Pathology Flashcards
What complement factor is a potent chemotactic factor for many leukocytes?
What complement factor acts as an opsonin?
C5a
C3b
What cytokines are involved in acute inflammation? What are their roles?
TNF and IL-1
Induces synthesis of endothelial adhesion molecules
Induce synthesis of other chemical mediators
Induce enzymes involved with matrix remodeling
Increase the thrombogenicity of endothelium
TNF acts to prime PMNs
What are the functions of NO?
Potent vasodilator
Some antimicrobial actions
Reduces platelet aggregation and adhesion
Regulates leukocyte recruitment and other aspects of inflammation
What mediators control vasodilation, increased vascular permeability, chemotaxis, fever, pain, tissue damage?
- Vasodilation: PGs, NO and Histamine
- Vascular Permeability: kinins, complement, serotonin, leukotrienes, PAF, histamine
- Chemotaxis: TNF, IL-1, chemokines, complement, leukotriene B4
- Fever: IL-1, TNF, PGs
- Pain : PGs and bradykinin
- Tissue Damage: lysosomal enzymes of leukocytes, ROS, and NO
In chronic inflammation, macrophages have two faiths influenced by different cytokines. Describe
Classical: Macrophage are phagocytic mediated by microbial products and TNF-gamma
M2: Activation by IL-4 and IL-13, functions to promote tissue repair
What three macrophage derived cytokines produce the systemic effects of inflammation? What are some types of systemic effects?
IL-1, IL-6 and TNF alpha
Fever - increased of cyclooxygenases convert arachidonic acid to PGs –> act on hypothalmus to reset body temp
Leukocytosis - left shift and bands
Acute Phase Proteins - fibrinogen, CRP, serum amyloid A protein
Describe the following diseases with respect to cause and tissue morphology?
TB - mycobacterium tuberculosis; caseating granuloma, epitheloid cells rimmed by fibroblasts, lymphocytes, histiocytes, central necrosis
Leprosy - mycobacterium leprae; acid fast bacilli in macrophage; noncaseating granuloma
Syphilis - treponema pallidum; gumma (non cancerous growth), visible lesion, enclosing wall of histiocytes, plasma cell infiltrate, central cells necrotic without loss of cellular outline
Cat-Scratch Disease - gram negative bacillus; rounded or stellate granuloma containing granular debris and recognizable PMNs, giant cells uncommon
Sarcoidosis - noncaseating granulomas with abundant activated macrophages
Crohn Disease - occasional noncaseating granulomas in the wall of the intestine with dense chronic inflammatory infiltrate
Discuss the 6 major growth factors involved in proliferation of cells.
Epidermal GF (EGF) - widely distributed in tissue fluids. Role in wound healing; produced by macrophages and other cells stimulating keratinocytes migration and granulation tissue formation Transforming GF alpha - produced by many cells types and tissues and is similar to EGF Vascular Endothelial GF (VEGF) - promote angiogenesis in chronic inflammation, wound healing and in tumors Platelet Derived GF (PDGF) - stored in platelet granules and is released on platelet activation. Also produced by macrophages, endothelia cell and smooth muscle cells. Causes migration and proliferation of fibroblasts, smooth muscle and inflammatory cells. Also plays a role in cirrhosis Fibroblastic GF (FGF) - produced in many cells (macrophages, endothelial cells) and is chemotactic for fibroblasts, stimulates keratinocytes migration and angiogenesis Transforming GF beta (TGF beta) - produced by platelets and lymphocytes among other cells, role: inhibitor of epithelial cells; generally stimulates proliferation of fibroblasts and smooth muscle cells and their migration. Promotes fibrosis in chronic inflammatory conditions. It has an anti-inflammatory effect and enhances some immune function
What are the components of extracellular matrix?
Collagen - uses Vit C
Elastin - consists of elastin, fibrillin and elastic fibers, found in tissues that need elastic recoil (BV, skin, uterus, lung). Fibrillin is the scaffolding for elastic fibers and defects lead to Marfan’s
Cellular Adhesion Proteins (adhesive glycoproteins) or CAMs - allow for transmission of signal that allow a specific cell to react. Four types: immunoglobulins, cadherins, integrins (mediate adhesiveness) and selectins. Cadherins and integrins link the cell surface with the cytoskeleton via beta catenin. Cadherins also mediate actions btw cells of the same type.
Proteoglycan - core proteins linked to polysacharides. Named based on the core protein and repeating disaccharide (heparin sulfate) Role is in regulation of tissue structure and permeability and act as modulators of cell growth and differentiation
Hyaluronic Acid - type of polysaccharide, binds water and allows for tissue compression. Inhibits cell to cell adhesion and facilitates cell motility.
What is the definition of granulation tissue?
Hallmark of healing formed 24-72 hours after injury. Consists of both fibroblastic proliferation and angiogenesis (endothelial cells) Fibroblasts are scattered spindle shaped cells producing collagen. Tissue appears edematous.
What are the processes in scar formation?
Fibroblastic proliferation, extracellular matrix and tissue remodeling. It goes beyond granulation tissue. TGF-beta most important GF b/c it promotes fibroblast proliferation and collagen synthesis. Overall there is net collagen deposition with some ECM degradation
What processes are involved in tissue remodeling (maturation)?
There has to be a balance of ECM degradation and collagen deposition. Matrix metalloproteinases degrade collagen (collagenases and gelatinases). Proteins spatially and temporally regulate wound healing process. There is wound contraction following via myofibroblasts - wound strength reaches 75% by end of 3rd month.
