Inflammation Flashcards
Define inflammation
This is the body’s natural response to injury and infection that involves a sequence of interrelated events that bring plasma proteins and blood cel to the injured area to initiate tissue repair
What are the 4 cardinal features of inflammation
Heat
Redness
Swelling
Pain
What is the heat from inflammation caused by
Increased blood flow and release of inflammatory mediators
What is the redness from inflammation caused by
Increased vascularity of the region
What is the swelling from inflammation caused by
Exudation of fluid, proteins and cells into the area of tissue damage
What is the pain from inflammation caused by
Caused by activation of pain receptors by inflammatory mediators in inflammatory exudate
Name a few ways that inflammation can be triggered
- Physical agents - heat, cold, radiation
- Foreign bodies - splinters, dirt, sutures
- Chemicals - acids, alkali
- Infections - bacteria, viruses, fungi
- Immune mediated - immune complexes, hypersensitive
What are the functions of inflammation
- Destroy and remove pathogens or injuring foreign bodies
- Limiting and confining the effects of pathogens and their products
- Repairing and replacing damaged tissue
Describe the characteristics of acute inflammation
Occurs early and consists of transient episodes (days, weeks)
Characterised by neutrophil infiltration
Describe the characteristics of chronic inflammation
Longer lasting - months/years
Characterised by lymphocytes and macrophages
Why do inflammation responses need to be tightly regulated
They can become harmful and are sometimes linked to heart disease or stroke and autoimmune disorders like rheumatoid arthritis and lupus
What receptors are used to recognise pathogens
PRRs = Pattern recognition receptors
What on pathogens is used by cells to identify them
PAMPs = Pathogen associated molecular patterns
Name a few types of bacterial PAMPs
LPS Lipoproteins Flagellin DNA RNA
Name some PAMPs for viruses
DNA
RNA
Structural proteins
Describe the inflammation process (7 points)
- Pathogen breaches physical barrier
- Platelets secrete blood clotting-factors
- Mast cells promote vasodilation, vascular constriction and delivery of plasma/cells to injured area
- Neutrophils kill and degrade the pathogens
- Phagocytosis by neutrophils and macrophages
- Macrophages secrete cytokines that attract and activate immune rcells to induce tissue repair
- Inflammatory response continues until infectious/foreign material is removed and tissue repaired
What are platelets
Small fragments of megakaryocytic with a significant role in modulating clot formation
What types of granules are expressed by platelets
Alpha
Dense
Lysosomal
What can be found in alpha granules of platelets
Chemokines Coagulation factors Growth factors Fibrinogen Fibronectin
What can be found in dense granules of platelets
Ca2+ Mg2+ Nucleotides Serotonin Histamine
What can be found in Lysosomal granules of platelets
Proteases
Collagenase
What are the roles/functions of platelets
- Contribute to NET formation
- Block spreading of infection by clot formation
- Induction of pro-inflammatory cytokines
- Breakdown of microbes by lysosome granules
- Contribute to engulfing of bacteria
What happens after the antigens of a pathogen bind to mast cells
- Signals degranulation, releasing histamine and proteases
- Signals for activation of PLA2 that makes membrane phospholipids to make PAF and arachidonic acid
- Initiate formation of cytokines and chemokines
What can arachidonic acid be converted into
Protaglandins and Leukotrienes
What immediate responses do mast cells cause
Vasodilation
Vascular leakage - allowing macrophages to site
Smooth muscle spasm
What allows leukocytes to associate with tissues
Integrins found on their surface and selectins on the tissues allows leukocytes to associate with tissues
What is leukocyte extravasation
This is the movement of leukocytes out of the circulatory system towards the site of tissue damage or infection
Describe the process of leukocyte extravasation
- Leukocytes from the bloodstream bind to selectins on the endothelial surface using integrins on their surface
- The integrins on the leukocytes undergo conformational changes as they bind more to the endothelial surface and enter higher-affinity states
- This allows them to move through the endothelial surface and interact with fibrin and fibronectin in the infection site
What is wrong in the LAD1 and LAD2 leukocyte adhesion deficiencies
LAD1 - There is a lack of ITGB2
LAD2 - There is a lack E-selectin
What happens to the leukocytes and neutrophils in patients with Leukocyte adhesion deficiency
Leukocytes are unable to leave the circulatory system
Neutrophils are unable to aggregate and the neutrophil counts are commonly twice the normal level
Describe the process of phagocytosis
- chemotaxis and adherence of microbe to phagocyte
- Ingestion of microbe by phagocyte
- Formation of a phagosome 4. Fusion of the phagosome with a lysosome to form a phagolysosome
- Digestion of ingested microbe by enzymes
- Formation of residual body containing indigestible material
- Discharge of waste materials
What is interleukin 1 (IL-1)
One of the most potent inflammatory molecules and has a huge number of target cells in the body (almost all of them)
What 2 categories of effects can interleukin-1 produce
Local effects
Systemic effects
What are the effects of IL-1 on leukocytes
- Activation
- Production of cytokines
Aids inflammation
What are the effects of IL-1 on Fibroblasts
- Proliferation
- Increased collagen synthesis
Uses for repair
What are the effects of IL-1 on the vascular endothelium
- Increased expression of leukocyte adhesion molecules
- Production of IL-1 chemokines
- Increased pro-coagulant and decreased anticoagulant activity
Aids inflammation
What are some of the systemic effects of IL-1
- Fever
- Leukocytosis
- Increased acute phase proteins
- Decreased appetite
- Increased sleep
AY BAWS CAN I HABE DE NOTE PLZ
Basically because the pro-inflammatory factors are so potent like IL-1 the regulation of inflammation is superrrrr important
Name some molecules that are anti-inflammatory and describe them a little idk
Anti-inflammatory cytokines - TGFbeta and IL-10 inhibit secretion of pro-inflammatory cytokines
Lipoxin and Resolvins from Arachidonic acid metabolism have anti-inflammatory actions
How long do neutrophils and most mediators actions last for
Neutrophils only have a short life span (hours) and most mediators are short lived and are degraded immediately
What cells and molecules are most dominant in the onset of inflammation
- Leukotrienes
- TNFalpha
- Prostaglandins
- IL-1beta
What cells and molecules are dominant in the resolution of inflammation
- TGFbeta
- Resolvins
- IL-10
- Lipoxins
- Protectins
- Inhibitors of PLA2
- Glucucorticoids
What processes occur in the onset of inflammation
- Production of inflammatory mediators
- Neutrophil recruitment
- Increased neutrophil lifespan
- Classically activated macrophages
What processes begin/occur in the onset of resolution of inflammation
- Chemokine depletion
- Lipid mediator class switching
- De novo AnxA1 synthesis
- Cytokine induced ACTH
- Release of neutrophil microparticles
- Downregulations of pro-inflammatory cytokines (neg feedback)
What processes occur in the resolution of inflammation
- Production of pro-resolving mediators
- Abrogation of neutrophil recruitment
- Alternatively activated macrophages
Defects in the regulation of inflammation can lead to what kind of disorders and give examples
Autoimmune e.g. hashimoto’s thyroiditis, MS, vitiligo
Immunodeficiency
What are some triggers for autoimmune disorders
- Stress
- Hormones
- Metals
- Food
- Antigens
- Pesticides and Poisons
