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General Pathology 3

Bruton's agammaglobulinemia X-linked recessive. No B cells, No Igs. Recurrent staph, haemophilus and strep infections after 6 months. Increased pre-B cells. Mutation of B-cell Bruton tyrosine kinase (btK).
Common variable immunodeficiency B-cell maturation defect. Hypogammaglubulinemia, recurrent bacterial infections, giargia lamblia.
DiGeorge syndrome Failure to develop 3rd and 4th pharyngeal puches results in absence of parathyroid and thymus glands, hypocalcemia, tetany, T-cell deficiency, recurrent viral infections, heart defects, chronic candidiasis
SCID B and T cell deficiency due to mutation of IL-2 receptor (x-linked), adenosine deaminase deficiency (AR) or failure to make MHC II. Recurrent infections and susceptibility to candida, CMV and p. carinii
Wiskot-Aldrich syndrome X-linked recessive. "WIPE": recurrent infections, thrombocytopenic purpura, eczema, risk of lymphomas, low IgM
Ataxia-Telangiectasia Ataxia, spider angiomas, low IgA, defect of DNA repair enzyme
Chronic granulomatous disease Low NADPH oxidase. Recurrent catalase+ infections, negative nitroblue tetrazolium test.
Leukocyte adhesion deficiency Defect of CD-18 (LFA-1 beta chain), no pus formation, failure of umbilical cord to detach
Chediak-Higashi Defect in microtubulus with no phagocytosis by lysosome. Partial albinism, peripheral neuropahty, recurrent infections
Hereditary andioedema Edema at mucosal surfaces. Defect of C1-INH (esterase inhibitor). Decreased C1, C2, C4
Hyper IgM Defect of CD-40L on T-lymphocytes. No isotope switching, increased IgM
MHC-I deficiency Normal CD4, no CD8. Failure of TAP-1 to transport peptides to MHC-I groove
Amyloid stains Stains red with Congo-red stain then apple green birefringence under polarized light
Signs and symptoms of amyloidosis Nephrotic syndrome, renal failure, arrythmias, CHF, hepatosplenomegaly, macroglosia
Mediators of leukocyte margination Selectins mediate margination. P and E selctins on endothelium bind Sialyl-Lewis on leukocyte; GlyCAM/CD34 on endothelium binds L-selectin on leukocyte
Mediators of leukocyte adhesion Integrins mediate adhesion. ICAM, VCAM on endothelium bind LFA-1 and VLA on leukocyte
Regulators of leukocyte margination and adhesion Histamine upregulates P-selectin. IL-1 and TNF induce E-selectin, ICAM and VCAM. Chemotactic agents cause conformational change of LFA-1
Leukocyte adhesion deficiency Defect of CD18 (beta chain subunit of LFA-1 integrin on leukocytes). Recurrent infections, no pus formation, failure of umbilical cord to detach
Chemotactic factors N-formyl methionine, leukotriene B4, C5a, IL-8
Opsonins Fc portion of IgG, c3b, C reactive protein
Chediak-Higashi syndrome Defect of microtubule polymerization causes defect in chemotaxix and degranulation. Partial albinism, peropheral neuropathy
CGD NADPH oxidase deficiency. No production of superoxide for respiratory burst. Recurrent catalase+ infections, negative nitroblue tetrazolium test
Arachidonic acid products AA producedd by phospholipase A2 (inhibited by steroids). Produces leukotrienes, prostaglandins and thromboxane A2
Lypoxigenase pathway Arachidonic acid is converted to leukotrienes by 5-lypoxigenase. LTB4 --> chemotaxis. LTC4, D4, E4 --> bronchoconstriction
Cycloxigenase pathway Arachidonic acid is converted to TXA2 and prostaglandins (NSAIDs block). TXA2 --> vasoconstriction, platelet aggregator. PGI2, PGE2, PGF2
Mediators of vasodilation Histamine , bradikinin, PGI2, PGD2, E2, F2
Mediators of pain Bradikinin, PGE2
Mediators of increased permeability Histamine, Bradikinin
Mediators of vasoconstriction TXA2, LTC4, D4, E4
Mediators of bronchoconstriction LTC4, D4, E4, bradikinin
Mediators of fever IL-1, PGD2, E2, F2
Anaphilotoxins C3a, C5a. Directly stimulate histamine release from basophils, mast cells and platelets
C3b Opsonin; neutrophils, macrophages and monocytes have C3b receptros
Bradikinin synthesis and actions Synthesized from activation of prekalikrein by factor XII (Hageman). Kalikrein cleaves HMWK into bradikinin. Vasodilator, increased permeability, brnchoconstrictor, pain
PGE2 Vasodilation in kidneys, increases renal blood flow, increases gastric mucosal blood flow (mucoprotection), activates osteoclasts, fever, pain, maintains ductus arteriosus
Prostacyclin (PGI2) Vasodilation and inhibits platelet aggregation
IL-1 Stimulates PGE2 synthesis in hypothalamus --> fever; B-cell stimulation to synthesize Ig; osteoclast activation (released by osteoblasts under PTH stimulation); lytic bone lessions of multiple myeloma; increases adhesion molecules in endothelium; increase
Hageman factor Activates intrinsic coagulation system, kinin cascade and fibrinolytic system
PGF Uterine muscle contraction (cause pf primary amenorrhea)
gamma interferon Produced by CD4 cells and NK cells. Activates macrophages; antiviral properties; class I and class II antigens; increases IL-2, IL-12 production by CD4 cells
IL-2 Produced by CD4 cells. T cell growth factor. Promotes B cell and NK cell proliferation
IL-6 Synthesis of acute phase reactants
Factors that increase adhesion molecule synthesis C5a, LTB4, IL-1, TNF
Key cells in acute and chronic inflammation Acute: neutrophil has IgG and C3b receptros; Chronic: macrophage has receptors for IgG and C3b, process antigen and secrete IL-1, IL-12 and TNF
Chronic granulomatous inflammation Epitheloid cells and multinucleated giant cells surrounded by a rim of lymphocytes with central caseous necrosis
Created by: Asclepius



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