Lecture 24 Flashcards
What is negative regulation in the immune system?
Negative regulation controls the immune response using receptors, mechanisms, and specific cell types (like Tregs) to prevent excessive or prolonged activation.
Which cell type is important in negative regulation of the immune system?
Treg (regulatory T) cells.
How long does the immune response typically last before contracting?
10–14 days.
What happens to most lymphocytes after the antigen (Ag) is removed?
Most lymphocytes are no longer needed and undergo apoptosis (programmed cell death).
How do Treg cells help regulate immune responses after the antigen is removed?
Treg cells release inhibitory cytokines to suppress immune responses.
What happens to most newly generated B and T cells at the end of the primary immune response?
They are lost through apoptosis.
Why are most effector cells no longer needed after the antigen (Ag) is cleared?
The immune response is no longer needed once the threat is removed.
How do most effector cells die after the antigen is cleared?
By apoptosis (programmed cell death).
How does the intrinsic pathway of apoptosis work?
- Called “death by neglect”
- IL2Rα and other cytokine receptors have transient expression
- Lack of signaling through these receptors → absence of survival signal → apoptosis
How does the extrinsic pathway of apoptosis work?
- Triggered by Fas-FasL interaction
- Involves cytotoxic T lymphocytes (CTLs)
- Leads to apoptosis
What happens to most effector T cells after the immune response ends?
At least 90% die, leaving behind antigen-specific memory T cells.
How do memory T cells respond to a subsequent exposure to the same antigen?
They respond with heightened reactivity, leading to a faster and more robust secondary response.
What is the function of CTLA-4 in T cell regulation?
CTLA-4 downregulates T cell activation, proliferation, and survival by binding to B7.1/B7.2 with higher affinity than CD28, shutting down signaling pathways and preventing excessive immune responses.
When is CTLA-4 induced and when does it peak after T cell activation?
CTLA-4 is induced within 24 hours after activation and peaks 2–3 days post-stimulation.
How does CTLA-4 compete with CD28 for B7 binding?
CTLA-4 binds to B7.1/B7.2 with higher affinity than CD28, sequestering B7 and preventing CD28 from binding.
Where is CTLA-4 found before and after activation?
CTLA-4 is found intracellularly and is expressed on the cell membrane after phosphorylation.
How many B7 molecules can one CTLA-4 molecule bind?
One CTLA-4 molecule can bind two B7 molecules.
How can CTLA-4 strip B7 molecules from antigen-presenting cells (APCs)?
In some cases, CTLA-4 can physically remove B7 molecules from APC surfaces, further reducing CD28 stimulation.
What is the difference between CTLA-4 and CD28 expression in naïve vs. activated T cells?
- CD28 is expressed by naïve T cells.
- CTLA-4 is only expressed on the surface after activation of naïve T cells (after receiving signals 1 and 2).
How does CTLA-4 affect T cell sensitivity and IL-2 production?
CTLA-4 makes activated T cells less sensitive to stimulation by APCs and reduces IL-2 production.
What is the overall effect of CTLA-4 on the immune system?
CTLA-4 prevents overgrowth of lymphocytes and limits excessive immune responses.
When is PD-1 expressed on T cells?
PD-1 is expressed on activated T cells.
What are the ligands for PD-1 and where are they found?
PDL-1 → Expressed by many cells
PDL-2 → Expressed on APCs during inflammation
What is the function of PD-1 signaling in T cells?
PD-1 signaling downregulates T cell activation, proliferation, and function.
