Lect 2 Flashcards
In what ways do microbes interact with cells?
Can become phagocytosed - or can bind to receptors on cell surface like in epithelial cells
What cells respond to MHC class II molecules and how does the pathway work?
On surface of DCs, B cells and macrophages – present antigen to CD4 T cells – peptide from antigen processing in vesicle gets fused with MHC class II molecule in another versicle from ER and the two vesicle fuse together and move to surface of antigen presenting cell on plasma membrane
What cells respond to MHC class I molecules and how does the pathway work?
CD8 CTLs respond to MHC class I molecule when proteasome cuts up peptide in cytosol and is brought into ER by TAP (transporter activated protein) where it fuses with MHCI molecule and is brought out in vesicle to surface
Is MHCII and MHCI a peptide or monomer?
MHCII is a dimer, MHCI is a monomer
Which chains have the peptide binding region in MHCI and MHCII?
MHCI is alpha, MHCII is beta
How long is a peptide recognized by a TCR?
8-10 AA with side chains that are able to interact with side chains on MHC molecule
Why are there so many different alleles of MHC molecules?
Diversity – allows population to survive viral infections
Where does protein in MHC class I pathway come from?
Cytoplasm that is broken down by proteases - marked by ubiquitin (in class I protein is endocytosed)
What cells do not have MHC molecules?
Erythrocytes - no nuclei
What is occurring during lag phase of adaptive immunity?
Priming to allow cells to proliferate
What happens during priming of T cells?
CD28 on a naive T cell and B7 on APC costimulate eachother to activate T cell
What is an anergic T cell?
When T cell is non-functional because it did not receive CD28-B7 interaction, still alive but unable to respond only had MHC-TCR antigen interaction
What increases response of macrophages to bacteria through cell-mediated immunity and activvation?
Macrophages produce CD40 that is recognized by CD40L (ligand) on CD4 Lymphocyte, CD4 Lymphocyte also produce IFN-y which is recognized by IFN-y receptor on macrophage – leads to activation and allows for killing of phagocytosed bacteria and secretion of other cytokines
How do CTLs kill pathogens?
They use perforin to poke holes in membrane that allows entry of granzymes which activate caspases in apoptosis
How do viruses evade CTLs?
They down modulate MHC class I molecules by inhibiting antigen presentation by proteins that they produce (such as HSV, CMV, EBV)
What do NK cells do?
Contain granzymes and perforin to kill cells in mechanism similar to CTLs but do not need MHC – but recognize activation ligands triggered by DNA damage from stress
What is antibody-dependent cell-mediated cytotoxicity?
Uses antibodies that can be recognized by NK cell and be killed – bein gused in cancer immunotherapy
What is CD4 clonal expansion pathway?
A naive CD4 T cell is able to become a proliferating T cell that leads to immature effector T cells – subsets develop and TH1 leads to secretion of IFN-y and macrophage activation (phagocytic response) and TH2 leads to secretion of IL-4 and IL-5 leading to B cell activation and antibody secretion (extracellular pathogens)
What is the big difference between CD4 and CD8
CD8 is killing and CD4 is cytokine secretion to recruit other cells
What is CD28 dependent?
Priming of T cells
What is the normal antigen response b/w an APC and T cell compared to that leading to cell death (leukemia)
In normal response IL-2 is released by T cell bound to APC which can bind to cells that cause apoptosis
In cell death, there is either a cease in IL-2 production leading to apoptosis (which can come from PD-L1 binding to PD1 on T cells, or CTLA4 signaling to APC to make IDO to inhibit T cell) or expression of FasL that kind bind to Fas on apoptotic cell
What is antibody excess? and when does it occur?
When there is more antibody than antigen – and a B cell with immunoglobulin on surface will interact with antigen which will trigger Fc receptor yIIB to turn off B cell response
What % of B cells become memory cells? and what do memory cells abolish?
~5% – get rid of lag period
What is the difference in immunoglobulins and antibodies?
Antibodies are soluble immunoglobulins found in body fluids - but immunoglobulins also present as receptors on surface of B-cells – both recognize antigens