Rote learning Test 1 Flashcards
What are the chemical mediators linked to swelling and pain in inflammation?
Prostaglandin E2 and Bradykinin
What is Platelet activating factor derived from?
Lysophosphatidylcholine, through the action of phospholipase A2
What does arachidonic acid do in the inflammation response?
Generation of acute phase proteins such as prostaglandins and leukotrienes
How are prostaglandins formed?
Arachidonic acid reacts with Cyclooxygenases
How are Leukotrienes formed?
Arachidonic acid reacts with 5-Lipoxygenase
What is the function of TXA2?
Vasoconstriction and platelet aggregation
What is the function of PCI2?
Vasodilation and platelet dissociation
What is the function of PGE2?
Vasodilation, pain, fever
What is the function of LTB4?
Neutrophil chemotaxis and activation
What are the functions of cysTC4,D4,E4?
Vasopermeability and bronchoconstriction
What is the function of C3a and C5a?
Promote mast cell degranulation, vascular permeability and neutrophil chemotaxis
What is the function of C3B?
Opsonization
What is the function of C5b?
Part of the membrane attack complex for bacterial cell lysis
What DAMPs do toll-like receptors bind?
ECM fragments,
intracellular proteins,
DNA and RNA
What binds to RAGE receptors?
intracellular proteins
What binds to P2X7 purinergic
ATP
What receptor binds crystals?
Components of inflammasomes
What does signalling from TLRs and P2X7Rs do?
Activation of inflammasomes resulting in the release of IL-1alpha when cells undergo lysis causing endothelial cells to become adhesive for leukocytes
What stimulates the acute phase response?
Interleukin6
What causes fever?
Pyrogens TNF, Interleukin1 and Prostaglandin E2
Which region of the brain is affected by fever?
Hypothalamic thermoregulation
What stimulates regeneration in colon crypts?
LPS activates TLR4 on macrophages which activates COX2 Which activates PGE2
How do Kupffer cells induce hepatic regeneration?
Release of TNF, IL-6, HGF and TGFalpha
What transcription factors can induce terminally differentiated cells to once gain become pluripotent?
t4, Sox2, Klf4, Myc
M1 macrophages
Pro-inflammatory
Respond to IL-6, IL-1, ROS
M2 macrophages
Wound healing
Respond to PDGF, TGFB, VEGF, TNFa/EGF
Pro-resolution Macrophages
Remodelling
TGFB, IL-10
What is the role of tH1Cells?
Secretion of interferon-gamma which stimulates tH1 development and activates macrophage responses to intracellular pathogens
What is the role of tH2 cells?
Secretion of IL-4 which stimulates TH2 development and activates eosinophil responses to worms
What is the role of tH17 cells?
Secretion of IL-17 and IL-21 which stimulates tH17 development and activates epithelial responses to microbes (secretion of antimicrobial substances such as defensins and GM-CSF)
What is the role of tReg cells?
Secretion of cytokines such as TGFBeta which stimulates Treg development and suppression of inflammation
Which T cell types can cause autoimmunity?
TH1, TH17
Which T cell types can cause allergies?
TH2
Which T cell type would a deficiency result in damage?
Treg as a deficiency will result in excessive inflammation
What are the stress inducers, transcription factor and effects of DNA damage
Stress inducer: DNA damage, Hypoxia, ROS
Transcription factor: p53
Targets: DNA repair, cell cycle arrest, cell suicide
What are the stress inducers, transcription factor and effects of Antioxidants
Stress inducer: Oxidative Stress, ROS
Transcription factor: Nrf2
Targets: SOD1, Catalase
What are the stress inducers, transcription factor and effects of Heat shock (Proteotoxic)
Stress inducer: Denatured proteins
Transcription factor: HSPs
Target/effects: Chaperones (heat shock proteins)
What are the stress inducers, transcription factor and effects of Hypoxia
Stress inducer: Low oxygen
Transcription factor: HIFs
Target/effects: Glucose transporters, glycolytic enzymes, RBCs, blood vessels
What are the stress inducers, transcription factor and effects of unfolded proteins
Stress inducer: ER stress proteins
Transcription factor: several
Target/effects: Chaperone proteins
What are two types of physical damage to DNA?
UV and IR
What damage is caused by ionising radiation?
Water is broken to form H and OH free radicals which cause breaks in the DNA strand which can be misrepaired
What damage does U.V. radiation cause?
Damages DNA bases where adjacent C’s and T’s become linked causing potential misrepair leading to cancer or death of keratinocytes
What is a form of chemical damage to DNA?
Alkylation where aflatoxin B can cause liver injury at high doses, or G to T mutations underlying liver cancer
What is a form of biological damage to DNA?
Dietary deficiency in B9 and B12 prevents DNA synthesis and repair causing megaloblastic anaemia
What is a form of physical damage to lipids?
Crystal intake into lysosomes which then puncture activating inflammasomes and releasing hydrolytic enzymes
What is a chemical form of damage to lipids?
Reaction of lipids with free radicals
What is superoxide?
A oxgen diatomic molecule that is also a free radical and detoxified by superoxide dismutase to hydrogen peroxide and O2
What is the enzymatic reaction of hydrogen peroxide that occurs in cells?
Catalase detoxifies it to Oxygen and water
What is the reaction that occurs between an OH radical and a Lipid?
The OH breaks a hydrogen bond to make a lipid radical, which then reacts with oxygen to make a lipid peroxyl radical. This the reacts with another lipid to generate a lipid radical and a lipid hydroperoxide. The lipid hydroperoxide then forms dmagning aldehydes and ketones
What are the sources of reactive oxygen species?
Oxygen therapy, Inflammation, UV radiation, Damaged mitochondria, radio therapy
What is a biological form of damage to lipids?
Lipases are protiens that can cause damage to lipids as they digest them
What is acute haemorrhagic pancreatitis?
Damage to exocrine cells occurs, resulting in the release of activated digestive enzymes including phospholipases and lipases which digest cell membranes and triglycerides
What is a form of physical damage to proteins?
Heat as above 42 degrees proteins become denatured resulting in the release of heat shock proteins in an attempt to address the denaturation problems
What is a form of chemical damage to proteins?
Glycation - inhibit protein function. Cause proteins to cross-link and become insoluble. Generate ROS and bind to RAGE receptors to reduce blood flow and cause inflammation
Biological damage to proteins
Proteases e.g inflammation
Arthritis cleaves collagen in joints
Emphysema cleaved elastin in the lung extracellular matrix
Cancer invasion cleaved laminin allows cancer cells to migrate.
What is acute intracellular oedema?
When the ability of the cell to regulate ion concentrations is compromised resulting in swelling which is initially reversible
What is Abnormal storage?
Accumulation of products such as fat and glycogen resulting from either increased concentration or a reduced ability of hepatocytes to metabolism them