Inflamation

Question 1

What is inflammation

Answer 1

The body’s response to injury

Question 2

Causes of inflammation (endogenous and exogenous)

Answer 2

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)

Question 3

Signs of acute inflammation

Answer 3

redness, swelling, heat, pain, loss of function

Question 4

Phases of acute inflammation

Answer 4

Vascular phase: increased blood flow, increased vascular permeability.
Causing oedema
Depositing fibrin and other plasma proteins
Active emigration of polymorphs (leucocytes, and neutrophils)

Question 5

What do neutrophils do and how

Answer 5

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

Question 6

How do leukocytes enter the tissues

Answer 6

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

Question 7

problems caused by acute inflammation

Answer 7

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)

Question 8

What are glucocorticoids

Answer 8

adrenal gland hormones that inhibit most parts of the immune response

Question 9

What are cytokines? what effects do they have

Answer 9

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

Question 10

What happens after acute inflammation?

Answer 10

1. complete resolution
2. continued inflammation -> chronic inflammation -> the damage to the tissues develop connective tissue scars “fibrous repair”
   or
3. death

Question 11

The cells involved in chronic inflammation and how

Answer 11

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)

Question 12

causes of chronic inflammation

Answer 12

persistent infection
prolonged exposure to toxic agents - eg smoking
autoimmunity - eg Crones disease

Question 13

Effects of chronic inflammation

Answer 13

Fibrosis (scarring)
impaired function (eg scarring in intestines reduces ability to absorb nutrients)
stimulation of immune response (macrophage and lymphocyte interactions)

Question 14

Local vs systemic chemical mediators

Answer 14

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)

Question 15

How do allergies work

Answer 15

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

Question 16

Serotonin - synth and storage, what symptoms it causes, how it works in the body

Answer 16

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)

Question 17

The formation and inhibition of prostaglandins

Answer 17

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

Question 18

Platelet activating factor- synth and storage, receptor, effects

Answer 18

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

Question 19

NO synthase family

Answer 19

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

Question 20

Plasma proteases

Answer 20

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