Acute inflammation Flashcards
What are the 5 features of acute inflammation?
Calor (heat), Rubor (redness) Tumor (swelling) Dolor (pain) and Functio-laesa (loss of function)
What can cause inflammation? (4)
Infections, tissue necrosis, foreign bodies, immune reactions
What is acute inflammation generally?
The initial rapid response to infection or tissue damage.
Is acute inflammation more closely linked to innate or acquired immunity?
Innate
What two types of patterns stimulate macrophages, dendritic cells or mast cells to produce interleukin 1?
PAMPs or DAMPs.
What does Interleukin 1 do?
Recruits leucocytes (ie neutrophils and monocytes) inducing inflammation
What are the 5 steps of inflammation (5 Rs)
Recognition of the infectious agent
Recruitment of leucocytes
Removal of the agent
Regulation of the agent
Resolution
What are cytokines
Proteins which are secreted by many cell types (including activated lymphocytes, macrophages, dendritic cells) that mediate and regulate immune and inflammatory reactions
What are chemokines
A family of small proteins that act primarily as chemoattractants of specific types of leucocytes.
What is hageman factor? (factor XII)
Inactive pro-inflammatory protein produced by the liver, activated when exposed to sub-endothelial or tissue collagen
What does Hageman factor work to accomplish?
Vasodilation, increased vascular permeability
What are the 3 ways oof activating the complement system?
Classical pathway (Antigen binds to IgG or IgM, activating C1)
Alternative pathway (activation by direct exposure to microbial components)
Mannose-binding lectin pathway (MBL binds to mannose on the bacterial surface)
What do the 3 pathways of the complement system stimulate?
Actication ofC3 convertase which splits C3 into C3a and C3b. C3a recruits and activates leucocytes while C3b binds to the microbe (opsonisation)
C3B can also bind to others of itself to form C5 convertase splitting C5 to form C5a and C5b.
C5b bonds with C6, C7, C8, C9 to form a membrane attack complex causing lysis of the microbe
what do C3a, C4a, and C5a do together?
Cause histamine to be released from mast cells. C5a also acts as a chemotactic aactivation agent for neutrophils, monocytes, eosinophils and basophils.
What activates mast cells
Tissue trauma, C3a and C5a, and cross linkin gof cell surface IgE by antigen.
What do mast cells do
Release perforated histamine granules, cause the vasodilation of arterioles and increased vascular permeability (initial response)
The delayed response is the production of arachidonic acid metabolites (leukotrienes)
What is the Arachidonic acid pathway?
Phospholipase A2 can act on membrane phospholipids to form Arachidonic acid.
5-Lipoxygenase causes leukotrienes to form, yielding vasoconstriction, bronchospasm, and vascular permeability, (LTC)
LTB causes neutrophil attraction and activation
Or, arachidonic acid can be exposed to Cyclooxygenase 1+2. These from prostoglandins, yeilding vasodilation, vascular permeability, pain and fever.
What are toll-like receptors?
Receptors present on cells of the innate and adaptive immune system activated by PAMPs.
CD14 (co-receptor for TLR4) on macrophages recognises lipopolysaccharide (a PAMP) .
WHat causes Rubor and Calor?
Vasodilation increasing blood flow. Relaxed arteriolar smooth muscle, mediated by histamine, prostaglandins, bradykinin and nitric oxide.
What causes fever?
Pyrogens cause macrophages to release IL1 and TNF, increasing COX activity in the perivascular cells of the hypothalamus. Prostoglandin E2 raises the temperature set point.
What causes tumor?
Leakage of fluid from post-capillary venules into interstitial space (Exudate).
Mediated by histamine (endothelial cell contration) and tissue damage (endothelial cell disruption).
What is exudate?
An extravascular fluid that has a high protein concentration and contains cellular debris.
What is transudate
A fluid with low protein content, little or no cellular material and low specific gravity, due to osmotic or hydrostatic imbalance across vessels with normal vascular permeability.
What is oedema
A fluid with low protein content, little or no cellular material and low specific gravity, due to osmotic or hydrostatic imbalance across vessels with normal vascular permeability.
What is pus
A purulent exudate which is an inflammatory exudate rich in leucocytes (mostly neutrophils), the debris of dead cells and in many cases microbes.
What causes pain?
Bradykinin and PGE2 sensitise sensory nerve endings.
What are the seven stages of neutrophil arrival and function?
Margination Rolling Adhesion Transmigration and chemotaxis Phagocytosis Destruction of phagocytosed material
What happens during marginisation of neutrophils
Vasodilation slows blood flow in post-capillary vnules, cells marginate from centre of flow to periphery
What happens during the rolling phase?
Selectin speedbumps upregulated on endothelium. Interaction causes rollign of leucocytes aong the vessel wall
What happens during the adhesion phase
TNF1 and IL1 upregulate adhesion molecules on endothelial walls. C5a and LTb4 upregulate integrins o neutrophils.
What happens during the transmigration and chemotaxis phase?
Leucocytes transmigrate across the endothelium of post-capillary venules and move toward chemical attraxctants.
Neutrophils attracted by IL8, C5a, LTB4 and bacterial products
What happens during the phagocytosis stage
Pathogens or necrotic tissue consumed.
What happens as the phagocytosed material is destroyed?
O2 dependent
O2 dependent is the most effective mechanism, HOCL generated by oxidative burst in phagolysosomes destroys phagocytosed microbes
What are the two types of killing of phagocytosed materials?
O2 dependent and independent
What is chronic granulomatous disease
Poor o2 dependent killing, recurrent infection and granuloma formation.
What happens at the resolution stage?
Neutrophils undergo apoptosis within 24 hours of resolution of stimulus
How are macrophages involved in acute inflammation
Predominate after neutrophils, 2-3 days after stimulus found. Derived from monocytes, following the same process of neutrophils.
What are the four outcomes of acute inflammation
resolution and healing,
continued acute inflammation, abscess formation,
chronic inflamation
