Inflammation

 features of inflammation
o non specific
o Rapid response to cellular injury
o aims to remove cause and consequence
 Something that causes inflammation , by definition, is something that causes
non-apoptotic cell death
o main signs
 Rubor
 Redness
 Tumor
 swelling
 Calor
 Heat
 Dolar
 Pain
 loss of function
o Long term consequences
 Positive
 Clear inflammatory agent
 Restore function
 Negative
 XS tissue damage
o Prolonged angiogenesis
o Collagen out of ECM
 Forms scar
 Eg. Lung fibrosis

Steps of acute inflammation

1. Initially there is a steady state

2. Damage occurs
a. this causes non-apoptotic cell death
i. ie. Necrosis or Necroptosis
3. DAMPs (Damage-associated molecular patterns) released
a. These are actively secreted by hypoxic or stressed cells , or as degradation products
derived from proteolytically cleaved tissue matrix.
4. Foreign material from bacteria stimulate mast cell degranulation (As in Type 1
hypersensitivity)
a. This leads to;
i. secretion of molecules which cause
vasodilation
e.g. Histamine, Heparin
5. Endothelial cells separate
a. this increases vascular permeability

There are structural changes in the microvasculature

Vascular changes = increased permeability, dilation, reduced flow and plasma
leakage à exudate formation
Benefits

increase in antibodies

increase in protein

increase in barrier

increase in leukocyte migration

6. Immune cell recruitment

a. Chemokines
i. create a concentration gradient leading to the site of inflammation
ii. complementary leukocytes bind to Chemokines and follow the gradient to
inflammation
iii. e.g. CXCL8 / IL-8
1. G coupled 7 transmembrane protein recruit neutrophils
7. neutrophil recruitment
a. Rolling adhesion. Carbohydrate ligands in a low affinity state on neutrophils bind
selectins on the endothelial cell membrane
i. e.g. PSGL1 binds P and E selectins
b. Tight adhesion. Chemokines promote low to
high affinity switch in integrins LFA-1, Mac-1
enhance binding to ligands
c. Transmigration. Cytoskeletal rearrangement
and extension of pseudopodia. mediated by
PECAM interactions on both cells
 8. Neutrophil functions
a. pathogen recognition
i. using innate PAMPs (pathogen associated molecular patterns) in
pathogens
ii. activates when recognises pathogen
b. phagocytosis
i. reactive oxygen species (ROS)
ii. antimicrobial peptides
iii. Engulfing extracellular bacteria
c. Cytokine/chemokine secretion
d. NET formation
i. big clump of neutrophils
ii. release all of its contents
e. pathogen clearance
9. Wound healing
a. Leads to extracellular matrix deposition (eg. Collagen)

Different pathologies of inflammation

Acute
Immediate onset (lasts a few
days )
Vasodilation, increased vascular
permeability, leukocyte
response
Neutrophils predominate
Histamine release
Prominent necrosis
Outcomes include :
Complete resolution or
Progression to chronic
inflammation
Chronic
Delayed onset (may last
anywhere from weeks to
years)
Persistent inflammation,
ongoing tissue injury,
attempts at healing
Monocytes / macrophages
predominate
Ongoing cytokine release
Permanent scarring
Outcomes include :
Scarring
Loss of function

o Granulomatous
o distinct pattern of granuloma formation
 often spherical
 neat
 large
 few nuclei in granulomas
o triggered by strong T cell responses
o aggregation of activated macrophage is
 barrier designed for clearance
 EG
 tuberculosis
 o this doesn't kill tuberculosis
o makes it harder for tuberculosis to replicate
o Examples of granulomatous
 Tumour reactions
 TB
 Leprosy
 Foreign Body granuloma
 Eg. Silicone
 Chron’s disease
 Sarcoidosis
o Chronci inflammation
o Features
 Progressed
 Unresolvable
 Allergens
 Unclearable particles
o Eg. Silica
 Autoimmunity
 Persistent/prolonged infection
 Persistent toxic stimuli
o Pollution
 Main immune cells involved
 Macrophages
o Tissue residents since birth
o Monocytes differentiate into macrophages once they enter
tissue
o Pros
 Cytotoxic
 Phagocytise
 Anti-inflammatory
 Wound repair
o Cons
 (all the pros can be cons if too much)
 Inflammatory
 Pro-fibrotic
 Remodelling of tissue
 Lymphocytes
o B-cells
 Plasma cells secrete antibodies either locally or
remotely (via blood stream)
 Protective
 Inflammatory
o T-cells
 Activated and programmed
 Pro inflammatory
 Promote neutrophilia
 Cytotoxic
 Granzymes
 Perforin