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235 Cards in this Set

  • Front
  • Back
which cell types are lymphocytes?
- B cells
- T cells
- NK cells
desribe the developmental centers of B cells
- originate from bone marrow
- continue differentiation in BM and in periphery, where they cluster in:
- the GERMINAL CENTERS of lymph nodes
- the LYMPHOID FOLLICLES of the spleen
what percentage of the circulating blood lymphocytes are B cells?
describe the developmental centers of T cells
- originate from stem cells in the BM and differentiate in the thymus
- populate the paracorticla and deep medullary areas of lymph nodes
- populate the periarteriolar sheaths of the spleen
where do T cells reside in the lymph nodes?
- paracortical and depp medullary areas
where do T cells reside in the spleen?
- periarteriolar sheaths
what percentage of the circulating blood lymphocytes are T cells?
- 80%
CD4+ T cells make up what percentage of circulating T cells?
- 60%
CD8+ T cells make up what percentage of circulating T cells?
- 30%
what is the normal ratio of CD4 cells to CD 8 cells?
- 2:1
what is the ratio of CD4 cells to CD8 cells in AIDS patients?
- sometimes 0.5: 1 or less
what are NK cells also known as?
- large granular lymphocytes (LGLs) b/c of their large size, pale cytoplasm, and prominent granulation
what do NK cells do?
- kill tumor cells, fungi, cells infected by viruses
- so specific sensitization or antibody is involved with NK killing
- can also kill via the ADCC (antibody-dependent cell-mediated cytotoxicity mech
what percentage of circulating lymphocytes are NK cells?
- 15%
what do macrophages secrete?
- cytokines, including IL-1
- acid hydrolases
- neutral proteases
- prostaglandins
which immune cells are responsible for delayed type hypersensitivity reactions?
- macrophages
what are the dendritic cells of lymphoid tissue characterized by?
- dendritic cytoplasmic processes
what do DCs express on their surface?
- large quantities of cell surface HLA class II antigens
how are dendritic cells like and dislike macrophages?
- DCs are poorly phagocytic
- DCs, like macrophages, are APCs
what do Langerhans cells of the skin contain?
- Birbeck granules (tennis racket shaped cytoplasmic structures)
what are Langerhans cells?
- dendritic cells abundant in epidermis containing Birbeck granules
- On infection of an area of skin, the local Langerhans' cells will take up and process microbial antigens to become fully-functional APCs
- Generally, dendritic cells in tissue are active in the capture, uptake and processing of antigens. Once dendritic cells arrive in secondary lymphoid tissue however, they lose these properties while gaining the capacity to interact with naive T-cells.
what antigens do langerhans cells express?
- HLA class II antigens and are APCs
what initiates the classic complement pathway? what is at the end?
- initiated by antigen-antibody complexes
- the final lytic form of activated complement is the result of a series of enzymatic cleavages and recombinations of cleavage products
what initiates the alternate complement pathway?
- initiated by non-immunologic stimuli (e.g. invading microorganisms)
- also leads to cleavage products that mediates cell lysis
define the alternate pathway
- complement activation is not triggered by antibody, but by the binding of C3b to the surface of a pathogen; therefore a feature of innate immmunity
- also amplifies the classical pathway
what makes IL-1; what does it do?
- made: monocytes, macrophages
- fcn: stimulate T cell proliferation and IL-2 production
what makes IL-2; what does it do?
- made: macrophages, T cells, NK cells
- fcn: stimulates proliferation of T cells, B cells, and NK cells; activates monocytes
what makes IL-3; what does it do?
- made: T cells
- fcn: Growth factor for tissue mast cells and hematopoietic stem cells
what makes IL-4; what does it do?
- made: T cells
- fcn: promotes growth of B ad T cells; enhances expression of HLA class II antigens
what makes IL-5; what does it do?
- made: T cells
- fcn: promotes end-stage maturation of B cells inot plasma cells
what makes IL-6; what does it do?
- made: T cells, monocytes
- fcn: promotes maturation of B and T cells; inhibits growth of fibroblasts
what makes INF-a; what does it do?
- made: B cells and macrophages
- fcn: antiviral
what makes INF-b; what does it do?
- made: fibroblasts
- fcn: antiviral
what makes INF-g; what does it do?
- made: T cells and NK cells
- fcn: antiviral; activates macrophages; enhanges expression of HLA class II antigens
what makes TNF-a; what does it do?
- made: macrophages, T cells, NK cells
- fcn: stimulates T cell proliferation and IL-2 production: cytotoxic to some tumor cells
what makes TNF-b; what does it do?
- made: T cells
- fcn: stimulates T cell proliferation and IL-2 production; cytotoxic to some tumor cells
where is the major histocompatibility complex located?
- short arm of Chr 6
- codes for the histocompatibility genes
what are the two classes of HLA antigens?
1. Class I
2. Class II
which antigens are contained under Class I antigens? what do they do?
- HLA-A, B, C
- found in almost all cells
- principal antigens involved in tissue graft rejection
which antigens are contained under Class II antigens? what do they do?
- found in immunocompetent cells (Macrophages, DCs, langerhans cells, B cells, and some T cells)
how do you test for HLA-A and B antigens? why is this testing useful?
- serological tests
- useful for predicting likelihood of graft rejection
how do you test for HLA-DP, DQ, and DR antigens?
- standard serologic techniques or by mixed lymphocyte reactions
how do you test for the HLA-D antigens?
- identifiable only by mixed lymphocyte reactions
what is HLA-B27 antigen associated with?
- ankylosing spondylitis
specific HLA antigens are associated with which diseases?
- ankylosing spondylitis
- insulin-dependent DM
- RA
- uveitis
- Reiter syndrome
define: uveitis
Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye.
what is Reiter syndrome?
- Reactive arthritis, or Reiter's syndrome, is a condition with symptoms similar to arthritis or rheumatism. It is caused by another disease, and is thus "reactive", i.e., dependent on the other condition.
- urethritis
- conjunctivitis
- arthritis
what is ankylosing spondylitis?
is a chronic, painful, progressive inflammatory arthritis primarily affecting spine and sacroiliac joints, causing eventual fusion of the spine; it is a member of the group of the autoimmune spondyloarthropathies with a probable genetic predisposition.
what do type I, II, and III hypersensitivity reactions have in common?
- require the active production of antibody by plasma cells
why is type IV hypersensitivity different from the others?
- mediated by the interaction of T cells and macrophages
what are the steps in the progression of Type I (immediate, or anaphylactic) hypersensitivity?
1. IgE production by B cells is stimulated by antigen. IgE antibody binds to Fc receptor of basophils and mast cells
2. Later exposure to the same allergen, cross-links the bound IgE on sensitized cells -> degranulation
3. Degranulation -> histamine relase -> increase in vascular permeability
4. chemotactic molecules recruit eosinophils, resulting in eosinophilia
give some examples of Type I hypersensitivity reactions
- hay fever
- allergic asthma
- hives
- anaphylactic shock
- angioedema
what is a medical word for hay fever?
- seasonal rhinitis
what is the clinical word for hives?
- urticaria
describe the appearance of anaphylactic shock
- potentially fatal
- rapid onset of urticaria, bronchospasm, laryngeal edema, and shock
what is angioedema?
- acute edema of cutaneous or mucosal structures
- most commonly affects lips and eyelids
- laryngeal edema can be life threatening
what is hereditary angioedema caused by?
- deficiency of C1 esterase inhibitor
- not a manifestation of type I hypersensitivity
- serum C4 is low, and other complement components like C3 are consumed
describe the progression of type II (antibody-mediated, or cytotoxic) hypersensitivity
- complement fixing antibodes react directly with antigens that are components of the target cell.
- the interaction of complement with the cell surface results in RBC lysis and destruction
- serum complement is decreased
which antigens are usually involved with type II hypersensitivity?
- antigens that are usually localized to tissue BM or blood cell memebranes
what are clinical examples of type II hypersensitivity?
- warm antibody autoimmune hemolytic anemia
- hemolytic transfusion reactions
- hemolytic disease of the newborn (erythroblastosis fetalis)
- goodpasture syndrome
what is goodpasteur syndrome?
- antiglomerular basment membrane antibody disease, where the pulmonary alveolar and glomerular basement membranes are affected
describe antibody-dependent cell-mediated cytotoxicity (ADCC)
- antibody reacts with surface antigens of targeted cell
- free Fc portion of the antibody molecule reacts with the Fc receptor of many cytotoxic leukocytes (esp NK cells)
- target cells are killed by Fc receptor-bound cytotoxic leukocytes
- complement is not involved
what are the three types of type II hypersensitivity?
2. reaction of anti-receptor antibodies with cell surface receptor protein
3. complement-fixing antibodies that react wth antigens on the target cell
describe the reaction of anti-receptor antibodies with cell surface recptor protein component of type II hypersensitivity
- sometimes classified as class V hypersensitivity
- exemplified by Graves disease: Thyroid stimulating Ig reacts with TSH receptor of thyroid folliular cells
- antigen-antibody reaction mimics the effect of TSH on follicular cells -> glandular hyperplasia and hyperproduction of TH
describe type III (immune complex) hypersensitivity
- insolumbe complement-bound aggregates of antigen-antibody complexes are deposited in vessel walls or other extravascular sites
- the immune complexes bind complement, which is chemotactic for neutrophls to come to these sites and release enzymes, prostaglandins, kinins, and free radicals -> tissue damage
how does type III differ from type II hypersensitivity?
- in type III, the antigen is not an intrinsic component of the target cells
how are immune complexes usually removed?
- by cells of the mononuclear phagocyte system without adverse effect
- however, immune complexes that are deposited at extravascular sites are much harder to remove
what about immune complexes attacts neutrophils?
- the immune complexes bind complement, which is chemotactic for PMNs
what is activated in type III hypersensitivity?
- hageman factor (Factor XII)-> activates the intrinsic coagulation cascade -> thrombosis of nearby small vessels
- you eventaully get activation of the kinin system -> vasodilation and edema
what do you get with platelet aggregation in type III hypersensitivity?
- microthrombus formation -> release of vasoactive amines from platelet dense granules
what are the clinical examples of type III hypersensitivity?
- serum sickness
- arthus reaction
- polyarteritis nodosa
- immune complex mediated glomerular diseases
what is serum sickness?
- deposition of immune complexes at the heart, joints, and kidneys
- in the past, brought on by antibody-containing foreign serum (e.g. horse serum)
what is the arthus reaction?
- localized immune complex reaction that occurs when exogenous antigen is introduced, either by injection or by organ transplant, in the presence of PREFORMED antibodies
(remember arthus and his bunnies!)
name some immune complex mediated glomerular diseases?
- poststreptococcal glomerulonephritis
- membranous glomerulonephritis
- lupus nephropathy
describe type IV (cell mediated) hypersensitivity
- delayed hypersensitivity
- proliferation of antigen-specific CD4+ memory T cells, with secretion of IL-2 and other cytokines, which in turn recruit and stimulate phagocytic macrophages
- may also involve cytotoxic CD8+ T lymphocytic killing of specific target cells
describe the mechanism of type IV hypersensitivity
- CD4+ receptor on T cells interacts with antigen, presented by macrophages, and with HLA class II antigens on macrophages -> stimulation of antigen-specific CD3+ memory T cells
what happens with repeated exposure in type IV hypersensitivity?
- on subsequent contact with antigen, CD4+ memory T cells proliferate and secrete cytokines
- IL-2 and other cytokines secreted by the CD4+ T cells recruit and stimulate the phagocytic activity of macrophages
what are clinical examples of type IV hypersensitivity?
- tuberculin reaction (PPT)
- contact dermatitis
what is the tuberculin reaction?
- localized inflammatory reaction initiated by the injection of tuberculin
- proliferation of lymphocytes, monocytes, and small numbers of neutrophils
- tendency towards cellular accumulations about small vessels (perivascular cuffing)
- induration (from fibrin formation)
describe cytotoxic T lymphocyte-mediated cytotoxicity in type IV hypersensitivity
- direct CD8 T cell mediated killing of target cells (tumor or virus cells)
- target cell HLA class I antigens recognized as self antigens are required
- cytokines are not involved
what do you need for a suscessful graft transplant?
- donor and recipient must be matched for ABO blood groups, and for as many HLA antigens as possible
how do you surpress and immune response towards transplant?
- drugs
- radiation
- T cell depletion
what are the tree types of transplatn rejection?
1. hyperacute rejection
2. acute rejection
3. chronic rejection
describe hyperacute rejection
- antibody mediated
- occurs in the presence of preexisting antibodies to donor antigens
- occurs MINUTES after transplant
- a localized Arthus reaction, marked by acute inflamm, fibrinoid necrosis of small vessels, and extensive thrombosis
descibe acute rejection
- primarily T cell mediated
- occurs days to weeks after transplant
- characterized by infliltratin of lymphocytes and macrophages
- may show evidence of arteritis with thrombosis and cortical necrosis
describe chronic rejection
- caused by antibody mediated vascular damage
- may occur months to years after sucessful transplant
what do you see on histology for chronic rejection?
- vascular fibrointimal proliferation -> small scarred kidney (in the case of a kidney transplant)
what is graft-vs-host disease?
- problem in bone marrrow transplant
- immunocompetent cells are transplanted
- can also be caused by whole blood transfusion in patients with SCID
describe the pathology of graft-vs-host disease
- rejection of host cells by engrafted T and B cells
- CD8+ graft cells damage host
- cytokines from graft CD4+ cells recruit macrophages, that damage host
what are the clinical features of graft-vs. host disease?
- fever
- rash
- hepatosplenomegaly
- jaundice
which organs are principally affected in graft-vs-host disease?
- liver
- skin
- GI mucosa
list the immunodeficiency diseases
1. X linked agammaglobulinemia of Bruton
2. Isolated IgA deficiency
3. Common variable immunodeficiency
4. DiGeorge syndrome
6. Wiskott-Aldrich syndrome
when does X-linked agammaglobulinemia of Bruton occur?
- in male infants, but is not clinically manifested until after 6 mo b/c of the persistance of maternal antibodies
what is x-linked agammaglobulinemia of Burton?
a rare X-linked genetic disorder that affects the body's ability to fight infection. XLA patients do not generate mature B cells capable of manufacturing antibodies called immunoglobulins that the body uses to defend itself from infection.
describe the immune system defects of x-linked agammaglobulinemia of Burton
- block in maturation of pre-B cells due to mutation in B cell tyrosine kinase (Btk) -> failure of antibody synthesis
- does not affect cell mediated immunity
- absence of serum Igs
- absent germinal centers in lymphoid tissues
what are the clinical manifestations of x-linked agammaglobulinemia of Burton?
- propensity for recurrent bacterial infections with:
- pneumococci
- streptococci
- staphylococci
- H. inf
what is isolated IgA deficiency?
- inability of IgA B cells to mature to plasma cells
- all other Igs are normal
what is the incidence of isolated IgA deficiency?
- most common inherited B cell defect
- occurs in 1 in 700 people
what are the clinical manifestatsions of isolated IgA deficiency?
- occasional anaphylactic reactions to transfused blood
- may also be associated with infections, esp those involving mucosal surfaces
- diarrhea
what is common variable immunodeficiency?
- diverse group of disorders caused by failure of terminal B-cell maturation -> lowered plasma cell numbers -> hypogammaglobulinemia
what is the clinical of common variable immunodeficiency?
- recurrent bacterial infection
what is DiGeorge sydnrome? what abnormalities do you have?
- a congenital T-cell deficiency that results from defective development of the 3rd and 4th brachial arches
- hypoplasia of the thymus and parathyroid gland
- abnormal ear, mandible, and aortic arch
what are characteristic features of DiGeorge syndrome?
- failure of T-cell maturation -> lymphopenia
- B cell development is normal
what are the clinical manifestations of DiGeorge Syndrome?
- recurrent viral and fungal infections
- tetany from hypoparathyroidism with hypocalcemia
what acronym is associated with DiGeorge Syndrome?
- CATCH 22
- Cardaic defects
- Abnormal face
- Thymic hypoplasia
- Cleft palate
- Hypocalcemia
- microdeletion of chr 22
what is SCID also known as?
- Swiss-type agammaglobulinemia
what is SCID?
- deficiency of both B and T cells
- profound lymphopenia
- severe defects in humoral and cell-mediated immunity
what causes SCID?
- wide variety of genetic defects
- can occur as autosomal recessive and X-linked forms
what are the autosomal recessive forms of SCID caused by?
- 50% of SCID cases
- caused by adenosine deaminase (ADA) deficiency -> accumulation of deoxyadenosie and deoxy-ATP (toxic to lymphocytes)
what are the clinical manifestations of SCID?
- severe infection (bacterial, viral, and fungal)
- high incidence of malignancy
- failure to thrive (usually wiht fatal outcome in infancy)
- graft-vs-host disease with blood transfusions
what are the anatomic manifestations of SCID?
- thymic hypoplasia, with absent thymic lymphoid compartment
- hypoplasia of lymph nodes, tonsils and other lymphoid tissues
what are treatments for SCID?
- bone marrow or stem cell transplant
- ADA gene transplantation (currently on hold)
what is immunodeficiency with thrombocytopenia and exzema?
- aka Wiskott-Aldrich syndrome
- X-linked
- eczema, thrombocytopenia, recurrent infections and poor antibody respones to polysaccharide antigens
- total Ig normal
what causes AIDs?
- HIV infection
- most are caused by HIV-1 in Us and Europe
what is the mechanism of HIV infection?
- HIV viron expresses cell surface protein gp120 that binds to CD4+ on T cells
- coreceptors CCR5 and CXCR4 are involved in the entry of HIV into the cell
how might you be resistant to HIV?
- homozygous for mutated CCR5
what cell types are susceptible to HIV infection?
- cells containing CD4+:
- T cells
- monocytes
- macrophages
- DCs
- Langerhans cells
- microglial cells of the CNS
which cells may function as reservoirs of HIV infection?
- monocytes and macrophages
- may possibly be a vehicle for viral entry into the CNS
how may HIV infect neural cells?
- by CD4 receptors
- or, may compete (through the gp120 protein) for neural receptors sites for neuroleukin, a neural tissue growth factor
what happens after cellular binding of gp120 to CD4?
- internalization of HIV
- proviral DNA is synthesized by reverse transcription from genomic viral DNA
describe the proviral DNA seen in HIV infection
- is integrated into the genome
- in the proviral form, HIV can be latent for an extended time, until activation by other viruses (e.g. cytomegalovirus or EBV)
what occurs during the HIV latent period?
- low level viron production -> still infectius
in which bodily secretions is HIV found?
- blood
- semen
- vaginal secretions
- breast milk
- saliva
how do you diagnose HIV?
- ELISA test
- follow-up tests include western blot and direct assessment of viral RNA
list the AIDS high risk populations
- homosexuals
- IV drugs abusers
- heterozexual partners of persons in high risk groups
- patients with blood transfusions
- hemophiliacs
- infants with high risk parents
what % of HIV occurs in homosexual men?
- accounts for 75% of AIDS cases
- risk is greater with anal intercourse
- in central africa, incidence in both sexes is equal, and same for homosexual vs. heterosexual men
what % of HIV occurs in IV drug uses?
- 15% of cases
what % of HIV occurs in heterosexual partners of people in the high risk group?
- 4%
what % of HIV occurs in patients recieving blood transfusions? How do you screen for HIV?
- 2%
- rish has been diminished by screening donor blood for anti-HIV antibodies, HIV p24 antigen and HIV-1 RNA
what % of HIV occurs in hemophiliacs?
- 1% of cases
- most likely, the entire cohort of hemophiliacs who received factor VIII concentrates between 81 and 85 became infected with HIV
- since 85, screening and heat inactivation of HIV in factor VIII has become universal
what is the CD4:CD8 ratio in AIDS patients?
- low, often less than 1.0
what happens when you have a loss of CD4+ helper T cells in AIDS?
- loss of humoral and cell-mediated hypersensitivity reactions
what is somewhat paraxodical about AIDS?
- despite the inability to produce specific antibodies, AIDS patients have hypergammaglobulinemia from polyclonal B cell activation
what are the opportunistic infections seen in AIDS?
- oppurtunistic infections by:
- pneumocystic carinii
- Mucor species
- typical and atypical mycobacteria (e.g. M. avium-intracellulare)
- Candida, Cryptosporidium, Cocicdioides, Cryptococcus, Toxoplasma, Histoplasma, Giardia
which lesions and maligancies are pretty much only seen in the AIDS population?
- multifocal Kaposi sarcoma
- B cell non-Hodgkin lymphoma
- also an increased incidence of Hodgkin disease and hepatocellular carcinoma
what other clinical syndromes do you see with AIDS?
- central and PNS manifestions
- CNS tumors
what are the various stages of HIV infection?
- before fully developed AIDS occurs, there is acute illness resmbling mono, a long latent phase followed by generalized lymphadenopahty, and a stage marked by chronic fever, weight loss, and diarrhea
when does HIV seropositivity begin?
- soon after infection
- antibodies to gag, env, and pol can be demonstrated
- antibodies to gp120, and p24
what is the last stage of HIV infection marked by?
- HIV infection complicated by secondary opportunistic infection or malignant neoplasms
give the main examples of autoimmune diseases?
- autoimmune hemolytic anemia
- Hashimoto thyroiditis
- idiopathic adrenal atrophy
- connective tissue disorders (a group)
what are some characteristics of autoimmune diseases?
- autoantibodies (incidence increases with age)
- comorbidity with other autoimmune diseases
- morphologic changes like lymphoid follicle formation
- association with specific HLA haplotypes
name some antigens that are usually isolated from the immune systme, and then exposed during trauma and inflammation, and then recognized as foreign
- thyroglobulin
- lens protein
- spermatozoa
which autoimmune disorders have some genetic predisposition?
- hashimoto thyroiditis
- pernicious anemia
- type 1 DM
- Sjogrn syndrome
which HLA antigen is associated with Hashimoto thyroiditis?
which HLA antigen is associated with Type 2 diabetes?
what environmental factor may trigger Type 1 diabetes?
- some viruses trigger autoimmune islet cell inflammation
give me the general characteristics of connective tissue (collagen) diseases
- fibrinoid chnage in connective tissue
- ANAs often present
list the different connective tissue diseases
1. SLE
2. Progressive systemic sclerosis
3. Sjogren syndrome
4. Polymyositis
5. Mixed connective tissue disease
6. Polyarteritis nodosa
what is the epidemiology of SLE?
- prototype connective tissue disease
- mostly affects women (80% of patients)
what do you see in SLE? in the serum? in the organs?
- serum ANAs
- extensive immune complex-mediated inflammatory lesions involving the skin, serous membranes, lungs, and KIDNEY
what are the clinical manifestations seen in SLE?
- fever, malaise, weight loss, lymphadenopathy
- joint symptoms
- skin rashes
- Raynaud phenomenon
- serious inflammation
- diffuse interstitial pulmonary fibrosis
- endocarditis
- immune complex vasculitis
- glomerular changes
- CNS and psychiatric changes
- eye changes
what are the joint symptoms seen in SLE?
- arthralgia and arthritis
what are the skin rashes seen in SLE?
- characteristic butterfly rash over the base of the nose, and malar eminences
- often, photosensitivity
describe the serosal inflammation seen in SLE
- inflammation of the pericardium and pleura
describe the diffuse interstitial pulmonary fibrosis seen in SLE
- manifests as interstitial pneumonitis or diffuse fibrosing alveolitis
describe the endocarditis of SLE
- characteristic atypical nonbacterial verrucous (Libman-Sacks) form, where teh vegetations are seen on both sides of the Mitral valve
- Tricuspid valve is less frequently involved.
what is libman-sacks endocarditis?
- a form of nonbacterial endocarditis that is seen in SLE
- Libman-Sacks lesions rarely produce significant valve dysfunction and the lesions only rarely embolize. The pathology is the same as nonbacterial thrombotic endocarditis except focal necrosis (hematoxylin bodies) can be found only in Libman-sacks endocarditis.
describe the immune complex vasculitis seen in SLE
- vasculitis in vessels of almost any organ
- in the spleen, you get perivascular fibrosis with concentric rings of collagen around splenic arterioles -> onion skin appearance
what glomerular changes do you see in SLE?
- varies from minimal involvement to severe diffuse proliferative disease with marked subendothelial and mesangial immune complex deposition, endothelial proliferation, and thickening of the BM
in SLE, the thickening of the BM can be confused/indistinguishable with which disease?
- membranous glomerulonephritis
describe the subendothelial immune complex deposition seen in SLE
- found in the glomeruli
- wire-loop appearance seen in microscopy
what are the eye changes seen in SLE?
- yellowish, cotton wool-like fundal lesions (cytoid bodies)
what are the lab findings you see in SLE? (list)
1. LE test
2. positive ANA
3. decreased serum complement
4. immune complexes
5. biologic false-positive test for syphilis
what is the LE test?
- based on the LE phenomenon, which occurs in vitro
- morphologically characerisitic LE cells are formed in a mixture of mechanically damaged neutrophils and autoantibody-containing patient serum
- postitive in only 70% of cases of SLE. now replaced by other tests
describe the ANA test in SLE
- ANA is seen in almost all patients with SLE
- ANA is found in people with other connective tissue disorders
when do you get an ANA test that's almost specific for SLE?
- the antinuclear antibodies react with dsDNA
- you see a 'rim pattern' with immunofluorescence (peripheral nuclear staining)
- ANAs that react with Sm (Smith antigen) is also highly specific for SLE
what is Smith Antigen?
- an ribonucleoprotein that reacts with ANA, and is pretty specific for SLE
when do you see decreased serum complement?
- in SLE patients, esp if there's renal involvement
where do you see immune complexes in SLE?
- at dermal-epidermal junctions
- often seen in skin biopsies
why do you get a false test for syphilis with SLE?
- due to anticardiolipins- a form of antiphospholipid antibody, that occurs in 15% of SLE patients
- may be the earliest test abnormality in SLE patients
what is progressive systemic sclerosis?
- an autoimmune connective tissue disorder
- aka PSS, scleroderma
- involves widespread fibrosis and degenerative changes in the skin, GI tract (esp esophagus), heart, muscle, lung, and kidney
what is the incidence of progressive systemic sclerosis?
- PSS usually affects young women
how do you test for progressive systemic sclerosis?
- look for ANA anti-Scl-70
- present in 1/3 of patients
- ANA with anticentromemer activity is characteristic of a PSS varient: the CREST syndrome
what is the CREST syndrome?
Raynaude phenomenon
Esophageal dysfunction
what constitutes the initial presentation of progressive systemic sclerosis?
- skin changes
- polyarthralgias
- esophageal symptoms
what are characteristics of progressive systemic sclerosis?
- hypertrophy of collagent fibers of the subcutaneous tissue
- sclerodactyly
- raynaud phenomenon
- visceral organ involvement
describe the hypertrophy of collagen fibers seen in progressive systemic sclerosis
- hypertrophy of collagen fibers of the subcurtaneous tissue -> tightening of facial skin -> fixed facial appearance
what is sclerodactyly seen in progressive systemic sclerosis?
- claw-like hands
what percentage of progressive systemic sclerosis patients get raynaud's phenomenon?
describe the visceral organ involvement seen in progressive systemic sclerosis
- seen esp in the esophagus, GI tract, kidnies, and heart
- esophagus -> dysphagia
- interstitial pulmonary fibrosis- serious complication
- hypertension is common
who is mainly affected by the Sjogren syndrome?
- women of late middle age
what is the clinical manifestation of Sjogren syndrome?
- triad of:
1. xerostomia
2. keratoconjunctivitis sicca
3. connective tissue or autoimmune disease (most often rheumatoid arthritis)
- salivary gland involvement
- lacrimal gland involvement
define: xerostomia
dry mouth
define: keratoconjunctivitis sicca
- dry eyes
what are some associated disorders with Sjogren syndrome?
- polyyositis
- hashimoto thyroiditis
- Sicca syndrome
what is Sicca syndrome?
- a varient of Sjogren sydrome, characterized by xerostomia and keratoconjunctivitis alone
describe the salivary gland involvement seen in Sjogren syndrome
- bilaterally enlarged parotids diffusely infiltrated by lymphocytes and plasma cells
- the infiltration can obscure the parenchyma of the parotid gland, and can, in some instances, lead to malignant lymphoma
what are the lab findings associated with Sjogen syndrome?
- polyclonal hypergammaglobulinemia: broad based elevation of serum gamma globulins
- ANAs:
- highly specific anti-SS-B
- less specific anti-SS-A
what lab test is highly specific for Sjogen syndrome?
- ANA: anti-SS-B
what is polymyositis?
- a chronic inflammatory process that involves the proximal muscles of the extremities
- can also invovle skin
what are the clinical symptoms seen with polymyositis?
- with skin involvement, there's a reddish-purple rash over exposed areas of the face and neck -> dermatomyositis
what is dermatomyositis?
A rare autoimmune disease that causes patchy red rashes around the knuckles, eyes, and other parts of the body along with chronic inflammation of the muscles. It may occur along with other autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus.
what is the epidemiology of polymyositis? what can it cause?
- increased incidence in women
- often associated with malignancy
what are the lab results for a patient with dermatomyositis?
- increased serum creatine kinase (presence of ANAs)
- muscle biopsy shows necrotic muscle cells and lymphocytic infiltrate
what is the incidence of mixed connective tissue disease?
- aka MCTD
- 80% of patients are women
- peak incidence at 35-40 years
what are the clinical features of mixed connective tissue disease?
- shares clinical features with the other connective tissue disease, but RENAL INVOLVEMENT IS UNCOMMON
- arthralgias, Raynaud phenomenon, esophageal hypomotility, and myositis
define: myositis
Myositis: Inflammation of muscle tissue. There are many causes of myositis, including injury, medications, and diseases
what are the lab findings for mixed connective tissue disorder?
- high-titer anti-nRNP
- immunofluorescent specked nuclear appearance on mrophologic ANA analysis
what is polyarteritis nodosa?
- immune complex vasculitis
- segmental fibrinoid necrosis in the walls of small to medium arteries
what is the epidemiology of polyarteritis nodosa?
- seen primarily in men (in contrast to other connective tissue disorders)
which of the connective tissue disorders occurs primarily in men?
- polyarteritis nodosa
which antigen causes polyarteritis nodosa?
- hep B is implicated in 30% of cases
- Drugs: sulfonamides and penicillin may form immunogenic hapten-protein complexes
what are the clincial manifestations of polyartertis nodosa?
- abdominal pain, hypertension, uremia, polyneuritis, allergic asthma, urticaria or rash, splenomegaly, fever, leukocytosis, proteinuria
- lung: chest pain, cough, dyspnea, hemoptysis
what are some serious symptoms of polyarteritis nodosa?
- severe dyspnea and eosinophilia occur in 20% of patients
what is amyloidosis?
- a group of disorders characterized by depostiion of amyloid- a proteinaceous material with physicochemical features
what is the structure of amyloid?
- a group of substances that:
- have a b-pleated sheet configuration (seen on x-ray diffraction)
- can be formed by different proteins
amyloid protein: amyloid light chain from Ig light chains
Primary (immunocytic dyscrasia)
amyloid protein: amyloid- associated from precursor serum protein.
Secondary (reactive systemic)
Portuguese type ofpolyneuropathy
A4 amyloid (or aB protein)
Alzeimer's disease
Amyloid associated amyloid
Familial Mediterranean fever
Amyloid protein derived from calcitonin
Medullary carcinoma of the thyroid
Amylin (islet amyloid polypeptide, IAPP)
Insulin resistant DM
Senile amyloidosis
what are the morphologic features of amyloid
- extracellular
- accumulate proximate to basement membranes
- amorphous eosinophilic appearance in routine hematoxylin and eosin section
- stained by congo red
describe the congo red stain used to test for amyloid
- apple green birefringence when viewed under polarized light
what are other methods to look for amyloid other than congo red?
- immunochemical
- fluorescent
- metachromatic techniques
what are the two clinical patterns of amyloidosis?
Primary (immunocytic dyscrasia amyloidosis)
Secondary (reactive systemic amyloidosis)
what causes primary amyloidosis?
- deposition of amyloid derived from Ig light chains: AL (amyloid light chain) protein
where do you get amyloid deposition in primary amyloidosis?
- tissues of mesodermal origin: heart, muscle, tongue
- may also involve kidney-> deposition in the glomerular mesangium and the interstitial tissue between tubules
what is primary amyloidosis associated with?
- plasma cell disorders: myltiple myeloma, Waldenstrom macroglobulinemia, and other less defined disorders
what is secondary amyloidosis?
- deposition of fibrils consisting of amyloid protein AA protein
- formed from SAA
how is AA protein formed?
- formed from precursor ASS (serum-amyloid associated protein)
- SAA is caused by chronic tissue destruction
where do you get amyloid deposits in secondary amyloidosis?
- parenchymatous organs: KIDNEY (nephrotic syndrome is common), liver, adrenals, pancreas, lymph nodes, and spleen
- perifollicular involvement in spleen results in 'sago spleen'
what's sago spleen?
- seen in secondary amyloidosis of the spleen
- looks like tapioca-like granules
what can secondary amyloidosis arise from?
- usually a complication of chronic inflammatory disease:
RA, TB, osteomyelitis, syphilis, leprosy
- may also complicate noninflammatory diseases like renal cell carcinoma and Hodgkin disease
list the other forms of amyloidosis apart from primary and secondary
1. Portuguese type of polyneuropathy
2. Alzheimer disease
3. Familial Mediterranean fever
4. Medullary carcinoma of the thyroid
5. DM
6. Senile amyloidosis
7. Dialysis-associated amyloidosis
describe Portuguese type of polyneuropathy
- another type of amyloidosis
- associated with amyloid derived from a protein known as transthyretin (serum protein that TRANSports THYroxine and RETINol)
- characterized by peripheral nerve involvement from amyloid deposits
describe Alzheimers Disease in the context of amyloidosis
- deposits of A4 amyloid or amyloid B-protein
- genes that code for protein precursor of A4 is on Chr 21
describe Familial Mediterranean fever
- a type of amyloidosis
- autosomal recessive
- eastern mediterranean people
- episodic fever and olyserositis
- distribution and type of amyloid are similar to that of secondary amyloidosis (AA amyloid)
describe Medullary carcinoma of the thyroid
- a type of amyloidosis
- characterized by amyloid deposits within the tumor, derived from calcitonin
describe DM in the context of amyloidosis
- T2DM is characterized by deposits of amyloid in islet cells
- amyloid is thought to derive from insulin or glucagon, and is referred to as amylin (aka islet amyloid polypeptide).
what is the relationship between amyloid and insulin
- amyloid is thought to interfere with insulin sensing by beta cells
describe senile amyloidosis
- minor deposits of amyloid in the very elderly
- may involve the heart, brain
- when it occurs in the heart, the protein is derived from transthyretin
describe dialysis associated amyloidosis
- amyloid deposits in the joints of patients who have undergone hemodialysis for several years
- derived from b-microglobulin, which is not filtered by the dialysis machine