Local hormones: inflammation and anti-inflammatory agents Flashcards
what is inflammation a reaction to
- invasion - by pathogens or allergens
2. Injury - heat, UV, chemical, physical trauma
what type of immune system does inflammation involve
innate and adaptive immune system
what are the 5 cardinal sins of inflammation
- calor (warmth due to inc bf)
- rubor (redness due to inc bf)
- dolor (pain bc sensitisation of receptors
- tumor (swelling due to inc. post-capillary venule permeabiliity)
- functio laesa (loss of function (bc pain, swelling)
what are the 5 steps of acute inflammation
1 - recognition of injury (immediate microvascular changes and release of mediators)
- recruit leukocytes (cells accumulate at the site and get activated)
- removal of agent (engulf bacteria, remove allergens, remove debris)
- regulation of response (control/monitor the level of response. Systemic effects typically occur, resulting in things like fever)
- Resolution (repair damage done during inflammation)
when do microvascular changes occur and how long to they last
occur immediately and last for around 24hrs
what mediates the microvascular changes of inflammation
by local hormones like histamine and PGs and bradykinin
what microvascular changes occur in inflammation
inc. blood flow (histamine/PG)
histamine/bradykinin = inc endothelial permeability .’. in leakage of plasma (& immune cells) into interstitial space of tissue
characteristics of local hormones in inflammation
- produced in response to wide range of stimuli
- synthesised and released only when required
- act locally ONLY
- inactivated locally to prevent them from having systemic effects
what is histamine sythesised from
from the amino acid histidine by the enzyme histidine decarboxylase (histidine gets decarboxylated, loses CO2).
how is histamine broken down
by imidazole-N-methyltransferase (INMT) and diamine oxidase.
how is histamine released from mast cells
Synthesised and secreted from mast cells.
they express Fc receptors for IgE, C3a and C5a on their cell surface membrane.
When activated they mediate release of histamine.
where is histamine stored in mast cells
secretory granules within mast cells, which are degranulated when given signal
granules composed of hepain and acidic proteins
what cells can release histamine
- mast cells
- basophils
- neurones in the brain
- histaminergic cells in the gut
what happens when an allergen is present in the body
IgE binds to mast cell (or basophil) surface receptor
intracellular rise in Ca2+
degranulation and release of histamine
what is the effect of stimulating b-adrenoreceptors on mast/basophil cells
histamine release inhibited
what receptors do histamine work at
histamine receptors
H1, H2, H3 and H4
GPCR receptors
what GPCR is H1
Gq/11 -> linked to phospholiphase C -> PIP2->IP3+DAG
found in smooth muscle, endothelium, CNS
what GPCR is H2
Gs -> adenylyl cyclase ->cAMP produces
found on parietal cells of the stomach to inc HCl secretion and on heart
What GPCR is H3
Gi -> -vely linked to adenylyl cyclase -> decrease cAMP
located on presynaptic terminals
what GPCR is H4
Gi -> -vely linked to adenylyl cyclase -> decrease cAMP
found in basophils, BM, gut
which histamine receptors are involved in the inflammatory response
H1 & H2
Cardiovascular effects of H1/2 stimulation
- dilation of arterioles
.’. decrease in TPR and BP - inc permeabilty of postcapillary venules .’. decreased plasma vol (H1)
- inc in HR (try and maintain BP and stop it dropping too much) (H2)
non vascular effects of H1/H2
- nonvascular smooth muscle contraction (eg bronchoconstriction)
- algesia
- stimulates increase in H2 secretion
- increased exocrine secretions due to inc blood flow to exocrine glands
why does histamine cause algesia
histamine causes pain, itching and sneezing caused by sensitisation and stimulation of sensory nerves (H1)
