4. Adaptive Immunity

Cells of the adaptive immune system

Unlike the innate immune system, the adaptive immune system relies on fewer types of cells to carry out its tasks: B cells and T cells.Both B cells and T cells are lymphocytes that are derived from specific types of stem cells, called multipotent hematopoietic stem cells, in the bone marrow. After they are made in the bone marrow, they need to mature and become activated. Each type of cell follows different paths to their final, mature forms.

B cells

After formation and maturation in the bone marrow (hence the name “B cell”), the naive B cells move into the lymphatic system to circulate throughout the body. In the lymphatic system, naive B cells encounter an antigen, which starts the maturation process for the B cell. B cells each have one of millions of distinctive surface antigen-specific receptors that are inherent to the organism’s DNA. For example, naive B cells express antibodies on their cell surface, which can also be called membrane-bound antibodies.

B cell and membrane-bound antibodies

B cell and membrane-bound antibodiesWhen a naive B cell encounters an antigen that fits or matches its membrane-bound antibody, it quickly divides in order to become either a memory B cell or an effector B cell, which is also called a plasma cell. Antibodies can bind to antigens directly.

Antigen binding to B cell antigen binding site

Antigen binding to B cell antigen binding siteThe antigen must effectively bind with a naive B cell’s membrane-bound antibody in order to set off differentiation, or the process of becoming one of the new forms of a B cell.

B cell differentiation process resulting in plasma cell and memory B cell

B cell differentiation process resulting in plasma cell and memory B cellMemory B cells express the same membrane-bound antibody as the original naive B cell, or the “parent B cell”. Plasma B cells produce the same antibody as the parent B cell, but they aren’t membrane bound. Instead, plasma B cells can secrete antibodies. Secreted antibodies work to identify free pathogens that are circulating throughout the body. When the naive B cell divides and differentiates, both plasma cells and memory B cells are made.B cells also express a specialized receptor, called the B cell receptor (BCR). B cell receptors assist with antigen binding, as well as internalization and processing of the antigen. B cell receptors also play an important role in signaling pathways. After the antigen is internalized and processed, the B cell can initiate signaling pathways, such as cytokine release, 7 to communicate with other cells of the immune system. For more information on cell signalling, check out this article on cell-to-cell communication.

T cells

Once formed in the bone marrow, T progenitor cells migrate to the thymus (hence the name “T cell”) to mature and become T cells. While in the thymus, the developing T cells start to express T cell receptors (TCRs) and other receptors called CD4 and CD8 receptors. All T cells express T cell receptors, and either CD4 or CD8, not both. So, some T cells will express CD4, and others will express CD8.Unlike antibodies, which can bind to antigens directly, T cell receptors can only recognize antigens that are bound to certain receptor molecules, called Major Histocompatibility Complex class 1 (MHCI) and class 2 (MHCII). These MHC molecules are membrane-bound surface receptors on antigen-presenting cells, like dendritic cells and macrophages. CD4 and CD8 play a role in T cell recognition and activation by binding to either MHCI or MHCII.

Macrophage binding to T cell

Macrophage binding to T cellT cell receptors have to undergo a process called rearrangement, causing the nearly limitless recombination of a gene that expresses T cell receptors. The process of rearrangement allows for a lot of binding diversity. This diversity could potentially lead to accidental attacks against self cells and molecules because some rearrangement configurations can accidentally mimic a person’s self molecules and proteins. Mature T cells should recognize only foreign antigens combined with self-MHC molecules in order to mount an appropriate immune response.

T cell positive selection and negative selection

T cell positive selection and negative selectionIn order to make sure T cells will perform properly once they have matured and have been released from the thymus, they undergo two selection processes:

  1. Positive selection ensures MHC restriction by testing the ability of MHCI and MHCII to distinguish between self and nonself proteins. In order to pass the positive selection process, cells must be capable of binding only self-MHC molecules. If these cells bind nonself molecules instead of self-MHC molecules, they fail the positive selection process and are eliminated by apoptosis.
  2. Negative selection tests for self tolerance. Negative selection tests the binding capabilities of CD4 and CD8 specifically. The ideal example of self tolerance is when a T cell will only bind to self-MHC molecules presenting a foreign antigen. If a T cell binds, via CD4 or CD8, a self-MHC molecule that isn’t presenting an antigen, or a self-MHC molecule that presenting a self-antigen, it will fail negative selection and be eliminated by apoptosis.

These two selection processes are put into place to protect your own cells and tissues against your own immune response. Without these selection processes, autoimmune diseases would be much more common.

T cell positive selection and negative selection process

T cell positive selection and negative selection processAfter positive and negative selection, we are left with three types of mature T cells: Helper T cells (T\text{}_{H}H​start text, end text, start subscript, H, end subscript cells)Cytotoxic T cells (T\text{}_{C}C​start text, end text, start subscript, C, end subscript cells), and T regulatory cells (T\text{}_{reg}reg​start text, end text, start subscript, r, e, g, end subscript cells).

  • Helper T cells express CD4, and help with the activation of T\text{}_{C}C​start text, end text, start subscript, C, end subscript cells, B cells, and other immune cells.
  • Cytotoxic T cells express CD8, and are responsible for removing pathogens and infected host cells.
  • T regulatory cells express CD4 and another receptor, called CD25. T regulatory cells help distinguish between self and nonself molecules, and by doing so, reduce the risk of autoimmune diseases.
Helper T cell, Cytotoxic T cell, T regulatory cell diagrams

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