Inflammation Flashcards
Inflammation
- response to cell & tissue injury by vascularized tissue
- elicted to protect host
- By eliminating necrotic debris
- By eliminating initial cause
Features of Inflammation
- protective response
- Vascular= vasodilation & perm
- Cell= inflammatory cells (neutrophils, macrophages & lymphocytes)
- Via plasma proteins & cytokines
- Outcome elimination or persistence= chronic inflammation
Steps in Inflamm Response
- recognize injurious agent
- recruit leukocytes
- remove agent
- regulation of response
- resolution & repair
Acute inflammation
- heat
- redness
- swelling
- pain
- loss of function
Acute Inflammation
Vascular events in acute inflamm
alter vascular caliber & increase BF
Extravasation of plasma fluid & protein (leakage)
Cell events in acute inflamm
Leukocyte immigration & phagocytosis
*neutrophils first then macrophages*
Etiology of Inflammation
- microorg- bac, viral, fungal, parasitic
- tissue necrosis- uric acid, ATP, DNA, DNA binder HMGB-1
- hypoxia- mediatoer HIF1-a, effectors eg VEGF
- physical- trauma, thermal, chem
- foreign- splinter, dirt, suture
- immune- hypersensitivity, inappropriate immune rxn
Normal/Transudate/Exudate
Mechanism of Increased vascular perm
- Endothelial contraction- via his, bradykinin, leukotrienes, NO, SP. 15-30 min or 2-12 hr (sunburn)
- direct endothe injury- burns, UV, neutrophil damage
Increase Transcytosis
in venules
induced by VEGF
Exudate
Vasodilation
Increase blood viscosity
Decrease Colloid osmotic P
increased vascular perm
- transport
- nutrition
- make appropriate ground for neutrophils
Exudate
- fluid of acute inflammation
- high protein
- contain cell debris
- sp gravity >1.02
abscess
Transudate
- ultrafiltrate of blood plasma; increase hydrostatic P
- low protein
- no cells
- sp gravity <1.012
ascites
Lymphatics
- lymph flow increased to drain edema from extravascular space
- lymph drainage can also transport microbes in extensive inflammation
Lymphangitis- inflammation of lymph channels
lymphadenitis- inflammation of draining LN
Neutrophils
- from BW
- highly motile
- in tissue 24-48 hours
- high phagocytic capacity
- effective killers of bac
- use NADPH/Phagocyte oxidase= makes O2-*
- Myeloperoxidase= makes HOCl*
- NO oxidase= makes OONO-*
- Fenton= makes OH*
Leukocytes in inflammation Steps
- margination
- rolling
- activation
- adhesion
- pavementing
- emigration
- diapedesis
- chemotaxis
- phagocytosis
Leukocytes
P selectin on Endothelial Mem
Allows for rolling when bound; neutrophols, lymph & monocytes:
- to Sialyl Lewis X modified proteins on leukocytes
E selectin on endothelial mem
Allows for rolling & adhesion; neutrophils, T lymphocytes & monocytes, when:
- bound to sialyl lewis X modified prot on leukocyte
GlyCam-1, CD34 on endothelial
Allows for rolling, neutrophils & monocytes :
- when bound to L-selectin on leukocyte
ICAM-1 on endothe
Adhesion, arrest, transmigration; neutrophils, mono & lymphocytes
- when bound to CD11/CD18 integrins (LFA-1, Mac-1) on leukocyte
TNF & IL-1 activation of neutrophils
VCAM-1 on endothelial
Adhesion of eosinophils, moncytes & lymphocytes
- when bound to VLA-4 integrin on leukocyte
CD31 on endoth
Transmigration of all leukocytes aided by PECAM-1 on endothelial cell as well:
- when bound to CD31 on leukocyte
Chemotaxis
Escaped leukocytes reach injury site
Chemoattractans
- exogenous- bac agents N-formylmethionine terminal aa
- endogenous- chemokines, C5a, leukotriene B4
Inflammation
Recognition & Attachment
- C3b & IgG= opsonins
- Aid in phagocytosis
Phagocytosis
Bidn to R on leukocyte
Engulf
Fusion of lysosome with phagocytic vacuole
Destroy ingested particles- enz, ROS & nitrogen species
Use O2-*, HOCl* and OH* and OONO*
Granule contents may be exocytosed
Imp enz= MPO, iNOS and Phagocyte oxidase!
Phagocytosis
O2 indep mechanisms of killing
- lysozymes- from neutrophil granules destroy microbe mem
- major basic prot- from eosinophil granule kill prasite
- bactericidal perm increasing prot BP- cationic prot that strongly increases cell wall permeability
- defensins- in primary granules of neutrophils, can kill fungi & viruses & bac
Activated Macrophages
- Microbial prod- cytokines, IFNg, TLR ligands activate M1 (clasically activated macrophage)
- show inflamation!
- IL-1,12-23, chemolines
- ROS, NO, lysosomal enz
- helminths, IL-13 and IL-4 activate alternatively activated macrophage M2
- anti inflammtory & woulnd repair
- IL-10, TGFB
Leukocyte Induced injury
- tissues around leukocytes get injured
- reperfusion injury in MI
- autoimune & allergic responses
- activated luekocytes that don’t distinguish self/non self
- lysosomal enz
- ROS
- cytokines
Acute Leukocyte Induced Injury Inflamm Disorders
- acute resp distress yndrome- neutrophils
- acute transplant rejection- lymphocytes, Y & complement
- Asthma- eosinophils & IgE
- Glomerulonephritis- Y & complement, neutrophils & monocytes
- Septic shock- cytokines
- vasculitis- Y & complement, neutrophils
Chronic Leukocyte Induced Injury Inflamm Disorders
- Arthritis- lymph, macrophages & Y
- asthma- eosinophils, IgE & other leukocytes
- atherosclerosis- macrophages
- chronic transplatn rejection- lymphocytes & cytokines
- pulm fibrosis- macrophages & fibroblasts
Genetic Defects In Leukocyte function
- leukocyte adhesion def 1- defective leukocyte adhesion due to CD11/CD18 B chain mutation
- def 2- def leukocyte adhesion due to mut in fucosyl transferase needed for ligand syn for selectins
- chronic granulomatous disease- decrease ox burst
- x-linked- phagocyte oxidase in mem
- autsomal recessive- phagocyte oxidase in cytoplasm
- MPO def- decreased microbe killing, no H2O2 sys
- Chediak-Higashi syndrome- decreased due to mut affecting prot of lysosomal mem traffic.
Chediak Higashi Syndrome
LYST
albinism
n. defects
neutropenis
defective degranulation
Leukocyte giant observed
Acquired Defects
- BM suppression: tumors, radiation & chemotherapy- defect in producing leukocytes
- Thermal injury, diabetes, malignancy, sepsis, immunodef- defect in chemotaxis
- Hemodialysis, DM- defect in adhesion
- Leukemia, anemia, sepsis, diabetse, neonates, malnutrition- defect in phagocytosis & microbicidal activity
Inflammation
