What accumulates in interstitial space during acute inflammation
Neutrophils and edematous fluid
Present on macrophages qnd dendritic cells which recognize pathogen associated molecular patterns and lets body know there is infection
Toll like receptors
Toll like receptor on macrophage which recognizes lipopolysaccharide on gram neg bacteria
CD14
Key protein upregulated when toll like receptors are activated and turns on inflammatory response
NF kappa B
Inflammatory mediator released from cell membrane by phospholipase A2
Arachidonic acid
Product of cyclooxygenase pathway from arachidonic acid
Prostaglandin
PGI2, PGD2 and PGE2 mediates which actions
Vasodilation pf arterioles, increased vascular permeabity of post capillary venule
Prostaglandin which mediates fever and pain
PGE2
Product of lipooxygenase pathway from arachidonic acids
Leukotrienes
Leukotriene which attracts and activates neutrophils
LTB4
Four substances which attracts and activates neutrophils
Ltb4
C5a
IL8
Bacterial products
Leukotrienes which mediate vasoconstriction, bronchospasm, and increased vascular permeabity
(Smooth muscle contraction)
LTC4, LTD4, LTE4
Three ways mast cells can be activated
Tissue trauma
C3a and C5a
Cross linking of IgE by antigen
Histamine granules mediate?
Vasodilation of arterioles, increased vascular permeabity
What is the delayed response of mast cells?
Release of leukotrienes to allow continuation of inflammatory responser
Proinflammatory serum proteins which circulate as inactive precursors
Complement
Three mechanisms of complement activation
Classical pathway - C1 binds to IgG or IgM bound to antigen
Alternative pathway - Microbial products directly activate
Mannose-binding lectin pathway - MBL binds mannose on microorganisms and activates complement
Pathway to formation of membrane attack complex from complement activation
C3 convertase generated converts C3 to C3a and C3b
C3b helps produce C5 convertase to convert C5 to C5a and C5b
C5b produces C6-C9 which is part of membrane attack complex
Complement which is chemotactic for neutrophils
C5a
Complement which trigger mast cell degranulation
C3a and C5a
Complement which is an opsonin for phagocytosis
C3b
Inactive proinflammatory protein produced in liver which is activated upon exposure to subendothelial or tissue collagen
Hageman factor
Hageman factor plays an important role in which two disease entities
DIC
Gram negative sepsis
Hageman factor activates which three system
Coagulation and fibrinolytic systems
Complement system
Kinin system
Bradykinin mediates what
Vasodilation, increased vascular permeability, pain
Mechanisms of fever generation
Macrophage release IL1 and TNF
Perivascular cells of hypothalamus have increased COX activity
PGE2 increases which raises temp set point
Match the tcell receptor complex for t cells
CD4 and CD8
MHC class I and II
CD4 - MHC class II CD8 - MHC class I
Function of MHC
Binds to antigen and Presents antigen to Tcell
Mechanism for CD4 tcell activation
Extracellular antigen is phagocytosed on APC and is presented on MHC class II
B7 (second signal) on APC binds CD 28 on CD 4 T cell as activation signa
Examples of antigen presenting cells
Macrophage, dendritic cell
Mechanism of activated CD4 helper t cell
Secrete cytokines which help B cells or CD 8
Cytokines secrete by TH1 and fx
IL-2 - activates CD8 T cell
IFN gamma - activates macrophage
Cytokines secreted by TH2 and fx
IL-4 class switching to IgG and IgE IL-5 eosinophil chemotaxis and activation, maturation of B cells to plasma cell, class switching to IgA IL-10 inhibits Th1 phenotype
Mechanism of cell killing of CD8
Secrete perforins and granzyme to induce apoptosis
Expression of FasL, binds Fas on target cell to activate apoptosis
Naive B cells express which Immunoglobulin
IgM and IgD
Mechanism of B cell activation
Antigen binding by surface IgM or IgD, activating B cell to secrete that immunoglobulin
B cell present antigen to CD4 via MHC II and CD40 receptor on B cell binds to CD40L on helper Tcell, activating it to secrete IL4 and IL5 promoting ig switch and maturation to plasma cell
Morphology of granuloma
Epitheloid histiocytes (macrophage with abundant pink cytoplasm) - key feature of granuloma
Surrounded by giant cell and lymphocytes
Caseating vs noncaseating granuloma
Caseating has central necrosis
Mechanism of granuloma formation
Macrophage present antigen to CD4 via MHC II
Macrophage secrete IL 12
CD4 differentiates to Th1 subtype, which secretes IFN gamma and converts the macrophage to epitheloid histiocyte and giant cell
Marker for hematopoeitic stem cells (CD?)
CD34+
Types of tissues based on repair and give example
Labile -rapidly regenerating. Bowel, marrow, skin
Stable tissue - quiescent but can re enter cell cycle - hepatocytes, proximal renal tubule
Permanent tissue - no significant regeneration. Myocardium, skeletal muscle, neurons
Regeneration vs repair
Regeneration - replaced with native tissue
Repair - fibrous tissue
Components of granulation tissue
Fibroblast (deposit type III collagen), myofibroblast (contract wound), and capillary
Types of collagen
Type I - bone. Strong tensile strength, support
Type II - cartilage
Type III - pliable. Blood vessels, granulation, embryonic tissue
Type IV - basement membrane
Collagen in granulation vs collagen in scar?
What enzyme removes type III and cofactor required?
Granulation -type 3
Scar -type 1
Collagenase
Zinc
Growth factors functions if
TGF alpha, beta, PDGF, FGF, VEGF
TGF alpha -epithelial and fibroblast Beta - fibroblast. inhibits inflammation PDGF - (platelet derived GF) endothelium, smootg muscle, FGF FGF - angiogenesis, skeletal muscle VEGF - angiogenesis
Primary vs Secondary intention
Primary -wound edges brought together, minimal scar
Secondary - edges not approximate, granulation tissue fills defect, scar formation and wound contraction
Function of Vitamin C in wound healing
Procollagen needs to crosslink by hydroxylation
Gly-Pro/Lys-Hydroxypro/lys
Vitamin C hydroxylates pro and lys, and the hydroxylated ends allow crosslinking of more procollagen molecules to become mature collagen
Function of copper in wound healing
Lysyl oxidase cross links lysine and hydroxylysine?
Keloid is excess deposition of which type of collagen
Type III