Lecture 3-Inflammation Flashcards
What are the types of inflammation?
Acute
Chronic
What are the characteristics of acute inflammation?
Beneficial
Directs immune components to infection
Eliminates infection with rapid resolution
Increases blood supply, capillary permeability, WBC migration
30-60 min: Influx of neutrophils
4-6h: Influx of monocytes/macrophages and lymphocytes
What are the characteristics of chronic inflammation?
Harmful
Tries to wall off infection that cannot be eliminated
Granulométrie
Tissue destruction or fibrosis
Macrophages, epithelia cells, lymphocytes predominate
Contributes to heart disease, Alzheimer’s, diabetes, arthritis, cancer
What are the inducers of inflammation?
infections Allergies Burns Ischemia Cut Fractures Cuts Neoplasms
What are the local signs off inflammation?
Classic triad is: Pain Heat Redness Other signs are: Edema Loss of function
What are the systemic signs of inflammation?
Fever
Cytokine release
Acute phase protein release from liver
what are the characteristics of pathogen recognition by local macrophages?
PAMPS are expressed on microbes
Phagocytes bind to PAMPS via PRR
PRR-PAMP interactions:
Enhance phagocytosis
Up regulate adhesion molecule expression to id leukocyte extravasation and migration
Enhance cytokine production by phagocytes
Examples of PRR and PAMP?
PRR: fMet-Leu-Phe receptor
PAMP: fMet-Leu-Phe
Chemotactic for macrophages and neutrophils
PRR: TLR4 + CD14
PAMP: LPS (endotoxin)-outer membrane of gram negative
PRR: TLR2 + CD14
PAMP: Lipoteichoic acid- gram positive cell wall
What are the actions of some NLRs?
Assemble into the inflammasome
Inflammasome activates cas passé 1 that cleaves the precursor of interleukin 1 beta into its active IL-1 beta
What are the pro-inflammatory cytokines synthesized by PRR-PAMP interactions?
IL-1
Il-6
TNF-alpha
What actions are induced by pro inflammatory cytokines?
Septic shock
Fever
Acute phase protein release from the liver
ROS generation by phagocytes
Leukocyte extravasation through up regulation of adhesion molecule expression
What are the characteristics of septic shock?
TNF alpha is most potent Drop in blood pressure Hyper or hypothermia Shaking chills Weakness Tachypnea and tachycardia
What are the characteristics of fever?
IL-1 is most potent
IL-1 induces central and peripheral synthesis of PGE2
Central PGE2 raises hypothalamic set point
IL-1=endogenous pyrogens
LPS, lipoteichoic acid= exogenous pyrogens
What are the characteristics of acute phase protein (APP) release from the liver?
IL-6 is most potent inducer APPS aid host defense through opsonins, clots, tissue repair Positives APPs can induce: Complement CRP Serum amyloid A Clot buster precursor plasminogen Coagulation factors Ferritin
What are the characteristics of enhanced adhesion molecule expression, extravasation?
TNF alpha, IL-1 in importance
Extravasation/diapedesis: movement of leukocytes out of blood vessels and into tissues
What are the steps in extravasation of leukocytes?
Endothelial cells start expressing E- selection and ICAM-1 in response to TNF alpha and IL-1
Tethering and rolling via Sialyl Lewis X (CD15) on PMN binds to E-selection on endothelium
Adhesion/pavementing: IL-8 regulates LFA-1 expression on PMN,LFA-1 binds to ICAM-1 on endothelial cell
Transendothelial migration-PMN moves through endothelium
Chemotaxis-PMN moves up the concentration gradient of chemotaxins (IL-8, C5a, fMet-Leu-Phe)
What are the characteristics of leukocyte adhesion deficiency?
LAD1-no CD18 so no LFA-1
LAD2- no sialyl Lewis X
No extravasation
Leukocytosis (too many WBCs), especially neutrophilia
No pus, poor healing
Chronic/repeated bacterial infections of mouth and GI
Characteristics of the stimulation of the respiratory burst?
Respiratory/oxidative burst in macrophages and PMNs generates ROS
ROS damage proteins, lipids, DNA
IFN gamma, TNF alpha, GM-CSF stimulate respiratory burst in macrophages and PMNs
What are the steps in respiratory burst?
NADPH oxidase generates superoxide
Superoxide dismutase destroys superoxide, catalysés formation of hydrogen peroxide
Myeloperoxidase generates hypochlorite from hydrogen peroxide
CVatalasse reduces hydrogen peroxide to water and oxygen
What are the results of NADPH oxidase deficiency?
Chronic granulométrie disease (CGD)
Marked by repeated infections by catalase positive microbes
Pneumonia, lymphadenitis, abscesses in skin and viscera
What are the tests for CGD?
NBT reduction test- CGD phagocytes cannot reduce NBT to blue formatant dye (not used much now)
Dihydrorhodamine (DHR) test-normal phagocytes reduce DDHR to fluorescent rhodamine, quantified by flow cytometry
Genetic tests
