4 - Inflammation - Angyal Flashcards
Overall, what is the key result of inflammation?
Allows immune cells, defence molecules, coagulation factors to reach site of infection or tissue damage.
More specifically, what are the 4 things that occur during inflammation that allows the body to clear an infection?
- dilation of arterioles, venues, capillaries
- increased blood flow and permeability
- immune cell migration into inflammatory sites
- release of inflammatory mediators once pathogen detected
What are the 5 classic signs of inflammation?
redness, pain, swelling, loss of functional, heat
what are the 7 inflammatory mediators that are released once a pathogen has been detected?
- lipid mediators, prostaglandins
- chemoattractants, fMLP
- chemokine and cytokines, CXCL8, TNFa
- complement, C3a/C5a
- clotting factors
- small molecules eg ROS, RNS
- vasoactive amines
Describe the FULL process of extravasation
1) cytokines released by cells @ site of infection cause endothelial cells to express adhesion molecules (eg selectins, ICAM-1). Leukocytes also express counter receptors to ICAM1 known as Integrins which form weak interactions.
2) neutrophils are captured by the P/E selectins when glycoproteins (Sialyl Lewis) binds to them. Integrins on neutrophils also bind to ICAM-1/VCAM-1 - adhesion
3) neutrophils can squeeze between endothelial cells through an increasing number of interactions (therefore making them stronger) -> DIAPEDESIS
How can chronic inflammation occur, why is this bad and what are the causes?
- when acute inflammation goes on for too long. inefficient release of anti-inflammatory cytokines and molecules released
- TB and autoimmune conditions can cause this
- depletes the body’s resources
What are the 3 systemic actions of cytokines?
autocrine - act on themselves eg T cells produce IL2 but also have receptors for IL2
paracrine - act on nearby cells
endocrine - travel in bloodstream to reach a far away target eg IL1 acts on hypothalamus
Is it only immune cells that produce cytokines?
no, non immune cells can too
What are cytokines commonly referred to as?
hormones of the immune system
Cytokines have pleiotropic effects - what does this mean
cells w/ same receptor can be stimulated by same cytokine but may result in different effects
How are cytokines grouped into families?
grouped based on structure but may have different functions
Describe the 5 main classes of cytokines
- TNF. Exist as TM proteins, need to be cleaved & act as trimers
- haemopoietin superfamily eg IL2/4/6. responsible for cell growth and differentiation in bone marrow
- IFNs - response to viral infection following recognition of viral ssRNA uncapped
- chemokines - responsible for movement of cells eg IL-8 induces chemotaxis of neutrophils
- IL-1 family. made as inactive precursor. require activation by inflammasomes (caspase action)
Give 2 examples of cytokines; name the cells that produce them and what their role is
- IL2. Made by T cells. Induce T cell growth and differentiation
- IL8. Made by macrophages, dendritic cells. Chemotaxis of neutrophils
Give the 2 main ways in cytokine receptors signal
- enzyme coupled receptor dimers (JAK/STAT pathway)
- GPCRs
Give some examples of cytokines secreted in the early induced immune response by macrophages/dendritic cells
- CXCL8. chemotactic factor which recruits neutrophils and T cells to site of infection
- IL6 - activation of lymphocytes, increased Ab production
- TNFa - increases permeability of vascular endothelium allowing increased entry of IgG and complement to infection site. also, increased fluid drainage to lymph nodes.
- both IL6/TNFa give rise to systemic effects eg fever