Rubin's Chapter 4

Question 1

35 yo M has recurrent conjunctivitis with seasonal eye itching and runny nose. What is the mechanism of disease?

Answer 1

Hypersentitivity. Allergic rhinitis (hay fever) = hypersenstivity type I. Caused by pollen, house dust, animal dandruff and other allergens. Antigens inhaled react with IgE attached to basophils in the nasal mucosa, trigger the release of vasoactive substances. Histamine increases permeability of mucosal vessels.

Question 2

8 yo M presents w/ periorbital edema and throbbing headaches. His parents report he had strep throat 2 weeks ago. Urinalysis: 3+ heamturia. Renal biopsy shows hypercellular glomeruli and electron microscopic exam shows subepithelial humps on glomeruli. What is the pathogenesis of glomerulonephritis?

Answer 2

Deposition of circulating immune complexes. Type III hypersenstivity reactions are characterized by immune complex deposition, complement fixation and localized inflammation. Antibody directed against either a circulating antigen or an antigen that is deposited in a tissue can give rise to a type III reaction. Streptococcal infection led to depositing of antigens and antibodies in glomerular basement membranes, resulting in clinical features of nephritic syndrome - heamturia, oliguria and hypertension.

Question 3

A 21 year old woman presents w/ a 3 month history of malaise, joint pain, weight loss and sporadic fever. The patient appears agitated and has a fever. Physical: malar rash, erythmatous-pink plaques with telangiectatic vessels, oral ulcers and nonblanching purpuric papules on legs. Labs: elevated blood urea nitrogen and creatinine. Antibodies directed to which antigen would be expected in her serum?

Answer 3

Double stranded DNA. Systemic lupus erytematous is an autoimmune inflammatory disease that may involve almost any organ but characteristically affects the kidneys, joints, serous membranes and skin. Antibodies are formed against a variety of self antigens.

Question 4

Serum levels of complement proteins may be reduced during the active phase of disease in a patient with systemic lupus erythmatous. What is the mechanism of disease causing this?

Answer 4

Binding of compliment to immune complexes. Acquired deficiencies of early complement components occur in patients with autoimmune diseases, especially those associated w/ circulating immune complexes - lupus. Antigen-antibody complexes formed in the circulation during the active stage of these diseases lead to a marked reduction in circulating levels of complement proteins - hypocomplementemia.

Question 5

45 yo F complains of severe headaches and difficulty swallowing. Over the past 6 months she has noticed small red lesions around her mouth as well as thickening of the skin. She has stone facies on physical exam. What antigen is the most common and most specific target of autoantibody in patients w/ this disease?

Answer 5

Scl-70 (anti-topoisomerase I) Scleroderma is an autoimmune disease of connective tissue. Circulating male fetal cells have been seen in blood/blood vessel walls of women with scleroderma who bore male babies years before. Antibodies commonly
found in scleroderma include (1) nucleolar autoantibodies
(primarily against RNA polymerase); (2) antibodies to
Scl-70, a nonhistone nuclear protein topoisomerase and
(3) anticentromere antibodies, which are associated with
the calcinosis, Raynaud phenomenon, esophageal dys-
motility, sclerodactyly and telangiectasia (CREST) variant
of the disease. Scl-70 topoisomerase is the most common and specific to scleroderma.

Question 6

45 yo F complains of severe headaches and difficulty swallowing. Over the past 6 months she has noticed small red lesions around her mouth as well as thickening of the skin. She has stone facies on physical exam. Skin biopsy would show perivascular accumulation of which extracellular matrix protein?

Answer 6

Collagen. She has scleroderma, characterized by vasculopathy and excessive collagen deposition in the skin and internal organs such as the lung, GI tract, heart and kidney.

Question 7

During physical exam, 22 yo M gets injection of a purified protein derivative, isolated from Mycobacterium tuberculosis. 3 days later, injection site is raised and indurated. Which glycoprotein was involved in the antigen presentation during the initiation phase of delayed hypersensitivity in this patient?

Answer 7

Class II HLA molecules. Delayed-type hypersensitivity is a tissue reaction involving lymphocytes and mononuclear phagocytes, which occurs in response to a soluble protein antigen and reaches greatest intensity 24-48 hours after initiation. In the initial phase, foreign protein antigens or chemical ligands interact with accessory cells bearing
class II HLA molecules. Protein antigens are actively processed
into short peptides within phagolysosomes and are presented on the cell surface in conjunction with the class II HLA molecules. The latter are recognized by CD4+ T cells
which become activated to synthesize an array of cytokines.
The cytokines recruit and activate lymphocytes, monocytes,
fibroblasts, and other infl ammatory cells.

Question 8

54 yo F needs blood transfusion after a car accident. 5 hours later she becomes febrile and has severe back pain. Labs: intravascular hemolysis. Turns out she got type A Rh+ instead of her type, type B Rh+ blood. What explains the development of intravascular hemolysis?

Answer 8

Antibody mediated complement fixation. Hypersensitivity reactions are directed against fixed antigens. Preformed antibodies in the patient’s blood attached to foreign antigens using the complement cascade to destroy the target cell with a membrane attack complex. This type of complement-mediated cell lysis occurs in autoimmune hemolytic anemia.

Question 9

40 yo M, yellow skin/sclera, abdominal tenderness, dark urine, hepatomegaly. Labs: elevated bilirubin, decreased albumin and prolonged prothrombin time. Antibodies found to Hep B core antigen. Which glycoprotein is the principle cell surface receptor for viral antigens on B lymphocytes in this patient?

Answer 9

Membrane immunoglobin(mIg). This patient is a chronic HBV carrier with active hepatitis. Humoral immune response to specific viral antigens in this patient involve activation and differentiation of B lymphocytes into anti-body secreting plasma cells. mIg is the antigen binding receptor expressed by B cells.

Question 10

What glycoprotein on virally infected hepatocytes provides a target for cell-mediated cytotoxicity in a patient with chronic HBV and acute hepatitis?

Answer 10

Class I HLA molecules. Class I molecules of MHC present foreign peptides that are recognized by cytotoxic T lymphocytes during cell-medaited killing of virus infected tissues or during graft rejection. Class I HLA molecules provide targets for CD8+ T cells in cell-mediated cytotoxicity. Remember, all tissues express type I while type II is specific to macrophages and B lymphocytes.

Question 11

45 yo F, 1 year ho dry mouth and eyes. Biopsy of minor salivary glands shows infiltration of lymphocytes forming focal germinal centers. Which cellular organelle is a target for autoantibodies in this patient?

Answer 11

Nucleus. Sjogren sydrome is an autoimmune disorder characterized by kerotoconjunctivitis sicca and xerostomia in the absence of other connective tissue disease. The production of autoantiboides, particularly anti-nuclear antibodies directed against DNA or nonhistone proteins typically occurs in Sjogren.

Question 12

A month old F, ho recurrent pneumonia is found to have almost no circulating IgG. Ceullular immunity is normal. His brother had the same disease and died of echovirus enchephalitis. His parents and sisters have normal serum levels of IgG. What is his diagnosis?

Answer 12

X-linked agammaglobulinemia of Bruton. The congenital disorder of Bruton X linked agammaglobulinemia appears in male infants at 5-8 months of age, as maternal antibodies begin to decline. The infant suffers from recurrent pyogenic infections and severe hypogammaglobulinemia.

Question 13

52 yo F, ho systemic hypertension and chronic renal failure undergoes kidney transplantation but the graft fails to produce urine. A renal biopsy shows hyper acute transplant rejection. Graft rejection is caused by which mediator of inflammation of immunity?

Answer 13

Preformed antiboides. Hyperacute rejection occurs within minutes to hours after transplantation. It is manifested clinically as a sudden cessation of urine output with fever and pain in the graft area. This immediate rejection is mediated by preformed antibodies and complement activation products.

Question 14

30 yo F complains of impaired speech and frequency of aspiration of food. Physical: diplopia and drooping eyelids. A mediastinal mass is removed and diagnosed as thymoma. The symptoms of muscle weakness are caused by antibodies to which cellular component?

Answer 14

Acetylcholine receptor. She has myasthenia graves, a type II hypersensitivity disorder caused by antibodies binding to acetylcholine receptors.

Question 15

31 yo M w/ AIDS complains of difficulty swallowing. Examination of oral cavity shows white membranes covering tongue and palate. Endoscopy shows white, ulcerated lesions in the esophagus. These pathological findings are associated with loss of which immune cells?

Answer 15

Helper T lymphocytes. The fundamental lesion in HIV is infection of CD4 helper T lymphocytes, which leads to depletion of this cell population and impaired immune function –> opportunistic infections.

Question 16

Which enzyme converts the HIV genome into double-stranded DNA in host cells?

Answer 16

Reverse transcriptase (RNA dependent DNA polymerase) copies HIV’s RNA genome into double stranded DNA.

Question 17

20 yo F w/ ho asthma and allergies undergoes skin testing to identify possible allergens. Positive skin reaction would be mediated by which immunoglobulin class?

Answer 17

IgE. Type I, Immediate-type hypersensitivity is manifested by a localized reaction that occurs within minutes after exposure to an antigen/allergen to which the person has previously been sensitized. IgE antibodies bind to Fc receptors on mast cells and basophils.

Question 18

53 yo F, progressive weight loss, nervous-ness, sweating. Physical: tachycardia, exophthalmos. Diffusely enlarged, warm thyroid. Low TSH levels, high T3, T4 levels. What is the mechanism of disease in this thyroid condition?

Answer 18

Cytopathic autoantibodies. This is Graves disease - Type II hypersensitivity disorder caused by autoantibodies to the TSH receptor stimulates release of T3 and T4 from the thyroid into circulation, these suppress TSH production in the pituitary. Sweating, weight loss and tachycardia are due to hyper metabolism, characteristic of hyperthyroidism. Graves disease also gives exophthalmus.

Question 19

12 month old infant with ho recurrent infections, eczema, generalized edema, and easy bruising is diagnosed with an X-linked recessive, congenital immunodeficiency. CBC shows thrombocytopenia. What’s the diagnosis?

Answer 19

Wiskott-Aldrich syndrome - a rare syndrome characterized by: 1) recurrent infections
2) hemorrhages secondary to thrombocytopenia
3) eczema
In manifests in the first few months of life as petechiae and recurrent infections i.e.: diarrhea.

Question 20

24 yo F w/ leukemia receives an allogenic bone marrow transplant. 3 weeks later she has a skin rash and diarrhea. Liver function tests show elevated serum levels of AST and ALT. Skin biopsy shows sparse lymphocytic infiltrate in the dermis and epidermis, as well as apoptotic cells in the epidermal basal cell layer. Skin rashes and diarrhea in this patient are caused by which cells?

Answer 20

Donor lymphocytes. Graft-versus host disease is a severe complication of bone marrow transplants for immunodeficient patients. GVHD occurs when donor lymphocytes in grafted tissue recognize and reactant to the recipient tissue.

Question 21

20 yo gardener presents to his family physician for treatment of poison ivy. The patient’s hands and arms appear red and are covered with oozing blisters and crusts. What describes the pathogenesis of these skin lesions?

Answer 21

Delayed type hypersensitivity reaction. Poison Ivy is a type IV, delayed type hypersensitivity reaction to plants of the Rhus genus. This T-lymphocyte mediated allergic contact dermatitis presents as urticaria and bollous eruption. Blisters rupture and heal with crusts, usually without scarring.

Question 22

9 month old girl with ho recurrent pulmonary infections is found to have a congenital deficiency of adenosine deaminase, which is associated w/ virtual absence of lymphocytes in her peripheral lymphoid organs. What is the diagnosis?

Answer 22

Severe combined immunodeficiency, SCID, is a group of disorders of T and B lymphocytes that result in recurrent viral, bacterial, fungal and protozoal infections. Many are caused by adenosine deaminase deficiency.

Question 23

50 yo M complains of fever, weight loss, abdominal pain and bloody urine. Physical exam: red-purple discoloration of the skin. Positive P-ANCA test suggests auto-immune disease. Biopsy of lesional skin discloses fibrinoid necrosis of a small muscular artery. Which immune response explains the pathogenesis of inflammation and necrotizing vasculitis in this patient?

Answer 23

Immune complex disease, type III hypersensitivity reaction –> vasculitis. Antigen-antibody complexes are formed in circulation and deposited in tissues.

Question 24

Neonate develops spastic contractions on 2nd post-partum day. Lab studies show hypocalcemia. MRI shows aplasia of the thymus and parathyroid glands. What is the diagnosis?

Answer 24

DiGeorge Syndome - chromosomal defect that results in developmental anomalies of the pharyngeal pouches and organs that develop from them - thymus, parathyroids, aortic arch. These children present with tetany caused by hypoparathyroidism and deficiency of cellular immunity.

Remember: thyme aplasia = DiGeorge.

Question 25

50 yo F complains of intermittent tingling and pain in her finger tips. She also reports joint and muscle pain. Physical: lymphadenopathy. Labs: hypergammaglobulinemia. Antinuclear antibody test is positive but there’s no evidence of antibody against double-stranded DNA. Urinalysis is normal. Patient responds well to steroids. What is the diagnosis?

Answer 25

Mixed connective tissue disease. MCTD has features of some autoimmune diseases like SLE and scleroderma but is distinct. Patients typically have autoantibodies to ribonucleoproteins,
but unlike SLE, they do not have antibodies to Sm antigen or double-stranded DNA. Some patients with MCTD develop symptoms of scleroderma or rheumatoid arthritis, suggesting that MCTD may be an intermediate stage in a genetically determined progression. Whether
MCTD represents a distinct entity or simply an overlap of
symptoms in patients with other types of collagen vascular
diseases remains an open question. Intermittent episodes
of ischemia of the fingers, marked by pallor, paresthesias,
and pain, are referred to as Raynaud phenomenon.

Question 26

25 yo F complains of low-grade fever, fatigue and persistent rash over nose and upper chest. She has pain in her knees and elbows. Skin biopsy shows dermal inflammation and granular deposits of IgG and C3 complement along the basement membrane at the epidermal/dermal junction. Urinalysis reveals microscopic hematuria and proteinuria. Antinuclear antibody test is positive. Development of thromboembolic complications (DVT) in this patient is commonly associated with increased serum levels of antibody to which antigen?

Answer 26

Phospholipids - 1/3 of lupus patients have elevated concentrations of antiphospholipid antibodies, which predisposes them to thromboembolic complications: stroke, PE, DVT and portal vein thrombosis.

Question 27

30 yo F has congenital immunodeficiency that has remained largely asymptomatic throughout her life. What’s the diagnosis?

Answer 27

Selective IgA deficiency is the most common primary immunodeficiency syndrome with 1/700 incidence. Patients are often asymptomatic but sometimes present w/ respiratory or GI infections. They are predisposed to allergies and collagen vascular diseases. Patients with IgA deficiency have normal numbers of IgA-bearing B cells, and their varied defects result in an inability to synthesize and secrete IgA subclasses.

Question 28

60 yo F w/ type 2 diabetes and end-stage renal disease receives a kidney transplant. 3 weeks later the patient presents w/ azotemia and oliguria. If this patient has developed acute renal failure, which pathological finding would be expected on renal biopsy?

Answer 28

Interstital infiltrates of lymphocytes and macrophages. Transplant rejection reactions have been traditionally categorized into hyperacute, acute and chronic rejection based on the clinical tempo of the response and on the mechanisms involved. Acute rejection is characterized by an abrupt onset of azotemia and oliguria, which may be associated with fever and graft tenderness. A needle biopsy would show:
1) interstitial infiltrates of
lymphocytes and macrophages, (2) edema, (3) lymphocytic
tubulitis, and (4) tubular necrosis

Question 29

12 yo M presents w/ 5 day history of sore throat. He has a fever. Physical: inflamed tonsils and swollen cervical lymph nodes. Trafficking and recirculation of blood-borne lymphocytes through the cervical lymph nodes in this patient occurs primarily at which location?

Answer 29

High endothelial venues. Lymphocyte trafficking occurs through specialized post capillary venues termed high endothelial venues.

Question 30

28 yo F with ho drug abuse presents w/ an infectious mononucleosis like syndrome and lymphadenopathy. Blood tests indicate that she’s HIV +. What lymph associated proteins mediate entry of HIV into host cells?

Answer 30

CD4