Lecture 21 Flashcards
Main action of Type 1 IFN (alpha/beta)
Inhibit or slow viral replication
Anti-viral cytokine
Signal that permits killing by Natural killer cells
Absence of MHC Class 1
What do CTLs secrete
Type II IFN–>IFN gamma
Function of IFN gamma
1) Increase MHC class 1 expression (in neighbouring cells)
2) Activates macrophages and stimulates the production of chemokines (that then can recruit additional macrophages and CD8+ T cells to sites of infection)
Difference between Type 1 and Type 2 IFN
Type 1 IFN–>potent antiviral effects, effects of PRR activation
Type 2 IFN–>role in immune response against intracellular pathogens
What do TH1 T cells respond to
Infections by viruses and intracellular pathogens
What do TH2 T cells respond to
Parasites (Helminths), other extracellular pathogens, and also allergy
What do TH17 T cells respond to
Infections by extracellular bacteria and fungi, also in autoimmunity
What are TFH responses involved in
Activating B cells in the lymph node
TH1 associated cytokines
IFN gamma
CD40 ligand
TH2 associated cytokines
IL-4, IL-5, IL-13
CD40 ligand
TH17 associated cytokines
IL-17, IL-22
CD40 ligand
Treg associated cytokines
IL-10
TGF-beta
3 Types of cross-regulation
1) IL-4 secreted by TH2–>inhibits TH1 differentiation
2) IFN-gamma secreted by TH1–>inhibits TH2 differentiation
3) IL-4 secreted by TH2, OR IFN-gamma secreted by TH1–>inhibit TH17 differentiation
Which master transcriptional regulator suppress TH2 pathway
T-Bet
Which master transcriptional regulator suppresses TH1pathway
GATA3
Cytokine used for BOTH TH17 and Treg differentiation pathways
TGF-beta
Cytokine that induces TH17 pathway INSTEAD of Treg
IL-6 (Decision point, acts as a switch)
Which polarizing cytokines impact differentiation of T cells Signal 3
IL-4, IL-6, IL-12, IL-23
IFN-gamma
TGF-beta
Which effector cytokines are produced by differentiated T cells
IL-4, IL-5, IL-13, IL-17, IL-21, IL-22
IFN-gamma
Which cells leave lymph node and migrate to site of infection
TH1, TH2, and TH17 cells
Which cells stay in lymph node and activate B cells
TFH cells
TH1 associated polarizing cytokines (Signal 3)
IFN-gamma and IL-12
TH1 associated effector cytokine
IFN-gamma
TH1 associated master transcriptional regulator
T-Bet (transcription factor)
How does TH1 activate cellular immunity
1) Macrophage activation
2) Activation and differentiation of naive cytotoxic T lymphocytes precursors into effector CTL (through CD40L binding)
What do TH1 cell respond to
Intracellular pathogens (intracellular bacteria)
- ex. M. tuberculosis and Salmonella
Intracellular parasites
- ex. Leishmania and Toxoplasma
Viruses
Transcription factors associated to TH1 cells
T-Bet (master transcriptional regulator), STAT 1, and STAT 4
TH1 functions
1) Secrete IFN-gamma at point of interaction
2) Targets macrophages (TH1 cell TCR recognizes pMHC-II on surface of macrophage)
3) To aid in killing of microbes that persist in macrophage vesicles
