog (participate in the tapeworm life cycle) exposure. Initial infection is generally asymptomatic, with subsequent manifestations depending on cyst location and size. The liver is often affected (leading to hepatomegaly or right upper quadrant pain), but other organs such as the lungs or muscles can be involved. Unilocular lesions are typical of E granulosus, and multilocular lesions are typical of E multilocularis. When infection occurs, echinococcal larvae implant within the capillaries, triggering an inflammatory reaction involving monocytes and eosinophils. Some larvae encyst. Microscopic examination demonstrates an encapsulated and calcified cyst ("eggshell calcification") containing fluid and budding cells that will eventually become daughter cysts. The outer wall is composed of gelatinous sheets surrounded by a thick fibrous capsule. Imaging (ultrasound, CT, MRI) and serology testing can be used for diagnosis. Depending on the size of the cyst, surgery and adjunctive chemotherapy (eg, albendazole) are the treatment of choice for symptomatic patients. Cyst manipulation (eg, surgery, aspiration) should be performed with caution, as spilling of cyst contents can cause anaphylactic shock, which likely occurred in this patient.

A 44-year old man with diabetic nephropathy undergoes a renal transplant. One week later, he develops low-grade fever, body aches, and decreased urine output. Temperature is 37.2 C (99 F), blood pressure is 124/76 mm Hg, and pulse is 88/min. Physical examination shows mild tenderness over the graft on palpation. Serum creatinine is 2.2 mg/dL, an increase from 1.2 mg/dL two days ago. Arterial and venous Doppler studies reveal adequate graft perfusion. Graft biopsy demonstrates dense interstitial infiltration by mononuclear cells. Which of the following is the most likely cause of this patient's current condition? A. Graft B-cell sensitization against host MHC antigens B. Graft T-cell sensitization against host MHC antigens C. Host B-cell sensitization against graft MHC antigens D. Host T-cell sensitization against graft MHC antigens E. Preformed antibodies against graft ABO antigens

This patient with impaired renal function within the first few weeks following renal transplant likely has acute rejection. This process is mostly cell-mediated and results from sensitization of recipient T cells to donor graft MHC antigens (human leukocyte antigens). Humoral (antibody-mediated) immunity may also be involved in acute rejection, but it typically plays a smaller role. Acute rejection usually occurs within the first 6 months following transplantation. Patients often have an asymptomatic rise in serum creatinine, but they may also have low-grade fever, malaise, joint pains, and graft tenderness. Histology reveals a dense lymphocytic infiltrate sometimes accompanied by vascular inflammation. Acute rejection is typically reversible and usually treated with high-dose glucocorticoids. Chronic immunosuppression with a calcineurin inhibitor-based regimen (eg, tacrolimus plus mycophenolate and low-dose prednisone) helps prevent acute rejection episodes.

Normally, wound contraction, a normal part of the proliferative phase of wound healing, involves contraction of actin in myofibroblasts to approximate wound edges. ________ promotes differentiation of fibroblasts into myofibroblasts and should diminish on completion of wound repair. In keloids, _____ is produced excessively without regulation. As a result, keloids extend beyond the borders of the original wound, do not regress, and often recur after resection. They arise following minor (eg, ear piercing) or major (eg, full-thickness burn) trauma and can be raised, painful, and pruritic.

Transformation growth factor-beta (TGF-β) TGF-β

Transmembrane ligand-gated ion channels (ionotropic receptors) allow a regulated flux of calcium, sodium, potassium, and chloride ions across the cell membrane. Neurotransmitters that work via ion channel-linked receptors include

acetylcholine, serotonin, N-methyl-D-aspartate, and gamma-aminobutyric acid.

Interferon gamma (IFN-γ)

activates macrophages, increases MHC expression, and promotes TH1 cell differentiation. It is produced primarily by activated T cells and natural killer cells.

Alanine and glutamine play an important role in transporting nitrogen throughout the body. Glutamine is produced by most body tissues and is catabolized primarily by the gut and kidney for maintenance of cellular metabolism and acid-base regulation, respectively. A significant portion of the glutamine used by these tissues is converted to_____ and released into the circulation.

alanine

A 36-year-old man comes to the office due to a 2-month history of a pruritic rash over the elbows and knees. The patient has been using skin emollients, but the lesions have not improved. He also has a prolonged history of episodic abdominal discomfort, flatulence, and voluminous greasy stools. Cardiopulmonary examination is normal. The abdomen is soft and nontender. Skin examination shows a papulovesicular skin rash in groups with erosion and excoriations. Which of the following is most likely to be seen in this patient?

alarm bells should be going off for celiac with dermatitis herpetiformis! Increased intestinal intraepithelial lymphocytes

Echinococcus granulosus- Depending on the size of the cyst, surgery and adjunctive chemotherapy (eg, albendazole) are the treatment of choice for symptomatic patients. Cyst manipulation (eg, surgery, aspiration) should be performed with caution, as spilling of cyst contents can cause _______

anaphylactic shock, which likely occurred in this patient.

Axillary lymph node dissection is a risk factor for the development of chronic lymphedema involving the ipsilateral arm. Chronic lymphedema predisposes to the development of

angiosarcoma (Stewart-Treves syndrome) - multiple firm violaceous nodules on her right upper arm.

The patient appears ill. Blood cultures grow motile gram-positive rods that produce a very narrow zone of beta hemolysis on blood agar. The bacteria are also found to grow well at refrigerated temperature. Which of the following processes is most important for eliminating these bacteria from the body? Cell-mediated immunity Eosinophil action Immunoglobulin secretion Mast cell activation Terminal complement cascade

cell mediated immunity Listeria monocytogenes is a facultative, intracellular, gram-positive rod that produces a very narrow zone of beta hemolysis on blood agar, shows tumbling motility at room temperature, and can grow at refrigerated temperatures. Intracellular pathogens such as Listeria are largely eliminated by the cell-mediated immune response (eg, T-cells, macrophages, cytokines). Patients with impaired cell-mediated immunity are at risk for invasive Listeria infections

A 45-year-old man comes to the office with groin pain and swelling. About a month ago, he noticed a sore on his penis but did not seek medical attention because the ulcer was not painful and disappeared within a week. Several days ago, he began to experience painful swelling in his inguinal region, with inflammation of the overlying skin and eventual formation of several draining ulcers. He also has mild fever and malaise that began around the same time as his groin symptoms. The patient is a sailor. His other medical problems include well-controlled hypertension and hyperlipidemia. Cell scrapings from his lesions show cytoplasmic inclusion bodies. Which of the following is the most likely cause of this patient's condition?

chlamydia trachomatis (LGV)

Chronic lymphedema is a risk factor for the development of

cutaneous angiosarcoma, also known as Stewart-Treves syndrome. Radical mastectomy with axillary lymph node dissection is a classic predisposing procedure, although any form of chronic lymphedema can be implicated. Histopathologically, angiosarcoma will show infiltration of the dermis with slit-like abnormal vascular spaces. The prognosis for patients with angiosarcoma is poor because the tumor is usually widespread by the time of diagnosis. There is controversy regarding use of the term angiosarcoma versus lymphangiosarcoma, as it appears that this entity arises from blood vessels rather than from lymphatic vessels.

EM represents a cell-mediated immune process, with an inflammatory infiltrate predominated by ______. EM is most frequently associated with infections (especially herpes simplex virus and mycoplasma) and may be due to an immune response against antigens deposited in the skin. EM can also be seen in association with certain medications (eg, sulfonamides), malignancy, and collagen vascular diseases.

cytotoxic CD8+ lymphocytes

This patient's rapidly growing lesion is consistent with an infantile hemangioma, a common, benign vascular tumor characterized by neoplastic proliferation of _____ cells. Infantile hemangiomas occur most often on the head or neck. They present within weeks of birth as a solitary red papule or nodule. The lesion shows characteristic rapid growth for several months followed by spontaneous, gradual regression over several years.

endothelial

Enterotoxin production within the intestine by

enterotoxigenic Escherichia coli (ETEC) and Vibrio cholera, whose toxins cause watery diarrhea, and enterohemorrhagic E coli (EHEC) and Shigella, whose toxins cause inflammatory/bloody diarrhea

Janus kinase (JAK) is a cytoplasmic protein activated by ligand binding to transmembrane receptors. JAKs activate cytoplasmic transcription factors called signal transducers and activators of transcription (STAT), which enter the nucleus to promote gene transcription. Examples of hormones using a JAK/STAT messenger system include

erythropoietin, growth hormone, and prolactin.

Keloids result from ______ during the remodeling phase of wound healing. They present as raised, painful, and pruritic nodules that grow beyond the wound borders.

excessive collagen formation Excessive collagen formation during the remodeling phase of wound healing can result in a keloid or hypertrophic scar. Keloids and hypertrophic scars consist of connective tissue rich in fibroblasts, myofibroblasts, and bundles of collagen fibers that are arranged in a disorganized fashion (black arrow) in keloids and in parallel in hypertrophic scars.

Accessory nipples are the most common congenital breast anomaly resulting from

failed regression of the mammary ridge in utero. They are usually asymptomatic but can become tender along with breast tissue during times of hormonal fluctuation.

Acute phase reactants (APRs) are proteins whose serum concentrations change by ≥25% during periods of inflammation. Several APRs have diagnostic and prognostic utility and can be interpreted on the basis of serum concentrations: Positive APRs (serum levels rise in acute inflammatory states) include

fibrinogen, C-reactive protein, ferritin, hepcidin, ceruloplasmin, haptoglobin, von Willebrand factor, and complement. The erythrocyte sedimentation rate (the time required for erythrocytes to settle from suspension) is an indirect measure of positive APRs.

The pathogenesis of DH is associated with that of celiac disease. Following absorption of dietary gluten,

gliadin is deaminated by tissue transglutaminase in a process involving formation of covalent crosslinks between the two. Because of this, the subsequent immune response against gliadin also targets tissue transglutaminase, leading to the production of IgA and IgG tissue transglutaminase autoantibodies. In the skin, these antibodies cross-react with epidermal transglutaminase, and the resulting inflammation leads to the characteristic manifestations of DH.

Foreign bodies (eg, retained sutures) can elicit a ____ response

granulomatous response, seen clinically as a tender, erythematous, brown or purple papule, nodule, or plaque. Granulomas are characterized microscopically by aggregates of activated macrophages that assume an epithelioid appearance. They are often surrounded by a rim of lymphocytes that synthesize the cytokines responsible for granuloma maintenance. Multinucleated giant cells, derived from the fusion of several macrophages, can also be found in granulomas. Granuloma formation is a complex process that occurs over several days to weeks in response to an antigen that cannot be eradicated by more acute inflammatory mechanisms (eg, killing by neutrophils). As infiltrating macrophages engulf the antigenic debris, material resistant to digestion persists in the cytoplasm and causes macrophage activation. This results in further macrophage maturation and formation of a granuloma, which walls off the offending agent.

Complement components C3a, C4a, and C5a are inflammatory anaphylotoxins that trigger_____

histamine release from mast cells, resulting in vasodilation and enhanced vascular permeability.

Lichen planus presents with pruritic, purple/pink, polygonal papules and plaques that can affect the flexural surfaces of the wrists and ankles, along with the nails, oral mucous membranes, and genitalia. Histologic findings include

hyperkeratosis (thickening of stratum corneum), lymphocytic infiltrates at the dermoepidermal junction, hypergranulosis (prominent granular layer), sawtooth rete ridges, and scattered eosinophilic colloid bodies.

During infection, macrophages and surrounding endothelial cells release cytokines such as _____ that trigger neutrophils to enter the site of infection via chemotaxis.

interleukin-8 (IL-8) IL-8 also induces phagocytosis in neutrophils once they have arrived.

This patient's flow cytometry shows normal numbers of CD3+ cells (reflecting circulating T cells) and CD19+ cells (reflecting circulating B cells). However, an absence of HLA-DR+ cells indicates defective expression of ______

major histocompatibility complex (MHC) class II molecules. Major histocompatibility complex (MHC) class II molecules are encoded by the HLA-DP, HLA-DQ, and HLA-DR genes and present extracellular antigens processed in acidified lysosomes by antigen-presenting cells (eg, B cells, macrophages). Absence of MHC class II expression impairs activation of B and T cells, resulting in a form of severe combined immunodeficiency. This patient's flow cytometry shows normal numbers of CD3+ cells (reflecting circulating T cells) and CD19+ cells (reflecting circulating B cells). However, an absence of HLA-DR+ cells indicates defective expression of major histocompatibility complex (MHC) class II molecules. The human leukocyte antigen (HLA) genes encode MHC molecules expressed on the cell surface for antigen presentation. There are 6 major HLA loci: HLA-DP, HLA-DQ, and HLA-DR genes encode MHC class II molecules, which are expressed on antigen-presenting cells (eg, B cells, macrophages) after an extracellular antigen has been loaded onto the MHC class II molecule in an acidified lysosome. HLA-A, HLA-B, and HLA-C genes encode MHC class I molecules, which are expressed on nucleated cells after a cytosolic antigen has been transported into the endoplasmic reticulum and loaded onto the MHC class I molecule (Choice E). Because expression of the MHC class II-peptide complex is necessary for activation of B and T cells, its absence (eg, bare lymphocyte syndrome type II) causes a form of severe combined immunodeficiency.

Oral thrush, interstitial pneumonia, and severe lymphopenia during the first year of life are consistent with

mother-to-child vertical transmission of HIV-1. The risk of HIV infection occurring in an infant born to an HIV-positive mother who received no prenatal antiretroviral therapy (ART) can be as high as 35%. ART during pregnancy reduces the risk of perinatal transmission to 1%-2%. All pregnant women with HIV should take ART, regardless of their CD4 cell count or viral load. Antiretroviral therapy during pregnancy reduces the risk of perinatal transmission of HIV to 1%-2% and is recommended for all pregnant women with HIV.

Histopathologic examination of syphilitic lesions (at all stages) classically demonstrates

proliferative endarteritis of small vessels with a surrounding plasma cell-rich infiltrate.

S pyogenes are catalase-negative, β-hemolytic, gram-positive cocci in chains. S pyogenes is unique among β-hemolytic streptococci as it is susceptible to bacitracin. Because the bacitracin test is not very specific for S pyogenes, it has been replaced in many laboratories by the______

pyrrolidonyl arylamidase (PYR) test; S pyogenes is PYR-positive

Alanine is also released by skeletal muscle tissue during protein catabolism as part of the glucose-alanine cycle that helps remove excess nitrogen. Alanine is then transported to the liver, where it serves as a vehicle for nitrogen disposal and as a source of carbon skeletons for gluconeogenesis. In the liver, alanine is transaminated by alanine aminotransferase to _____ with the amino group being transferred to_____ to form glutamate.

pyruvate α-ketoglutarate to form glutamate

HBV vaccination is recommended for all health care providers and other high-risk individuals (eg, intravenous drug users). The vaccine utilizes _____ to generate protective immunity against the virus.

recombinant HBsAg Immunity is due to the virus' inability to enter into hepatocytes HBsAg is a collection of envelope glycoproteins found on the surface of HBV; these glycoproteins mediate attachment of the virus to hepatocytes and subsequent viral entry. Patients who adequately respond to the HBV vaccine generate anti-HBs antibodies, which bind to circulating viral particles and prevent attachment to and penetration of hepatocytes. Patients who have been immunized against HBV as well as those who have cleared the virus after acute infection will have anti-HBs antibodies. These 2 populations are distinguished by the presence of anti-HBc antibodies, which are seen only in those who have been exposed to the virus (not in immunized patients).

C5a also

recruits and activates neutrophils, monocytes, eosinophils, and basophils. C4a is the least active of these complement components and plays a minor role in leukocyte recruitment.`

Leukotriene B4....

stimulates neutrophil migration to sites of inflammation. Other important chemotactic agents include 5-HETE (leukotriene precursor), complement component C5a, and IL-8.

what organism is this

strep pneumo Streptococcus pneumoniae is a gram-positive, lancet-shaped organism that grows in pairs (diplococci). It colonizes the nasopharynx and is a leading cause of community-acquired pneumonia, bacterial meningitis, sinusitis, otitis media, and sepsis. Patients with HIV have increased susceptibility, as the virus dramatically hampers the production of opsonizing antibodies and the recruitment of phagocytes to areas of infection.

Urticaria is a transient hypersensitivity disorder characterized by pruritic erythematous plaques that arise suddenly and resolve over hours. They are most often caused by IgE-mediated degranulation of mast cells, leading to increased permeability of the microvasculature with edema of the

superficial dermis.

Chronic lung transplant rejection is due primarily to progressive scarring of ________. Manifestations occur months or years after transplantation and include obstructive lung disease (eg, reduced FEV1) with dyspnea and dry cough.

the small airways, leading to bronchiolitis obliterans

Familial hypocalciuric hypercalcemia (FHH) is a benign autosomal dominant disorder caused by defective CaSRs in the parathyroid gland and kidneys. Calcium-sensing receptors (CaSRs) are (what kind of receptor?)

transmembrane Gq protein-coupled (metabotropic) receptors that regulate the secretion of parathyroid hormone (PTH) in response to changes in circulating calcium levels. Binding of calcium to CaSRs leads to the inhibition of PTH release, whereas low calcium levels allow increased PTH release.

Insulin and insulin-like growth factor work by stimulating transmembrane receptors with intrinsic_______ activity in the intracellular domain, initiating a downstream phosphorylation cascade.

tyrosine kinase

Alanine is the major amino acid responsible for transferring nitrogen to the liver for disposal. During the catabolism of proteins, amino groups are transferred to α-ketoglutarate to form glutamate. Glutamate is then processed in the liver to form

urea, the primary disposal form of nitrogen in humans. Free ammonia is also excreted into the urine by the kidney for regulation of acid-base status

Thromboxane A2 is an eicosanoid synthesized by platelets that causes

vasoconstriction and platelet aggregation

Bradykinin is a component of the kinin system. It causes

vasodilation, increases vascular permeability, stimulates smooth muscle contraction, and helps mediate pain.

Enteropathogenic E coli (EPEC) attaches to enterocytes and effaces their surface, resulting in

watery diarrhea; this strain does not produce toxins

Almost all aminotransferase enzymes use ______ as the amino group acceptor.

α-ketoglutarate Thus, amino groups are funneled into glutamate during protein catabolism. Glutamate is further metabolized by the enzyme glutamate dehydrogenase, which liberates free ammonia and regenerates α-ketoglutarate. Ammonia then enters the urea cycle to form urea, the primary disposal form of nitrogen in humans. Urea subsequently enters the blood and is excreted in the urine