Inflamm & Immune [21-22] Flashcards
Signs of acute inflammation
Redness
Swelling
Heat
Pain
What cells are involved in acute inflammation
Neutrophils
What causes redness and heat
Vasodilation in inflammation
Increases blood flow to tissues
What causes swelling
Increased vascular permeability
Endothelial retraction
Gaps for WBC
What is the cellular component to acute inflammation
Emigration of leukocytes to tissue
What cells are involved in chronic inflammation
Macrophages
Activate lymphocytes via APC
Activate cytokines and antibodies
Drugs classes to reduce inflammation
NSAIDs
Steroidal anti inflammatory
Anti-histamines
What do steroidal anti inflammatories do and example
Block phospholipids A2 using GR agonist (lipocortin)
Can’t make arachidonic acid
Can’t make leukotrienes, prostaglandins, thromboxanes (inflammatory mediators)
NSAIDs MOA
Inhibit cyclooxygenase and also a leukotriene inhibitors
(After arachidonic acid production)
What is COX1
Housekeeper
Side effects exerted through COX1 inhibition
Makes thromboxane
When is COX2 induced
Upon inflammatory cell activation
NSAIDS exert their effect on COX2
Process of inflammation from pathogen
PAMP on pathogen / DAMP from damaged cell binds toll like receptor on macrophage
Activates NF-kB
Cytokine secretion
Inflammation
Adverse effects of NSAIDS
Rashes
Bronchospasm
What does inhibiting COX2 do
Causes COX1 pathway to increase
Makes more thromboxanes
Blot clots
Allergy pathway
Allergen
APC
T helper 2
B cells
Ab class switch to IgE
Sensitisation (binding to mast cell)
Degranulation (release histamine)
What is type 1 hypersensitivity
Hay fever
How is hay fever mediated by H receptors
H1 receptors stimulant phospholipase C to convert PIP2 into IP3
Increases Ca2+ conc
Bronchoconstriction
Difference between first gen and second gen anti histamines
First gen cross BBB
Second gen don’t so are non drowsy (Loratidine)
What is anaphylaxis and how is it treated
Systemic release of histamine from mast cells
- low bp
- swelling
- sustained bronchoconstriction
Treated with B2 agonist - adrenaline
What are most antihistamines
Inverse agonists instead of neutral antagonist (reverses activity rather than stops it)
Immunosuppressive drugs
Glucocorticoids
Calcineurin inhibitors
mTOR inhibitors
IL-2 receptors antagonists
Nucleic acid synthesis antagonists
How to immunosuppressant exhibit their effect
Block expression and activity of T cell growth factor and activate IL-2
3 processes after plasma cell releases antibodies in immune response
Opsonisation (binding)
Agglutination (clumping)
Neutralisation (killing)
4 functions of antibodies
Enhance phagocytosis (agglutination, chemoattraction)
Neutralisation
NK cell activation
Classical complement cascade activation (C3b MAC)
APC to cell cycle replication pathway
MHCII on APC binds TCR
Activates calcineurin pathway
IL-2 gene releases IL-2
Binds IL-2 receptor
mTOR pathway
Cell cycle
Glucocorticoid immunosuppression effect
GR binds p65 subunit of NF-kB
Prevents activation of inflammatory genes
Also promotes IkBa synthesis (inhibitor)
Suppresses T cell activation
Calcineurin inhibitor example and how it works
Cyclosporine
Binds cyclophilins
Inhibits Calcineurin phosphatase
Prevents IL-2 formation
What are immunosuppressive drugs needed for
Transplantation
The require life long immuno suppression
Needs narrow therapeutic window
Side effects of immunosuppressants
Poor wound healing
Coagulation disorders
How do many auto immune diseases and cancers arise
Over expression of PDL
PDL tells PD1 on T cells to deactivate themselves
Evades immune system by not being recognised
