T Cell Mediated & Innate Immunity

• • B cells recognize stuff as it exists in fluids, serum, etc. (humoral)
  • T cell recognition requires antigen processing and an APC (MHC restriction)
• Antibody-Mediated Immunity is primarily important for molecular antigens such as toxins and allergens, extracellular infections like common pyogenic bacteria, the extracellular phase of intracellular infections like viremia, and some cellular antigens such as those involved in transfusion reactions
• In the extracellular phase of intracellular infections, Antibody-Mediated Immunity is important for dealing with aspects like viremia
• B cells bind epitopes on complete immunogen molecules, such as molecules involved in virulence like surface antiphagocytic capsules, surface binding sites for host cells, or soluble toxins
• T cells bind epitopes formed by the combination of metabolized immunogen fragments with MHC molecules
• The T cell response is specific, follows a similar time-course, and is both specific and heterogeneous with primary and secondary responses, requiring the help of Helper T cells
• The interaction between a T cell and the immunogenic complex on the surface of the antigen-presenting cell results in different responses depending on the type of the antigen-presenting cell and the type of the T cell
• T Cell Receptors (TCR) are analogous to Immunoglobulins in structure and genetics
• The major products of T cells are cytokines, not immunoglobulins
• Cytokines are not specific for an antigen like antibodies
• Effector T cells are specific for the antigen
• Cytokines are more analogous to hormones, as they are a form of communication between cells
• T cell recognition of immunogens requires antigen processing by an antigen-presenting cell (APC) and is MHC-restricted
• CD4+ T cells recognize Class II MHC molecules, while CD8+ T cells recognize Class I MHC molecules
• The T cell response gives rise to Helper cells (helper, Treg, Th17) and effector cells (Cytotoxic or CTL)
• CD stands for Cluster of Differentiation in the context of surface molecules on T-Lymphocytes
• The pathway for the development of T cells is from Stem Cells (Bone Marrow) to Thymocytes (Thymus) to Peripheral T cells (Lymphoid Tissue)
• 100% of peripheral T cells express the TCR molecule
• The CD3 molecule is a 6 molecule complex closely associated with the TCR involved in signal transduction
• Most T cell development occurs in the thymus
• The construction of the genes for the T cell receptor (TCR) proteins is influenced by V/(D)/J Recombinase
• The majority of thymocytes die and do not survive the maturation process
• Thymocytes that express neither CD4 nor CD8 are called Double-negative thymocytes
• Thymocytes at a later but still immature stage express low levels of the TCR and CD3, along with both CD4 and CD8
• Positive selection in T cell development promotes the survival of thymocytes whose TCRs recognize peptides complexed to self-MHC molecules
• Thymocytes that do not recognize self-MHC do not thrive
• Negative selection results in the deletion of thymocytes whose TCRs recognize peptides derived from self-proteins, leading to tolerance
• Apoptosis and deletion of self-reactive clones in double-positive thymocytes are induced by immunogenic stimulation by self antigens expressed on dendritic cells
• Mature T cells found in the periphery are single-positive and express either CD4 or CD8, but not both
• The T cell receptor has a disulfide-linked heterodimer structure anchored by transmembrane segments
• The molecular weights of the alpha and beta chains of the T cell receptor are approximately 45,000 and 55,000, respectively
• Each chain of the T cell receptor has variable and constant domains
• The antigen-binding site of the T cell receptor is composed of both alpha and beta chains contributing to the antigen-binding site located in the amino-terminal variable region
• The T cell receptor recognizes the processed antigen-MHC complex
• TCR genes have variable (V), diversity (D), joining (J), and constant (C) segments similar to Ig light and heavy chain genes, but TCR VJ and VDJ do not undergo somatic hypermutation
• The hypervariable loops on the variable domain of the TCR are called Complementary Determining Regions (CDR)
• The diversity of TCR is the same as for Ig up until an antigen is encountered
• TCR does not diversify after encountering an antigen
• The T cell receptor does not have an effector function like immunoglobulins
• The gamma delta T cell receptor does not use CD4 or CD8 and does not need MHC for antigen recognition