Antigen presenting cells (APCs) are important cells in the activation of T cells. That means that the cell-mediated branch of the adaptive immunity cannot be activated without APCs. The APCs are specialized immune cells that present antigens to T-cells.
These cells are involved in the activation of both innate and adaptive immunity. The link the two branches of the immune system. Therefore, APCs play a role in the regulation of the immune system by activating T-cells.
In this article, we shall discuss the different types of APCs, and how they process and present antigens to T cells. We shall also discuss how the T lymphocytes respond to the signals by APCs eventually becoming activated.
Types of Antigen Presenting Cells
Nearly all nucleated cells in your body can present antigens and hence serve as APCs. This is particularly the case with all virally infected cells and cancer cells. They can process and present antigen to CD8+ cytotoxic T lymphocytes.
To underscore the importance of APCs here, I need to mention that scientists have made artificial APCs that activate this type of T cells in the treatment of cancer.
Apart from this type of APCs, there are three types of professional APCs in our bodies that present antigens to the CD4+ T helper cells for recognition and subsequent amplification of the immune response.
The three include macrophages, dendritic cells, and the B cells. The first two are descendants of monocytes. The B cells emanate from the common lymphoid progenitor become plasma cells which produce antibodies.
The three types of APCs are termed professional because they can cross-present antigens through MHC class 1 pathway. Thats means they can present antigens in the context of both MHC class I and class II.
Exogenous antigens are presented to CD4+ T cells using the MHC class II pathway while the endogenous antigens are presented to the CD8+ cytotoxic T cells using MHC class I pathway.
Let’s now provide a little bit of details about the three types of APCs here:
Dendritic cells
Dendritic cells (DCs) as already mentioned develop from monocytes. That is to say that DCs are descendants of the common myeloid progenitor cells. The DCs are responsible for initiating immune responses by processing antigens and presenting them to T-cells.
When it comes to antigen presentation, DCs are the most efficient in cross-presentation. They can prime both the CD8+ cytotoxic T cells and the CD4+ T helper cells. They are professional APCs.
DCs have two major subtypes: myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC). The mDCs are found throughout the body and are specialized at capturing antigens and transporting them to lymph nodes where they present them to T-cells.
On the other, pDCs reside primarily in the spleen and bone marrow. The dendric cells phagocytose antigens, process them before they can present them to T cells through MHC molecules.
Macrophages
Macrophages are phagocytic cells that engulf foreign particles and pathogens. They are derived from monocytes and are classified based on their morphology and function.
There are three main types of macrophages: M0, M1, and M2. M0 macrophages are non-activated and do not express any specific markers.
M1 macrophages are activated by interferon gamma (IFNγ), lipopolysaccharide (LPS), and tumor necrosis factor alpha (TNFα).
M1 macrophages produce proinflammatory cytokines that include IL-12, IL-23, and TNFα. As for the M2 macrophages, they are activated via Th2 cytokines including IL4 and IL13.
M2 macrophage activation results in the production of anti-inflammatory cytokines such as TGFβ and IL10.
These cytokines are important in slowing down inflammation and hence avert the inflammatory response-related cellular damage in your body.
B Cells
B cells are white blood cells that are responsible for producing antibodies that fight off foreign invaders. However, they too process and present antigens to T cells.
However, different from other APCs the B cells use receptor-mediated endocytosis to capture the antigen, process and present them to T cells. There are two types of B cells, namely B lymphocytes and plasma cells.
B lymphocytes are the primary producers of antibodies. They are responsible in fighting off bacteria and viruses. Plasma cells are the final stage of B cell development and are the only ones involved in antibody production.
Therefore, plasma cells are responsible for secreting antibodies into your blood bloodstream. Those antibodies are of course then involved in several types of effector mechanisms resulting in the elimination of antigens.
The antibodies also known as immunoglobulins are of five classes including IgA, IgD, IgE, IgG and IgM. They have different properties with some like IgD and IgM bound on the B cell membrane while the rest are soluble free serum proteins in your blood circulation.
Antigen Processing
The antigen presenting cells engulf antigens, then catalytically process them into short peptides ready for presentation to the T cells.
The T cells cannot directly recognize and bind to antigens like other immune cells would do. The APCs possess major histocompatibility complex (MHC) molecules on their surface which they use to present antigens to the T cells.
The major histocompatibility complex (MHC) is a group of genes located on chromosome 6. MHC genes encode proteins that help the immune system distinguish between self and non-self.
This is certainly important to ensure that your immune system doesn’t fight your own cells which would result in autoimmunity. There are two types of MHC molecules involved in antigen presentation to T cells. These are MHC class I and MHC class II molecules.
MHC class II molecules are proteins on the surface of certain types of cells (e.g., Dendritic cells and macrophages) that present peptides to the CD4+ helper T-cells.
Peptides are short chains of amino acids that are produced inside your APCs during an infection. Helper T-cells recognize peptide fragments bound to MHC class II molecules on the surface of antigen presenting cells.
On the other hand, a CD8+ T-cell recognizes antigens presented by the MHC class I molecules. As stated earlier there are many cells in your body that express MHC class I molecules but the most notable ones are the virally infected cells and the cancerous cells.
T cell Activation by APCs
T cells activation occurs when APCs present antigens them. The process of activation of the T cells by the APCs is a two-signal process. These two signals must be delivered to ensure complete activation and functionality of the T cells.
In the case where signal 2 has not been fully delivered, the T cells instead of being activated become anergic or die by apoptosis. Anergy is a state of unresponsiveness and that means that such T cells would not help in clearing the antigen that triggered its activation in the first place.
Signal 1
This signal involves the interaction between the T cell receptor (TCR) on the T cells and MHC molecules on the surface of the APCs. During this process your T cells are said to have recognized the antigen.
That means we can simply call signal 1, the recognition stage of the T cell activation process. This stage is critical because without it then specific clones of T cells with specific TCRs for the antigen would not be selected.
Signal 2
This signal involves co-stimulation where CD28 markers on the surface of the T cells interact with the B-7 molecules on the APCs to amplify the activation of T cells. The B7 molecules on APCs include B7-1 (CD80) and B7-2 (CD86).
The absence of this signal leads to the ‘abortion’ of the T cell activation process. The cells being activated will go into a state of unresponsiveness called anergy. Anergy can also be result of upregulation of CTLA-4 (CD152) instead of CD28 for co-stimulation.
There could also be involvement of CD40L (CD154) on Th2 instead of CD28 in signal 2. CD40L interacts with its counter receptor on the B cells when the B cells serve as antigen presenting cells.
The presence of the CD40L-CD40 interactions leads to the ability of B cells to class switch in antibody production. The absence of this signal causes the lack of this important T cell-dependent effector mechanisms on the part of B cells.
Conclusion
Antigen presenting cells are very important cells of the immune system. The T cells which are the most important cells of the adaptive immune system cannot recognize antigens unless presented by the APCs. The APCs possess either MHC class I or II through which they interact with the TCRs on the surface of T cells.
A second signal where the B-7 molecules on the APCs interact with CD28 on the T cells help complete the activation of T cells. Without signal 2, the T cells become anergic and hence not helpful in eliminating the microorganisms or other antigens.
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Thanks a lot, Mary and always welcome to learn more…
Helful one
very helpful indeed, salute sir