Immune Dysfunction

Front 1

What are lymphocytes?

Back 1

1) B cells
2) T cells
3) Natural Killer (NK) cells
4) Identified by cell-surface glycoproteins specific for both cell type and stage of differentiation.

Front 2

What are B cells?

Back 2

1) Originate from stem cells in the bone marrow.
2) Continue their differentiation within the bone marrow and peripherally, where they cluster in the germainal center of lymph nodes and in the lymphoid follicles of the spleen.
3) Characterized by the presence of surface immunoglobin.
4) Account for approximately 15% of circulating peripheral blood lymphocytes.

Front 3

What are T cells?

Back 3

1) Originate from stem cells in the bone marrow and differentiate in the thymus.
2) Populate the paracortical and deep medullary areas of lymph nodes and periarteriolar sheaths of the spleen.
3) Account for approximately 70% of circulating peripheral blood lymphocytes.

Front 4

What are the subclasses of T cells?

Back 4

1) CD4; account for approximately 60% of circulating T cells.
2) CD8; account for approximately 30% of circulating T cells.
3) the normal 2:1 ratio is dramatically altered in some disease states.

Front 5

What are natural killer cells?

Back 5

1) Also called large granular lymphocytes because of their distinctinve large size, pale cytoplasm, and prominent granulation.
2) Secrete a variety of cytokines, including interleuking-1, as well as other products, including acid hydrolases, neutral proteases, and prostaglandins.

Front 6

What are Macrophages?

Back 6

1) Derivatives of peripheral blood monocytes adn are members of the mononuclear phagocyte system of cells.
2) Secrete a variety of cytokines, including IL-1, as well as other products, including acid hydrolases, neutral proteases, and prostaglandins.
3) Process and present antigen to CD4.
4) Participate in delayed hypersensitivity reactions.
5) May be capable of directly killing tumor cells.

Front 7

What are dendritic cells?

Back 7

1) Characterized by dendritic cytoplasmic processes.
2) Express large quantities of cell surface HLA class II antigens.
3) In contrast to macrophages, are poorly phagocytic but resemble macrophages in that they are antigen-presenting cells.

Front 8

What are Langerhans cells of the skin?

Back 8

1) Are marked ultrastructurally by the presence of Birbeck granules, tennis racket-shaped cytoplasmic structures.
2) Similar to dendritic cells of lymphoid tissue in that they express HLA class II antigens and are antigen-presenting cells.

Front 9

What are cytokines?

Back 9

1) Are soluble proteins secreted by lymphocytes, monocytes-macrophages, and NK cells, as well as other cell types.
2) Act as effector molecules influencing the behavior of B cells, T cells, NK cells, monocytes, macrophages, hematopoietic cells, and many other cell types.

Front 10

Describe the complement system.

Back 10

Consists of about 20 plasma proteins and their products, which can be activated by way of the classic or alternate pathway to form a final product - the membrane attack complex - that lyses target cells.

Front 11

What is the source and function of IL-1?

Back 11

Monocytes, macrophages, and other cells.
Stimulates T cell proliferation and IL-2

Front 12

What is the source and function of IL-2?

Back 12

Macrophages, T cells, and NK cells
Stimulates proliferation of T cells, B cells, adn NK cells; activates monocytes.

Front 13

What is the source and function of IL-3?

Back 13

T cells
Acts as growth factor for tissue mast cells and hematopoietic stem cells

Front 14

What is the source and function of IL-4?

Back 14

T cells
Promotes growth of B adn T cells; enhances expression of HLA class II antigens.

Front 15

What is the source and function of IL-5?

Back 15

T cells
Promotes end-stage maturation of B cells into plasma cells.

Front 16

What is the source and function of IL-6?

Back 16

T cells, onocytes, and other cells
Promotes maturation of B and T cells; inhibits gowth of fibroblasts

Front 17

What is the source and function of interferon-alpha?

Back 17

B cells and macrophages
Has antiviral activity.

Front 18

What is the source and function of interferon-beta?

Back 18

Fibroblasts
Has antiviral activity

Front 19

What is the source and function of interferon-gamma?

Back 19

T cells and NK cells
Has antiviral activity; activates macrophages; enhances expression of HLA class II antigens.

Front 20

What is the source and function of Tumor necrosis factor alpha?

Back 20

Macrophages, T cells, and NK cells
Stimulates T cell proliferation and IL-2 production: cytotoxic to some tumor cells.

Front 21

What is the source and function of Tumor necrosis factor-beta?

Back 21

T cells
Stimulates T cell proliferation and IL-2 production; cytotoxic to some tumor cells.

Front 22

What is the Human Leukocyte Antigen (HLA) system?

Back 22

1) Consists of a group of related proteins referred to as HLA antigens. The genes that code for HLA antigens are called histocompatibility genes and are localized to a region on the short arm of chromosome 6, know as the major histocompatibility complex (MHC).
2) Important in organ transplantation, where HLA typing and matching of donor and recipient are now widely used to predict tissue compatibility.

Front 23

What is the classic complement pathway?

Back 23

1) Initiated by reaction with antigen-antibody complexes.
2) The final lytic form of activated complement is the result of a series of enzymatic leavages and recombinations of cleavage products.

Front 24

What is the alternate complement pathway?

Back 24

1) Initiated directly by nonimmunologic stimuli, such as invading microorganisms, and, like the classic pathway, leads to cleavage products that cause cell lysis.
2) Bypasses the initial stages of the classic pathway.

Front 25

What are class I HLAs?

Back 25

1) Include the HLA-A, HLA-B, adn HLA-C antigens, which are found on almost all human cells.
2) Are the principal antigens involved in tissue graft rejection. Serologic testing for HLA-A and HLA-B antigens is used to predict the likelihood of long-term graft survival.

Front 26

What are class II HLAs?

Back 26

1) Chiefly found on immunocompetent cells, including macrophages, dendritic cells, Langerhans cells, B cells, and some T cells.
2) Including the HLA-DP, HLA-DQ, and HLA-DR antigens, identifiable by standard serologic techniques or by mixed lymphocyte reactions, and HLA-D antigens, identifiable only by mixed lymphocyte reactions.

Front 27

What disease is HLA-B27 associated with?

Back 27

90% of cases of ankylosing spondylitis

Front 28

List four disease states that are associated with specific HLA antigens?

Back 28

1) Insulin-dependent diabetes mellitus
2) Rheumatoid arthritis
3) Uveitis
4) Reiter syndrome

Front 29

What is a general definition of the mechanisms of immune injury?

Back 29

1) Adverse reactions cauesd by immune mechanisms are termed hypersensitivity reactions.
2) The classification of Gel and Coombs divides hypersensitivity reactions into four types.
3) Types I, II, and III require the active production of antibody by plasma cells (terminally differentiated B cells).
4) Type IV is mediated by the interaction of T cells and macrophages.

Front 30

Describe the mechanism of type I hypersensitivity.

Back 30

Antigen reacts with IgE bound to surface of basophils or tissue mast cells, causing degranulation with release of histamine and other substances, many of which are vasoactive, smooth muscle spasm-including, or chemotactic.

Front 31

Give four examples of type I hypersensitivity.

Back 31

1) Hay fever
2) Allergic asthma
3) Hives
4) Anaphylactic shock

Front 32

What is the mechanism of type II hypersensitivity?

Back 32

1) Antibodies react with antigens that are intrinsic components of cell membrane or other structures, such as basement membranes, resulting in direct damage, complement-mediated increased susceptibility to phagocytosis, or antibody-dependent cell-mediated cytotoxicity; also may be caused by inactivation of cell-surface receptors by anti-receptor antibodies.

Front 33

List four examples of type II hypersensitivity.

Back 33

1) Warm antibody autoimmune hemolytic anemia
2) Hemolytic disease of the newborn
3) Goodpasture syndrome
4) Graves disease

Front 34

What is the mechanism of type III hypersensitivity?

Back 34

Insoluble complement-bound aggregates of antigen-antibody complexes are deposited in vessel walls or on serosal surfaces or other extravascular sites.
2) Neutrophils are chemotactically attracted adn release lysosomal enzymes, prostaglandins, kinins, and free radicals, resulting in tissue damage.

Front 35

List five examples of type III hypersensitivity.

Back 35

1) Serum sickness
2) Arthus reaction
3) Polyarteritis nodosa
4) SLE
5) Immune complex-mediated glomerular diseases

Front 36

What is the mechanism of type IV hypersensitivity?

Back 36

Delayed hypersensitivity
2) Proliferation of antigen-specific CD4 memory T cells, wiht secretion of IL-2 and other cytokines, which in turn recruit and stimulate phagocytic macrophages
3) May also involve cytotoxic CD8 T lymphocyte kiling of specific target cells.

Front 37

List four examples of type IV hypersensitivity.

Back 37

1) Tuberculin reaction
2) Contact dermatitis
3) Tumor cell killing
4) Virally infected cell killing

Front 38

What is hereditary angioedema?

Back 38

1) Caused by a deficiency of C1 esterase inhibitor
2) Serum C4 is low and other complement components such as C3 are consumed.

Front 39

What is systemic anaphylaxis?

Back 39

Potentially fatal reaction, characterized by the rapid onset of urticaria, bronchospasm, laryngeal edema, and shock after exposure to an offending antigen

Front 40

Describe coomplement-fixing antibodies.

Back 40

1) React directly with antigens that are interal components of the target cell. The interaction of complement with the cell surface results in cell lysis and destruction. Serum complement is characteristically decreased.
2) The antigens involved are usually localized to tissue basement membranes or blood cell membranes.
3) Clinical examples include warme antibody autoimmune hemolytic ease of the newborn, in which the antigens are components of red blood cell cembranes; adn goodpasture syndrome, in which the pulmonary alveolar and glomerular basement membranes are affected.

Front 41

What are antibody-dependent cell-mediated cytotoxicity (ADCC)?

Back 41

1) Antibody reacts directly with integral surface antigens of targeted cells.
2) Free Fc portion of the antibody molecule reacts with the Fc receptor of a variety of cytotoxic leukocytes, most importantly NK cells. Other leukocytes, including monocytes, neutrophils, and eosinophils, also bear Fc receptors and can participate in ADCC.
3) The target cells are killed by teh Fc receptor-bound cytotoxic leukocytes. Complement is not involved.

Front 42

What is the reaction of anti-receptor antibodies with cell-surface receptor protein?

Back 42

1) This variant, sometimes classified separately as type hypersensitivity, is exemplified by the reaction of thyroid-stimulating immunoglobulin with the thyroid-stimulating hormone (TSH) receptor of thyroid follicular cells in Graves disease.
1) In this disorder, the antigen-antibody reaction mimics the effects of TSH on the follicular cells and results in glandular hypeplasia and hyperproductin of thyroid homone with clinical hyperthyroidism.

Front 43

What is serum sickness?

Back 43

1) Systemic deposition of antigen-antibody complexes in multiple sites, especially the heart, joints, and kidneys.
2) In the past, antibody-containing foreign serum was administered therapeutically for passive immunization against microorganisms or their toxic products. Because of the danger of serum sickness, this mode of therapy is no longer employed.

Front 44

What is SLE?

Back 44

Multisystem immune complex disease.

Front 45

What is Arthus reaction?

Back 45

Localized immune complex reaction that occurs when exogenous antigen is introduced, either by injection or by organ transplant, in the presence of an excess of preformed antibodies.

Front 46

What is polyartitis nodosa?

Back 46

Generalized immune complex disease especially involving smal- and medium-sized arteries.

Front 47

What is immune complex-mediated glomerular diseaes?

Back 47

Include poststreptococcal glomerulonephritis, membranous glomerulonephritis, and lupus nephropathy.

Front 48

What are some general considerations of transplant immunology?

Back 48

1) For a successful graft, donor and recipient must be matched for ABO blood groups and, ideally, for as many HLA antigens as possible.
2) Adverse immune responses can be suppressed by immunosuppressant drugs, radiation or recipient T cell depletion. However, these processes can result in clinically significant immunodeficiency.

Front 49

What is a hyperacute rejection?

Back 49

1) Primarily antibody-mediated and occurs in the presence of preexisting antibody to donor antigens.
2) Most often occurs within minutes of transplantation.
3) Localized Arthus reaction marked by acute inflammation, fibrinoid necrosis of smal vessels, and extensive thrombosis.

Front 50

What is acute rejection?

Back 50

1) Primarily T cell-mediated
2) Generally occurs days to months after transplantation.
3) Characterized by infiltration of lymphocytes adn macrophages.
4) May, when antibody-mediated mechanism are prominent, show evidence of arteritis with thrombosis and cortical necrosis.

Front 51

What is chronic rejection?

Back 51

1) Primarily caused by antibody-mediated vascular damage.
2) May occur months to years after an otherwise successful transplantation.
3) Characterized histologically by marked vascular fibrointimal proliferation, often resulting in a small, scarred kidney.
4) Becoming more common with the success of immunosuppressoin in overcoming acute rejection.

Front 52

What is Graft-versus-host disease?

Back 52

1) Significant problem in bone marrow transplantation because immunocompetent cells are transplanted in this procedure.
2) Can also be caused by whole blood transfusion in patients with severe combined immunodeficiency (SCID).
3) Characterized by the rejection of "foreign" host cells by engrafted T and B cells
4) CD8 T cells from graft directly damage host cells
5) cytokines from graft CD4 T cells recruit macrophages, which damage host cells.
6) Clinical features include fever, rash, and hepatosplenomegaly.
7) Principal target organs are liver, skin, and gastrointestinal mucosa.

Front 53

What is X-linked agammaglobulinemia of Bruton?

Back 53

An X-linked disorder that presents in male infants but is usually not manifest clinically until after 6 months of age because of the persistence of maternal antibodies.

Front 54

What are the immune system defects of X-linked agammaglobulinemia?

Back 54

1) Failure of antibody synthesis caused by a block in maturation of pre-B cells to B cells due to a mutation in the tyrosine kinase gene; cell-mediated immunity is unaffected.
2) Absence of plasma cells in tissue, resulting in virtual absence of serum immunoglobulins.
3) Absent or poorly defined germinal centers in lymphoid tissue.

Front 55

What are the effects of X-linked agammaglobulinemia of Bruton?

Back 55

1) Propensity to recurrent bacterial infections with organism such as pneumococci, streptococci, staphylococci, and Haemophilus infuenzae
2) Does not affect resistance to viral and fungal infection or phagocytosis and killing of bacteria by neutrophils.

Front 56

What is Isolated IgA deficiency?

Back 56

1) The most sommon inherited B cell defect, occurring in approximately in 700 persons.
2) Results from the inability of IgA B cells to mature to plasma cells. Other immunoglobuins are normal.
3) Characterized by occasional anaphylactic reactions to transfused blood and infections, especially those involving mucosal surfaces.

Front 57

What is common variable immunodeficiency?

Back 57

1) A diverse group of disorders caused by failure of terminal B cell maturation, resulting in diminution in the number of plasma cells and thus hypogammagloulinemia.
2) Manifest clinically by recurrent bacterial infection.

Front 58

What is DiGeorge syndrome (thymic hypoplasia)?

Back 58

1) A congenital T cell deficiency resulting form aberrant embryonic development of the third and fourth brnachial arches, wiht resultant hypoplasia of the thymus and parathyroid glands as well as abnormalities of the mandible, ear, and aortic arch.
2) characterized by failure of T cell maturation, leading to lymphopenia. B cells remain unimpaired
3) Manifest clinically by recurrent viral and fungal infections and tetany from hypoparathyroidism with hypocalcemia.
4) Can be summed up by the popular acronym CATCH 22, which denotes Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia, and microdeletion of chromosome 22.

Front 59

What is Severe combined immunodeficiency disease (SCID)?

Back 59

1) also known as Swiss-type agammaglobulinemia.
2) Characterized by marked deficiency of both B and T cells manifest as profound lymphopenia and severe defets in both humoral and cell-mediated immunity.
3) Can be caused by a wide variety of genetic defects.
4) Occurs in both autosomal recessive and X-linked forms. Approximately 50% of autosomal recessive cases are caused by adenosine deaminase (ADA) deficiency, which leads to an accumulation of deoxyadenosine and deoxy-ATP, substances that are toxic to lymphocytes.

Front 60

What are the clinical manifestations of SCIDs?

Back 60

1) Severe infections (bacterial, viral, and fungal)
2) High incidence of malignancy
3) Failure to thrive, usually with fatal outcome in infancy.
4) Graft-versus-host disease as a result of blood transfusions.

Front 61

What are the anatomic manifestations of SCIDs?

Back 61

1) Thymic hypoplasia wiht absent or greatly reduced thymic lymphoid component.
2) Hypoplasia of lymph nodes, tonsils, and other lymphoid tissues.

Front 62

What are the treatments for SCIDs?

Back 62

1) Bone marrow or stem cell transplantation
2) ADA gene transplantation

Front 63

What is Immunodeficiency with thrombocytopenia and eczema (Wiskott-Aldrich syndrome)?

Back 63

1) Characterized by eczema, thrombocytopenia, recurrent infections, and poor antibody response to polysaccharide antigens.
2) An X-linked disorder.
3) Most often displays normal total immunoglobulins

Front 64

What is Acquired immunodeficiency syndrome (AIDS)?

Back 64

Caused by human immunodeficiency virus (HIV) infection and has become a worldwide epidemic siince the first clinical description in 1981. The vast majority of AIDS cases in the US and Europe are caused by infection with the retrovirus HIV-1.

Front 65

What is the mechanism of HIV infection?

Back 65

1) HIV virion expresses a cell surface protein, gp120, with binding sites for the CD4 molecule on the surface of CD4 T cells. The interaction of viral gp120 with cellular CD4 explains the affinity of HIV for CD4 T cells.
2) Other CD4 cell types that are targets for HIV infection include monocytes, macrophages, dendritic cells, Langerhans cells, and microglial cells of the central nervous system (CNS).
3) Monocytes and macrophages may function as reservoirs for HIV and possibly as vehicles for viral entry into the CNS.
4) HIV may infect neural cells directly by way of CD4 receptors or may compete for neural receptor sites for neuroleukin, a neural tissue growth factor.
5) After cellular binding of gp120 to CD4 and internalization of HIV into the cell, proviral DNA is synthesized by reverse transcription from genomic viral RNA
6) Proviral DNA is integrated into the host genome which may remain latent for an extended period until actiation, possibly by infection with other viruses, such as CMV or EBV. Low level virion production, with resultant infectivity, occurs even during the latent period.
7) The HIV virus is found in blood, semen, vaginal secretions, breast bilk, and saliva.
8) Diagnosis by the ELISA test is presumptive; follow-up tests include Western blot and direct assessment of viral RNA.

Front 66

List the high-risk populations for AIDS in the US?

Back 66

1) Homosexual or bisexual men (75%)
2) Intravenous drug abusers
3) Heterosexual partners of persons in high-risk groups
4) Patients receiving multiple blood transfusions
5) Hemophiliacs
6) Infants of high-risk parents

Front 67

What is the pathogenesis for AIDS?

Back 67

1) Caused by infection with HIV and resultant depletion of CD4 T cells. the number of circulating lymphocytes has greatly decreased, and this decrease is accounted for by a loss of CD4 T cells. The CD4:CD8 ratio is also greatly redued, often to less than 1.0
2) Loss of CD4 (helper) T cells causes failure in humoral and cell-mediated hypersensitivity reactions.
3) Despite the inability to produce specific antibodies, patients with AIDS paradoxically demonstrate hypergammaglobulinemia form polyclonal B cell activation.

Front 68

What are the clinical characteristics of AIDS?

Back 68

1) Severe immunodeficiency manifested by opportunistic infection with organisms such as Pneumocystic carinii, CMV, Mucor species, and typical and atypical mycobacteria such as avium-intracellulare, Candida, Cryptosporidium, Coccidioides, Cryptococcus, Toxoplasma, Histoplasma, and Giardia.
2) Increased incidence of malignancy, particularly multifocal Kaposi sarcoma, and B cell non-Hodgkin lymphoma, Hodgkin disease adn hepatocellular carcinoma.
3) Central and peripheral nervous system manifestations occur to opportunistic infections, CNS tumor, or direct neural infection with HIV.

Front 69

What are the stages of HIV infection?

Back 69

1) May be asymptomatic for many years
2) Before the fully developed syndrome, stages include an acute illness resembling infectious mononucleosis, persistent generalized lymphadenopathy, and AIDS-related complex (ARC), marked by chronic fever, weight loss, and diarrhea.
3) Marked by HIV seropositivity beginning soon after initial HIV infection. Antibodies to the protein coded by the genes of retroviral gag, env, and pol regions can be demonstrated, especially antibodies to the gp120 and p24 proteins. HIV infection can also be demonstrated by amplification of viral genetic sequences by polymerase chain reaction or by viral culture.
3) The last stage, defined as AIDS, is marked by HIV infection complicated by specified secondary opportunistic infection or malignant neoplasm.

Front 70

What is autoimmunity?

Back 70

1) Results in disease caused by immune reactions directed toward tissues of the host, with apparent inability to distinguish self from nonself.
2) May be mediated by a number of possible mechanisms.

Front 71

Name four types of autoimmune diseases.

Back 71

1) Autoimmune hemolytic anemia
2) Hashimoto thyroiditis
3) Idiopathic adrenal atrophy
4) Variety of CT diseases

Front 72

What associations is autoimmunity characterized by?

Back 72

1) Presence of autoantibodies (incidence increase with age)
2) Co-morbidity with other autoimmune diseases
3) Morphologic changes such as lymphoid follicle formation, as prominently exemplified by Hashimoto thyroiditis
4) Association with specific HLA haplotypes.

Front 73

What are antigens within the scope of autoimmunity?

Back 73

1) host antigens may be recognized as nonself if modified by infection, inflammation, or complexing wiht a drug.
2) Antigens usually isolated from the immune system may be exposed by trauma or inflammation and become recognized as foreign. Examples included thyroglobulin, lens protein, and spermatozoa.

Front 74

What are Antibodies in the scope of autoimmunity?

Back 74

1) Many autoimmune disorders are characterized by the presence of specific autoantibodies, antibodies directed against host tissue.
2) The demonstration of autoantibodies is presumptive (but not entirely conclusive) evidence of the autoimmune naature of a disorder.

Front 75

What is disordered immunoregulation in the scope of autoimmunity?

Back 75

1) Iincrease in T helper cell function or decrease in T suppressor cell function.
2) Nonspecific B cell activation by EBV may trigger polyclonal antibody formation
3) Thymic defects or B cell defects

Front 76

What are the genetic factors in autoimmunity?

Back 76

1) Genetic predisposition is suggested because several autoimmune disorders, including Hashimoto thyroiditis, pernicious anemia, insulin-dependent diabetes mellitus, and Sjogren syndrome, are associated with an increased incidence of other autoimmune disorders.
2) Some HLA antigens are associated with increased incience of certain autoimmune disorders. For example, incidence of Hashimoto thyroiditis is increased in HLA-DR5 and HLA-B5 positive people and incidence of IDDM is increased in HLA-DR3 and HLA-DR4 positive people.

Front 77

What are the environmental factors involved in autoimmunity?

Back 77

1) Infection (particularly viral) or other environmental agents may initiate autoimmune reactions in genetically susceptible individuals.
2) Some viruses apparently trigger autoimmune islet cell inflammation and resultant IDDM.

Front 78

What are CT/Collagen diseases?

Back 78

1) Encompass a group of loosely related conditions, most of which feature fibrinoid change in connective tissue.
2) May be of autoimmune origin; antinuclear antibodies (ANAs) and various other autoantibodies are often present.

Front 79

What is SLE?

Back 79

1) The prototype connective tissue disease.
2) Most often affects women (80%), usually those of childbearing age.
3) Marked by the presence of a spectrum of ANAs and by extensive immune complex-mediated inflammatory lesions involving multiple organ systems, especially the joints, skin, serous membranes, lungs, and kidneys. The lesions of greatest clinical importance in SLE are those in the kidney.

Front 80

List the clinical manifestations of SLE?

Back 80

1) Fever, malaise, lymphadenopathy, and weight loss.
2) Joint symptoms, including arthralgia and arthritis.
3) Skin rashes, including a characteistic butterfly rash.
4) Raynaud phenomenon
5) Serosal inflammation
6) Diffuse interstitial pulmonary fibrosis
7) Endocarditis
8) Immune complex vasculitis
9) Glomerular changes
10) Neurologic and psychiatric manifestations
11) Eye changes, with yellowish, cotton wool-like fundal lesions

Front 81

Describe the endocarditis associated with SLE.

Back 81

Atypical nonbacterial verrucous (Libman-Sacks) form, in which vegetations are seen on both sides of the MITRAL valve leaflet. The tricuspid valve is less frequently involved.

Front 82

What is the immune complex vasculitis associated with SLE?

Back 82

Occurs in vessels of almost any organ.
In the spleen, perivascular fibrosis with concentric rings of collagen around splenic arterioles results in a characteristic onion-skin appearance.

Front 83

What are the glomerular changes associated with SLE?

Back 83

1) Varying form minimal invlvement to severe diffuse proliferative disease with marked subendothelial and mesangial immne complex deposition, endothelial proliferation, and thickening of basement membranes; an be indistinguishable from idiopathic membranous glomerulonephritis.
2) Subendothelial immune complex deposition in the glomeruli has considerable diagnostic significance. This change results in the wire-loop appearance seen by light microscopy.
3) Thickening of basement membranes can result in changes indistinguishable from those of membranous glomerulonephritis.

Front 84

What is an LE test?

Back 84

1) A phenomenon which occurs in vitro
2) Morphologically characteristic LE cells are formed in am ixture of mechanically damaged neutrophils adn autoantibody-containing patient serum
3) The LE test is postive in only about 70% of cases and has now been largely replaced by more sensitive determinations.

Front 85

What is a postive test result for ANA?

Back 85

1) Seen in almost al patients with SLE. ANAs are also found in patients with other CT diseases
2) ANA test becomes almost specific for SLE whin the antinuclear antibodies react with double-stranded DNA. Whn this reaction is assessed by microscopic exam of cels using immunoflourescent techniques, a characteristic peripheral nuclear staining or "rim" pattern is seen.
3) ANAs that react woth Smith antigen, a ribonucleoprotein, are also highly specific for SLE.

Front 86

What makes serum complement greatly decrease within CT diseases?

Back 86

Association with active renal involvement.

Front 87

What are found in skin biopsies within CT diseases?

Back 87

Immune complexes at dermal-epidermal junction.

Front 88

What can be the earliest laboratory abormality found in SLE?

Back 88

Biologic false-positive test for syphilis.
Approximately 15% of patients.

Front 89

What is Progressive systemic sclerosis (PSS, scleroderma)?

Back 89

1) Widespread fibrosis and degenerative changes that affect the skin, gastrointestinal tract (esp esophagus), heart, muscle and other organs cush as the lung and kidney.
2) Occurs most frequently in young women.
3) Marked by the presence of ANA anti-Scl-70 in one third of patiens.
4)ANA with anti-centromere activity is characteristic of PSS variant, the CREST syndrome.
5) Usually presents initially with skin changes, polyarthralgias, and esophageal symptoms.

Front 90

What is scleroderma characterized by?

Back 90

1) Hypertrophy of collagen fibers of the subcutaneous tissue, leading to tightening of the facial skin and a chracteristic fixed facial appearance
2) Sclerodactyly (claw-like appearance of the hand)
3) Raynaud phenomenon in approximately 75% of patients
4) Visceral organ involvement, especially of the esophagus, gastrointestinal tract, kidneys, lungs, and heart.

Front 91

What are the clinical manifestations of Sjogren syndrome.

Back 91

1) A triad oincluding xerostomia (dry mouth), Keratoconjunctivitis sicca (dry eyes), and one of several connective tissue or other autoimmune diseases, most often RA
2) Involvement of salivary glands, often with bilaterally enlarged parotids diffusely infiltrated by lymphocytes and plasma cells. This cellular infiltration can partly or completely obscure the parenchyma of the parotid gland and can mimic, or in come cases lead to, malignant lymphoma.
3) Involvement of lacrimal glands

Front 92

What are the laboratory findings of sjogren syndrome?

Back 92

1) Significant polyclonal hypergammaglobulinemia (a broad-based elevation of serum gamma globulins demonstrable by electrophoresis)
2) ANAs, including the highly specific anti-SS-B and soewhat less specific anti-SS-A

Front 93

What is polymyositis?

Back 93

1) Chronic inflammatory process especially involving the proximal muscles of the extremities. When the skin is also involved, with a characteristic reddish-purple rash over exposed areas of the face and neck, the condition is called dermatomyositis.
2) Occurs mainly in women and is often associated with malignancy
3) Characterized by increased serum creatine kinase and frequently presence of ANAs
4) Can be confirmed by muscle biopsy, which demonstrates necrotic muscle cells and lymphocytic infiltrate.

Front 94

What is mixed CT disease?

Back 94

1) Occurs mainly in women, with a peak incidence at 35 to 40 years of age.
2) Shares clinical features with other CT disorders, but in contrast, renal involvement is uncommon in MCTD
3) Often manifest clinically by arthralgias, Raynaud phenomenon, esophageal hypomotility, and myositis.
4) Most uniquely characterized by specific ANAs (high-titer anti-nRNP and an immunoflurescent speckled nuclear appearance on morphologic ANA analysis.)

Front 95

What is polyarteritis nodosa?

Back 95

1) An immune complex vasculitis characterized by segmental fibrinoid necrosis in the walls of small and medium arteries of almost any organ.
2) Occurs preddominantly in MEN (unlike other CT diseases)

Front 96

What are the antigens present in polyarteritis nodosa?

Back 96

1) Hepatitis B antigen is implicated in 30% of cases
2) Drugs, such as sulfonamides and penicillin, may form immunogenic hapten-protein complexes.

Front 97

What are the clinical manifestations of Polyarteritis nodosa?

Back 97

1) May include abdominal pain, hypertension, uremia, polyneuritis, allergic asthma, urticaria or rash, splenomegaly, fever, leukocytosis, and proteinuria
2) May involve the lung, resulting in chest pain, cough, dyspnea, and hemoptysis. Severe dyspnea and eosinophilia occur in 20% of patients.

Front 98

What is amyloidosis?

Back 98

1) Group of disorders characterized by the deposition of amyloid, a proteinaceous material with certain physicochemical features.

Front 99

What is the structure of amyloid?

Back 99

1) Not a single substance but a group of substance that share a common physical structure that can be formed by a number of different proteins.
2) Always has Beta-pleated sheet configuration.

Front 100

What are the morphologic features of amyloid?

Back 100

1) Charracteristically extracellular in distribution, most often appearing as accumulations proximate to basement membranes.
2) Has an amorphous eosinophilic appearance in routing hematoxylin and eosin sections.
3) Charactically stained by CONGO RED dye, demonstrating apple green birefringence when viewed under polarized light and confirming the suspected presence of amyloid.
4) Can be demonstrated by a variety of other methods, including immunochemical, fluorescent, and metachromatic techniques.

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What are the clinical patterns of primary amyloidosis (immunocytic dyscrasia amyloidosis)?

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1) Caused by eposition of amyloid fibrils derived from immunoglobulin light chains, referred to as AL (amyloid light chain) protein.
2) Most characteristically marked by amyloid deposition in tissues of mesodermal origin, such as heart, muscle, and tongue.
3) May involve the kidney, with amyloid deposits in the glomerular mesangium as well as in the interstitial tissue between tubules.
4) Includes the amyloidosis frequently associated with plasma cell disorders such as multiple myeloma and Waldenstrom macroglobulinemia.

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What are the clinical patterns of secondary amyloidosis (reactive systemic amyloidosis)?

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1) Marked by deposition of fibrils consisting of the amyloid protein called AA protien, which is formed from a precursor, serum amyloid-associated protein (SSA). Chronic tissue destruction leads to increased SAA
2) Usually involves parenchymatous organs, especially the kidney (nephrotic syndrome is very common), liver, adrenals, pancreas, lymph nodes, and spleen. Perifollicular involvement in the spleen results in "sago spleen" an appearance reminiscent of tapioca-like granules.
3) Characteristically is a complication of chronic infammatory disease such as rheumatoid arthritis, tuberculosis, osteomyelitis, syphiis, or leprosy.
4) Also may complicate noninflammatory disordes such as renal cell carcinoma and Hodgkin disease.

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List seven types of amyloidosis.

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1) Portuguese type of polyneuropathy
2) Alzheimer disease
3) Familial Mediterranean fever
4) Medullary carcinoma of the thyroid
5) Diabetes mellitus
6) Senile amyloidosis
7) Dialysis-associated amyloidosis

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What is Portuguese type of polyneuropathy?

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1) Associated iwth amyloid derived form a protein known as transthyretin (a serum protein that TRANSports THyroxine and RETINol)
2) Characterized by severe peripheral nerve involvement caused by amyloid deposits.

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What is alzheimer disease?

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Characterized by deposits of an amyloid protein referred to as A4 amyloid, or amyloid Beta-protein, which differs for AL, AA, and transthyretin-derived amyloid. The gene tha tcodes for the protein precursors of A4 amyloid has been localized to chromosome 21.

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What is Familial Mediterranean fever?

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1) Autosomal recessive disorder occurring in persons of Eastern Mediterranean origin.
2) Characterized by episodic fever and polyserositis.
3) Distribution and type of amyloid similar to that of secondary amyloidosis (AA amyloid).

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What is medullary carcinoma of the thyroid?

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Characterized by prominent amyloid deposits within the tumor, apparently derived from calcitonin.

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What is Diabetes mellitus in regards to amyloid deposit?

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Insulin-resistant adult-onset is characterized by deposits of amyloid in islet cells. This amyloid is thought to be derived from either insulin or glucagon and is referred to as amylin or alternatively, islet amyloid polypeptide. It is postulated that amylin interferes with insulin sensing by beta cells.

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What is senile amyloidosis?

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1) Characterized by minor deposits of amyloid found at autopsy in the very elderly.
2) May involve the heart, brain, and other organs. When senile amyloidosis occurs in the heart, the amyloid protein in derived from transthyretin.

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What is dialysis-associated amyloidosis?

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Characterized by amyloid deposits in the joints of patients who have undergone hemodialysis for several years. The amyloid is derived form Beta-microglobulin, a protein not readily filtered by the dialysis membrane.