Lecture 20 - T cells Flashcards
How does the immune system respond to a viral infection?
(1) Type I IFNs (α/β): Key antiviral cytokines that inhibit or slow viral replication.
(2) Natural Killer (NK) Cells: Recognize and kill infected or tumor cells that lack MHC class I.
(3) Virus-Specific Cytotoxic T Lymphocytes (CTLs): Directly kill infected cells.
How do CTLs exert their effects via cytokines?
(1) CTLs secrete IFNγ (Type II IFN).
(2) IFNγ effects:
- Increases MHC class I expression in neighboring cells.
- Activates macrophages and stimulates chemokine production, recruiting macrophages and
- CD8+ T cells to infection sites.
What is the difference between Type I and Type II IFNs?
(1) Type I IFN (α/β): Potent antiviral effects, induced by PRR activation.
(2) Type II IFN (IFNγ): Supports the immune response against intracellular pathogens, secreted by T cells.
How do CD8+ T cells get activated?
CD8+ T cells often require CD4+ T cell help for activation.
How do effector CTLs kill infected cells?
- Direct killing via pMHC:TCR interaction → apoptosis
–> Fas-FasL pathway
–> Granules: Perforin & Granzyme B
What cytokine do CTLs produce, and what is its function?
- CTLs produce IFNγ (Type II IFN).
- Functions:
- Increases MHC class I expression.
- Activates macrophages.
- Recruits CD8+ T cells to infection sites.
How are effector CD4+ T cells influenced by cytokines?
Different STAT proteins are activated within each cell in response to cytokines.
Where do polarizing cytokines come from, and what is their role?
1) Source: Secreted by dendritic cells and neighboring innate/adaptive immune cells.
2) Function: Provide Signal 3, guiding CD4+ T cell differentiation.
What infections do different effector CD4+ T cell subsets respond to?
(1) TH1: Viruses & intracellular pathogens.
(2) TH2: Parasites & extracellular pathogens (also allergy).
(3) TH17: Extracellular bacteria & fungi (also autoimmunity).
Helminths & extracellular
pathogens
(4) TFH: Activates B cells in lymph nodes.
How does the type of infection influence the T cell response?
The cell-mediated response is dominated by one T cell subset based on the type of infection.
What do CD8+ and CD4+ T cells recognize?
(1) CD8+ T cells: Peptide + MHC Class I
(2) CD4+ T cells: Peptide + MHC Class II
What are key effector molecules of Cytotoxic T cells (CTLs)?
Perforin
Granzyme B
Fas ligand
IFNγ (Type II IFN)
What are key cytokines of TH1 cells?
IFNγ
CD40 ligand
Fas ligand
What are key cytokines of TH2 cells?
IL-4
IL-5
IL-13
What are key cytokines of TH17 cells?
IL-17
IL-22
CD40 ligand
What are key cytokines of Treg cells?
IL-10
TGF-β
How does cross-regulation affect T cell responses?
The immune response includes multiple T cell subsets, but one dominates.
How do TH1 and TH2 cells regulate each other?
(1) IL-4 (from TH2) inhibits TH1 differentiation.
(2) IFN-γ (from TH1) inhibits TH2 proliferation.
How do IL-4 and IFN-γ affect TH17 differentiation?
IL-4 or IFN-γ inhibit TH17 differentiation.
How do effector cytokines reinforce T cell subsets?
Each T cell subset secretes cytokines that help maintain its own dominance.
How do transcription factors regulate TH1/TH2 differentiation?
(1) T-Bet → Suppresses TH2 pathway gene expression.
(2) GATA3 → Suppresses TH1 pathway gene expression.
What key cytokine is required for both TH17 and Treg differentiation?
TGF-β
What cytokine acts as a “switch” for TH17 differentiation?
IL-6
How does the balance between TH17 and Treg affect immune responses?
(1) Normal state → More iTreg to suppress inflammation.
(2) Infection (IL-6 production) → More TH17 for antibacterial response.
What is Signal 3 in T cell differentiation?
Polarizing cytokines guide T cell differentiation.
What do differentiated T cells produce?
Effector cytokines that help fight infection.
Where do effector T cells go after differentiation?
- Most leave the lymph node and migrate to the infection site.
- TFH cells stay in the lymph node to activate B cells.
How do cell surface molecules differ between naïve and effector T cells?
Effector T cells express different cell surface molecules to target specific tissues depending on the site of infection.
How is the migration of effector T cells determined?
- Effector T cell migration is influenced by which lymph node they are activated in.
- For example, if activated in a skin-draining lymph node, they up-regulate homing molecules to target the skin.
What are the polarizing cytokines (Signal 3) for TH1 differentiation?
IFN-γ and IL-12
What is the effector cytokine secreted by TH1 cells?
IFN-γ
What is the master transcriptional regulator for TH1 cells?
T-bet
How does TH1 help in immune responses?
(1) Activate cellular immunity:
- Macrophage activation
- Activation and differentiation of naïve cytotoxic T lymphocytes (CTL) into effector CTLs (via CD40L binding)
What type of pathogens does TH1 primarily respond to?
Intracellular pathogens:
Bacteria (e.g., M. tuberculosis, Salmonella)
Parasites (e.g., Leishmania, Toxoplasma)
Viruses
What is the transcription factor activation pathway for TH1?
- STAT1 and STAT4 proteins are activated.
- T-bet gene activation leads to differentiation.
How do TH1 cells interact with macrophages?
- TH1 cell TCR recognizes pMHC-II on macrophage surface.
- TH1 secretes IFN-γ to help kill microorganisms that persist in macrophage vesicles.
