Core Concepts-L10- Dendritic Cells and activation of adaptive immune system/CD4, MHC II

discuss T cell trafficking and surveillance

• travel through the blood and lymph nodes and back into the blood and looks for antigens

• pathogens will stay in lymph nodes until T cells encounter them

discuss the differences between naive and effector T cells

naive

• in the blood and lymph nodes and haven’t encountered an antigen yet. originated in the thymus after positive and negative selection

effector

• at the site of infection

• proliferate, make cytokines and cytoxicity

why does proliferation occur and when does it happens?

• after a naive T cells encounters an antigen, it proliferates as only a few T cells recognise a specifc antigen

• proliferation generates clone to make a good immune response to eliminate it

types of APCs

1. dendritic cells- professional antigen presentation- in the lymph nodes and spleen

2. macrophages- interact with effector T cells usually- In the lymph nodes and tissues- less effective

3. B cells

why are DCs the most effective APC?

1. highly phagocytic

2. larg surface area- have spikes to increase chance of antigen encounter

3. tissue residency- samples early

4. migration- can transport them to the lymph nodes

what are the jobs of a dendritic cell?

1. sample and phagocytose- immature DCs are very phagocytic but poor at APC

2. once encounters pathogen- triggers TF and translation changes. DC stops and switches from phagocytosis mode to migrate mode, chemokine receptors CCR7:CXCL7 are up regulation to allow migration

3. migrate to the lymph node by chemokine receptors and waits for naive T cell to present to

4. up regulates MHC molecules and costimualtory molecules like cd80/86 to become fully mature

what are the 3 signals naive T cells need for activation?

1. APC via MHC

2. costimuatlion- need CD28 binding to B7 to act as confirmation and shows what type of pathogen it is

3. cytokine environment- determines T cell differentiation

immune responses tailored by pathogen type

1. viruses- inside host cytoplasm. viruses are intracellular and are hidden from antibodies. requires cytotoxic T lymphocytes

2. mycobacteria like TB- replicate within macrophages. intracellular but in vesicles and need activated macrophages and Th1 response

3. extracellular bacteria- antibodies are soluble and reach them, and complement can neutralise them

what are bacteria vs viruses presented on?

viruses- MHC I- CD8

bacteria-MHC II-CD4

structure of MHC II molecules

• 2 chains-

• alpha 1 and alpha 2- anchored in the membrane and short cytoplasmic chain- doesn’t signal

• beta chain- beta 1 and beta 2- anchored in the membraned

• have peptide binding groove- where peptides bind

• 2 alpha helices and makes a wall and has beta pleated sheets

discuss MHC II and how it works- EXOGENOUS

1. sampling by APC into endosomes

2. MHC II is made in the ER and the invariant chain(not alpha or beta, stops it from binding self) guides MHC II to the ER where the bacterial peptides are

3. endosome fuses with MHC II vesicle and breaks down bacteria not small peptide fragments and removes most of the invariant chain leaving CLIP

4. HLA-DM removes CLIP and allows peptides from bacteria to bind

5. peptide-MHC II complex moves to the cell surface and presents it