T Independent Antigens

During humoral immune response, Ab production is brought about by B lymphocytes. Based on the ability to induce Ab formation, antigens can be classified into T independent and T dependent antigens. Some antigens can directly induce the B cells to produce the Abs and are called T Independent Ans. However, some Ans require the help of T lymohocytes for the production of Abs from B cells. These Ans are called T Dependent Ans.

T Independent (TI) Antigens

Most of the protein Ans require the help of T cells for the production of Abs by B lymphocytes. However, Ans like bacterial capsular polysaccharides and bacterial lipopolysaccharides and some polymeric proteins like flagellar protein flagellin, can directly stimulate the B Cells to produce Abs, without the involvement of T cells. They can directly activate B cells with out An processing and presentation to the T cells.  Such Ans are called T Cell or Thymus Independent (TI) antigens. They are structurally simple and carry repeating epitopes. These repeating epitopes cross link the BCRs and act as first signal of activation. Eventhough T lymphocytes are not involved in Ab production, they assist the B cell proliferation and differentiation. For complete activation of B cells a dual signal is required and the second signal usually comes from T cells. But here, as T cells are not, the second signal should come from other sources.

TI Ans are metabolized slowly and remain in the body for long periods. There are two types of TI Antigens. TI-1 antigens and TI-2 antigens. TI-1 are usually bacterial lipopolysaccharides (LPS) which have mitogenic properties can deliver dual signal to B cells by themselves. First signal by binding to BCR and second by binding to the lipid moiety of LPS whose nature is not well studied.

TI-2 antigens are non-PAMP compounds, such as polysaccharides, that lack mitogenic properties and activate B cells through a T cell-independent mechanism. These antigens have multiple repeating sugar units that cause extensive cross-linking of B cell receptors (BCRs), generating a strong activation signal that can partially compensate for the absence of co-stimulatory signals from T helper cells. However, a second signal is still required for full activation. This secondary signal can come from the engagement of toll-like receptors (TLRs) with pathogen-associated molecular patterns (PAMPs), such as flagellin, or interactions with components of the complement system. Here, flagellin serves as a PAMP that can provide the necessary secondary signal to support B cell activation.

Toll-like receptors are receptor proteins help in the recognition of wide array of pathogens and are found on the membranes of leukocytes including dendritic cells, macrophages, natural killer cells, immune cells like T cells and B cells, and also on non-immune cells like epithelial and endothelial cells, and fibroblasts.  PAMPs are Pathogen Associated Molecular Patterns found on infectious agents which are recognized by Toll like receptors.  

Once the B cells are activated, they undergo clonal proliferation and daughter cells differentiate into plasma cells. Plasma cells are antibody factories that secrete large quantities of antibodies. Abs produced by TI Ans are mainly IgM Abs. Type switching to IgG can take place with the help of T lymphocytes. Here, there is no production of memory cells and no immunological memory. Hence immune response is effective in primary infection and not effective in secondary infection and also short lived. Also, immune response by TI Ans are dose dependent. Means, too little An is not immunogenic and too much An cause immunological tolerance than immunity.