Inflammation Flashcards
What is inflammation?
State where the body is trying to home the immune response to a certain area
What are the functions of receptors?
Provide information to tell the cells where they are and what is around them
Allows cells to sense the environment
Transmit signals from the cell surface to the nucleus to change gene expression and function
What are cytokines?
Soluble messengers between cells
What are the different families of cytokines?
Interleukins
Interferons
Tumour Necrosis Factor
Colony-stimulating factors
Chemokines
Features of cytokines
Work through synergistic or antagonistic ways
Can de redundant
Can be pleiotropic
Which cells produce cytokines?
Activated immune cells
Epithelial cells
Stromal cells
What types of cytokines are released in the induction phase of inflammation?
Pro-inflammatory cytokines
Interferons
Examples of pro-inflammatory cytokines
TNF-a
IL-6
IL-1b
Examples of interferons
IFNa
IFNb
What are the effects of pro-inflammatory cytokines?
Local effects
Long range effects through travelling in the blood including liver, acute phase protein release and fever induction
What induces the release of interferons?
Viral infection
What are the effects of interferons?
Prevent viral replication
Activate dendritic cellls, macrophages and NK cells
Induce chemokines
What is released during the resolution phase?
Anti-inflammatory cytokines
Examples of anti-inflammatory cytokines
TGFb
IL-10
What is the main role of chemokines?
Attract other cells
Features of chemokines
Lots of redundancy in chemokine function
Several chemokines display similar activity and show shared receptor usage
Relevance behind naming system for chemokines
In the beginning, chemokines had more functionally descriptive names like Monocyte Chemotactic Protein-1
Now they have complex names denoted by L for ligand and a number linked to the receptor number
When are chemokines released?
During inflammation
Which molecules work in close association with chemokines?
Cell adhesion molecules
Work to get immune cells from the blood into the tissue
What dictates the type of leukocytes recruited into tissues?
Cellular distribution of receptors and cellular adhesion molecules
What is inflammation?
Process that rapidly recruits cells of the immune system to the sites of injury or infection
What are the signs of inflammation?
Swelling
Elevated temperature
Pain
What causes the signs of inflammation?
Increased blood flow
Entry of leukocytes into the tissue
What are examples of pattern recognition receptors?
TLR
Scavenger receptors
Lectin
NOD like receptors
Complement prteins
Ficolins
Collections
What are examples of surface PRRs?
TLR
Scavenger receptors
Lectin
What are examples of solubles PRRs?
NOD like receptors
Ficolins
Lipopolysaccharide-binding proteins
What is the complement system?
Key component of inflammation
30 or more proteins which act in an enzymatic amplification cascade to generate active complement components in several aspects of the immune response
In which processes is complement important?
Opsonization
Inflammation
What are the 3 ways to activate complement?
Classical
Lectin
Alternative
What triggers the classical pathway?
Antibody antigen complexes
What triggers the lectin pathway?
Mannose binding lectin
What triggers the alternative pathway?
Bacterial wall components
What is a key event in complement activation?
Splitting of C3
Describe the splitting of C3
C3a and C3b are formed by cleavage by C3 convertase
How do complement make MAC
- Complex of four (C5b. C6, C7, C8) complement proteins bind to the outer surface of the plasma membrane
- This complex binds many copues of C9 that hook up to one another, forming a ring in the membrane
- The ring structure is a pore in the membrane that allows free diffusion of molecules in and out of the cell
- If enough pores form, the cell is no longer able to survive
What are the 3 phases of acute inflammation?
Vascular
Cellular
Removal of infectious agent
Describe the vascular phase
Increased blood flow to infected tissues
Localised increased permeability
Endothelium becomes adhesive to allow chemotaxis into the tissues
Describe the cellular phase
Leukocytes accumulate in local vasculature
Leukocyte migration into infected tissue
Which two cells are important in acute inflammation?
Mast cells
Macrophages
How are mast cells involved in acute inflammation?
Become activated by antigen receptors and complement
Contain granules with pre-formed histamine
Histamine causes blood cells to become more permeable
Mast cells become lipid mediators which break down arachidonic acid into leukotrienes and prostaglandins, which recruit more neutrophils
How are macrophages involved in acute inflammation?
Release lipid-derived inflammatory mediators
Cytokines
Chemokines
Present antigens to T cells
What is the acute phase response?
Once the local response has happened, the blood mediators travel to the periphery
Cytokines act on the liver to increase the secretion of APPs
This increases the release of complement, C-reactive proteins and coagulation factors
What other organs do cytokines affect?
Brain
Causes fatigue and lack of appetite
What is a key feature of inflammation?
Neutrophils enter the tissue
Describe the process by which neutrophils enter the tissue
- Neutrophils are normally swimming in the blood
- When they approach inflamed area, the endothelium increases expression of P-selectin, causing the neutrophils to travel more slowly
- If endothelium is activated, TNF and other inflammatory mediators cause it to express VCAM
- Neutrophils have core receptors for these proteins, causing the neutrophils to bind firmly to the endothelium wall
- The neutrophil then crawls between gaps in the endothelium during diapedesis following a chemotactic gradient
What is the resolution phase?
End point of acute inflammation
Aims to stop cells from entering the tissues once the inflammatory response has been effective
Which cells are involved in the resolution phase?
Neutrophils mop up extra soluble mediators
Monocytes differentiate into macrophages and then into resolution macrophages
Neutrophils then undergo apoptosis, and are ingested by macrophages which leads to the macrophages switching off
What are causes of chronic infection?
Persistent injury or infection - ulcer, TB
Prolonged exposure to a toxic agent
Autoimmune diseases
What happens when individuals age?
There is a low-grade inflammation which leads to many conditions and prevents the immune system from working properly
Which conditions have been linked to chronic infection?
Diabetes
Cancer
Neurological diseases
Autoimmune diseases
Pulmonary diseases
Arthritis
Complement involved with clearance of immune complexes
C3b
Complement involved with B-cell activation
C3d
Complement involved with mast cell degranulation
C3a, C4a and C5a
Complement involved with chemotaxis
C5a
Complement involved with opsonization
C3b, C4b
Complement involved with cell lysis
C5b-C9