Receptor interactions involved in T-cell activation Flashcards
Autoimmune disease
Harmful immune reactions to self proteins
Immune response
A collective and coordinated response to the introduction of foreign substances in an individual, mediated by the immune system
T-lymphocytes
Cells that mediate cell-mediated immune responses
Mature in the thymus
Circulate in blood and are recruited to peripheral sites of antigen exposure
B-lymphocytes
Only cells capable of producing antibodies
Central cellular component of humoral immune response
Develop in the bone marrow
Four phases of the immune response
Recognition
Activation
Effector
Memory
Subsets of T-lymphocytes
CD4+ T-cells (helper)
CD8+ T-cells (cytotoxic)
T-lymphocytes - functional subsets based on cytokine secretion
Th1
Th2
Th1
T-cells that secrete IFN-gamma
Stimulate phagocyte-mediated defence against foreign proteins
Th2
T-cells that secrete IL-4 and IL-5
Stimulate IgE/mast cell-mediated immune response
Antigen processing
The intracellular conversion of foreign proteins into peptides and loading onto proteins (MHC molecules) for presentation to T-cells
Antigen presentation
The display of peptides bound to MHC molecules on the surface of an antigen presenting cell that permits recognition by T-cells
Antigen presenting cell
A cell that processes protein antigens and expresses MHC molecules for presentation of the antigen to T-cells
Exogenous antigen presentation
Proteolytic enzymes in endosomal vesicles break down/process proteins
MHC class II molecules are synthesised and transported to the endosome
MHC class II associates with the peptide, which is subsequently transported to the cell surface
Endogenous antigen presentation
Endogenous proteins are broken down by the proteosome complex
Peptides are transported from cytosol to the ER via the carrier protein TAP
Peptides bind to MHC class I in ER and transported to the cell surface
Properties of MHC molecules
Extracellular antigenic peptide binding groove
Extracellular co-receptor binding region (surrounds peptide binding groove)
Transmembrane domain
Structural basis of peptide binding to MHC
Floor of MHC binding cleft contains “pockets”; AA side chains fit into pockets; bind through hydrophobic interactions
Anchor amino acids
Properties of T-cell antigen recognition
Most T-cells recognise peptides not proteins
T-cell recognise linear peptide antigens
T-cell recognise cell-associated antigens not soluble proteins
CD4+ and CD8+ cell preferentially recognise antigens sampled from extra- and intracellular environment respectfully
Most T-cells recognise peptides not proteins - explanation
Only peptides bind to MHC
T-cell recognise linear peptide antigens - explanation
Peptides bind to a linear cleft and cannot form conformational determinants
T-cell recognise cell-associated antigens not soluble proteins - explanation
MHC molecules are membrane bound & display peptides of the cell surface
CD4+ and CD8+ cell preferentially recognise antigens sampled from extra- and intracellular environment respectfully
Extracellular and intracellular antigens are processed differently and displayed on either MHC class I or II
CD4+ receptor interacts with MHC class II
CD8+ receptor interacts with MHC class I
2 signal hypothesis for initiation of T-cell activation
Signal 1 - peptide antigen cross-linking MHC and the T-cell receptor
Signal 2 - Additional receptor signals provided by antigen-presenting cells
Chemokine receptors
Cell surface proteins expressed on immune cells
Interact with chemokines that transduce signals stimulating the migration of cells to specific tissues
16 different receptors have been identified
Chemokines
Small, soluble proteins released from inflamed tissues that stimulate movement of immune cells from blood to tissues
