lecture 5 Flashcards
TNF-a
- produced by activated macrophages
- induced by LPS of gram - bacteria
- mediator of acute inflammation - recruits neutrophils and macrophages to sites of infection
- PRO-INFLAMMATORY
IL-1
- produced by activated macrophages
- similar to TNF-a but also helps activate T-cells
- PRO-INFLAMMATORY CYTOKINE
IL-10
- produced by activated macrophages and TH2 cells (CD4)
- inhibits cytokine production by activated macrophages, expression of MHC II and co-stimulatory molecules on macrophages and inhibits production of IFN-y by T-cells which shifts immune response from attack to repair functions
- INHIBITORY CYTOKINE (dampens immune response)
IL-12
- produced by activated macrophages and dendritic cells
- stimulates IFN-y and induces differentiation of Th cells to become Th1 cells
- enhances cytolytic functions of Tc and NK cells
TH1
- cell-mediated immunity and inflammation
- intracellular pathogens (viruses, bacteria)
- autoimmunity
- inflammation
IL-12 , IFN-y –> IL-2, IFN-y, TNF-a
TH2
- antibody-mediated immunity
- promotes humoral immunity (B)
- extracellular parasites
- asthma, allergy
IL-2, IL-4 –> IL-4, IL-5, IL-6, IL-10, IL-13
TH17
- extracellular bacteria (skin, lining of intestine)
- promotes innate immunity
- fungi
- autoimmunity
IL-6, TGF-B –> IL-17, IL-21, IL-22
Treg
- immune tolerance
- lymphocyte homeostasis
- regulation of immune responses
- control/ dampen immune response (inhibits adaptive response)
- maintain tolerance to self antigens
- prevent autoimmune disease
do this by: inhibitory cytokines, cytolysis, targeting dendritic cells, metabolism disruption
IL-12, TGF-B –> TGF-B, IL-35, IL-10
TH0
Naieve T-cell
TH1 response
cell-mediated, intracellular attack
cytokines lead to:
- macrophage activation (enhanced microbial killing)
- complement-binding and opsonizing antibodies
- neutrophil activation (enhanced microbial killing)
TH2 response
humoral focus
- production of neutralizing IgG antibodies
- production of IgE (mast cell degranulation)
- suppression of macrophage activation
- eosinophil activation
*TH1 and TH2 counter eachother
T-cell activation –> naieve effector –> memory cells
initiation (naieve) –> clonal expansion (effector cells) –> contraction –> maintenance (memory cells)
IL-1 and IL-6 and TNF-a are important in…
inflammation (pro-inflammatory?)
how do immune cells exit circulation?
selectin -
integrin -
help get immune cells to exit circulation into tissue
ICAMs -
IL-2
inflammation and proliferation
membrane TLRs
ex. LPS can’t get into cell (fragments of bacteria)
endosome TLRs (from endocytosis, virus was sucked up into the cell)
ex. more viral things
PRRs (DAMP/ PAMP expression)
- TLRs
- RLR (rig-like-receptor) - IFNa/B (look for viral RNA)
- NLR (NOD-like-receptor) - inflammatory, cytoplasm
- lectin like receptors - surface, recognize funguses
*expressed in various compartments where they will potentially encounter their ligands
etc..
sentinal cells
DCs, macrophages, NKs all over lots near surface
anti-viral response
type 1 interferons
is complement a primary response?
no, it’s later
APCs
macrophages, dendritic cells, B-cells
TLR1: TLR2
bacterial lipopeptides
TLR2
bacterial peptidoglycan
TLR4
LPS (gram-)
TLR5
bacterial flagellin
TLR2: TLR6
bacterial lipopeptides
extracellular TLRs
1,2,4,5,6
endosomal TLRs
3,7,8,9
TLR3
dsRNA
TLR7
ssRNA