Lecture 22 Flashcards
How do TH1 cells help macrophages fight intracellular pathogens?
- TH1 cells recognize pMHC class II on macrophages.
- TH1 cells use CD40L to bind to CD40 on macrophages.
- TH1 cells secrete IFNγ, which boosts macrophage antimicrobial activity.
- This also promotes production of TNFα by macrophages, further enhancing their ability to kill pathogens.
What are two strategies pathogens use to persist inside macrophages?
(1) Inhibit fusion of phagosome & lysosome (prevents exposure to lysosomal enzymes).
(2) Prevent acidification (lysosomal proteases require low pH to activate).
What receptor-ligand pair is involved when a TH1 cell activates a macrophage?
- CD40L on TH1 cell binds to CD40 on macrophage.
What cytokine does a TH1 cell secrete to activate macrophages? What does it do?
- IFNγ
- Boosts macrophage antimicrobial activity.
After TH1 activation, what cytokine do macrophages produce to enhance their response?
TNFα
What are M1 macrophages and how are they induced?
- Classically-activated macrophages.
- Induced in the context of TH1 responses.
- Boosted antimicrobial mechanisms.
What cytokine do M1 macrophages secrete to provide themselves with a survival signal?
- TNFα (acts via autocrine signaling to promote macrophage survival).
What does CD40L binding do for M1 macrophages?
- Activates macrophages.
- Increases expression of IL-12 (important for TH1 cell signal 3).
What cytokines work together to increase MHC I & II, CD40, B7, and IL-12 expression in M1 macrophages?
TNFα
IFNγ
How do M1 macrophages and TH1 cells create a feed-forward loop?
- M1 macrophages produce IL-12, which enhances TH1 differentiation/activation.
- TH1 cells produce IFNγ, which enhances M1 macrophage activation.
- This loop boosts both TH1 and M1 responses.
Besides TH1 cells, what other immune cells can activate M1 macrophages and how?
Effector CTLs (CD8+ T cells) can also secrete IFNγ, which activates M1 macrophages.
Under what circumstances do TH1 cells kill macrophages?
When macrophages are chronically infected and unable to clear the infection.
How do TH1 cells recognize infected macrophages?
TH1 cells recognize pMHC-II on the macrophage surface.
What ligand-receptor pair is used when TH1 cells trigger apoptosis of infected macrophages?
FasL on TH1 cell binds Fas on infected macrophage.
This triggers apoptosis.
What happens to bacteria released from an infected macrophage after it is killed by a TH1 cell?
The released bacteria are phagocytosed by freshly recruited macrophages.
What cytokine do TH1 cells secrete to help CD8+ T cells, and what does it do?
- IL-2
- Stimulates CD8+ T cell proliferation and differentiation into cytotoxic T lymphocytes (CTLs).
Where does TH1 help for CD8+ T cells happen?
In the secondary lymphoid organ (usually the lymph node).
How do CTLs recognize infected macrophages?
By binding to pMHC-I on the macrophage surface.
What do CTLs do to infected macrophages after recognizing pMHC-I?
Kill the infected macrophages.
How do TH1 cells stimulate increased differentiation of monocytes in the bone marrow?
- TH1 cells secrete IL-3 and GM-CSF, which act on precursors in the bone marrow.
- This is an endocrine effect (cytokines circulate through the blood to reach bone marrow).
What type of signaling is it when IL-3 and GM-CSF act on bone marrow precursors?
Endocrine signaling (cytokines travel through the blood to a distant site).
How do TH1 cells recruit more macrophages by changing adhesion molecule expression?
- TH1 cells secrete cytokines that alter the expression of adhesion molecules on endothelial cells.
- This facilitates the recruitment of more macrophages to the infection site.
How do TH1 cells recruit macrophages to the site of infection?
TH1 cells secrete CCL2, a chemokine, which attracts macrophages to the infection site via chemotaxis.
How does chronic M. tuberculosis infection lead to granuloma formation and what are the key features of the granuloma?
- M. tuberculosis infects macrophages in the lung, often resistant to their antimicrobial effects, leading to chronic infection.
- Granuloma formation occurs with:
(1) Core of infected macrophages.
(2) Surrounded by activated macrophages.
(3) Layer of TH1 cells on the outermost layer. - The center of the granuloma often becomes necrotic due to lack of oxygen and the cytotoxic effect of activated macrophages, leading to cell death.
