Inflammation Flashcards
Inflammatory pathway
Inducers - Sensors - Mediators - Target tissues/cells
Inducers
pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), other mediators
Sensors
macrophages, dendritic cells (both have receptors on surface for PAMPs/DAMPSs), mast cells (secrete mediators)
Mediators
soluble molecules
Target tissues/cells
blood cells, epithelial cells, organs
Phagocyte
cellsthat protect the body by ingesting (phagocytosing) harmful foreign particles,bacteria, and dead ordyingcells
Macrophage
leukocytethat engulfs and digests cellular debris, foreign substances,microbes, cancer cells, and anything else that does not have the types of proteins specific to the surface of healthy body cells on its surface in a process calledphagocytosis - releases chemical signal to recruit other cells
Neutrophil
most abundant (40% to 75%) type ofleukocyte, formed from stem cells in the bone marrow, short-lived and highly motile, one of the first-responders of inflammatory cells to migrate towards the site of inflammation, pus=dead neutrophils
Phagocytosis definition
the internalisation of particulate matter by cells
Phagocytosis steps
(prephagocytosis: tissue injury releases chemical signals, blood vessels dilate and allow phagocytes to move across the wall) 1. binding to surface receptor 2. engulfment into phagosome 3. fusion of phagosome with lysosome (in compartments) 4. killing and degredation of bacterium by lysozyme, proteases, acid hydrolases (break hydrogen bonds) and free radicals
Necrosis
uncontrolled cell death
Apoptosis
controlled cell death
Platelets
initiate clotting
Mast cells
release mediators (degranulation), kill parasites, role in allergy and anaphylaxis
Basophil
leukocyte, release mediators (degranulation), kill parasites and viruses, role in allergy
Eosinophil
leukocyte, release mediators (degranulation), kill parasites and viruses, role in allergy and asthma
Lymphocyte
leukocyte, slow response, include NK cells, T cells, B cells
NK cells
directly kill virally infected cells and tumour cells
B cells
recognise whole pathogens, make antibodies, developed in bone marrow
T cells
recognise fragments of pathogens bound to MHC molecules on cell surface, developed in thymus - CD8 and CD4
CD8 (cytotoxic) T cells
kill infected cells
CD4 (helper) T cells
help B cells make antibody or activate macrophages
“Naïve” T and B cells
undergo education program to eliminate “self” reactive cells - negative selection
Antigen
any substance that causes your immune system to produce antibodies against it
Antibody
(aka immunoglobulin) large, Y-shape protein used to identify and neutralize pathogens
Lymphatic system
route to return fluid from tissues to blood, transports immune cells, pathogens and antigens from tissues to lymph nodes (activates T and B cells)
Chemotaxis
the movement of leukocytes up a gradient of chemicals towards it source
Leukocyte pathway
- Margination (accumulation and adhesion to blood vessel walls at site of injury) 2. Diapedesis (leaving the blood) 3. Chemotaxis 4. Phagocytosis
Role of soluble mediators
dilation of blood vessels, increased permeability of blood vessels, activation of endothelium (allow adhesion of leukocytes), chemotaxis, amplification of immune response, resolution of acute inflammation
Kinin
any of a group of substances formed in body tissue in response to injury
Examples of soluble mediators
plasma cascades, histamine, lipid mediators (prostaglandins, leukotrienes), cytokines
Acute inflammation
immediate response, movement of leukocytes, leakage of plasma and soluble mediators, inflammation resolves, compontents: changes in vascular flow, increased vascular permeability, emigration of leukocytes from circulation to injury site
Chronic inflammation
long term, tissue destruction w attempts at repair, mononuclear cell infiltration (macrophages, lymphocytes), abnormal repair (fibrosis, angiogenesis)
Types of anti-inflammatory drugs
NSAIDs, corticosteroids, biologicals. Note: need for more effective and safer anti-inflammatory drugs
NSAIDs
Non-steroidal anti-inflammatory drugs: reduce pain, fever, inflammation, inhibit cyclooxygenase enzymes. Side effects: stomach bleeding, thrombosis/heart attack. Eg. Asprin, Ibuprofen, Celebrex, Vioxx
Cyclooxygenase enzymes
catalyze prostaglandin production from arachidonic acid
Corticosteroids
Supress inflammation: down-regulate expression of genes involved in inflammation, up-regulate expression of anti-inflammatory proteins. Eg. Dexamethasone, Prednisone
Classes of corticosteroids
Glucocorticoids: anti-inflammatory, Mineralocorticoids: control electrolyte/water levels
Biologicals
Soluble proteins that block actions of key cytokines or chemokines that drive inflammation. Expensive and can compromise immune system. Eg. Etanercept (anti-TNF), soluble IL-1 Receptor
