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direct Abs or cell mediated vasculitis
Giant cell and kawasaki
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Immune complex mediated vasculitis is an example of type ___ hypersensitivity
III
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Type III hypersensitivity rxn
rxn is initiated when Ag combines w/ Ab w/in circulation --> immune complexes --> deposited in vascular endothelium or in capillary beds, such as those in skin, kidneys or lungs.
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C3a from complement activation via immune complexes induces
degranulation of mast cells
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corticosteroids
inhibit cytokine gene transcription --> decr maturation of monocytes and macs, decr T cell activation, decr NK cell fxn, decr expression of adhesion molecules by endothelial cells
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Cyclosporin
blocks IL12, inhibits calcineurin
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Cyclophosphamide.
- inhibits DNA synthesis, reduces Ag specific Ab production, & lowering of T cell numbers. Particularly useful in aggressive autoimmune
- diseases such as Wegener’s granulomatosis and SLE vasculitis
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Endocarditis microbes that enter/spread via oral cavity
Strep mutans (viridans strep), HAECK group (heamophilus, actinobacilus, cardiobacterium, eukenella, kingella)
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endocarditis agents that enter/spread via airway
Strep, staph epidermis
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endocarditis agents that enter/spread via GI tract
Strep, staph epidermidis, neisseria
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IVIG in suppression autoimmune vasculitis
- effective for kawasaki. FcRn normally recycles IgG, providing increased half life for IgG. High dose IVIG may bind up all FcRn, blocking
- recycling of endogenous Ab (which includes the autoreactive stuff) thus lowering titers of autoreactive antibody
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Henoch-Schonlein Purpura:
most common type of childhood vasculitis. Systemic disorder caused by vascular localization of immune complexes containing mostly IgA, which activates alternative complemt pathway. Thus, find more deposits of C3, than C1q and C4
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vasculitis involving small arteries, as well as glomerulonephritis and arthritis. also a tendency to cause ischaemic damage by plugging of small blood vessels with large #’s of inflammatory cells. Fibrinoid necrosis.
SLE
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immunoglobulins which form precipitates, gels or even crystals at low temperatures. generated secondary to neoplasms of lymphoid system or during periods of prolonged immune stimulation
Cryoglobulins
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characterized by presence of monoclonal Ig, usually IgM, no recognizable Ab activity. underlying malignancy (lymphoma or myeloma)
Monoclonal=recognize same Ag, same Ag receptor. All Ab come from same clonal B cell
Type 1 cryoglobulin
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mixed type in which monoclonal protein (usually IgM) attacks Fc portion of IgG (Rf activity). precipitation occurs when complexes of IgM-anti-IgG Ab are formed. Strongly assoc w/ chronic hep C, or less often w/ B cell malignancy or SLE
Type II cryoglobulin
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mixed type, but contain poly- or oligoclonal IgM directed against Fc portion of IgG. Strong assoc w/ Hep C, others assoc w/ RA, SLE, PAN or other chronic infection
Type III cryoglobulin
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major cause of sudden unexpected death in adults <40yr
myocarditis
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Laboratory tests may show leukocytosis, an elevated sedimentation rate, eosinophilia, or an elevation in the cardiac fraction of creatine kinase. Cardiac troponin (troponin I or T) may be elevated
myocarditis
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Viral causes of myocarditis
Cox B, ECHO, influenza, HIV, and opportunistic infections
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parasitic causes of myocarditis
trypanosome, toxo, and trichinella
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ANCAs are type ____ hypersensitivity
II
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Diagnosing ANCAs
ELISA and western blot. detect anti IgG agent.
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Churg strauss syndrome
allergic/asthmatic granulomatosis. small vessel necrotizing vasculitis classically assoc w/ asthma, allergic rhinitis, lung infiltrates, peripheral hypereosinophilia, and extravascular necrotizing granulomas. high levels of IL-5 and the presence of IgE immune complexes
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most common world wide cause of myocarditis
Chagas dz. Trypanosome. South and Central americas. Trasmitted by reduviids (kissing bugs).
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inflammation caused by an immune response to an infective agent, or to viral or bacterial superantigens. IVIG has been shown to prevent coronary aneurysm formation, lessen fever and reduce myocardial inflammation
kawasaki
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vasculitis often assoc w/ granuloma formation. Presence of activated CD4 T cells in lesion, HLA class II predisposition to dz
Giant cell/temporal arteritis.
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Macs produce what to promote leukocyte recruitment in atherosclerosis?
IL-1, TNFa & chemokine, MCP-1
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atherosclerotic lesion contains cytokines, such as ___ and ___ that promote Th1 differentiation
IL 12 and IL18
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___ and ____ produced by activated Th1 CD4 T cells further stimulate macrophage activation and release of NO, proteases and other pro-inflammatory cytokines (IL1)
IFNg and TNFa
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Picorna virus --> enterovirus. all SS RNA, linear non enveloped, + sense
poliovirus, echovirus, coxsackie, rhinovirus, and Hep A
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parvovirus B19 also causes
myocarditis. infection of endothelial cells
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TGF beta
produced by endothelial cells, smooth muscle cells, and Th2/reg T cells to inhibit Th1 cell differentiation/proliferation, reduce TNFa and IFNg --> decr inflammation
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risk of cardiovascular dz
Increased levels of CRP and IL-6. high mac colony stimulating factor or low TGFb-1 (poor outcome of CAD)
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activated macrophages and T cells produce
IL1, TNFa, IFNg
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myocarditis can lead to ...
dilated heart. IV septum shifts to the right.
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diagnosis method for endocarditis
3-4 blood cultures in a 24 to 48-hour time period (each from a separate venipuncture). With at least 1-3 hours between draws
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Strep A characteristics
Catalase -, coagulase -, Bacitracin sensitive, Hyaluronic capsule, M-protein, Lipoteichoic acid. Extracellular dextran, FimA mediated adherence. Enzymes (Hemolysins, Streptokinase)
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Causes of endocarditis
rheumatic heart (community acquired), mitral valve prolapse (congenital), prosthetic heart valves, IV drug use (most severe, progresses rapidly, tricuspid valve)
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Prothetic heart valve microbes in endocarditis
- S. epidermidis- Acute. Catalase +, coagulase -
- S. aureus- Acute
- Gram negative bacilli- Acute
- C. albicans- Acute
- Streptococci- subacute
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IV drug microbial causes of endocarditis
- Staphylococcus aureus: Catalase positive, Coagulase positive. utilizes fibrinogen-binding protein to bind strongly to fibrinonectin, coagulase allows formation of fibrin clots
- Streptococci: Extracellular dextran, FimA mediated adherence
- Enterococcus faecalis: Gram positive cocci (clusters). Catalase negative. Alpha, beta, or gamma hemolytic. grows in 6.5% NaCl. Bind
- fibrinogen. Cell wall lipoteichoic acid
- pseudomonas
- Candida albicans
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statins
may interfere with transcriptional induction of MHC class II molecules, NF-kappa B function (responsible for induction of inflammatory cytokines), CRP levels, ICAM-1 levels
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libman sacks
valvular endocarditis caused by lupus. immune complexes and antiphospholipid antibodies may cause endothelial damage and promote atherosclerosis
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antibodies directed against M proteins of certain strains of streptococci cross-react w/ glycoprotein antigens in heart, joints and other tissues
Strep A rheumatic fever
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Tissue bound antibody elicits inflammatory neutrophil and macrophage response. (Type II hyp.)
CD4+ T cells specific for streptococcal peptides react w/ self proteins in heart, and produce cytokines that activate macrophages. (Type IV hypersensitivity rxn). Responsible for formation of granulomas (Aschoff nodules)
chance resemblance of pathogen and host antigens that leads to targeting of host tissues is called molecula mimicry.
acute Rheumatic fever myocarditis
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It is proposed that CD4+ T cells responding to an as yet unidentified Ag accumulate in tissues and release cytokines that activate inflamm cells and fibroblasts.
Evidence for inappropriate activation of humoral immunity & presence of various autoantibodies provides diagnostic and prognostic information
Pericarditis with effusion and myocardial fibrosis, along with thickening of intramyocardial arterioles, occurs in 1/3 of pts.
Scleroderma (systemic dz)
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