Flashcards
Week 5
Flashcards do conjunto (32)
- 1What are the clinical signs of inflammation?-Erythema
-Oedema
-Heat
-Pain - 2What is inflammation?An innate immune response to tissue injury.
Caused by: chemical agents, heat/cold, trauma, microbe invasion - 3What is the purpose of inflammation?Destroy, dilute or wall off the injurious agent and induce repair
Can be harmful if uncontrolled - 4Describe the innate immune defence vs. acute phase response-Innate immune defence provides a rapid local response to pathogens if the barrier immune system fails
-Acute phase response is the result of activating the innate immune system - 5How are pathogens detected?-PRRs (Pattern Recognition Receptors) recognise PAMPs (Pathogen Associated Molecular Patterns)
-PRRs are on every innate immune cell (mast cells play a key role) - 6What do mast cells do?-Detect injury
-Release histamine
-Initiate inflammatory response - 7What does histamine do?-Vasodilation
-Endothelial junction widening
-Irritation of nerve endings (itch/pain) - 8What role does eicosanoids play as a mediator of inflammation?-Cause vasodilation
-Prolong oedema - 9What role do leukotrienes play as a mediator of inflammation?-Chemotaxins
-Vasoconstrictors in lung smooth muscle
-Bronchospasm
-Increased vascular permeability - 10What are anti-histamines used in?Allergy response to block histamine induced vasodilation
- 11What are COX inhibitory/ anti-prostaglandins used in?COX inhibitory- block with NSAIDs/aspirin to reduce pain and fever
Anti-prostaglandins- used in pulmonary hypertension - 12What are leukotriene inhibitors used in?Asthma to reverse leukotriene induced bronchospasm
- 13Describe the causes of the signs we see in inflammationErythema- vasodilation
Oedema- increased vascular permeability
Heat- cytokines
Pain- mediators - 14Describe the mechanisms of inflammation1) Vasodilation which increases blood flow and pooling
2) Results in erythema and warmth
3) Plasma proteins and cells leak out causing oedema. Water follows due to increase in osmolality
4) Increase in [RBC] resulting in stasis of blood
5) Immune cells migrate towards offending agent down chemotaxic gradient - 15What are the 3 main acute phase cytokines?IL-1
TNF-alpha
IL-6 - 16What is the effect of acute phase cytokines on endothelium?-Vasodilation and increased permeability
-Activated cells can get into tissues - 17What is the effect of acute phase cytokines on the hypothalamus?Stimulates fever to decreased pathogen replication
- 18What is the effect of acute phase cytokines on fat and muscle?-Protein/energy mobilisation for fever and immune response
-Results in weight loss - 19What is the effect of acute phase cytokines on the liver? What cytokine is especially involved?IL-6
Produced acute phase proteins (CRP) for opsonisation and complement activation - 20What is the effect of acute phase cytokines on bone marrow?Neutrophil mobilisation for increased phagocytosis
- 21What is the effect of acute phase cytokines on dendritic cells? What cytokine is especially involved?TNF-alpha
-Stimulates migration to lymph nodes and maturation for the adaptive response (T cells) - 22How can we block the acute phase therapeutically? Consequences of this?Anti- TNF alpha: for IBD and RA
Anti IL-1 &IL-6: RA
It blocks the ability to recognise and fight infection so the patient would not have a fever or neutrophilia - 23How does septic shock arise?1) Endotoxin from gram -ve bacteria enter the blood circulation
2) Huge macrophage activation in liver/spleen
3) Overproduction of TNF-alpha and IL-1
4) Widespread dilation of blood vessels, oedema and blood clotting
5) Multiple organ failure (+ death) - 24What are the outcomes of acute inflammation?-Complete restitution
-Healing with scar formation
-Abscess formation (encapsulation and pus)
-Granuloma formation- TNF is needed
-Chronic inflammation eg. SLE, arthritis - 25How is acute inflammation terminated?Anti-inflammatory cytokines (TGF-beta and IL-10) can inhibit the production of pro-inflammatory cytokines
- 26What biomarkers increase in response to infection and inflammation?-CRP
-C3/C4 (complement)
-Fibrinogen
-Ferritin - 27What biomarkers decrease in response to infection and inflammation?-A1 anti-trypsin
-Albumin
-Transferrin - 28What is CRP?-Pathogen recognition molecule
-Opsonises pathogen
-Activates classical complement cascade by binding to C1q
-Goes up within 24-48 hours - 29What does the Erythrocyte Sedimentation Rate show?-Rate at which erythrocytes settle out of unclotted blood in 1 hour
-Normally, RBCs settle slowly are they repel each other
-In presence of acute phase reactants: erythrocytes aggregate due to loss of -ve charge - 30Describe the classical pathway in the complement system-Activated by antigen/antibody complexes
-Acts via C3a, C5a
-Results in inflammation- mast cells degranulate and act as chemo-attractant - 31Describe the lectin pathway in the complement system-Activated by lectin which binds to carbohydrates on pathogen surfaces
-Acts via C3b (creates a feedback loop to create more C3 convertase)
-Results in opsonisation and enhanced phagocytosis - 32Describe the alternate pathway in the complement system-Activated by pathogen surfaces (not previously encountered)
-Acts via C5b (mostly)
-Results in a pore in the bacterial membrane causing lysis