AssessmentsCell-mediated immunity of CD4 cells
Content Reviewers:Rishi Desai, MD, MPH
The key cells of the adaptive immune response are the lymphocytes - the B and T cells.
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.
Cell mediated immunity refers to the part of the immune response that’s based on cellular interactions, and cannot be transferred through serum from one person to another.
That makes sense since CD4 helper T cells interact with other immune cells to stimulate them.
Now, when a T cell is initially formed it’s considered naive.
This naive T cell is a bit like a student in school that isn’t ready to choose a career path.
Later when that T cell encounters an antigen - it gets activated or primed - and turns into an effector T cell.
This process of priming requires two signals.
The first signal is the antigen itself, which is usually presented on an MHC molecule on the surface of an antigen presenting cell like a macrophage or dendritic cell.
This antigen has to bind perfectly to the T cell receptor.
The second signal is called costimulation - and it’s when a ligand called CD28 on the surface of a T cell binds to a ligand called B7 on the antigen presenting cell.
This region, which includes the T cell receptor which binds to the MHC-Antigen, and CD4 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 an activated T cell.
An activated T cell is one that’s ready to become an effector T cell and the developmental path it chooses often depends on the cytokines in the environment.
Going back to the student analogy, an activated student is one that’s gotten the signals it needs to graduate from college and is finally prepared to choose a career path.
There’s also a class of T cells called T regulatory cells, or T regs, but these aren’t considered T helper cells because they are mostly involved in contraction of the immune response.
Within the immune synapse, antigen presenting cells, or APCs, send out different combinations of cytokines, depending on the type of pathogen.
These cytokines help tailor the immune response to the specific pathogen.
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 bind to IL-2 that they make - 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.
Now let’s go through the types of T helper cells - the career paths - one at a time.
Macrophages and dendritic cells infected with viruses and intracellular bacteria produce IL-12, and natural killer cells produce interferon-gamma.
In addition, any virally infected cell will produce interferon-alpha, and interferon-beta.
When these cytokines are found in the same area as a T cell that’s becoming activated they bind to the T cell and cause it to make transcription factors like Stat1, Stat4, and T-bet.
These transcription factors cause a number of genes to get expressed within the T cell, transforming it into a Th1 cell.