T Cells Lacey Jeong

What is a T Cell?? Thymus cell – produced and processed by the thymus gland Lymphocyte (white blood cell) – protect body from infection Stronger Immune System There are several different types of T cells in the body, each with a specific function. – T helper cell : makes cytokines to attack infectious invaders. – Memory cell : remembers repetitive infections to prevent a person from getting the same infection multiple times – Cytotoxic T cell (CD8+T cells) : destroy virally infected cells, tumor cells & prevent autoimmune diseases – Natural killer T cells (NKT cells) : connect the adaptive immune system & the innate immune system

Overview The T cell antigen receptor (TCR) – controls the activation and the growth of T lymphocytes T cell activation makes antigen specific T cell clonal expansion and differentiation – regulated by signal transduction pathways controlled by antigen receptors and other molecules. Foreign peptide bound to major histocompatibility complex (MHC) – encoded molecules on the surface of professional antigen-presenting cells (APC) such as dendritic cells (DC) ->These drive the activation. TCR -> α/β subunits γδ - mystery

Type of Receptor T cell receptors – TCRs stuck on the surface of T cells alpha/beta (αβ) T cells - TCR is a heterodimer of an alpha chain w/ a beta chain. – Each chain - variable (V) region & constant (C) region – V regions : 3 hypervariable regions which make up the antigen-binding site gamma/delta (γδ) T cells - TCR is a heterodimer of a gamma chain w/ a delta chain T cells use a transmembrane dimeric protein as a receptor for a particular combination of an antigen fragment nestled in the histocompatibility molecule.

Signal Mechanism : What is the ligand? Antigens – production of antibodies Antigens can be proteins, polysaccharides, or a conjugate of lipids of both! Antigens are presented to the TCR as exogenous or endogenous Exogenous antigens – Antigens that enter the body from the outside environment – Inhaled, ingested, injected Endogenous antigens – Antigens generated inside the cell – Proteins encoded by genes of viruses – Proteins encoded by mutant genes

Pathway Exogenous antigens - antigen-presenting cells (APCs) – APCs engulf the antigen by endocytosis – Endosome combines with lysosome - where the antigen is – Fragments (short peptides) - displayed at the surface of the cell in a class II histocompatibility molecule – Can be recognized by CD4+ T cells. Endogenous antigens – Fragments (short peptides) in the cell - displayed at the surface of the cell in a class I histocompatibility molecule – Can be recognized by CD8+ T cells

Specifics of Cellular Response & Organismal Response Immune System – attack infectious invaders. – remember repetitive infections – connect the adaptive immune system & the innate immune system – Antigens - Production of antibodies – Antibodies identify and neutralize invaders like bacteria or viruses

Faulty Mechanism Immunological Tolerance – Fail to mount an immune response to an antigen – Natural (“self”) tolerance– fail to attack good proteins/antigens, but if immune system respond, autoimmune diseases – Induced tolerance – created by manipulation to allow transplants, protection from allergies, or research for treatments. T cell deficiency – lymphocytopenia of T cells – Defects of individual T cells. – Herpes, fungal infections, etc. Cancer of T cells – Also called T-cell lymphoma – 1 in 10 cases of non-Hodgkin lymphoma.

Current Direction of Research Altered forms of t cells to attack different cancer cells – big last year a girl beats Leukemia HIV attacks t cells – immune system