Adaptive Immunity: How does it Work?


Adaptive Immunity
In vertebrates, two separate but functionally interlinked immune systems known as the innate immune system and the adaptive or the acquired immune system provide protections against pathogens. Innate immune system, the first line of defense that provides general protections, consists of physical and chemical barriers as well as certain cell-intrinsic properties. Adaptive immunity, by contrast, is provided by two major types of white blood cells known as B lymphocytes and T lymphocytes. The immune response produced by B lymphocytes is known as the antibody mediated or humoral immune response. Pathogens or particles that initiate an immune response are known as antigen. T cells, on the other hand, produce immune response known as cell mediated immune response. Unlike innate immune system, adaptive immunity is specific to the pathogen that elicits the immune response. It also provides long-term protections.

Two subset of T cells known as helper T cells and cytotoxic T cells are involved in cell-mediated immune response. Cytotoxic T cells bind to and destroy host cells infected with pathogens, thus preventing the propagation of the pathogens. Helper T cells, as the name implies, helps in activating cytotoxic T cells, B cells as well as immune cells involved in innate immune response such as macrophage and dendritic cells. A basic difference between the B cells and T cells is that B cells can recognize and bind to native antigens, whereas, T cells recognizes only antigens that are modified and presented by specialized antigen presenting cells (APCs).

Dendritic cells present in tissues play crucial role as antigen presenter cells (APCs) in initiating adaptive immune response. They identify pathogens or their fragments by the presence of microbe specific molecular motifs known as pathogen associated molecular patterns (PAMPs) on their surface. Molecules on the surface of dendritic cells known as pattern recognition receptors recognize PAMPs and bind to them. Binding of the receptors and PAMPs activates dendritic cells.

Activated dendritic cells phagocytose pathogens or their fragments and break them down to small peptides, which bind to a class of protein known as major histocompatibility complex (MHC). Antigen-MHC complexes are then expressed on the cell surface and the dendritic cells migrate to nearby lymphoid tissues where the na've T cells reside. In the lymphoid tissues, na've cytotoxic and helper T cells bind to antigen-MHC complex through specialized receptors known as T cell receptors, which leads to activation of the bound T cells. Most of the T cells, upon activation by antigen-MHC complex, differentiate and proliferate as effector T cells, others forming the memory T cells. Effector cytotoxic T cells recognize and kill host cells that are infected with the cognate pathogen. Effector helper T cells, on the other hand, play important role in activation of B cells, macrophages and dendritic cells.

Activation of circulating B cells by cognate antigen may or may not require signaling from helper T cell depending on the nature of the antigen. B cells contain specialized protein molecules, known as B cell receptors (BCL), on their surface, which recognize and bind to specific antigens. However, in most cases binding of antigen to BCL is not enough to activate B cells. Additional signals induced by cytokines produced by helper T cells are also required for activation of B cells. This process of B cell activation is known as T cell dependent activation. However, some antigens containing multiple BCL binding domains can initiate both the signals and do not need help from T cells for activating B cells. This process is known as T cells independent activation of B cells.

Activated B cells produce antibodies, a class of soluble protein known as immunoglobulin. In mammals, there are four major types of antibodies known as IgA, IgG, IgE and IgM. IgA is predominantly found in mucosal linings and play crucial role in mucosal immunity. It is also found in secretory fluids such as saliva, tears, cololstrum. IgA is also present in secretion from genitourinary and gastrointestinal tract and respiratory epithelium. IgG is mostly present in circulation. It petrol the body and provides protection against bacteria, virus, fungus, and many other microorganisms. It is also present in colostrum. IgE is the least abandoned antibody in the circulation. It provides protection against parasites. IgM is the first antigen to appear following infection and provide the first line of humoral immune response. It is present in the circulation in low amount.

Memory T and B cells produced during an infection play crucial role in producing rapid and more intensive immune response during subsequent encounter with the same pathogen. Memory cells live for long time, even for years. During subsequent attack by the same pathogen, memory cells rapidly propagate to produce a large number of effector cells, thus decreasing the response time and increasing the intensity of the response.

Written by Musharraf Ashraf (Ph.D. (Health Chemistry). Medical & life science)

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Edited by: Rajesh Bihani ( Find me on Google+ )

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