Acute inflammatory response

Question 1

immunity

Answer 1

“protection from infection or disease”

But includes autoimmunity where the target = one’s own tissues

Question 2

failure of immunity

Answer 2

results in symptoms

Question 3

infection

Answer 3

microbes colonising a host

Question 4

inflammation

Answer 4

Part of immunity and stimulated by infection and other injury

Question 5

chemical mediators

Answer 5

leucocytes

tissue cells

microvasculature

plasma precursors

nerves

Question 6

what are the 4 cardinal signs of inflammation?

Answer 6

1. heat and redness
2. swelling
3. pain
4. loss of function

Question 7

heat + redness

Answer 7

Arteriolar dilation

Increased blood flow to inflamed tissue

Question 8

swelling

Answer 8

Leakage of plasma + WBCs from blood vessels into tissue (plasma extravasation)

Question 9

pain

Answer 9

external physical or chemical injury = endogenous generation of chemical mediators of inflammation

Question 10

loss of function

Answer 10

tissue re-modelling + destruction

fibrin deposition (scarring)

Only occurs in chronic inflammation -> source isn’t removed

Question 11

Cellular components of inflammatory response - leucocytes (WBCs)

Answer 11

Granulocytes (polymorphonuclear leukocytes, PMNs)
- Neutrophils
- Eosinophils
- Basophils

Lymphocytes
- T, B cells, NK

Monocytes

Question 12

Cellular components of inflammatory response - tissue mast cells

Answer 12

Type 1 immediate hypersensitivity via IgE

Question 13

Endothelium

Answer 13

NO causes arteriolar dilation

Endothelial contraction makes venules leaky - Increased permeability (increased gap)
= OEDEMA (swelling)

Question 14

difference between chemical mediators of inflammation and antibodies?

Answer 14

chemical mediators have low specificity

Question 15

triple response

Answer 15

1. Redness due to vasodilation (arterioles)
2. Flare
   
   • Activation of sensory nerves
   • Pain and itch
   • Neuropeptide release
3. Swelling

Question 16

Histamine receptors in inflammation - H1

Answer 16

[ALLERGIC INFLAMMATION]

Gαq/11 - Phospholipase C stimulation

Vasodilator (arterioles) via nitric oxide generation

Endothelial cell contraction
- Increased vascular permeability
- OEDEMA

Sensory nerves - pain and itch pathways

Question 17

Histamine receptors in inflammation - H4

Answer 17

Gαi/O

• Activates PLC via βɣ subunits

Sensory nerves
- Pain and itch pathways
- Role in leucocyte chemotaxis

Question 18

effect of histamine on blood vessels

Answer 18

relaxation of arteriolar smooth muscle

contraction of venular endothelium

increased permeability

Question 19

histamine in pain

Answer 19

histamine released from mast cells and act on sensory nerve fibres (C fibres)

Question 20

effect of histamine on blood vessels with amplification by neuropeptides

Answer 20

NKA + CGRP = neuropeptides

bind to NK1 + CGRP R (receptors) on blood vessels to enhance effects

Question 21

examples of H1 receptor antagonists - “anti-histamine”

Answer 21

Chlorpheniramine (chlorphenamine/Piriton)

New drugs, lower lipophilicity
- Astemizole
- Loratidine

Question 22

which pathway are H1 receptor antagonists involved in?

Answer 22

“wakefulness” pathway - can cause drowsiness

Useful in allergy, urticaria and nasal congestion

Question 23

what does plasma extravasation lead to?

Answer 23

oedema

Question 24

neutrophil independent inflammation

Answer 24

via histamine, bradykinin, NKA

Question 25

neutrophil dependent inflammation

Answer 25

via C5a, LTB4, IL-8

Question 26

synergy

Answer 26

when inflammatory mediators act together to create bigger response

Question 27

Bradykinin (BK)

Answer 27

inflammatory substance formed from plasma precursor

Question 28

Prostaglandin E2 (PGE2)

Answer 28

inflammatory substance formed from lipid membrane

Question 29

Temporal release of mediators in response to local injury - SECONDS

Answer 29

Pre-formed substances - histamine

Production of mediators from membrane lipids
- eicosanoids (PGE2, PGI2), leukotrienes
(LTB4)

Release of peptides from stimulated neurons
- Neurokinin A

Calcitonin gene related peptide (CGRP)

Question 30

Temporal release of mediators in response to local injury - SECONDS to MINS

Answer 30

Production following proteinase activation
- Bradykinin
- Complement fragments (C3a, C5a)

Production of infiltrating cells

Question 31

Temporal release of mediators in response to local injury - HOURS

Answer 31

Transcription and translation of proteins
iNOS, COX-2, cytokines

Question 32

Benefits of inflammation

Answer 32

increase supply of cells and chemical mediators to site of inflammation
- Redness - increased blood flow
- Swelling - increased vascular permeability
- Allow removal of damaged tissue,
infectious agents
- Supply new materials for repair

Tells body to rest
- Pain

Loss of function

Question 33

inflammatory mediators sources + targets - MAST CELL STORES; LEUCOCYTE GRANULES

Answer 33

MEDIATORS - histamine; proteases

CHEMICAL NATURE - amines; enzymes

TARGET - vasculature, sensory nerves, tissues plasma precursors

Question 34

inflammatory mediators sources + targets - SENSORY NERVES

Answer 34

MEDIATORS - CGRP; neurokinins

CHEMICAL NATURE - peptides

TARGET - vasculature, mast cells

Question 35

inflammatory mediators sources + targets - CELL MEMBRANE

Answer 35

MEDIATORS - prostaglandins; leucotrienes

CHEMICAL NATURE - lipid

TARGET - vasculature, sensory nerves, leucocytes

Question 36

inflammatory mediators sources + targets - PLASMA

Answer 36

MEDIATORS - bradykinin complement

CHEMICAL NATURE - peptide; protein

TARGET - vasculature, sensory nerves, leucocytes

Question 37

inflammatory mediators sources + targets - NEWLY SYNTHESISED

Answer 37

MEDIATORS - cytokines, O2-, NO radical

CHEMICAL NATURE - protein radicals

TARGET - vasculature, leucocytes, tissue cells