Immunodermatology Flashcards

Question

25- The most definitive HLA association with psoriasis is: A. HLA-Cw6 B. HLA-B27 C. HLA-B13 D. HLA-B17 E. HLA-B37

Answer 1

►A HLA-Cw6 is associated with a 9-15x greater risk for developing psoriasis. All of the other HLA antigens listed are associated with various types of psoriasis, but at with lesser strength of association.

Answer 2

►A These indolent tumors present as solitary or multiple nodules usually on the extremities. The cells have been reported to have CD-20 (B cell marker) and have been reported to be bcl-2 positive.

Answer 3

►E Ro 60 kDa autoantigen is a major target for patients with SLE and Sjogrenǁs syndrome. Neonatal lupus occurs in newborns of mothers with anti-Ro antibodies and leads to children with photosensitive skin lesions and a cardiac conduction defect, a third degree heart block.

Answer 4

►A IL-4 is the cytokine that polarizes the immune response towards Th2. IL-5 is an eosinophil growth factor. IL-10 is a general down-regulator of immunity. TNF and IFN-gamma are TH1 cytokines, not TH2 cytokines. IFN-gamma is secreted by TH1 cells, and is the main macrophage-activating cytokine.

Answer 5

►C Eosinophil chemotactic factors include all of the following: Histamine, soluble immune complexes, C5a, and HETE

Answer 6

►D Erythema multiforme associated with herpes simplex has been reported to have an increase of HLA-B15.

Answer 7

►D In a homeless patient with poor nutrition, acrodermatitis enteropathica due to zinc deficiency can presents with a scaling eruption of the periorificial regions. In addition to a low zinc level, levels of alkaline phosphatase, a zinc dependent enzyme, are decreased.

Answer 8

►E Immunoglobulins (Ig) differ in their ability to activate complement. IgM is the largest Ig, is the major Ig in the primary immune response, and consists of a pentamer that activates the classic complement pathway. IgG is the most abundant Ig and the major Ig in the secondary immune response. Four subclasses of IgG exist based on the amino acid residue sequences of their constant region, IgG1 through IgG4. IgG1 and IgG3 are potent activators of the classic complement pathway, IgG2 is less effective and IgG4 is unable to do so.

Answer 9

►A There are 4 types of Hypersensitivities: ("ACID") Type I: Anaphylactic and Atopic: Exampl es Urticaria, Asthma, and Allergic Rhinitis Type II: cytotoxic: examples - Transfusion reactions, ABO incompatibility, Rh disease (erythroblastosis fetalis), Autoimmune reactions, Hemolytic disease of newborn, Goodpasture's syndrome Type III: Immune complex, Serum sickness, and arthrus reactions: examples -PAN, glomerulonephritis, SLE, Rheumatoid arthritis, and serum sickness Type IV: Delayed (cell-mediated)typesL examples -TB skin test, transplant rejection, contact dermatitis, interactions and skin repsonsiveness to bacteria, fungi, viruses, and protozoa, photo-allergies, insect bites, etc

Answer 10

►D Porphyria cutanea tarda has been shown to be associated with hemochromatosis. Patients with hemochromatosis have mutations in the HFE gene, and early detection of mutations can improve life expectancy for these patients.

Answer 11

►A Langerhans cells are found in the epidermis and on mucosal surfaces. After antigen exposure and activation, they migrate to regional lymph nodes where they mature into antigen presenting cell s. Adhesion to keratinocytes in the epidermis is mediated by e-cadherin.

Answer 12

►A CD1 is a surface antigen specific for epidermal Langerhans cells. It is not expressed in other epidermal structures. The other characteristic ultrastructural feature of Langerhans cells is the Birbeck granule. CD4 is found on T-helper cells and occasionally on Langerhans cells. CD7 is a T- cell marker that is often lost in cutaneous T-cell lymphoma. CD8 is found on cytotoxic T-cells. CD20 is a B-cell marker.

Answer 13

►D Interleukin-4 (IL-4) is a cytokine involved in B-cell proliferation. Along with IL-5 and IL-13, IL4 is classified as a TH2 cytokine.

Answer 14

►D Chemotaxis is the process of cells moving through a gradient of towards increasingly higher concentrations. IL-8 has activating and chemoattractant properties on neutrophils.

Answer 15

►A A report of 13 patients indicated IgA is most commonly associated with EED.

Answer 16

►E Interferon gamma is Th1 cytokine which downregulates Th2 responses. The remaining are Th2 cytokines active in atopic dermatitis. IL-4 is a B-cell growth factor and active in signaling isotope switching from IgM to IgE. IL-5 is an eosinophil growth factor. IL-10 downregulates Th1 immunity and IL-13 signals isotope switching along with IL-4.

Answer 17

►E HLA-DQ (A1*0501, B1*02) genes are present on 90% of all patients with Dermatitis Herpetiformis. The remainder of patients have the HLA-DQ8 gene. Other associations include: HLA-B8, HLA-DR3 and DR5/DR7.

Answer 18

►A Autoimmune thrombocytopenia has been reported with hepatitis C infection but not as commonly as autoimmune thyroiditis.

Answer 19

►A Psoriatic arthritis, as well as generalized psoriasis,is associated with HLA-B27. HLA-Cw6 is associated with psoriasis, Bw35 with cutaneous lichen planus, B8 with oral lichen planus, and B51 with Behcet's disease.

Answer 20

►C Calcium. Both pimecrolimus and tacrolimus penetrate cutaneous T-cells, forming a complex with calcineurin, which blocks the activation of NF-AT, thus blocking the transcription of a variety of genes with a resultant decrease in T-cell mediated inflammation. This pathway is calcium dependent. The other ions are not involved in this process.

Answer 21

►D NK cells focus on the destruction of infected or malignant cells. They achieve this via recognition of IgG on target cells, the so-called 'antibody-dependent cellular toxicity.' NK cells also eliminate cells by secreting perforin, which makes holes in the cell membrane, through which granzyme is injected. Granzyme induces apoptosis by activating the caspase cascade. In addition, NK cells do not target cells expressing MHC class I molecules on their surface; some virus downregulate MHC class I molecules to evade recognition by cytotoxic T cells, which may make them susceptible to NK cell attack. Neutrophils kill ingested organims using myeloperoxidase.

Answer 22

►A Erlotinib, along with cetuximab and gefitinib, are epidermal growth factor receptor inhibitors that are used for the treatment of multiple visceral malignancies, including metastatic colon cancer. They have all been associated with an acneiform eruption.

Answer 23

►A Tacrolimus and pimecrolimus are non-steroidal calcineurin inhibitors that act as antiinflammatory medications. In dermatology, they are most commonly used in topical preparations. These medications form complexes with FK506 binding protein, which inhibits calcineurin activity. A key regulatory step in the activation of T cells is the activation of calcineurin via calmodulin.

Answer 24

►A Keratinocytes express MHC Class I molecules and therefore can be attacked by CD8+ Tc cells, in particular after viral infection. Although keratinocytes do not express MHC Class II molecules under normal conditions, they can be induced to do so in the setting of inflammatory conditions.

Answer 25

►A “oBsonization” The classical pathway of complement is activated by antigen-antibody complexes. C3a is a neutrophil chemoattractant. C3b is an opsonin. C5a is an anaphylatoxin. C5b forms a part of the membrane attack complex.

Answer 26

►A The involvement of T cells in the pathophysiology of psoriasis vulgaris is well-recognized. Availability of monoclonal antibodies has allowed for extensive characterization of T cell subsets and other mediators increased in psoriasis lesions. CD8+ T cells are highly concentrated in psoriatic epidermis and studies have demonstrated increased IL-2R and HLA-DR surface molecules indicative of persistent activation. Clonal expansion of CD8+ T cells has been observed suggesting that this subset is the major antigen-reactive population.

Answer 27

►A IL-1 is a pyrogenic cytokine responsible for the fever in sunburn. It also is causes B cell maturation and proliferation and NK cell activation.

Answer 28

►D Major basic protein is the only protein located in the core of an eosinophil. Eosinophil cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase are all located in the matrix. Chymase is a mediator stored in granules of a mast cell.

Answer 29

►B IgA paraproteinemia has been reported in over 10-18% of pyoderma gangrenosum.

Answer 30

►A IL-4 is a B cell growth factor. IL-5 is an eosinophil growth factor. IL-10 is a general downregulator of TH1 immunity. IL-13 (along with IL-4) promotes an isotype switch from IgM to IgE. IFN- gamma is not a TH2 cytokine. It is secreted by TH1 cells, and is the main macrophage activating cytokine.

Answer 31

►B Mast cells are an integral portion of immediate type hypersensitivity. CD3 is a T cell marker.

Answer 32

►A Hepatitis C infections can present as urticaria or papable purpura and cryoglobulinemia.

Answer 33

►A The picture shows Kaposi's scarcoma(KS). It is controversial whether KS represents neoplasia or hyperplasia; all clinical variants are viewed as a virally induced disease - human herpesvirus 8 (HHV-8) is the suspected agent. Cutaneous lesions present as variably distributed pink patches, blue-violet to black nodules or plaques, and polyps, depending on clinical variant and stage. Variable staining can occur with CD31, CD34, Ulex europaeus and factor VIII-related antigen. CD XIIIa is positive in dermatofibroma.

Answer 34

►D Hydroa vacciniforme a photodermatitis that typically occurs with sun exposure in the spring has been reported with NK/T cell lymphomas in childhood.

Answer 35

►E In the skin, histamine is mainly contained within the granules of dermal mast cells. Histamine is present in mast cells, basophils, and platelets.

Answer 36

►B Allergies to nickel (Ni(2+)) are the most frequent cause of contact hypersensitivity (CHS) in industrialized countries. The efficient development of CHS requires both a T lymphocytespecific signal and a proinflammatory signal. Ni(2+) triggers an inflammatory response by directly activating human Toll-like receptor 4 (TLR4). Studies with mutant TLR4 proteins revealed that the non-conserved histidines 456 and 458 of human TLR4 are required for activation by Ni(2+) but not by the natural ligand lipopolysaccharide.

Answer 37

►A Desmoglein 3 is the dominant target auto-antigen in pemphigus vulgaris and is in the cadherin family.

Answer 38

►E IL-8 is primarily responsible for the stimulation of neutrophils. IL-5 stimulates eosinophils. IL-4 stimulates mast cells and IgE isotype switching

Answer 39

►D HHV-8 has been repeatedly associated with all forms of Kaposiǁs sarcoma.

Answer 40

►E Superantigens are able to bypass many elements of the normal immune response. They are not processed by antigen presenting cells. Instead, they bind directly to the MHCII complex and interact with T cells in a relatively non-specific fashion. Whereas conventional antigens require recognition in all 5 elements of the T-cell receptor (V-alpha, J-alpha, V-beta, D-beta, J-beta), superantigens are recognized by V-beta alone.

Answer 41

►A Eosinophils provide many functions of the immune system, including protection against helminths. They are activated by IL-5.

Answer 42

►B Relapsing polychondritis has been reported to have autoantibodies to type II collagen.

Answer 43

►B C3 is the central component of the complement cascade. It plays a key role in the opsonization of bacteria. An autosomal recessive deficiency of C3 may result in susceptibility to pyogenic infections, glomerulonephritis, and partial lipodystrophy.

Answer 44

►C IL-5 is an eosinophil growth factor. IL-10 is a general down-regulator of TH1 immunity. IL-13 (along with IL-4) promotes an isotype switch from IgM to IgE. TNF and IFN -gamma are TH1 cytokines. IFN-gamma is secreted by TH1 cells, and is the main macrophage-activating cytokine.

Answer 45

►B This description of the skin disorder is compatible with either erythema multiforme or erythema elevatum diutinum, both of which have been reported in association with HSV.

Answer 46

►D ICAM-1 on the antigen presenting cell interacts with LFA1 on the T-cell. By interrupting this interaction, T-cell activation is blocked by preventing the pairing of LFA1 with ICAM -1. This prevents costimulatory signals from being given to the T-cell. T-cell ability to traffic into the skin is also inhibited in the arrest stage of trafficking.

Answer 47

►A The answer is atopic dermatitis. Cathelicidin 37 (LL-37) and Human Beta 2 Defensins (HBD-2) have been reported reduced in atopic dermatitis and normal or elevated in psoriasis. This could be one factor that predisposes atopics, but not psoriatics to bacterial and viral infections.

Answer 48

►D Nickel is found in virtually all metals of common use. It is the most common sensitizer in women, and is detected by the dimethylglyoxime test.

Answer 49

►A The classical pathway of complement is activated by antigen-antibody complexes. C3a is a neutrophil chemoattractant. C3b is an opsonin. C5a is an anaphylatoxin. C5b forms a part of the membrane attack complex.

Answer 50

►B IgG opsonizes bacteria, fixes complement, neutralizes bacterial toxins and viruses, crosses the placenta. It has the highest serum concentration of all immunoglobulins.

Answer 51

►A IPEX syndrome is a rare x-linked disorder. Mutation of FOXP3 results in absence of regulatory T cells and is the cause of this syndrome, which includes immune dysregulation, polyendocrinopathy, and enteropathy.

Answer 52

►B IFN-gamma is the main macrophage-activating cytokine, and is secreted by TH1 cells.

Answer 53

►A Effects of UV radiation on the immune system: UV radiation inhibits function of Langerhans cells (A-False). It causes DNA damage, can reactivate HSV, suppresses immune system, and can induce allergic hypersensitivity reaction

Answer 54

►B Ipilimumab is an anti-CTLA 4 receptor antibody. Side effects include rash and coitis. Vemurafenib is a BRAF inhibitor specifically for patients with V600E mutation. Vismodegib inhibits the hedgehog signaling pathway.

Answer 55

►D Supplemental vitamin E can inhibit platelet function and predispose to hemorrhagic stroke. It can be particularly hazardous in patients with beta-thalassaemia mutations.

Answer 56

►E Autoantibodies to tissue transglutaminase are an area of active investigation in both celiac disease and dermatitis herpetiformis.

Answer 57

►C Cutaneous lymphocyte antigen (CLA) allow memory T cells to home to the skin, where it binds to its ligant E-selectin on cutaneous microvessels. Transmigration of memory T cells into the dermis, however, further requires interaction between leukocyte functional antigen 1 (LFA-1) and ICAM-1, and B-integrin very late antigen 4 (VLA-4) and VCAM-1. L-selectin is expressed on post-capillary venules in the lymph nodes and serves as the attachment points for naive T cells.

Answer 58

►C Oxybenzone is the most common sunscreen agent causing photoallergic contact dermatitis. Patients sensitive should be instructed to avoid sunscreens containing oxybenzone.

Answer 59

►C This patient has pemphigus folicaceus, and indirect immunofluorescence works best on guinea pig esophagus.

Answer 60

►B Rituximab targets the CD20 antigen which is predominantly expressed on mature B cells but not plasma cells, T cells, or dendritic cells. Therefore, even when used in antibody-mediated diseases (such as pemphigus vulgaris), the response to therapy requires a long duration of time as the drug targets B cells which must then differentiate into plasma cells that ultimately produce the pathogenic antibodies in their secreted form.

Answer 61

►C IgE is an anaphylactic antibody that is involved in nearly all immediate allergic and anaphylactic type reactions and commonly seen in elevated levels in patients with atopic dermatitis. Mast cells, basophils, Langerhans cells, dermal dendritic cells as well as monocytes from atopic individuals all express high-affinity FcERI receptor which can bind IgE. More recently, it became clear that can bind monomeric IgE via the high-affinity FcRI IgG is the antibody that can cross the placenta and the most common antibody found in circulation. IgA is found in mucous membrane secretions and is able to agglutinate antigens and activate the alternate but not the classic complement pathway. IgD is not found in circulation other than in hyper-IgD syndrome, an autosomal recessive disorder caused by mutations in the mevalonate kinase gene. A significant elevation of serum IgD is seen in 95% of these patients. IgM is the antibody produced in the early stages of antibody responses. It is a pentamer which can agglutinate antigen and active the classic complement pathway.

Answer 62

►B C4 is the best screening test for hereditary angioedema (Quinke's edema). There are two types of hereditary angioedema. In type I, there are low antigenic and functional levels of a NORMAL C1 esterase inhibitor protein. In type II, there is a normal or elevated level of a DYSFUNCTIONAL C1 esterase inhibitor. The low C4 level is a result of continuous activation and consumption of complement components.

Answer 63

►E Psoriasis is linked with HLA-Cw6. Patients with this HLA type have a relative risk of having psoriasis that is 9-15 times normal.

Answer 64

►D The major hisotcompatibility complex (MHC) consists of a linked set of genes encoding for MHC Class I, Class II, Class III, and Class IB. The level of Class I and II expression can be modulated by cytokines.

Answer 65

►A MHC class I molecules bind stably to peptides derived from proteins sythesized and degraded in the cytosol, while MHC class II molecules bind stably to peptides derived from proteins degraded in endocytic vesicles. MHC class I molecules bearing viral peptides are recognized by cytotoxic T- cells that subsequently kill the infected cell. MHC Class II molecules bearing peptides trigger helper T-cells and are recognized by TH1 or TH2 cells. Class I molecules such as HLA-A, B, and C, are present on all nucleated cells, whereas Class II molecules are on B cells, monocytes, dendritic cells, and are inducible on keratinocytes and endothelial cells. The MHC is located on chromosome 6 in humans, its polygenic and polymorphic nature contributes to the ability of the immune system to respond to a multitude of different and rapidly evolving pathogens.

Answer 66

►A CR1 (also known as CD35) is the main receptor for C3b. It plays an important role in mediating clearance of immune complexes, phagocytosis, and immune adherence of antibody-coated bacteria to erythrocytes.

Answer 67

►C Desmoglein 1, the dominant target antigen of the autoantibody involved in pemphigus foliaceus, is also the target of the exfoliative toxin of group II staphylococcus aureus that is usually responsible for bullous impetigo.

Answer 68

►B Vancomycin is an antibiotic frequently used in subjects allergic to penicillin. It has been reported to produce subepidermal blistering disease with linear IgA deposits.

Answer 69

►B Behcet's is a triad that includes oral ulcerations, genital ulcerations and uveitis. Behcet's also displays arthritis and gastrointestinal disease. Blindness is the most-feared outcome, and relates to the uveitis.

Answer 70

►A Denileukin diftitox is a fusion of a fragment of diphtheria toxin and IL-2. It binds to high affinity IL-2 (CD25) receptors on T cells. As the medication is internalized, the toxin leads to cell death. This medication has been approved for cutaneous T cell lymphoma.

Answer 71

►E IgM is the antibody produced in the early stages of antibody responses. It is a pentamer which can agglutinate antigen and active the classic complement pathway. IgG is the antibody that can cross the placenta and the most common antibody found in circulation. IgA is found in mucous membrane secretions and is able to agglutinate antigens and activate the alternate but not the classic complement pathway. IgD is not found in circulation other than in hyper-IgD syndrome, an autosomal recessive disorder caused by mutations in the mevalonate kinase gene. A significant elevation of serum IgD is seen in 95% of these patients. IgE is an anaphylactic antibody that is involved in nearly all immediate allergic and anaphylactic type reactions.

Answer 72

►D Eotaxin, which attracts eosinophils, is produced by T cells in Kimuraǁs disease.

Answer 73

►B The Langerhans cell phagocytizes the haptens in the epidermis or dermis, begins the process of maturation and migrates to the regional lymph node, where naǁve T-cells are educated to expand to a clone of CLA positive memory T-cells. These cells then can expand and extravasate with subsequent exposure to the same allergen. Melanocytes, B-cells, Mast cells and macrophages are not involved in the sensitization process of allergic contact dermatitis.

Answer 74

►B Lepromatous leprosy is Th2 biased. The remaining conditions are Th1 predominant responses. Leishmaniasis which show strong cell-mediated immunity to the parasite and with self-resolving lesions are Th1 responses. In indolent/progressive leishmaniasis, a Th2 pattern is predominant.

Answer 75

►C The sensitizer in rhus dermatitis is a pentadecacatechol found in the oleoresin of anacardaciae plants, including poison ivy/oak/sumac, mango rinds (but not pulp), cashew nutshells and oil, Indian marking nut oleoresin, gingko fruit pulp, and Japanese lacquer tree oleoresin.

Answer 76

►E Wiskott-Aldrich syndrome is an X-linked recessive disorder that presents with thrombocytopenia, small defective platelets, eczema, autoimmune disease, infections, and lymphoreticular malignancy. 101- Which of the following diseases occur with an increased frequency in persons deficient in C2? A. Psoriasis B. Dermatitis Herpetiformis C. Androgenetic Alopecia D. DLE E. Leiner's disease

Answer 77

►D Among the complement deficiencies, C2 deficiency is most frequently seen. Most of these patients are healthy. Diseases that occur with increased frequency in patients with C2 deficiency are SLE, SLE-like syndrome, frequent infections, anaphylactoid purpura, lethal dermatomyositis, vasculitis, disseminated cutaneous lupus erythematosus, and cold urticaria.

Answer 78

►A HLA-DR3 is the most commonly found HLA association in herpes gestationis. HLA-DR4 is also found in addition to HLA-DR3 in about 50% of patients. There is nearly 100% incidence of antiHLA antibodies patients affected by herpes gestationis.

Answer 79

►B Bacteria can induce inflammation through activation of Toll receptors, which are present on a variety of cutaneous cells including macrophages, dendritic cells, keratinocytes, and mast cells. Typically, Toll 2 receptors are activated by peptidoglycans and lipoproteins on the surface of gram positive bacteria and yeast. Toll 4 receptors are activated by lipopolysaccharides on the surface of gram negative bacteria. Nuclear factor kappa B is a final common pathway of toll receptors and other immune receptors involved in initiating a variety of proinflammatory cytokines.

Answer 80

►E IL-22 has recently been shown to be critical in causing epidermal acanthosis. Interleukin (IL)-23, a cytokine involved in the development of IL-17-producing T helper cells (Th17 cells), was found to have a potential function in the pathogenesis of psoriasis. IL-22 is preferentially produced by Th17 cells and mediates the acanthosis induced by IL-23. IL-23 can directly induce the production of IL-22 in human naive T cells. Furthermore, IL-22 mediates IL-23-induced acanthosis and dermal inflammation through the activation of Stat3.

Answer 81

►B Imiquimod is a topical immunomodulator that increases a variety of cytokines including interferon- alpha.

Answer 82

►D Alefacept is a soluble form of LFA-3 that blocks the immunologic synapse between CD2 on the T cell and LFA-3 on the antigen presenting cell. Furthermore, alefacept targets CD2+ activated T cells for apoptosis.

Answer 83

►B This rare chronic bullous disease of childhood is a subepidermal blistering disease with a homogeneous IgA deposits at the epidermal basement membrane. This occurs in children usually less than 5 years of age.

Answer 84

►A HLA-B27 is associated with an increase in psoriatic arthritis as well as pustular psoriasis and acrodermatitis continua of Hallopeau.

Answer 85

►D Dermatitis herpetiformis is associated with HLA-B8, -DR3, and -DQw2.

Answer 86

►A Patients allergic to the peel of a mango can also be allergic to other plants/products of the Anacardiaceae family. Cross-reactions can occur with exposure to any plants of the genus Toxicodendron, to the oil from the cashew nut shell, to the Brazilian pepper tree, to lacquer from the Japanese lacquer tree, to ink from the Indian marking nut, and to the fruit pulp of the ginkgo tree, and others.

Answer 87

►C HLA-CW6 has been seen in up to 90% of patients with early onset psoriasis, 50% with late onset psoriasis and only 7.4% of the general population. HLA-DR1 and DR4 are both related to Rheumatoid Arthritis and have a 7x increased relative risk (RR) for developing disease. HLAB27 is linked to ankylosing spondylitis, postinfection arthridites and Reiterǁs disease, with increase relative risks of 100x, 10-20x, and 35x respectively.

Answer 88

►B The geometric pattern of erythema suggests "outside job". Allergic contact dermatitis is a delayed type hypersensitivity reaction mediated by Th2. The cytokines up-regulated in this process are IL-4, 5, 10.

Answer 89

►B MHC Class I molecules are present on all nucleated cells. They are recognized by receptors on surfaces of CD8+ T cells, and, when complexed with antigen, trigger cytotoxic T cells. The other statements apply to MHC Class II molecules.

Answer 90

►A MHC Class II molecules are on B cells, monocytes, dendritic cells, and are inducible on keratinocytes and endothelial cells.

Answer 91

►E NEMO/IKK gamma is an essential component of the nuclear factor kappa B pathway, which is a common signaling pathway for many cytokines. Mutation in this pathway have been found to cause incontinentia pigmenti.

Answer 92

►B NK cells do not express CD 3 molecules. The other statements are true. Nk cells express CD2.

Answer 93

►A Tuberculoid leprosy is characterized by a type I immune related response. Tuberculoid leprosy has increased amounts of TH1 cytokines including IL-2, interferon gamma, and IL-12. These lead to a t-cell and macrophage mediated cytotoxic response. IL-4, IL-5, and Il-10 are typically downregulated in tuberculoid leprosy.

Answer 94

►C IgE is an anaphylactic antibody that is involved in nearly all immediate allergic and anaphylact ic type reactions and commonly seen in elevated levels in patients with atopic dermatitis. Mast cells, basophils, langerhans cells, dermal dendritic cells as well as monocytes from atopic individuals all express high-affinity FcRI receptor which can bind IgE. More recently, it became clear that can bind monomeric IgE via the high-affinity FcRI IgG is the antibody that can cross the placenta and the most common antibody found in circulation. IgA is found in mucous membrane secretions and is able to agglutinate antigens and activate the alternate but not the classic complement pathway. IgD is not found in circulation other than in hyper-IgD syndrome, an autosomal recessive disorder caused by mutations in the mevalonate kinase gene. A significant elevation of serum IgD is seen in 95% of these patients. IgM is the antibody produced in the early stages of antibody responses. It is a pentamer which can agglutinate antigen and active the classic complement pathway.

Answer 95

►E Mast cells are the central cell in immediate-type hypersensitivity, and are very important in cutaneous inflammation. They reside near small blood vessels, and when activated release substances that affect vascular permeability. They orchestrate allergic responses and protect mucosal surfaces against pathogens. They have receptors for IgE and certain fragments of complement on their cell surface.

Answer 96

►D A urinalysis should be ordered in patients with palpable purpura. Red blood cells and proteinuria are often seen in Henoch-Schönlein syndrome.

Answer 97

►A Langerhans cells are important dendritic antigen-presenting cells in the epidermis and mucosa. The characteristic Birbeck granules are part of the endosomal recycling compartment.

Answer 98

►B Dermatofibroma, the more common benign histiocytoma, is usually CD34 negative and factor XIIIa positive. DFSP is usually CD34 positive and factor XIIIa negative.

Answer 99

►A In a typical humoral response, isotype switching occurs subsequent to exposure to antigen. Switching is regulated by T cell derived cytokines. IgG is promoted by IL-4, IL-6, IL-2 and IFNgamma. IgA is promoted by IL-5 and TGF-beta. IgE is promoted by IL-4.

Answer 100

►C Infliximab is a monoclonal antibody given intravenously that binds to membrane-bound and soluble TNF-alpha.

Answer 101

►B The appropriate screening test for a complement deficiency is the CH50. The CH50 will detect deficiencies in the classical pathway and membrane attack pathways.

Answer 102

►D IgG is the antibody that can cross the placenta and the most common antibody found in circulation. IgA is found in mucous membrane secretions and is able to agglutinate antigens and activate the alternate but not the classic complement pathway. IgD is not found in circulation other than in hyper-IgD syndrome, an autosomal recessive disorder caused by mutations in the mevalonate kinase gene. A significant elevation of serum IgD is seen in 95% of these patients. IgE is an anaphylactic antibody that is involved in nearly all immediate allergic and anaphylactic type reactions. IgM is the antibody produced in the early stages of antibody responses. It is a pentamer which can agglutinate antigen and active the classic complement pathway.

Answer 103

►A Toll-like receptors are pattern recognition receptors involved in innate immunity. They are most highly expressed on monocytes, dendritic cells, and B cells. Imiquimod works through binding to toll-like receptor 7. The native ligand for TLR7 is single-stranded RNA.

Answer 104

►B HLA-B51 has been reported with increased relative risks in European, Asian and Middle Eastern populations.

Answer 105

►A Neutrophils' major function is phagocytosis. The other statements are correct.

Answer 106

►B The complement system plays an important role in innate immunity. Of this group, C5a is the most powerful neutrophil chemoattractant. C3 represents the endpoint for the classic, alternative and lectin pathways, and results in the generation of immunologically active substances. C3a and C4a cause mast cell degranulation. Assembly of C5b, C6, C7, C8, C9 components results in the membrane attack complex (MAC), which perforates cell membranes causing death by osmotic lysis.

Answer 107

►A Latex allergy is a TH2 form of contact sensitivity that is IGE mediated. Using the old Gel and Coombs classification, it was classified as type I hypersensitivity.

Answer 108

►C Neutrophils, eosinophils, and basophils are collectively known as granulocytes. Neutrophils have receptors for IgG and complement. IL-5 enhances all functions of eosinophils. Langerhans cells are dendritic cells found in high concentration in epithelial surfaces and some areas of lymph nodes and spleen. They have a high density of class II MHC molecules and express CD1 on their surface. They are poorly phagocytic.

Answer 109

►D The lesion is high immune or tuberculoid leprosy, which is associated with TH1 cytokines including IFN-gamma, IL2, IL12, IL15, IL18 and IL23.

Answer 110

►A Alefacept is a human fusion protein of LFA-3 with Fc protion of IgG1. It binds CD2 on CD45RO memory effector T cells, thus blocking the 2nd signal of T cell activation and leading to apoptosis. A provider must monitor the CD4 T cell count while a patient is on this medication.

Answer 111

►B Textile dermatitis has been reported to be associated with purpuric contact dermatitis.

Answer 112

►A Langerhans' cell function primarily in the afferent limb of the immune response by providing for the recognition, uptake, processing, and presentation of antigens to sensitized T lymphocytes. They are normally found scattered among keratinocytes of the stratum spinosum, or prickle cell layer. of the epidermis. They can be stained with CD1a or S-100. They originate in the bone marrow. They contain intracytoplasmic Birbeck granules.

Answer 113

►E IL-8 is chemotactic for neutrophils. The other cytokines elicit other types of immune cells, IL-2 (T- ells), IL-3 (mast cells), IL-5 (eosinophils), IL-6 (plasma cells).

Answer 114

►A The answer is bullous pemphigoid, which shows a characteristic antibasement membrane antibody to Bp180.

Answer 115

►C Interferon-gamma is the main cytokine secreted by Th1 CD8+ effector T -cells and is active in blocking viral replication. IL-2 is also released in Th1 reactions and causes T cell proliferation and differentiation, macrophage, NK, & Tc cell activation. It also acts as a Th1 autocrine growth factor. IL-1 is a pro-inflammatory cytokine and a pyrogen. IL-4 is a B-cell growth factor and active in signaling isotope switching from IgM to IgE. IL-5 is an eosinophil growth factor. Both IL-4 and -5 are secreted by Th2 T-cells.

Answer 116

►A The answer is pemphigus vulgaris, which typically has autoantibodies to desmoglein 3. While mixed forms of pemphigus can occur, the histology in this case confirmed pemphigus vulgaris.

Answer 117

►C “You want to Exit Efalizumab? No.” Efalizumab is a humanized monoclonal antibody to CD11a that blocks the immunologic synapse between LFA-1 on the T-cell and ICAM-1 on the antigen presenting cell. By targeting LFA-1 efalizumab specifically blocks the ability of T cells to leave the vasculature and enter the skin.

Answer 118

►D Predisposition to sporadic and occasionally recurrent meningococcal disease occurs in patients with congenital or acquired complement deficiencies, particularly late acting components C5-9

Answer 119

►A Langerhans cells are dendritic cells found in high concentrations in epithelial surfaces and some areas of lymph nodes and spleen. They express CD1 on their surface and have a high density of Class II MHC molecules. They are poorly phagocytic.

Answer 120

►A Neutrophils are the most abundant leukocyte. The major function of neutrophils is phagocytosis.

Answer 121

►A The answer is gamma interferon, which is the TH1 cytokine associated with a hyperproliferative epidermis and with micaceous scale as seen in psoriasis.

Answer 122

►D Prolene is a nonabsorbable suture material that evokes only minimal inflammation.

Answer 123

►A Anti-centromeric antibodies are associated with CREST syndrome. Anti-RNP antibodies are associated with MCTD, anti-dsDNA, ssDNA, and Sm associated with SLE, anti-Jo-1 associated with polymositis, and anti-Scl 70 associated with PSS.

Answer 124

►A The Jarish-Herxheimer reaction may occur after the initiation of treatment of many systemic infections including syphillis. It is an indirect drug induced effect caused by bacterial endotoxins or microbial antigens liberated by the destruction of micro-organisms. Clinical manifestations may include fever, lymphadenopathy, arthralgias, and exacerbation of pre-existing cutaneous lesions. Tumor necrosis factor-alpha is the primary cytokine that mediates this reaction.

Answer 125

►B IL-23 facilitates the differentiation and induces complete maturation of Th17 cells. Lesional psoriatic skin has increased levels of IL-23. IL-6 is essential for development of the IL-23elicited responses and is required for the development of epidermlal hyerplasia.

Answer 126

►D Psoriasis is generally described as a TH1 autoimmune disease where IL-12/IFN-gamma pathway is dominant. IL-10 is the prototype of TH2 and calcipotriene application results in increased levels of IL-10, thus decreasing TH1 disease.

Answer 127

►D Sezary syndrome is the leukemia phase of mycosis fungoides (cutaneous T-cell lymphoma) and is usually a TH2-biased CD4+ leukemia.

Answer 128

►B MHC/TCR engagement occurs without costimulatory molecules. MHC Class III molecules are not involved in this process. The MHC III region encodes for soluble proteins of the complement cascade and the tumor necrosis family. Fas-FasL interactions promote apoptosis on the target cell, not stimulation. IL-2 is a stimulatory molecule, produced by Th1 T-cells. It does not produce anergy. HLA-DM facilitates loading of proteins processed by antigen presenting cells into the MHC class II molecule before being brought to the cell surface.

Answer 129

►A CD40 activation on B cells by CD40-ligand (CD154) on T cells induces isotype switching from an IgM to IgG response. Defects in the expression of CD40-ligand result in an immunodeficiency state (hyper-IgM syndrome) characterized by low levels of IgG, IgA and IgE, but elevated IgM. CD19, CD20, CD22 are pan-B cell markers.

Answer 130

►E TLRs recognize pathogen-associated molecular patterns (PAMPs) present in a variety of pathogens and activate signaling pathways involved in innate immunity, as well as augmenting adaptive immunity. The mechanism of action of imiquimod involves activation of these pathways via TLR7. None of the other medications listed above involve TLRs as their main mechanism of action.

Answer 131

►D Chronic idiopathic urticaria is associated with HLA -DR4, -DRB4, and -DQ8.

Answer 132

►E This patient likely has a fragrance allergy. Patients allergic to fragrances also need to avoid certain spices like cinnamon.

Answer 133

►C IL-23 and Th17 cells producing IL-17A and IL-22 are found in excess in skin affected by psoriasis. IL-6, IL-22, and IL-17A have all been shown to be critical in mediating epidermal hyperplasia in psoriasis in response to IL-23.

Answer 134

►D The lesion is low immune or lepromatous leprosy, which is associated with TH2 cytokines including IL-4, IL-5, IL-10, and IL-13.

Answer 135

►A Tacrolimus and pimecrolimus are topical macrolide immunomodulators that inhibit lymphokine or cytokine production via binding to macrophilin. This complex inhibits calcineurin, a phosphatase involved in the activation of NF-AT. This suppresses the production of IL-2 and IFN-gamma (TH1 cytokines) as well as IL-4, 5 and 13 (TH2 cytokines). In addition, they decrease the expression of IgE receptors on Langerhans cells and reduce mast cell degranulation.

Answer 136

►C The Th2 response is important in promoting humoral immunity. IL-4 promoted Th2 differentiation, isotype switching and inhibition of macrophages. IL-5 activates eosinophils. IL-6 assists in the proliferation and differentiation of B cells. IL-10 decreases expression of MHC II. IL-13 is related to IL-4, and is implicated in allergic inflammation.

Answer 137

►A EBV utilizes the CR2 receptor for cell entry and infection. the CR2 receptor (also known as CD21) presents antigen to B cells and is a co-receptor for B cell signalling.

Answer 138

►A Activation of T cells requires two signals. The first is T cell receptor binding to MHC molecule on the antigen presenting cell. THe second signal involves CD28 on T cell interacting with B7 molecules on the antigen presenting cells. CD80 is expressed on Langerhans cells after activation. CD1a is a Langerhans cell surface marker.

Answer 139

►C IL-5 is critical in the development and maturation of eosinophils. IL-2 is an autocrine factor for activated T cells. IL-4 is involved in B-cell class switching and Th2 differentiation. IFN-alpha is a major part of the antiviral response. IFN-gamma is involved in macrophage activation and specific isotype switching.

Answer 140

►E Mononuclear phagocytes are components of the innate immune system. Once in tissues they are called macrophages. All of the above are correct.

Answer 141

►C The classical complement pathway is activated by antigen-antibody complexes, while the alternate complement pathway can be activated in the absence of antibody. IgM and IgG are capable of activating the classical pathway, but IgG4 does not activate complement. The proteins of the classical pathway are C1, C2, C3, and C4. Factor B, Factor D, properdin, and C3 are proteins in the alternate pathway. Biologic activities of complement include opsonization, chemotaxis, anaphylaxis, immune complex solubilization, membrage damage, and B cell activation.

Answer 142

►B Activation of natural killer cells occurs via interleukin 2 (IL-2). IL-2 is a key component of the Th1 (cell-mediated) immunity. It acts to promote growth, proliferation and activation of T cells, B cells and natural killer cells.

Answer 143

►E Proteins in the alternate complement pathway are Factor B, Factor D, properdin, and C3. The alternate complement pathway is active against pathogenic microorganisms, virus-infected cells, and neoplastic cells. The proteins of the classical pathway are C1, C2, C3, and C4.

Answer 144

►B Systemic lupus erythematous is associated with a Th2 cytokine profile, whereas the other conditions are associated with a Th1 cytokine profile. Th2 cells are typified by secretion of IL-4, IL-5, IL-6, IL-9, IL-10 and IL-13, whereas Th1 cells are typified by secretion of IFN-gamma, TNF-beta, and IL-2.

Answer 145

►A Oral lichen planus is a relatively common condition that can cause significant morbidit y. Oral lichen planus is associated with HLA-B8. HLA-Cw6 is associated with psoriasis, Bw35 with cutaneous lichen planus, B27 with psoriatic arthritis, and B51 with Behcet\'s disease.

Answer 146

►E Naive T cells express CD45RA whereas memory T cells express CD45RO. CD19, 20, and 79 are B cell surface markers.

Answer 147

►A CD2 molecules are T cell surface receptors that bind to LFA-3 on endothelial cells and antigen presenting cells to participate in adhesion and activation.

Answer 148

►A Pemphigus is associated with HLA-DR4 or DRw6.

Answer 149

►B The MHC is highly polygenic and polymorphic, and this contributes to the ability of of the immune system to respond to a multitude of different and rapidly evolving pathogens. The MHC is located on chromosome 6 in humans.