[mtle] immunosero pt. 3

autoimmunity

result of breakdown in self-tolerance that leads to immune system responding to self-molecules as if they were foreign

type 1 diabetes

autoimmune disease

-selective destruction of insulin producing beta cells of islets of Langerhans in pancreas

-90% carry HLA-DR3 and HLA-DR4

antibodies to insulinoma antigen 2, anti-insulinoma antigen 2betaA, anti-insulin antibodies, antibodies to glutamic acid decarboxylase, islet cell antibodies

autoantibodies present in prediabetic individuals and newly diagnosed patients; antibodies present in TYPE I DIABETES

(1) rheumatoid arthritis

(1) autoimmune disease

-chronic systemic inflammatory disorder in which joint cartilage, ligaments, and tendons are destroyed

erosive arthritis of peripheral joints that affect heart and lungs

-STRONGEST association with HLA-DR4

(2) rheumatoid arthritis

(2) autoimmune disease; symptoms are morning stiffness, swelling of soft tissues, swelling of proximal interphalangeal, metacarpophalangeal, wrist joints, symmetric arthritis, subcutaneous nodules, radiographic evidence of erosions in joints of hands, wrist, or both

rheumatoid factor

-antibody seen in RHEUMATOID ARTHRITIS

-IgM directed against Fc receptor of IgG

-NOT specific for RA

-IgM antibodies combined with IgG and these immune complexes become deposited in JOINTS causing TYPE III HYPERSENSITIVITY

(1) systemic lupus erythematosus

(1) autoimmune disease

-immune complexes are formed and lodge in basement membrane of KIDNEY, SKIN, JOINTS

-deposition of immune complexes in SUBENDOTHELIAL TISSUE and THICKENING of basement membrane -> RENAL FAILURE (frequent cause of death)

(2) systemic lupus erythematosus

(2) autoimmune disease

-JOINT INVOLVEMENT most frequent manifestation (subject to polyarthralgias arthritis)

-SKIN MANIFESTATION after joint involvement causing ERYTHEMATOUS RASH may appear on any area of body exposed to ULTRAVIOLET LIGHT

(3) systemic lupus erythematosis

(3) autoimmune disease

-appearance of CLASSIC BUTTERFLY RASH across nose and cheeks ("lupus"); in discoid lupus, skin lesions have central atrophy and scarring

- diffuse proliferative GLOMERULONEPHRITIS causing cellular proliferation present of glomeruli

-STRONG association with HLA-DR3 and HLA-DR4

LE cell phenomenon

diagnose systemic lupus erythematosus; neutrophil has engulfed antibody coated nucleus of another neutrophil

indirect immunofluorescence (fluoroscent antinuclear staining)

antinuclear antibodies (most striking feature of disease but NOT diagnostic); mouse kidney or human epithelial HEp-2 cells are fixed to slide; ANTIHUMAN IMMUNOGLOBULIN with fluorescent tag or enzyme label (horseradish peroxidase) added

anti-dsDNA

autoantibody; double stranded DNA is characteristic of antigen

-homoggenous or nuclear (peripheral) pattern in INDIRECT IF

-most pathognomic and MOST SPECIFIC for SLE

anti-ssDNA

autoantibody; related to PURINES and PYRIMIDINES is characteristic of antigen

-NOT detected on ROUTINE screen

-associated with SLE and many other diseases

anti-histone

autoantibody; different classes of HISTONES characteristic of antigen

-HOMOGENOUS pattern in INDIRECT IF

-associated with DRUG-INDUCED SLE and others

anti-DNP

autoantibody; DNA-histone complex characteristic of antigen

-HOMOGENOUS pattern in INDIRECT IF

-associated with SLE, DRUG-INDUCED SLE

anti-Sm

autoantibody; EXTRACTABLE NUCLEAR ANTIGEN (RNA component) characteristic of antigen

-SPECKLED pattern in INDIRECT IF

-HIGHLY SPECIFIC for SLE

anti-Scl-70

autoantibody; DNA topoisomerase I characteristic of antigen

-ATYPICAL SPECKLED pattern in INDIRECT IF

-associated with SYSTEMIC SCLEROSIS, SCLERODERMA

nuclear rim (peripheral) pattern

staining pattern of ANA; results from antibodies to DNA (nDNA, dsDNA, DNP)

-ACTIVE stage of SLE

-associated with Sjorgen's syndrome and lupus nephritis

homogenous (solid or diffuse) pattern

staining pattern of ANA; results from ANTI-DNA-NUCLEOPROTEIN antibodies (nDNA, dsDNA, ssDNA, HISTONES, DNP)

-seen in RHEUMATOID DISORDERS and other connective tissue defect and SLE

speckled (mottled) pattern

staining pattern of ANA; involves extractable nuclear antigens such as Smith antigen and ribonucleoprotein

-anti-Sm seen HIGHLY specific for patients with SLE and marker antibody

-present in SCLERODERMA

nucleolar pattern

staining pattern of ANA; reflects ANTIBODIES to NUCLEOLAR RNA; RARE in SLE or RA

-present in PROGRESSIVE SYSTEMIC SCLEROSIS, SJORGEN'S SYNDROME

thready pattern

staining pattern of ANA; seen in SLE but not in RA

(1) grave's disease

(1) autoimmune disease

-COMMON cause of HYPERTHYROIDISM; manifested as THYROTOXICOSIS with ENLARGED, SOFT GOITER

-UNREGULATED secretion of T3 and T4 due to stimulation of TSH receptor by antibody

-associated with HLA-DR3

(2) grave's disease

(2) autoimmune disease; symptoms are nervousness, insomnia, depression, weight loss, heat intolerance, sweating, rapid heartbeat, palpitations, breathlessness, fatigue, cardiac dysrhythmias, restlessness, exophthalmos (hypertrophy of eye muscles and increased connective tissue in orbit -> eyeball BULGE OUT)

(3) grave's disease

(3) autoimmune disease

-antigen-antibody occurs which mimics normal action of TSH and results in receptor stimulation with release of THYROID HORMONES to produce symptoms of HYPERthyroidism

-INCREASED T3 and T4; LOW TSH; INCREASED radioactive iodine uptake

anti-TSH receptor antibodies

antibodies seen in GRAVE'S DISEASE

(1) hashimoto's thyroiditis (chronic autoimmune thyroiditis)

(1) autoimmune disease

-DESTRUCTION of THYROID GLAND; develop combination of GOITER (or enlarged thyroid), HYPOthyroidism, THYROID AUTOANTIBODIES

-GOITER is irregular and rubbery and IMMUNE DESTRUCTION of thyroid gland

(2) hashimoto's thyroiditis (chronic autoimmune thyroiditis)

(2) autoimmune disease; symptoms are dry skin, decreased sweating, puffy face with edematous eyelids, pallor with yellow tinge, weight gain, dry and brittle hair

-associated with HLA-DR5

anti-thyroid peroxidase, anti-thyroglobulin

antibodies seen in HASHIMOTO'S THYROIDITIS; destroy THYROGLOBULIN and produce symptoms associated with HYPOthyroidism

pernicious anemia

autoimmune disease; destruction of PARIETAL CELLS of STOMACH MUCOSA leading to INTRINSIC FACTOR DEFICIENCY

anti-parietal cell antibodies, anti-intrinsic factor antibodies

autoantibodies seen in PERNICIOUS ANEMIA

(1) myasthenia gravis

(1) autoimmune disease

-neuromuscular transmission disorder due to antibodies that inhibit and block ACETYLCHOLINE binding

-affects NEUROMUSCULAT JUNCTION; characterized by WEAKNESS and fatigability of skeletal muscles

(2) myasthenia gravis

(2) autoimmune disease

-antibody-mediated damage to acetylcholine receptors in skeletal muscle leads to progressive muscle weakness

-signs are DROOPING of EYELIDS and inability to retract corners of mouth (SNARLING appearance)

-associated with HLA-A1, HLA-B8, HLA-DR3

antibody to ACH receptors

autoantibodies seen in MYASTHENIA GRAVIS; MAIN contributor to PATHOGENESIS of disease

-ACETYLCHOLINE released from nerve endings to generate action potential that cause MUSCLE FIBER to contract

-ANTIBODY combines with receptor site, binding of ACH is blocked and receptors are DESTROYED because of action of antibody and complement

scleroderma

autoimmune disease; SKIN FIBROBLASTS reproduce faster and secrete more collagen; weak association with HLA-DR3

sjorgen's syndrome

autoimmune disease; clinically present as DRY EYES and MOUTH; presence of RHEUMATOID FACTOR and ANTI-NUCLEAR ANTIBODIES are indicative of systemic disease with many tissues involved

-associated with HLA-DR3

(1) goodpasture's syndrome

(1) autoimmune disease

-characterized by presence of autoantibody to glomerular, renal tubular, and alveolar basement membrane resulting primarily in injury to glomerulus that can rapidly progress to RENAL FAILURE

-associated with HLA-DR15 or HLA-DR4

(2) goodpasture's syndrome

(2) autoimmune disease

-autoantibody reacts with COLLAGEN in glomerular or alveolar basement membranes

-immune deposits accumulate and complement fixation cause INJURY because of relase of tubular, glomerula, and pulmonary alveolar basement membranes

antibasement antibodies

-autoantibody seen in GOODPASTURE'S SYNDROME

-demonstrated by FORMATION of SMOOTH, LINEAR RIBBON-LIKE pattern on direct immunofluorescent assay of glomerular basement membrane from patients with disease

antineutrophilic cytoplasmic antibodies

autoantibody seen in WEGENER'A GRANULOMATOSUS

antimitochondrial antibodies

autoantibody seen in PRIMARY BILIARY CIRRHOSIS

antismooth muscle antibodies

autoantibody seen in CHRONIC ACTIVE HEPATITIS

monoclonal gammopathy

immunoproliferative disorders; benign or malignant results from SINGLE clone of LYMPHOID-PLASMA CELLS producing ELEVATED levels of M PROTEIN or PARAPROTEIN (single class of and type of immunoglobulin)

multiple myeloma

plasma cell dyscrasia

-MALIGNANCY of MATURE PLASMA CELLS; EXCESS PLASMA CELLS in BONE MARROW, MONOCLONAL IMMUNOGLOBULIN in plasma or urine, LYTIC BONE LESIONS

-IgG MOST COMMON followed by IgA, IgM, LIGHT CHAINS only

-MOST SERIOUS and MOST COMMON of plasma cell dyscrasia

hematologic manifestation

manifestation of multiple myeloma related to FAILURE of BONE MARROW to produce NORMAL number of hematopoietic cells and MYELOMA CELLS progressively replace leading to ANEMIA, THROMBOCYTOPENIA, NEUTROPENIA

skeletal manifestation

manifestation of multiple myeloma involving BONE and forming MULTIPLE LYTIC LESIONS leading to BONE PAIN and FRACTURES (HYPERCALCEMIA common because MYELOMA promotes bone resorption)

immunologic manifestation

-manifestation of multiple myeloma wherein there is EXCESS production of ABNORMAL immunoglobulin accompanied by progressive DECREASE in NORMAL immunoglobulin

-deficiency of NORMAL ANTIBODY response and HIGHER incidence of infectious disease

myeloma cells

produce LIGHT CHAINS that is RAPIDLY excreted in urine

bence jones proteins

free immunoglobulin light chains excreted in urine seen in multiple myeloma; TOXIC to tubular epithelial cells and damage kidneys by precipitating in tubules causing INTRARENAL OBSTRUCTION

(1) waldenstrom's macroglobulinemia

(1) plasma cell dyscrasia

-malignant proliferation of IgM producing lymphocyte and corresponds tp LYMPHOPLASMACYTOID LYMPHOMA

-PLASMACYTOID LYMPHOCYTES infiltrate bone marrow, spleen, lymph nodes

(2) waldenstrom's macroglobulinemia

(2) plasma cell dyscrasia

-symptoms are infiltration of malignant cells into BONE MARROW, SPLEEN, LYMPH NODES with overproduction of monoclonal IgM

-MONOCLONAL IgM accumulate in tissue forming deposits leading to INFLAMMATION and TISSUE DAMAGE

(3) waldenstrom's macroglobulinemia

(3) plasma cell dyscrasia

-IgM paraproteins behave as cryoglobulins (precipitate at COLD temperatures and OCCLUDE SMALL vessels)

-OCCLUSIONS of SMALL VESSELS lead to development of SKIN SORES or NECROSIS of portion of FINGERS or TOES

hodgkin's lymphoma

lymphoma

-characterized by presence of REED-STERNBERG CELLS in affected lymph nodes and lymphoid organs

-patients has ELEVATED levels of ANTIBODY to EBV (causative agent of infectious mononucleosis)

lymphocyte-rich

type of hodgkin's lymphoma; 5% of cases; found in slightly OLDER patients

nodular sclerosis

type of hodgkin's lymphoma; MOST COMMON subtype with BEST prognosis

-characterized by infiltration of mixture of NORMAL macrophages, lymphocytes, granulocytes

-SMALL numbers of RS cells, MARKED fibrosis

mixed cellularity

type of hodgkin's lymphoma; MIXED INFILTRATES of normal cells

-GREATER numbers of RS cells; LESS fibrosis

lymphocyte depleted

type of hodgkin's lymphoma; FEW infiltrating normal cells

-GREATEST number of RS cells; WORST prognosis

B cell lymphoma

lymphoma

-MAJORITY of NON-hodgkin's lymphoma; lymphoma progressively develop MORE AGGRESSIVE phenotype over course of disease (lymphoma progression)

-three characteristics are SURFACE IMMUNOGLOBULIN, CELL SURFACE PROTEINS (CD19 and CD20; REARRANGED immunoglobulin genes

low risk group

group containing chronic lymphocytic leukemia or lymphoma, follicular lymphomas, MALT lymphomas

intermediate risk group

group containing diffuse large B cell lymphoma (MOST COMMON) and Burkitt's lymphoma

high risk group

group containing mantle cell lymphoma and lymphoblastic lymphoma

T cell lymphoma

NON hodgkin lymphoma that are DIFFICULT to characterize

acute lymphoblastic leukemia

lymphoblastic leukemia

-characterized by presence of VERY POORLY differentiated precursor cells (blast cells) in bone marrow and peripheral blood

-cells infiltrate SOFT TISSUES to organ dysfunction; seen in CHILDREN and treatable

(1) chronic lymphocytic leukemia or lymphoma

(1) lymphoblastic leukemia

-almost exclusively of B cell origin; composed chronic lymphocytic leukemia, small lymphocytic lymphoma, prolymphocytic leukemia, hairy cell leukemia

-COMMON hematopoietic malignancy that involves expansion of clone of B cells with small mature lymphocytes

(2) chronic lymphocytic leukemia or lymphoma

(2) lymphoblastic leukemia

-NORMAL lymphocytes accumulate in bone marrow, blood, spleen, lymph nodes

-MALIGNANT lymphocytes INCREASE, replacement of normal elements in bone marrrow which cause anemia and thrombocytopenia; LYMPH NODE ENLARGEMENT prominent in EARLY disease

-seen in patients 45 years of age

hairy cell leukemia

lymphoblastic leukemia

-characterized by infiltration of bone marrow and spleen by leukemic cells without involvement of lymph nodes

-MALIGNANT LYMPHOCYTES are round with "bland" cytological appearance with irregular "hairy" cytoplasmic projections from their surface

-strongly express B cell markers are CD19, CD20, CD22

(1) chronic granulomatous disease

(1) defects of neutrophil function

-x-linked or autosomal recessive gene that affects NEUTROPHIL MICROBICIDAL FUNCTION; MOST common and BEST characterized

-defect in NADPH OXIDASE system causing REDUCED intracellular killing of ingested organisms

(2) chronic granulomatous disease

(2) defects of neutrophil function

-specific molecular defects cause inability of patient's neutrophils to produce reactive forms of oxygen necessary for normal bacterial killing

-three different autosomal recessive genes affects subunits of NADH oxidase

nitroblue tetrazolium test

used to diagnose chronic granulomatous disease; reduction caused by production of hydrogen peroxide and other reactive forms of oxygen

blue precipitate

in nitroblue tetrazolium test, reduction due to chronic granulomatous disease cause colorless NBT to change color

Neutrophil glucose-6-phosphate dehydrogenase deficiency

defects of neutrophil function; leads to inability to generate enough NADPH to supply reducing equivalents to NADPH oxidase system leading to DEFECT in HYDROGEN PEROXIDE production

(1) leukocyte adhesion deficiency

(1) defects of neutrophil function

-CD18 (component of adhesion receptors on neutrophils and monocytes and on T cells) is defective

-defect leads to ABNORMAL ADHESION, MOTILITY, AGGREGATION, CHEMOTAXIS, and ENDOCYTOSIS by affected leukocytes

(2) leukocytes adhesion deficiency

(2) defects of neutrophil function; clinical manifestations are delayed wound healing, chronic skin infections, intestinal and respiratory tract infections, and periodontitis

myeloperoxidase deficiency

defects of neutrophil function; deficiency of MYELOPEROXIDASE which is an important microbicidal agent in neutrophils

chediak-higashi syndrome

defects of neutrophil function; IMPAIRED chemotaxis and phagosome degranulation; presence of GIANT GRANULES in leukocytes

job's syndrome

defects on neutrophil function; neutrophils demonstrate DEFECTIVE chemotaxis

lazy leukocyte syndrome

defects on neutrophil function; DEFECTIVE chemotactic and RANDOM MOVEMENT by neutrophils

tuftsin deficiency

defects on neutrophil function; deficiency of TUFTSIN, phagocytosis-promoting serum tetrapeptide that is cleaved from an immunoglobulin-like molecule, leukokinin in spleen

(1) transient hypogammaglobulinemia of infancy

(1) B cell deficiency; results when onset of immunoglobulin synthesis is DELAYED; HYPOGAMMAGLOBULINEMIA is common in infants between 5th to 6th months of life

(2) transient hypogammaglobulinemia of infancy

(2) B cell deficiency

-SEVERE pyrogenic sinopulmonary and skin infections as protective maternal IgG is cleared

-cause related to DELAYED maturation of one or more components of immune system (T helper cells)

(1) X-linked bruton's agammaglobulinemia

(1) B cell deficiency

-genetic defect in LONG arm of X chromosome; BLOCK in maturation of pre B cells

-affects males; lack circulating mature CD19 B cells and lacks immunoglobulins of all classes; have NO plasma cells in lymphoid tissues but have pre-B cells in bone marrow

(2) X-linked bruton's agammaglobulinemia

(2) B cell deficiency

-caused by arrested differentiation as pre-B cell stage leading to complete absence of B cells and plasma cells -> deficiency of Bruton tyrosine kinase in B cell progenitor cells

-lack of B cells; tonsils and adenoids are small or absent; lymph nodes LACK normal germinal centers

(3) X-linked bruton's agammaglobulinemia

(3) B cell deficiency; develop recurrent bacterial infections beginning in infancy as maternal antibody is cleared and commonly develop sinopulmonary infections caused by encapsulated organisms (Streptococci, Meningococci, H. influenzae)

IgA deficiency

B cell deficiency

-MOST COMMON CONGENITAL immunodeficiency; MOSTLY aymptomatic; if IgA is <5 mg/mL, deficiency is considered SEVERE

-RECURRENT sinopulmonary infections; anti-IgA produced by this patients cause ANAPHYLACTIC reactions when blood products containing IgA are transfused

selective immunoglobulin deficiency (dysgammaglobulinemia)

B cell deficiency; arrest in development of B cell is the culprit

(1) common variable immunodeficiency

(1) B cell deficiency

-characterized by hypogammaglobulinemia that leads to recurrent bacterial infections (sinusitis and pneumonia)

-deficiency in both IgA and IgG (selective IgG deficiency may occur)

-patients with recurrent bacterial infections demonstrate LOW serum IgG level

(2) common variable immunodeficiency

(2) B cell deficiency

-in contrast to X-linked agammaglobulinemia, CVI has normal mature B cells but does NOT differentiate normally into immunoglobulin-producing plasma cells

-associated with sprue-like syndrome characterized by malabsorption and diarrhea

DiGeorge anomaly

T cell deficiency

-developmental abnormality of 3rd and 4th pharyngeal pouches that affects THYMIC development causing deletion in chromosome 22q11

-QUANTITATIVE defect in THYMOCYTES causing NOT enough mature T cells are made but those present are functionally NORMAL

chronic cutaneous candidiasis

T cell deficiency; impaired synthesis of migratory inhibitory factor by T cells

bare lymphocyte syndrome

T cell deficiency; deficiency in expression of MHC II gene products on T cell surface leading to failure of antigen presentation

(1) purine nucleoside phosphorylase deficiency

(1) T cell deficiency

-RARE autosomal recessive trait

-RECURRENT or CHRONIC pulmonary infections, ORAL or CUTANEOUS candidiasis, DIARRHEA, SKIN infections, URINARY TRACT infections, FAILURE to THRIVE in infants

(2) purine nucleoside phosphorylase deficiency

(2) T cell deficiency

-affects enzyme involved in metabolism in PURINE producing moderate to severe defect in cell-mediated immunity with NORMAL or MILDLY impaired humoral immunity

-number of T cells progressively DECREASES because of accumulation of DEOXYGUANOSINE TRIPHOSPHATE

(1) severe combined immunodeficiency disease

(1) combined deficiencies

-combined defect of both HUMORAL and CELL mediated immunity; autosomal recessive type associated with ADENOSINE DEAMINASE deficiency

-related diseases that ALL affect T and B cell function but with differing causes

-RARELY survive beyond age 1 if NO treatment

(2) severe combined immunodeficiency disease

(2) combined deficiencies

-have ADENOSINE DEAMINASE DEFICIENCY which affects enzyme involved in metabolism of PURINES

-toxic metabolites of PURINES accumulate in LYMPHOID CELLS and impair proliferation of both B and T cells

X-linked SCID

type of severe combined immunodeficiency disease

-ABNORMAL gene codes for common gamma chains (involves codes for protein chain) which is common to receptors for INTERLEUKINS -> gene referred to IL2RG gene located on X chromosome

-NORMAL signaling can NOT occur in cells with DEFECTIVE receptors which HALTS natural maturation

JAK3 deficiency

type of severe combined immunodeficiency disease

-withOUT common GAMMA chain deletion leading AUTOSOMAL RECESSIVE form of SCID (affects both male and female)

-LACK of intracellular KINASE JAK3 -> lymphocytes are unable to transmit signals from IL2 and IL4

nezelof's syndrome

combined deficiencies; THYMIC DYSPLASIA resulting in DECREASED to ABSENT T cell immunity; usually have MARKED lymphadenopathy and hepatosplenomegaly

(1) wiskott-aldrich syndrome

(1) combined deficiency

-rare X-linked recessive syndrome; defined by TRIAD of immunodeficiency, eczema, thrombocytopenia

-lethal in childhood because of infection, hemorrhage, malignancy causing DECREASE in platelet number and size with PROLONGED bleeding time

(2) wiskott-aldrich syndrome

(2) combined deficiency

-bone marrow contains NORMAL or INCREASED number of megakaryocytes

-abnormalities in BOTH cellular and humoral arms of immune system related to general defect in antigen processing -> manifest as SEVERE deficiency of naturally occurring antibodies to blood group antigens

(3) wiskott-aldrich syndrome

(3) combined deficiency

-genes responsible for defect is WASp gene and located on X chromosome p11 -> abnormalities cause DEFECTIVE ACTIN POLYMERIZATION and affects its signal transduction in LYMPHOCYTES and PLATELETS