NOTE: This section features additional review questions that are not included in the text.
For each question, choose the ONE BEST answer or completion.
The germinal centers found in the cortical region of lymph nodes and the peripheral region of splenic periarteriolar lymphatic tissue
In a diagnostic laboratory a technician prepared plastic assay plates for ELISA by coating a solution of the antigen, gp120 (a glycoprotein derived from the human immunodeficiency virus, the etiologic agent of AIDS), to the plastic surface. Several samples of serum from suspected infected individuals were tested for the presence of antibodies to gp120. When the assay was performed, all the test samples were positive, including control samples that were known not to contain anti-gp120 antibodies. What explanation best fits the facts?
If an IgG antibody preparation specific for hen egg lysosome (HEL) is treated with papain to generate Fab fragments, which of the following statements concerning the avidity of such fragments is true:
The administration of antibody generated in a different species, such as the horse, for passive protection in humans can lead to serum sickness. This is characterized by all of the following except:
A preliminary clinical trial showed that a humanized anti-CD28 monoclonal antibody prolonged the graft survival in patients who had had a kidney allograft (i.e. from a genetically non-identical donor). The probable mechanism responsible for this effect is best explained by
A 16-year-old male went to see his dermatologist because of a red rash he developed on his left earlobe. The young man reported that he had been wearing a surgical steel earring for two months without any problem. He had recently replaced the steel with a gold earring and observed the rash the following day. A skin biopsy revealed the presence of T cells, macrophages and fibrin. What is the likely diagnosis?
Interaction between which of these receptor-ligand pairs facilitates T cell migration through vessel walls?
Which of the following surface receptors does not transduce a signal into the T cell?
Infection with Mycobacterium tuberculosis evokes which of the following cytokine profiles?
Peptide fragments generated in the cell's cytoplasm are transported into the endoplasmic reticulum by which of the following?
The most common clinical consequence(s) of C3 deficiency is (are)
Hector Martinez developed hives all over his body within 10 minutes of ingesting shrimp at a party. He became very nervous upon seeing the hives and immediately went to the emergency room. He complained of incredible itchiness from his hives but reported no other symptoms. His breathing was normal and he had no difficulty in swallowing. What is the likely diagnosis and how should his symptoms be treated?
Which of the following is not characteristic of Bruton's disease
Use the following options to select the most likely diagnosis to the three clinical vignettes below:
Vignette 1: A 2-year-old girl was admitted to the hospital after she developed a severe infection of the large intestine. She had a history of recurrent infections and impaired wound healing. She was previously hospitalized at 3 weeks of age because of swelling and redness around the umbilical stump and high fever. Laboratory tests revealed a high white blood count, normal proportions of B and T lymphocytes and normal levels of IgM, IgG and IgA antibodies. However an additional test demonstrated a lack of migration of lymphocytes to the site of a localized skin abrasion. Furthermore, flow cytometric analysis revealed that relatively few of the child's blood lymphocytes reacted with a monoclonal antibody to CD18.
Vignette 2: A 12-year-old junior high school boy was taken to the emergency room because of severe abdominal pains, vomiting and localized swelling of the face. He was also having some difficulty breathing. A history of the patient and his family revealed that the boy suffered from recurrent episodes of abdominal pain since he was 4 years old, as did his mother and maternal grandmother. A complete immunological workup revealed markedly reduced levels of C4 and C1INH in the boy's blood.
Vignette 3: A 4-year old boy with recurrent infections caused by Streptococcus pyogenes, Hemophilus influenza, and Pneumocystis carinii was admitted to the hospital following a 3-day sinus infection. His mother noted that he had developed a productive cough, now had a high fever. His white blood cell count was 4200/ul (normal count 5000-9000/ul). Twenty-six percent of his white cells were neutrophils (very low), 56% were lymphocytes (normal), and 28% were monocytes (elevated). A serum work-up revealed that his IgG level was 25 mg/dl (normal 600-1500 mg/dl), IgA was undetectable (normal 150-225 mg/dl) and his IgM level was 210 mg/dl (normal 75-150 mg/dl). A flow cytometric analysis of his peripheral blood cells revealed that all of his B cells were IgM+, IgD+. The boy may be suffering from:
Use the following options to select the most likely diagnosis to the two clinical vignettes below:
Vignette 4: A 65-year-old construction worker went to see his physician complaining about double vision (diplopia). He also reported having difficulty in chewing and swallowing food and slurring of speech at times. He was referred to a neurologist who observed a weakness in the patient's facial muscles and tongue and an abnormality in his ocular movements and droopy eyelids (ptosis). An ELISA on serum antibodies revealed elevated titers of antibodies to the acetylcholine receptor.
Vignette 5: A 29-year-old women visited her doctor after experiencing joint pain and stiffness in the mornings for several months. A blood test for antiphospholipid antibody was ordered and came back positive. Results from other blood tests revealed elevated titers of serum IgG and antibodies specific for ribonucleoproteins. A urine test was positive for protein.
Answers to Review Questions
1. D As discussed in Chapters 2 and 7, germinal centers are sites in which mature B cells differentiate to plasma cells and undergo class switch and memory cell formation. Early stages of lymphoid cell differentiation take place in the primary lymphoid organs. Damaged red blood cells are removed in the red pulp of the spleen.
2. A As discussed in Chapter 5, false positive results can be obtained in solid phase assays if the plates are not 'blocked' with a control protein, unrelated to the antigen or antibody which is being tested. After coating plates with a solution of the antigen of interest, the control or 'irrelevant' protein (such as serum albumin) fills up sites on the plate's surface which otherwise would bind the reagents applied in the subsequent steps. None of the other possible choices would give all positive results.
3. A As discussed in Chapters 4 and 5, a Fab fragment of an antibody is a univalent fragment of an antibody, which binds an antigenic epitope. Avidity is a measure of the total binding energy of the interaction with the antigen, which is larger for a multivalent, intact antibody molecule (i.e. with multiple antigen binding sites), than for a univalent Fab fragment.
4. B As discussed in Chapter 15, an antibody generated in a different species can stimulate immune responses if administered to humans. Serum sickness develops generally 7-10 days after the administration of foreign antibody when complexes of host and foreign antibodies are deposited in different sites in the body. Complex deposition leads to an inflammatory response, including complement activation.
5. C As discussed in Chapter 10, CD28 is expressed on T cells, and interacts with the B7.1 and 7.2 molecules (CD 80 and 86) on B cells and other antigen presenting cells to transduce a costimulatory signal required for full activation of naive T cells. Binding of antibody specific for CD28 to CD28 expressed on the T cell surface likely blocks this important costimulatory signal. As described in Chapters 11 and 19, preventing one or more critical steps in the activation of the T cell can result in the induction of long term T cell tolerance, particularly useful in trying to prevent transplant rejection.
6. A As discussed in Chapter 16, the localization and timing of the appearance of symptoms after exposure to the gold earring (24 hours later), and the nature of the cells at the site of irritation, strongly indicate that this is a type IV, contact sensitivity response. Gold in the earring likely complexes with proteins of the host to modify their shape or structure in some way; as a result, a T cell response is made to a modified self-molecule.
7. C As discussed in Chapters 9 and 12, the interaction of LFA-1, expressed on leukocytes such as the T cell and the neutrophil, with ICAM-1 expressed on the specialized region of the vascular endothelium at the boundary of lymph nodes, plays a key role in the migration of cells out of blood and into tissues. The other pairs in the remaining choices are critical in T cell-antigen presenting cell interactions.
8. B As discussed in Chapter 10, all of the molecules apart from the a and b chains of the TCR are associated with tyrosine kinases which transduce a signal into the T cell following ligation.
9. B As discussed in Chapters 10 and 12, M. tuberculosis infection evokes the early synthesis of IL-12 by cells of the innate immune system which drives the differentiation of CD4+ TH0 cells to TH1 cells which synthesize IL-2, IFN-g, and TNF-a.
10. B As discussed in Chapter 8, products of the TAP-1 and TAP-2 genes transport peptides of 8-9 amino acids generated by the proteasome into the endoplasmic reticulum, where they bind to MHC class I and b2-microglobulin. HLA-DM and the invariant chain (CD74) are involved in the MHC class II pathway of peptide binding which takes place in acid compartments of the cell.
11. D C3 deficiencies are clinically most severe and are often associated with immune complex disease and susceptibility to recurrent bacterial infections. This is due to the fact that C3 plays a central role in activation of C5 and formation of MAC and is important for both classical and alternative pathway. C3 plays a critical role in converting a humoral antibody response in to an effective host defense mechanism. Products of C3 or opsonic fragments of C3 have receptors on various cells which help in phagocytosis of opsonized pathogens.
12. E Various foods (e.g. shrimp) can induce localized anaphylaxis in allergic individuals. Some individuals develop atopic urticaria, commonly known as hives, when a food allergen is carried to sensitized mast cells in the skin causing swollen (edematous), red (erythematous) eruptions; this response is known as a wheal and flare reaction. The mechanism underlying a type 1 hypersensitive reaction is as follows: exposure to an allergen activates B cells to form IgE-secreting plasma cells. The secreted IgE molecules bind to IgE-specific Fc receptors on mast cells and basophils. Food allergens can be transported to the skin to encounter the mast cells in the skin. Second exposure to the allergen leads to cross-linking of the bound IgE by the allergen, triggering the release of pharmacologically active mediators from mast cells. Reactions are very rapid, occurring with in few minutes following challenge to the allergen. Histamine is formed by decarboxylation of the amino acid histidine; because it is stored-preformed in the granules, its biological effects are observed with in 10-15 minutes of mast cell activation. Most of the biological effects of histamine in allergic reactions are mediated by the binding of histamine to H1 receptors. Histamine causes increased vascular permeability and smooth muscle contraction. Anti-histamines have been the most useful drugs in alleviating allergic symptoms. These drugs act by binding to the histamine receptors on target cells and blocking the binding of histamines.
13. E Choices a-d are important characteristics associated with Bruton's agammaglobulinemia. Graft rejection is a cell-mediated immune response which is not defective in patients with Bruton's disease.
Answers to Case Studies
Vignette 1. A LAD involves an impairment in which neutrophils, monocytes and leukocytes are unable to adhere to vascular endothelial cells, thus preventing extravasation of these cells into tissue spaces. Also impaired are the abilities of CTLs and NK cells to adhere to their target cells and of helper T cells and B cells to form conjugates. LAD is due to defective biosynthesis of the b-chain component (CD18) of one subfamily of integrin adhesion molecules, that include CR3, CR4 (complement receptors), LFA-1, ICAM-1. The b-chain defect results in a near-total loss of all these membrane glycoproteins. Individuals with this defect manifest recurrent bacterial infections (high white blood count is an indication) and impaired wound healing.
Vignette 2. C The C1INH (C1-esterase inhibitor) regulates the activation of the classical pathway by preventing excessive C4 and C2 activation by C1. Without this inhibitor, the activation of C1, C2 and C4 are uncontrolled resulting in generation of large amounts of vasoactive peptides. These peptides cause increased permeability of the blood vessels, resulting in localized edema of the tissue. This deficiency results in a disease called Hereditary angioedema. The edema can be in subcutaneous tissues, or within the bowel or upper respiratory tract, where it causes abdominal pain or obstruction of the airway.
Vignette 3. F The activated T cell expresses surface CD40L. CD40L then interacts with CD40, which is constitutively expressed on the B cell, and this cognate interaction induces B cell proliferation, differentiation, and heavy chain isotype switching to IgG, IgA and IgE. T cell derived cytokines also participate in this class switching. In hyper IgM syndrome, CD40L is mutated preventing its interaction with CD40 on B cells. This prevents isotype switching. Consequently, IgM antibodies accumulate, whereas little IgG, IgE or IgA antibodies are produced. Patients with X-linked hyper IgM syndrome are highly susceptible to infection with pyogenic (pus-forming) bacteria such as Streptococcus pyogenes and Haemophilus influenzae because they are unable to produce an opsonizing IgG antibody responses to these pathogens. The polysaccharide capsules of these bacteria are resistant to destruction by phagocytes unless they are opsonized. IgG is an opsonizing immunoglobulin beacuse it binds to IgG-specific Fc receptors expressed by phagocytes. Patients with hyper IgM syndrome also have defective cell mediated immunity because of an inability of their macrophages to be optimally activated. Such activation also depends upon engagement of CD40 on macrophages with CD40L on T cells.
Vignette 4. P As described in Chapters 15 and 17, the symptoms described are characteristic of the severe muscle weakness observed in myasthenia gravis. The disease results from the production of auto-antibody specific for the acetylcholine receptor, which blocks acetylcholine's transmitter function at the neuromuscular junction.
Vignette 5. Q As described in Chapter 17, the symptoms described are characteristic of Systemic Lupus Erythematosus (SLE). This is a systemic autoimmune disorder which predominantly affects women, in which antibodies to multiple intracellular components such as DNA, phospholipids, and ribonucleoproteins are formed. Complexes of these intracellular antigens and auto-antibody deposit in sites such as the kidney (causing damage measured as protein in the urine), and the joints (causing inflammation and pain).
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