Immunology Week 6 Review

Immunology Week 6 Review  OBJECTIVES FROM 9/23 & 9/25  Compare & contrast phagocytosis & macropinocytosis (again )  Identify & explain the purpose, function, & steps of antigen processing & presentation  Elaborate on steps of both MHC I & MHC II processing/presentation, & compare &...

Immunology Week 6 Review  OBJECTIVES FROM 9/23 & 9/25  Compare & contrast phagocytosis & macropinocytosis (again )  Identify & explain the purpose, function, & steps of antigen processing & presentation  Elaborate on steps of both MHC I & MHC II processing/presentation, & compare & contrast  Identify proteins of the peptide-loading complex that aid the assembly and peptide loading with MHC  Compare & contrast MHC I & MHC II processing and presentation  Understand the significance of the invariant chain  Describe the steps of dendritic cell maturation and its importance in antigen presentation  How can a peptide-derived from an intracellular pathogen that circumvents phagolysosome vesicles load into a class II molecule? (Importance of cross presentation)  REVIEW OF LAST CLASS  Compare & contrast phagocytosis & macropinocytosis  REVIEW OF LAST CLASS  Identify & explain the purpose, function, & steps of antigen processing & presentation  T cells are restricted- aka TCR can not bind free antigen in body (aka MHC restriction)  Antigens must first be processed & presented to T cells via antigen presenting cells (APCs)  Antigen presentation- process by which protein antigen is presented to lymphocytes in form of short peptide fragments  When ingested proteins are enzymatically degraded & resulting peptide fragments are loaded into MHC class molecules (forming pMHC class I or II)  Steps 1. Pathogens & antigens (& dendritic cells carrying pathogens & antigens) arrive at a lymph node in afferent lymph draining the infected tissue 2. Pathogens & debris are removed by macrophages 3. Dendritic cells become residents & move to T-cell areas, where they encounter small lymphocytes that have entered LN from blood (green) 4. Dendritic cells orchestrate division & differentiation of small pathogen-specific lymphocytes into effector cells (blue)  Some helper & cytotoxic T cells leave in efferent lymph & travel to infected tissue  Other helper T cells stay in LN to stimulate division of pathogen-specific B cells & their differentiation into plasma cells (yellow) (B cell follicles → germinal centers) 5. Plasma cells move into medulla of lymph node, where they secrete pathogen-specific antibodies  Other plasma cells leave LN & travel to bone marrow, where they secrete pathogen-specific antibody in quantity 6. Antibodies travel to infected tissue by efferent lymph & blood  REVIEW OF LAST CLASS  Elaborate on the steps of both MHC I & MHC II processing/presentation, & compare & contrast  MHC I- Peptides produced by protein degradation in cytosol are pumped into lumen of ER where they are loaded onto MHC class I & taken by exocytic vesicles through Golgi to plasma membrane.  MHC II- Pathogens taken up from extracellular fluid are transported via endocytic vesicles to lysosomes, where proteins are degraded to peptides & transported via endocytic vesicles to fuse with vesicles containing MHC class II. Peptides are loaded onto class II molecules & taken to plasma membrane  Compare & contrast MHC I & MHC II processing and presentation  MHC I- found on all nucleated cells; presents intracellular material; structurally has 3 alpha pieces & β 2 microglobulin (β2m); can fit smaller peptides; “pita”  MHC II- found on APCs; presents extracellular material; structurally has a 32-38 kDa α chain & a 29-32 kDa β chain form a binding groove; can fit larger peptides; “hotdog”  REVIEW OF LAST CLASS  Identify proteins of the peptide-loading complex that aid the assembly and peptide loading with MHC  pMHC-  Proteosome-  TAP-  ERAP/ERAAP-  Calnexin-  Tapasin-  ERp57-  Calreticulin-  Invariant chain-  CLIP-  HLA-DM- REVIEW OF LAST CLASS  Compare & contrast MHC I & MHC II processing and presentation  *sorry, this is a bit of a duplicate objective, so I added this answer on the earlier slide to keep it all in one place. Kept this objective slide here in case you’re going in order and thought I missed one- I covered in earlier  But definitely comparing and contrasting structures and organization, how the molecules themselves are built, key players in building/structuring/helping with binding, and other differences between two like exogenous vs. endogenous antigens, loaded in the ER vs. loaded in vesicles, etc.  REVIEW OF LAST CLASS  Understand the significance of the invariant chain  Invariant chain prevents MHC class II from binding peptides in the endoplasmic reticulum  The invariant chain prevents peptides from binding to MHC class II until the invariant chain:MHC class II complex reaches the site of extracellular protein degradation. In the endoplasmic reticulum (ER), MHC class II α and β chains are assembled with an invariant chain that fills the peptide-binding groove; this complex is transported to the acidified vesicles of the endocytic system. The invariant chain is broken down, leaving a small fragment called class II–associated invariant-chain peptide (CLIP) within the peptide- binding site. The membrane protein DM, which is resident in these vesicles, catalyzes the release of the CLIP fragment and its replacement by a peptide derived from endocytosed antigen that has been degraded within the acidic interior of the vesicles.  REVIEW OF LAST CLASS  Describe the steps of dendritic cell maturation and its importance in antigen presentation  When an immature dendritic cell senses an invasive threat, it rapidly begins to mature  Threat sensing causes D.C. to migrate to nearby lymph nodes, decrease their phagocytic & macropinocytic activity, & increase MHC class II synthetic activity  REVIEW OF LAST CLASS  How can a peptide-derived from an intracellular pathogen that circumvents phagolysosome vesicles load into a class II molecule?  Some intracellular antigens are broken down & their peptide fragments are loaded into MHC class I (forming pMHC class I) molecules  To avoid detection by the adaptive immune system, some pathogens employ a “stealth mechanism” by circumventing phagolysosome vesicles altogether. Others may enter the cell in phagosomes but are able to leave them and enter the cytoplasm. But their ruse is not perfect, as some infected cells die, prompting dendritic cells to take up dead cells and cellular debris by either phagocytosis or macropinocytosis. The proteolytic peptides are then displayed in class II molecules. Mystery solved!  Cross-presentation- ability of certain professional antigen-presenting cells (mostly dendritic cells) to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells (cytotoxic T cells)  OBJECTIVES FROM 9/27  State where you would expect to find antigen receptors of the adaptive immune system  Describe the structure and organization of the immunoglobulins of the adaptive immune system (BCR, & antibodies, TCR, etc.)  Compare and contrast BCR & TCR  List the components & their functions, of the T Cell Receptor (TCR) complex  Describe the Organization and rearrangement of the T-cell receptor genes to create a final TCR product  Compare & contrast αβ & γδ TCRs (more later too)  Define & use vocab words associated with this lecture (CDR, Fab, TCR etc.)  Know the key chromosomes & segments  REVIEW OF LAST CLASS  State where you would expect to find receptors of the adaptive immune system within the context of the cell  B-cell receptors (BCRs)- cell- surface bound monomeric immunoglobulin associated with disulfide-linked heterodimers called Igα and Igβ; B cells  T-cell receptors (TCRs) are heterodimers, consisting of either an αβ or a γδ chain pair (an αβ receptor is shown left; γδ receptors have similar structures); T cells  Describe the structure & organization of immunoglobulins of the adaptive immune system (antibodies, BCR, TCR) BCRS VS. TCRS  REVIEW OF LAST CLASS  List the components & their functions, of the T Cell Receptor (TCR) complex  The T-cell receptor (TCR)- membrane- bound heterodimer composed of an α chain of 40–50 kDa & a β chain of 35–46 kDa (obviously different if it’s γδ- obviously one chain is γ & one chain is δ).  The TCR COMPLEX- TCR+ CD3 complex + accessory molecule (CD4 or CD8) REVIEW OF LAST CLASS  Compare & contrast αβ & γδ TCRs (more later too)  REVIEW OF LAST CLASS Compare & contrast αβ & γδ TCRs (more later too) AND Know the key chromosomes & segments αβ TCR α chain- Chromosome 14; Has V & J segments, and 1 constant segment β chain- Chromosome 7; Has V, D, & J segments, & 2 potential constant segments γδ TCR γ chain- Chromosome 7 ; Has V & J segments and TWO constant segments δ chain- Chromosome 14 (within α chain locus); Has V, D, & J segments and ONE constant segment  Gamma is like alpha with the V & J, but like beta with the TWO constants, while delta is like beta with the VDJ, but like alpha with the ONE constant. Make sense now? I saw it and knew there would be confusion  REVIEW OF LAST CLASS  Define & use vocab words associated with this lecture (CDR, Fab, TCR etc.)  B-cell receptors (BCRs)  T-cell receptors (TCRs)  CD3  CD4  CD8  Plasma cells  Constant (C) domain  Variable (V) domain  Diversity (D)  Joining (J)  “Fragment with Antigen Binding” (Fab)  Complementarity-determining regions (CDR)  Hypervariable regions (HV)