T-cell Immune Responses
T-cell Immune Responses
T-cell-independent Immune Response
- Activation of the immune system towards the thymus-independent pathway is provoked by a relatively limited number of antigenic substances restricted by their structural organization and molecular charge.
- As a result, a polymeric complex Ag binds to specific Ab receptors of IgM class anchored within the cytoplasmic membrane of B cells. This leads to cross-linking of two or more molecules of superficial Ab receptor resulting in next signal transmission and B cell activation.
- Activated B lymphocytes start the transformation into plasma cells that intensively produce specific Ab but of IgM class only.
- Without T cell help (particularly of IL-4 absence) B cells are unable to switch Ab synthesis from IgM to other Ig classes thereby averting further Ab maturation.
- Thus, T cell-independent response has essential limitations demonstrating a rather low grade and specificity.
- By contrast, the specific response against thymus-dependent Ags initiates multiple immune reactions that profoundly affect the host immune system.
T Cell-dependent Immune Response
T cell-dependent immune response demonstrates three principle phases:
- Antigen processing and presentation.
- Inductive phase with activation and differentiation of T helper cells.
- Effector phase.
Antigen Processing and Presentation
- Processing and presentation of Ags is the main function of specialized antigen-presenting cells (APC). Among them are dendritic cells (DC) of myeloid and plasmacytoid origin, Langerhans` cells, follicular dendritic cells, and some others. B lymphocytes are also capable of presenting Ags for T cells.
- Once captured by APCs (e.g., by different types of DCs) exogenous Ag degrades within APC endosome up to small antigenic peptides (antigen processing).
- Resulting fragments of Ag are next coupled with HLA II class molecules inside APC cytoplasm.
- This interaction requires specific binding of intracellular HLA chains predominantly to an antigenic peptide that demonstrates high affinity to them. Therefore, processed antigenic substances that don’t match well any HLA molecule will evade T cell response.
- After transportation, the specific complex (antigenic peptide – HLA II class molecule) is exposed upon APC membrane for recognition by Th0 cells (antigen presentation).
- The protein antigens of intracellular microbial pathogens (viruses, chlamydiae, rickettsiae and others) are processed directly inside the cytoplasm of infected cells within the special cytoplasmic protease complex known as the proteasome.
- Resulting antigenic peptides associate with HLA I class molecules for further presentation to cytotoxic T cells.
- It is generally ascertained that antigen-presenting dendritic cells of various origin play a key role in the activation of T cell-dependent reactions. These reactions hinge strongly on the type of initial Ag recognition by APC.
- Ag-presenting cells bear multiple pathogen-binding receptors (PBR) of different types. For instance, high pathogen-binding activity is essential for molecules of Toll-like receptor (TLR) family.
- These receptors possess the strong binding capacity to pathogen-associated molecular patterns (PAMP) – structural units that are similar or common for vast groups of microbial pathogens. Other families of receptors (e.g., NOD) are also implicated to primary binding of some groups of Ags.
- Hence, antigenic uptake by dendritic cells via TLR-4 activates the production of pro-inflammatory cytokines (IL-1, IL-6, IL-12, IL-18, TNF-α). This leads to the next transformation of Th0 to Th1, promoting cell-mediated reactions and inflammation.
- By contrast, immune activation resulted from Ag binding to TLR-2 upon APC membrane triggers the secretion of another set of regulatory cytokines (IL-4, IL-10, IL-13, etc.)
- The latter ensures conversion of Th0 into Th2 lymphocytes thereby promoting B cell transformation and antibody secretion by plasma cells (see below). This pathway is also stimulated by antigen-presenting B lymphocytes.