Cell-mediated immunity of CD4 cells

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Cell-mediated immunity of CD4 cells

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A 47-year-old man presents to a rural clinic for evaluation of fevers and abdominal pain, which have been ongoing for the past month. Laboratory testing demonstrates an elevated eosinophil count and elevated IgE level. ELISA testing confirms the presence of Toxocara cana antigens. Which of the following is released by the type of T-cell involved in mediating these laboratory changes and helping the body fight this infection?  

External References

First Aid

2024

2023

2022

2021

CD4+ T cells (HIV) p. 173

Helper T cells

cell surface proteins p. 108

cytokine secretion p. 106

in granulomatous diseases p. NaN

T cells p. 409

helper p. 98

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The key cells of the adaptive immune response are the lymphocytes - the B and T cells. And there are two types of T cells. T helper cells which express CD4 on their surface, and cytotoxic T cells which express CD8 on their surface. 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.

Now, within the broad category of T helper cells there are subcategories like T helper type 1, or Th1, T helper type 2, or Th2, T helper type 17, or Th17, and T follicular helper cells or Tfh. 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 activated T helper cell also begins making lots of cytokine IL-2, and upregulates its IL-2 alpha receptor. 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.

A Th1 cell then secretes interferon-gamma, which reinforces the process. Interferon-gamma also boosts the macrophages ability to kill ingested pathogens by increasing their production of reactive oxygen species, nitric oxide, and lysosomal proteases. Th1 cells also express CD40 ligand on their cell surface, and that binds to the CD40 receptor on macrophages, which also stimulates them.

Th1 cells also produce IL-2 which makes natural killer cells, CD8+ T cells, and B cells proliferate. So in short, Th1 cells stimulate themselves and they stimulate a number of other immune cells as well. When Th1 responses are not carefully controlled, this can sometimes lead to autoimmune reactions.

Next up are the Th2 cells. When there’s a parasitic worm that’s too large to get phagocytosed, it gets destroyed by eosinophils, basophils, and mast cells which dump their toxic granules full of proteases and hydrolases. This kills the parasite, and its antigens get picked up by scavenging macrophages and dendritic cells. These antigen presenting cells produce IL-4, IL-5, and IL-10 within the immune synapse with a T cell. When these cytokines are released within an immune synapse they bind to the T cell and cause it to make transcription factors like Stat 6 and Gata-3. These transcription factors cause a number of genes to get expressed within the T cell, transforming it into a Th2 cell. Once it has become a Th2 cell it produces cytokines like IL-4, IL-5, IL-10, and IL-13, which stimulate B cells to make IgE which can coat the worms. In addition, Th2 cells stimulate mast cells and basophils to bind the Fc region of IgE and degranulate, so that they can kill the parasite.

Summary

CD4 cells are white blood cells that play a vital role in the body's cell-mediated immunity. Cell-mediated immunity is the part of the immune system which relies on phagocytes, cytotoxic T-lymphocytes, and the release of various cytokines to fight off an infection. CD4 cells recognize and destroy infected cells by binding to special proteins on the surface of the infected cells called antigens. Once attached, the CD4 cells release molecules called cytokines which activate other immune cells to destroy the infected cell.