LECTURE 5 Flashcards
describe cytokines in general
low MW –> 5-25 kDa
regulate nature, intensity, and duration of response
3 cytokines originally named based on their function
- Lymphocyte activating factor = IL1
- B cell growth factor = IL4
- B cell differentiation factor = IL5
6 main groups of cytokines
- lymphokines –> made by lymphocytes (IL2)
- monokines –> made by monocytes (TNF, IL1)
- interleukins –> made by leukocytes
- IFN –> pro-inflammatory, anti-viral
- CSF –> growth of immune cells at maturation stages (G-CSF)
- chemokines –> IL8/CXCL8
where are chemokines secreted?
at infection site or allergy
how do chemokines cause cell movement?
cause cells to follow concentration gradient
- promote cell shape change thru actin polymerization and breakdown
- leukocytes extend pseudopodia for cell movement
another function of chemokines besides cell movement?
promote recruitment and activation of cells
how do immune cells differ from other cells with regards to movement?
other cells have polarity inherently that allows movement
4 classes of chemokine receptors
- C –> 2 cysteines + 1 bond (lymphotactin/XCL1)
- CC –> 4 cysteines (1st 2 adjacent) + 2 bonds (rantes/CCL5)
- CXC –> 4 cysteines (1st 2 have aa btwn) + 2 bonds (IL8/CXCL8)
- CX3C –> 4 cysteines (1st 2 have 3 aa btwn) + 2 bonds (fractalkine/CXC3L1)
describe extravasation process
- pro-inflammatory cytokines
- selectin on endothelium, integrin on leukocytes
- leukocytes bind endothelium
- cell moves from blood to tissue
role of chemokines in LN/spleen
3 examples
allows immune cell segregation
- stromal cells –> CCL21 –> DCs move into LN
- DCs –> CCL19 –> recruit T cells to T cell zone
- fDCs –> CXCL13 –> recruit B cells to follicle
what is autocrine?
cytokine acts on the cell it came from –> ex. IL2 for T cell activation
what is paracrine?
cytokine acts on nearby cells –> IFN protects nearby cells from viral infection
5 major cytokine receptor families
- Type 1 (hematopoietic)
- Type 2 (IFN)
- TNFR
- IL1R
- chemokine receptor
examples of cytokines signaling thru type 1 receptors
- and signaling pathway
IL2-9, IL11, IL12, G-CSF
signals thru diff combos of JAK and STAT
how does IL6 signaling work?
- IL6 binds common alpha chain and gp130 chain
- JAK binds and is phosphorylated
- STAT3 is phosphorylated and dimerizes
- STAT3 goes to nucleus
- activates TFs for apoptosis, proliferation, and survival genes
examples of cytokines signaling thru type 2 receptors
- and signaling pathway
IFNalpha, IFNbeta, IFNy, IL10, IL20, IL24, IL26
signals thru diff combos of JAK and STAT
role of Type I IFN and signaling path
Type I IFN = a and B –> anti-viral
phosphorylates STAT1/STAT2 complex –> binds IRF9
role of Type II IFN
Type II IFN = y –> activate macrophage, anti-viral
examples of cytokines signaling thru TNF receptors
- and signaling pathways (3)
TNFa, TNFB, LTb, FasL, CD40L, and NGF
- NF-kB –> pro-inflammatory
- AP1 –> proliferation + differentiation
- Caspase 8 –> apoptosis
General effects of TNF
- vasodilation/vascular leak
- recruit leukocytes
- coagulation, NETs