Immune Dysfunction Flashcards

Terms Definitions
What are lymphocytes?
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.
What are B cells?
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.
What are T cells?
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.
What are the subclasses of T cells?
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.
What are natural killer cells?
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.
What are Macrophages?
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.
What are dendritic cells?
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.
What are Langerhans cells of the skin?
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.
What are cytokines?
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.
Describe the complement system.
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.
What is the source and function of IL-1?
Monocytes, macrophages, and other cells.
Stimulates T cell proliferation and IL-2
What is the source and function of IL-2?
Macrophages, T cells, and NK cells
Stimulates proliferation of T cells, B cells, adn NK cells; activates monocytes.
What is the source and function of IL-3?
T cells
Acts as growth factor for tissue mast cells and hematopoietic stem cells
What is the source and function of IL-4?
T cells
Promotes growth of B adn T cells; enhances expression of HLA class II antigens.
What is the source and function of IL-5?
T cells
Promotes end-stage maturation of B cells into plasma cells.
What is the source and function of IL-6?
T cells, onocytes, and other cells
Promotes maturation of B and T cells; inhibits gowth of fibroblasts
What is the source and function of interferon-alpha?
B cells and macrophages
Has antiviral activity.
What is the source and function of interferon-beta?
Has antiviral activity
What is the source and function of interferon-gamma?
T cells and NK cells
Has antiviral activity; activates macrophages; enhances expression of HLA class II antigens.
What is the source and function of Tumor necrosis factor alpha?
Macrophages, T cells, and NK cells
Stimulates T cell proliferation and IL-2 production: cytotoxic to some tumor cells.
What is the source and function of Tumor necrosis factor-beta?
T cells
Stimulates T cell proliferation and IL-2 production; cytotoxic to some tumor cells.
What is the Human Leukocyte Antigen (HLA) system?
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.
What is the classic complement pathway?
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.
What is the alternate complement pathway?
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.
What are class I HLAs?
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.
What are class II HLAs?
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.
What disease is HLA-B27 associated with?
90% of cases of ankylosing spondylitis
List four disease states that are associated with specific HLA antigens?
1) Insulin-dependent diabetes mellitus
2) Rheumatoid arthritis
3) Uveitis
4) Reiter syndrome
What is a general definition of the mechanisms of immune injury?
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.
Describe the mechanism of type I hypersensitivity.
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.
Give four examples of type I hypersensitivity.
1) Hay fever
2) Allergic asthma
3) Hives
4) Anaphylactic shock
What is the mechanism of type II hypersensitivity?
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.
List four examples of type II hypersensitivity.
1) Warm antibody autoimmune hemolytic anemia
2) Hemolytic disease of the newborn
3) Goodpasture syndrome
4) Graves disease
What is the mechanism of type III hypersensitivity?
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.
List five examples of type III hypersensitivity.
1) Serum sickness
2) Arthus reaction
3) Polyarteritis nodosa
4) SLE
5) Immune complex-mediated glomerular diseases
What is the mechanism of type IV hypersensitivity?
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.
List four examples of type IV hypersensitivity.
1) Tuberculin reaction
2) Contact dermatitis
3) Tumor cell killing
4) Virally infected cell killing
What is hereditary angioedema?
1) Caused by a deficiency of C1 esterase inhibitor
2) Serum C4 is low and other complement components such as C3 are consumed.
What is systemic anaphylaxis?
Potentially fatal reaction, characterized by the rapid onset of urticaria, bronchospasm, laryngeal edema, and shock after exposure to an offending antigen
Describe coomplement-fixing antibodies.
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.
What are antibody-dependent cell-mediated cytotoxicity (ADCC)?
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.
What is the reaction of anti-receptor antibodies with cell-surface receptor protein?
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.
What is serum sickness?
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.
What is SLE?
Multisystem immune complex disease.
What is Arthus reaction?
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.
What is polyartitis nodosa?
Generalized immune complex disease especially involving smal- and medium-sized arteries.
What is immune complex-mediated glomerular diseaes?
Include poststreptococcal glomerulonephritis, membranous glomerulonephritis, and lupus nephropathy.
What are some general considerations of transplant immunology?
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.
What is a hyperacute rejection?
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.
What is acute rejection?
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.
What is chronic rejection?
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.
What is Graft-versus-host disease?
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.
What is X-linked agammaglobulinemia of Bruton?
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.
What are the immune system defects of X-linked agammaglobulinemia?
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.
What are the effects of X-linked agammaglobulinemia of Bruton?
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.
What is Isolated IgA deficiency?
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.
What is common variable immunodeficiency?
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.
What is DiGeorge syndrome (thymic hypoplasia)?
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.
What is Severe combined immunodeficiency disease (SCID)?
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.
What are the clinical manifestations of SCIDs?
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.
What are the anatomic manifestations of SCIDs?
1) Thymic hypoplasia wiht absent or greatly reduced thymic lymphoid component.
2) Hypoplasia of lymph nodes, tonsils, and other lymphoid tissues.
What are the treatments for SCIDs?
1) Bone marrow or stem cell transplantation
2) ADA gene transplantation
What is Immunodeficiency with thrombocytopenia and eczema (Wiskott-Aldrich syndrome)?
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
What is Acquired immunodeficiency syndrome (AIDS)?
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.
What is the mechanism of HIV infection?
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.
List the high-risk populations for AIDS in the US?
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
What is the pathogenesis for AIDS?
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.
What are the clinical characteristics of AIDS?
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.
What are the stages of HIV infection?
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.
What is autoimmunity?
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.
Name four types of autoimmune diseases.
1) Autoimmune hemolytic anemia
2) Hashimoto thyroiditis
3) Idiopathic adrenal atrophy
4) Variety of CT diseases
What associations is autoimmunity characterized by?
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.
What are antigens within the scope of autoimmunity?
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.
What are Antibodies in the scope of autoimmunity?
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.
What is disordered immunoregulation in the scope of autoimmunity?
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
What are the genetic factors in autoimmunity?
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.
What are the environmental factors involved in autoimmunity?
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.
What are CT/Collagen diseases?
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.
What is SLE?
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.
List the clinical manifestations of SLE?
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
Describe the endocarditis associated with SLE.
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.
What is the immune complex vasculitis associated with SLE?
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.
What are the glomerular changes associated with SLE?
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.
What is an LE test?
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.
What is a postive test result for ANA?
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.
What makes serum complement greatly decrease within CT diseases?
Association with active renal involvement.
What are found in skin biopsies within CT diseases?
Immune complexes at dermal-epidermal junction.
What can be the earliest laboratory abormality found in SLE?
Biologic false-positive test for syphilis.
Approximately 15% of patients.
What is Progressive systemic sclerosis (PSS, scleroderma)?
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.
What is scleroderma characterized by?
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.
What are the clinical manifestations of Sjogren syndrome.
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
What are the laboratory findings of sjogren syndrome?
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
What is polymyositis?
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.
What is mixed CT disease?
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.)
What is polyarteritis nodosa?
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)
What are the antigens present in polyarteritis nodosa?
1) Hepatitis B antigen is implicated in 30% of cases
2) Drugs, such as sulfonamides and penicillin, may form immunogenic hapten-protein complexes.
What are the clinical manifestations of Polyarteritis nodosa?
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.
What is amyloidosis?
1) Group of disorders characterized by the deposition of amyloid, a proteinaceous material with certain physicochemical features.
What is the structure of amyloid?
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.
What are the morphologic features of amyloid?
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.
What are the clinical patterns of primary amyloidosis (immunocytic dyscrasia amyloidosis)?
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.
What are the clinical patterns of secondary amyloidosis (reactive systemic amyloidosis)?
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.
List seven types of amyloidosis.
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
What is Portuguese type of polyneuropathy?
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.
What is alzheimer disease?
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.
What is Familial Mediterranean fever?
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).
What is medullary carcinoma of the thyroid?
Characterized by prominent amyloid deposits within the tumor, apparently derived from calcitonin.
What is Diabetes mellitus in regards to amyloid deposit?
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.
What is senile amyloidosis?
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.
What is dialysis-associated amyloidosis?
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.
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