Inflammation Flashcards
What are the 5 key aspects of inflammation?
Heat Swelling Redness Pain Loss of function
What is the immune process behind inflammation?
Mast cells/macrophages detect pathogen
Release inflammatory mediators - cause vasodilation
Polymorphonuclear cells activated - release proteases with anti-microbial activity and mediators that recruit leukocytes
Endothelial cells activated - express cellular adhesion molecules - leukocytes in blood adhere at site of inflammation
Neutrophils leave vasculature - migrate to stimulus site - kill/phagocytose pathogens
Monocytes enter site - differentiate to macrophages - phagocytose microbes and release mediators
T-cells activated if response unsuccessful - response repeated - chronic inflammation - can damage host cells
Name 6 groups of inflammatory mediators and their effects
NO - heat and redness - increases blood flow
Histamine - heat, redness, and swelling - increases blood flow and vascular permeability
Bradykinin - heat, redness, swelling, and pain
Lipases, proteases, free radicals - loss of function
Prostaglandins - heat, pain, and swelling
Cytokines - pro-inflammatory/anti-inflammatory - change gene expression in target cell via binding to CS receptors
What is the process of IgE activation of mast cells?
Antigen binds to B-lymphocyte in blood
B-lymphocyte releases IgE
IgE binds to mast cells - degranulation - histamine release
Which histamine receptor is involved in allergic reactions and what is its mechanism?
H1
Via Gq - increases Ca2+
Which histamine receptor is involved in gastric acid secretion and what is its mechanism?
H2
Via Gs - increases cAMP
Through which receptor does histamine stimulate C fibres?
H1
Name an H1 antagonist
Diphrenhydramine
Name an H2 antagonist
Ranitidine
What is the key difference between old and new antihistamines?
Old cross BBB - cause dizziness, drowsiness, tinnitus
New do not
How is bradykinin synthesised in plasma?
Factor XIIa + prekallikrein -> plasma kallikrein
Plasma kallikrein + HMV kininogen -> bradykinin
How is bradykinin synthesised in glands, pancreas, kidneys, and neutrophils?
LMV kininogen -> kallidin
Kallidin -> aminopeptidase + bradykinin
What are the classes of bradykinin receptors, what receptor type are they, and what is their key difference?
GPCRs
B1 - no internalisation - resistant to desensitisation
B2 - internalisation - desensitise
What breaks down bradykinin?
Peptidase
What causes angioedema?
Drug-induced - ACE inhibitors prevent bradykinin breakdown - swelling
Hereditary - C1 inhibitor missing - no bradykinin regulation - swelling
Which enzyme converts arachidonic acid to prostaglandins?
Cyclooxygenase
How do NSAIDs work?
Inhibit cyclooxygenase
What are the types of cyclooxygenase and what are their actions?
COX-1 - constitutive - gastric protection
COX-2 - induced at inflammation site - causes inflammation and cardiovascular protection
What is the key difference between new and old NSAIDs?
Old non-selective - cause GI tract ulcers
New selective for COX-2 - no GI tract ulcers - inhibits cardiovascular protective role - cardiovascular side effects
What is the mechanism of glucocorticoids in the HPA axis?
Hypothalamus releases corticotropin releasing factor (CRF) - onto anterior pituitary
Anterior pituitary releases adrenocorticotrophic hormone (ACTH) onto adrenal cortex
Adrenal cortex releases glucocorticoids - inhibit hypothalamus
What is the role of glucocorticoids?
Inhibit inflammatory mediators - anti-inflammatory
What are the individual inhibitory actions of glucocorticoids?
Neutrophil migration
Neutrophil and macrophage activation
T-lymphocyte activation and clonal expansion
What is Cushing’s syndrome and what is its treatment?
Excessive ACTH - adrenal cortex produces excess cortisol
Glucocorticoids as treatment - inhibit ACTH production - adrenal glands shrink - withdrawing treatment prevents adrenaline production - adrenaline crisis - must be weaned off treatment
What are biologics?
Biomolecules that target inflammatory mediators
Name a cytokine and describe its roles
Tumour necrosis factor (TNF) alpha
Causes fever, activates macrophages
