T independent antigen (TI)

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T independent antigen elicits antibody production by B lymphocytes without T lymphocyte involvement. There are 2 distinct subgroups of TI antigens, different in mechanism of activating B lymphocytes. TI-1 antigen, which has an activity that can directly activate B cells and TI-2 antigen, which has highly repetitive structure and causes simultaneous cross-linking of specific B cell receptors (BCR) on B lymphocyte. The most commonly released isotype of antibodies in this type of immune reaction is low affinity IgM. [1]

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Antibody production independent of T lymphocytes

For most protein antigens, the production of antibodies by B lymphocytes is dependent on stimulation of helper T cells. However bacterial polysaccharides and lipopolysaccharides, and some polymeric proteins, can stimulate B lymphocytes without involvement of helper T cells. The non-protein microbial antigens cannot stimulate classical T cell response by themselves, but they are able to elicit the production of antibodies, so that is why we call them T cell or thymus independent antigens. [2]

T independent antigens are divided into 2 classes by the mechanism of activating B cells.

T-Independent-1 antigen

TI-1 antigens have an intrinsic B cell activating activity, that can directly cause proliferation and differentiation of B lymphocytes without T cell stimulation and independently of their BCR specificity. TI-1 antigens activate B-cells via Toll like receptors, which are expressed in humans on the surface of B lymphocytes after BCR stimulation. TI-1 antigens are classified as B-cell mitogens, because they induce numerous cell divisions. In higher concentrations, TI-1 antigens bind to BCR and TLR of various clones of B lymphocytes, which leads to production of multiclonal antibodies. But when the concentration of TI-1 is lower, it can activate only B lymphocytes with specific binding of TI-1 on their BCR, and leads to production of monoclonal antibodies. [1] This part of immune response may be important in some early stages of infection by extracellular pathogens, because it is rapidly activated and does not require T cell help or clonal maturation and expansion. An example of TI-1 antigen is lipopolysaccharide (LPS) or bacterial DNA. [2]

T-Independent-2 antigen

Second group of TI antigens consists mainly of highly repetitive surface structures (epitopes) of encapsulated bacteria. They do not have an intrinsic B-cell activating activity. The activation of B lymphocytes is caused by cross-linking of a critical number of B cell receptors, which leads to accumulation of BCRs and cross activation of these receptors. It results in proliferation and differentiation of B lymphocytes and production of antibodies. TI-2 antigens can activate only mature B lymphocytes. Immature B cells are anergized, so they do not elicit any immune response. That may explain why children up to 5 years are not capable of producing effective antibodies against polysaccharide antigens, as the majority of their B cell population is immature. [2] Even though the response on TI antigens is not dependent on T lymphocytes, there are some cytokines, produced mainly by T lymphocytes and natural killer (NK) cells, necessary for eliciting reaction against these antigens. The most necessary are interleukin 2 (IL-2), interleukin 3 (IL-3) and interferon γ (IFN-γ). [1] Moreover, additional stimulation by dendritic cells (DC) and macrophages is required. [2]

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<span class="mw-page-title-main">DNA vaccine</span> Vaccine containing DNA

A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.

<span class="mw-page-title-main">B cell</span> Type of white blood cell

B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasma membrane where they serve as a part of B-cell receptors. When a naïve or memory B cell is activated by an antigen, it proliferates and differentiates into an antibody-secreting effector cell, known as a plasmablast or plasma cell. Additionally, B cells present antigens and secrete cytokines. In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, which is why the 'B' stands for bursa and not bone marrow as commonly believed.

<span class="mw-page-title-main">Cytotoxic T cell</span> T cell that kills infected, damaged or cancerous cells

A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.

<span class="mw-page-title-main">T helper cell</span> Type of immune cell

The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.

<span class="mw-page-title-main">Immunosuppressive drug</span> Drug that inhibits activity of immune system

Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.

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<span class="mw-page-title-main">Superantigen</span> Antigen which strongly activates the immune system

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<span class="mw-page-title-main">Memory B cell</span>

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<span class="mw-page-title-main">Adaptive immune system</span> Subsystem of the immune system

The adaptive immune system, also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates.

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<span class="mw-page-title-main">Interleukin 12</span> Interleukin

Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. IL-12 family is unique in comprising the only heterodimeric cytokines, which includes IL-12, IL-23, IL-27 and IL-35. Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects.

<span class="mw-page-title-main">CD40 (protein)</span> Mammalian protein found in Homo sapiens

Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.

<span class="mw-page-title-main">Fc receptor</span> Surface protein important to the immune system

In immunology, an Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system. Its name is derived from its binding specificity for a part of an antibody known as the Fc region. Fc receptors bind to antibodies that are attached to infected cells or invading pathogens. Their activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as flaviviruses use Fc receptors to help them infect cells, by a mechanism known as antibody-dependent enhancement of infection.

<span class="mw-page-title-main">B-cell receptor</span> Transmembrane protein on the surface of a B cell

The B-cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B-cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 transmembrane receptor protein, and is typically located on the outer surface of these lymphocyte cells. Through biochemical signaling and by physically acquiring antigens from the immune synapses, the BCR controls the activation of the B cell. B cells are able to gather and grab antigens by engaging biochemical modules for receptor clustering, cell spreading, generation of pulling forces, and receptor transport, which eventually culminates in endocytosis and antigen presentation. B cells' mechanical activity adheres to a pattern of negative and positive feedbacks that regulate the quantity of removed antigen by manipulating the dynamic of BCR–antigen bonds directly. Particularly, grouping and spreading increase the relation of antigen with BCR, thereby proving sensitivity and amplification. On the other hand, pulling forces delinks the antigen from the BCR, thus testing the quality of antigen binding.

<span class="mw-page-title-main">Polyclonal B cell response</span> Immune response by adaptive immune system

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<span class="mw-page-title-main">CD19</span> Biomarker for B cell lineage

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<span class="mw-page-title-main">Isotype (immunology)</span>

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References

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