Inflamation Flashcards
What is inflammation
The body’s response to injury
Causes of inflammation (endogenous and exogenous)
Exogenous: physical (fractures, sand, burns, freezing), chemical (toxic gases, acids, bases), biological (viruses, parasites, bacteria)
Endogenous: circulation disorders (thrombosis, haemorrhage), enzyme activation (amylase causing acute pancreatitis), deposits of metabolic products (uric acid)
Signs of acute inflammation
redness, swelling, heat, pain, loss of function
Phases of acute inflammation
Vascular phase: increased blood flow, increased vascular permeability.
Causing oedema
Depositing fibrin and other plasma proteins
Active emigration of polymorphs (leucocytes, and neutrophils)
What do neutrophils do and how
Phagocytosis
Contact
extra cellular receptors called opsonins (eg Fc and C3b) Recognise the bacterium
cytoskeletal changes Internalise the bacterium via the “zipper” effect into a phagosome
a lysosome full of enzymes surrounded in a cell membrane joins the phagosome to form a phagolysosome
enzymes break down the bacterium
the debris is removed by exocytosis
How do leukocytes enter the tissues
the stimulus activates the endothelium
passing leukocytes interact with receptors and roll along the endothelium
the cell passes through the gap junction via chemotaxis
migration -> rolling -> adhesion -> transmission
problems caused by acute inflammation
acute phase response - fever due to prostaglandins
spread of microorganisms and toxins
ENDOTOXIC SHOCK - low blood pressure to organs, which leads to death (consequence of spread of toxins)
What are glucocorticoids
adrenal gland hormones that inhibit most parts of the immune response
What are cytokines? what effects do they have
Low molecular weight signallers.
Pro-inflammatory cytokines: Interleukin 1, il6, il8, tumour necrosis factor alpha
anti-inflammatory cytokines: il10
When a macrophage is activated it produces Il1 and TNFa which cause:
in the acute phase: fever, increased sleep, decreased appetite, neutrophilia
endothelial effects: PGI synthesis, leukocyte adherence, procoagulant activity, and decreased anticoagulant
fibroblast effects: collagen synthesis, proliferation, protease, collagenase
Leukocyte effects: increased cytokine secretion
What happens after acute inflammation?
- complete resolution
- continued inflammation -> chronic inflammation -> the damage to the tissues develop connective tissue scars “fibrous repair”
or - death
The cells involved in chronic inflammation and how
Monocytes (in blood)/macrophages (in tissues) - when macrophages get activated they release pro-inflammatory cytokines
lymphocytes - t and b cells. b cells mature into plasma cells (prompted by activated macrophages)
plasma cells - produce immunoglobulins
fibroblasts - get activated by macrophages, and form collogen (scars)
causes of chronic inflammation
persistent infection
prolonged exposure to toxic agents - eg smoking
autoimmunity - eg Crones disease
Effects of chronic inflammation
Fibrosis (scarring)
impaired function (eg scarring in intestines reduces ability to absorb nutrients)
stimulation of immune response (macrophage and lymphocyte interactions)
Local vs systemic chemical mediators
Local: released at a cellular level. some are sored in the granules (eg histamine and serotonin), others are newly synthesised (prostaglandins, cytokines, platelet activated factors, nitric oxide)
Systemic: made in the liver and released into the bloodstream (e.g. compliment system, kinin system, coagulation system, fibrinolysis system)
How do allergies work
on first contact: allergen binds to b cell, turning it to a plasma cell.
that plasma cell releases a lot of IgE molecules for the allergen antigen
these IgE bind to mast cells
on a further contact: the IgE attached to the mast cells bind to the allergen
the mast cell releases histamine and cytokines to the environment
causing symptoms
Serotonin - synth and storage, what symptoms it causes, how it works in the body
Synthesised from L-tryptophan, stored in enterochromaffin cells, platelets, and neurons
Works on 5-HT receptors, which are mostly G protein coupled receptors
It works in neurotransmission (depression), broncho constriction, gastrointestinal smooth muscle (nausea and vomiting), pro-inflammatory actions (stimulating pain and itch, vasoactive effects, platelet aggregation)
The formation and inhibition of prostaglandins
When the lipid membrane of a cell is damaged, the phospholipids are exposed
phospholipases break them down into arachidonic acid (which can be inhibited by corticosteroids)
Arachidonic can be broken down by many enzymes however the relevant ones are the cyclooxygenases
COX-1 are constitutive and COX-2 is inducible. They can be inhibited by NSAIDs, and COX-2 inhibitors
They turn to Prostaglandin G2, then that to prostaglandin H2 (both of which are not biologically active), and then to the biologically active prostaglandins
PGD2, PGE2, and PGF2 cause vasodilation and cause oedema
Prostacyclin PGI2 causes vasodilation and inhibits platelet aggregation
Thromboxane TXA2 causes vasoconstriction, and promotes platelet aggregation
Platelet activating factor- synth and storage, receptor, effects
modified phospholipid, synthesised in monocytes, mast cells and polymorphonuclear neutrophils (PMNs)
g-protein linked receptor that sometimes works intracellularly
increase vascular permeability, pmn migration, bronchoconstriction, and other pro-inflammatory effects
NO synthase family
three enzymes: endothelial NOS (in the endothelium of the blood vessel), Neuronal NOS (both constitutive, require calcium to activate), inducible NOS (activated by pro-inflammatory cytokines, does not require calcium. released by macrophages that have phagocytosed a bacterium)
Nitric Oxide is a colourless gas that reduces platelet aggregation and adhesion, leukocyte adhesion, and cause vasodilation and smooth muscle relaxation
Plasma proteases
systemic mediators
two types: kinins and clotting factors
bradykinin stimulates nerve endings which causes increased capillary permeability (heat and redness) and pain
the clotting system forms plasmin which activates the compliment cascade with C3. the compliment system is a series of 30+ small inactive proteins that are always in the blood but get activated by stimuli of a previous point in the cascade being activated. the final point C5-9 is the membrane attack complex
