Lecture 22 - Cytokines and Chemokines Flashcards
Cytokine definition
Small molecules, either proteins or peptides, that upon release and binding to specific receptors elicit an immune response
Feature that is widespread among cytokine receptors
Mutimeric
Example of a cytokine that requires transpresentation
IL-15
Won’t elicit a response unless bound to IL-15R alpha
Why can IL-15 only affect nearby cells?
Must be bound to IL-15R alpha in order to generate a response
This can only occur near secreting cell
Number of proteins in TNF superfamily
19
Two major biological functions of TNF superfamily
1) Pro-inflamamtory (TNF, TRAIL, BAFF)
2) Cell survival, growth (NGF, FasL)
TNFalpha
1)
2)
3)
1) Strong pro-inflammatory molecule
2) Major pathological factor in rheumatoid arthritis
3) Belongs to TNF superfamily
Cachexia
Wasting
TNF actions 1) 2) 3) 4)
1) Neutrophil activation
2) Catabolic metabolism
3) Apoptosis
4) Perpetuation of pro-inflammatory cytokine loops
Common gamma-chain cytokines 1) 2) 3) 4) 5) 6)
1) IL-2
2) IL-4
3) IL-7
4) IL-9
5) IL-15
6) IL-21
What is the common gamma chain?
CD132
What do mutations in the CD132 gene lead to?
SCID
Signal transduction pathway used by common gamma chain interleukin receptors
JAK/STAT
IL-2 function 1) 2) 3) 4)
1) T cell growth factor
2) Augments NK cell function
3) Promotes B cell antibody production
4) Assists in Treg development
IL-4 function
1)
2)
3)
1) Th2 bias, function
2) Class switching to IgE
3) Mast cell activation
Il-7 role
Critical role in T cell development
Absence of IL-7 results in absence of T cells in SCID patients
IL-9 role
1)
2)
3)
1) Activation of epithelial cells
2) Activation of B cells
3) Activation of eosinophils, mast cells
IL-15 role
1)
2)
1) NK cell development - Absence of IL-15 responsible for NK cell absence in SCID patients
2) T cell homeostasis
IL-21 role
1)
2)
3)
1) important for Tfh cells
2) Stimulates B cell responses in germinal centres
3) Sustains CD8+ response in infections
Chemokines 1) 2) 3) 4)
1) Very small peptides (8-12kD)
2) Use GPCR as signal transduction pathway
3) Classified on the basis of cysteine residues in N-terminal (CC, CXC)
4) ~50 known chemokines
Key cytokine funcitons
1)
2)
3)
1) Recruitment of circulating leukocytes from blood to tissues
2) Regulate traffic of lymphocytes to and within lymphoid organs
3) Regulate migration of DCs from tissues to lymph nodes
Expression pattern of CCL19, CCL21
Constitutive
What produce CCL19, 21?
1)
2)
1) Stromal cells of the lymph node
2) Endothelial cells in HEV
What do stromal cells of the lymph node and endothelial cells of the HEV produce?
CCL19, CCL21
What express CCR7?
Naive T cells, naive B cells, DCs
How do cells follow chemokine gradient?
By amoeboid movement
What does a DC express when it phagocytoses and antigen?
CCR7
This causes it to begin moving into the lymph, towards a lymph node
