Week 2 Flashcards
what happens during inflammation?
- invasion of bacteria through the epithelial cell layer
- this will be recognised by mast cell or macrophages and they will release mediates e.g. lipid mediators, prostaglandins, leukotrienes, platelet activation factors, chemokines, cytokines
what happens when macrophages release cytokines like IL-1?
- the macrophages ingests a gram-negative bacterium,
- the bacterium is degraded in a vacuole, releasing endotoxins that induce the macrophages to produce IL-1
- IL-1 is released by the macrophage into the bloodstream, through which it travels to the hypothalamus of the brain
- lL-1 induces the hypothalamus to produce prostaglandins, which reset the bodys thermostat to a higher temperature producing a fever
what are the main symptoms of inflammation?
- rubor= redness
- dolour=pain
- calor= heat and fever
- tumour=swelling
- function laesa- loss of function
what causes an inflammation?
- response by the body to celluar insult by infectious agent, toxins and physical stress
- protective response, ultimate goal is to remove initial cause of injury
what s the sequence of the inflammatory response?
• Insult by trauma or pathogen causes acute phase reaction
• Platelet adhesion, transient vasoconstriction of efferent vessels
• Cytokine-induced vasodilation of afferent vessels (increased heat
/blood flow to area)
• Activation of complement, coagulation, fibrinolytic and kinin systems
• Leukocyte adhesion
• Increase vascular permeability and extravasation of serum proteins
(exudate) and leukocytes (→ neutrophils → macrophages →
lymphocytes) with resultant tissue swelling
• Phagocytosis of foreign material with pus formation
• Wound healing and remodelling
what is released during the acute phase reacton?
TNF-alpha, IL-1, IL-6
why does swelling, heat and redness occur during inflammaton?
due to vasodilation and increased vascular permeability
why do we feel pain during inflammation?
due to inflammortary cells migrating into tissue, releasing inflammatory mediators causing pain
what are the different components involved in an inflammatory response?
- Complement
- Acute phase proteins
- Interferons
- Cytokines, chemokines, adhesion molecules etc
- Prostaglandins and leukotrienes
- Histamine
- Kinins (bradykinin
how does transmigration of the cells through the endothelium layer?
- leukocytes/neurophils are floatng in the blood vessels at high speeds
- chemokines are released due to inflammation and become chemoattractants on the endothelial cell surface
- so when the neurophils are floating and rolling they capture these chemoattractants and slow them down leading to from adhesion on the surface
- leading to transmigration trough the endothelium layer to the ste of inflammation and cause a resolution of the inflammatory response.
what are the different stages of inflammation?
1) vasodilation- triggered to produce prostaglandins, histamines, kinin and leukotriene
2) migration and margination-margiination describes the binding of phagocytes to the blood vessel
- Tissue repair -dead and damaged cell are rebuild
what are the pro-inflammatory mediators, that are released that drive the inflammation?
- Acute phase proteins
- Complement
- Kinins
- Cytokines –
- Pro-inflammatory TNF, IL-1, IL6 etc
- Chemokines – CXCL-8, CCL2, CCL5 etc
- Growth factors – M-CSF, GM-CSF etc
- Adhesion molecules – VCAM-1, ICAM-1
- Matrix metalloproteinases – MMP-1, 2, 9 etc
- Clotting factors
- Prostaglandins
what is the role of cytokines that are involved in promoting inflammation?
- they activate immune and other cells in the local environment to the site of tissue and for recruitment
- growth factors stimulate immune and non-immune cell growth
- act as endogenous pyrogens
- induce acute phase proteins in the liver
what are acute phase proteins?
- they fluctuate in response to tissue injury and infection
- they are usually made by hepatocytes
- they are synthesised in response to pro-inflammatory cytokines
what are some acute phase proteins?
C Reactive Protein -Opsonin
Fibrinogen -Coagulation factors
Serum Amyloid A -Cell recruitment and MMP inducer
Complement factors -Opsonin, Lysis, Clumping, Chemotaxis
Haptoglobin and ferritin -Bind haemoglobin or Fe
what are the major pro-inflammortary cytokines?
Interleukin -1 (IL-1) -Vasculature (inflammation), hypothalamus (fever), liver (induces APP) Tumor necrosis factor alpha (TNFalpha) -Vasculature (inflammation), liver (induction of APP), induction of cell death, neutrophil activation, cachexia Interleukin 12 (IL-12) -NK cells, promotes TH1 subset of T lymphocytes (pro-inflammatory) Interleukin 6 (IL-6) -Liver ( induces APP), influences adaptive immunity (proliferation and antibody secretion by B cells) Interferon alpha and beta (IFNa/b) -Induces antiviral state, activates NK cells
what are the different sub-families for chemokines?
CC, CXC, C, CXXXC which bind to G-protein coupled
receptors (CCRs, CXCRs, XCR1, CX3CR1)
chemokines can act on different immune cell types, what do they attract?
• Interleukin 8 (CXCL8) attracts neutrophils
• Ig superfamily eg VCAM-1, ICAM-1, LFA-2
• Cadherins eg E, P, N (cell-cell adhesion)
• Selectins – E, P, L – recognise carbohydrates
• Integrins – 8 subfamilies, eg α4β1 (ECM and cell-cell) chemotactic protein 1 (MCP1/CCL2) attracts monocytes
• Eotaxin (CCL11) attracts eosinophils etc
but there is overlap in function
what are adhesion molecules?
they are transmembrane receptors that bnd to either otheer cells or to the extracellular matrix, which allow the rolling leukocyes can then be attaced the to the endothelium layer and move to the tissue
what are the 4 different classes of adhesion molecules?
- Ig superfamily eg VCAM-1, ICAM-1, LFA-2
- Cadherins eg E, P, N (cell-cell adhesion)
- Selectins – E, P, L – recognise carbohydrates
- Integrins – 8 subfamilies, eg α4β1 (ECM and cell-cell)
what are Metalloproteinases?
• Proteases whose catalytic function requires metal, usually zinc
• Three main families
- MMPs
- ADAMS
- ADAMTS
•Redundancy in the families – many have similar functions
what is the role of MMPs?
Degrade and remodel extracellular matrix
• Create chemokine gradients
what is the role of ADAMs?
Cleave cytokine and adhesion molecule receptors from cell surface
what is the role of ADAMTs?
- Cleave receptors also
* Degrade proteoglycans
