AssessmentsCell-mediated immunity of natural killer and CD8 cells
Cell-mediated immunity of natural killer and CD8 cells
USMLE® Step 1 style questions USMLE
A group of researchers are studying cells involved in both innate and adaptive immune responses. They identify a specific cell of the innate immune system that uses perforin and granzymes to induce apoptosis of virally infected cells and tumor cells. Which of the following cell types is most likely mediating the response described above?
Content Reviewers:Rishi Desai, MD, MPH
And there are two types of T cells.
Helper T cells primarily support other immune cells, whereas cytotoxic T cells kill cells that are infected with a pathogen or are cancerous.
That makes sense since both natural killer and cytotoxic T cells need to interact directly with a target cell in order to destroy it.
Now, when a T cell is initially formed it’s considered naive.
This process of priming requires two signals.
Cytotoxic T cells respond to intracellular antigens - like viruses, intracellular bacteria, and tumor antigens.
The naive cytotoxic T cell needs a high level of stimulation to become activated and it relies on a process called cross-presentation to reach that level.
These antigens typically come from extracellular pathogens or from tumor cells or virally infected cells.
The first signal is that the antigen has to bind perfectly to the T cell receptor or TCR.
This region, which includes the T cell receptor which binds to the MHC-Antigen, and CD8 and CD28 which bind with B7, is called the immune synapse.
Once the T cell receives both of these signals, a number of changes occur within the cell that transforms the naive T cell into a cytotoxic T cell.
The IL-2 receptor has three protein components - alpha, beta, and gamma.
A naive T cell only expresses the beta and gamma components of the IL-2 receptor, but these have low affinity for IL-2, in contrast to the alpha component of the IL-2 receptor which has a high affinity for IL-2.
Using just the beta and gamma components is like trying to eat an apple with only your lips and tongue.
And upregulating the alpha component is like using your teeth to take a big bite out of the juicy apple - much more effective and satisfying!
As a result active T cells make more IL-2 and then bind to the IL-2 that they make with their IL-2 receptors - a form of autocrine stimulation - a cell stimulating itself.
In response to the IL-2, the activated T cell starts to rapidly undergo cell division - a process called clonal expansion.
The cytotoxic T cell is now a lean, mean, killing machine that’s ready to attack.
This activated cytotoxic T cell only needs to see its antigen in the context of MHC I in order to kill the cell.
In other words, it no longer needs that costimulatory signal from CD28.
And the way that cytotoxic T cells find potential targets is by going cell-to-cell binding non-specifically.
They use adhesion molecules like LFA-1 on their surface to bind to molecules like ICAM which is found on the surface of most cells.
After loosely binding in this way, it tries to bind to that cell’s MHC I molecule.
If the cytotoxic T cell cannot bind because the correct antigen isn’t present, then the cytotoxic T cell disengages and moves on to the next cell.
Natural killer cells are innate lymphocytes that play a critical role in the early response to viral infection and cancer. They detect virus-infected cells and eliminate them before they can spread the infection. CD8 cells are cytotoxic T lymphocytes that recognize and kill infected or mutated cells. CD8 cells also secrete cytokines that stimulate the immune response. Both natural killer cells and CD8 cells are essential in protecting against cancer and infections.