Core Concepts-L11- Dendritic Cells and activation of adaptive immune system/CD4, MHC II

discuss T cell trafficking and surveillance for pathogens

• T cells will leave the blood and traffic into the lymph nodes and exit unless antigen is encountered

• pathogens stay in the lymph nodes presented by APC like DCs

discuss the differences between naive and effector T cells

naive

• mature from the thymus from positive/negative selection and haven’t encountered their antigen

• circulate through blood and lymph nodes

effector

• activated by APC and undergo proliferation to generate specific clones

• proliferate, make cytokines and cytoxicity- help B cells too

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. present to naive T cells

2. macrophages- interact with effector T cells usually- can be in the lymph nodes and tissues- less effective and don’t initiate early adaptive response

3. B cells

why are DCs the most effective APC? 5

1. highly phagocytic- engulf them efficiently

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

3. tissue residency- samples antigens early and locally

4. migration- can transport them to the lymph nodes

5. have Fc receptors and target opsonised pathogens

what are the jobs of a dendritic cell? 4

1. capture pathogen- takes a sample of pathogen and brings it to the nearest lymph node and waits for T cell to recognise the antigen

2. DCs stay in resident tissues all over the body and continuously samples and phagocytoses and remains stationary until activation.

3. chemokine regulation- once in the lymph nodes releases chemokines like CXCL7 to go to the lymph node and stop phagocytosing

4. APC maturation- immature good at phagocytosis but not good at activating T cells- upon pathogen capture up regulate MHC molecules, express CD80/86 for T cell activation, detects

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

1. APC via MHC

2. costimuatlion- need CD28(T cell) binding to B7(CD80/86) to act as confirmation and shows what type of pathogen it is

3. cytokine environment- determines T cell differentiation depending on the type of pathogen

discuss how and where pathogen replicate, what response is needed and how does this affect antigen presentation and MHC

1. viruses- inside host cytoplasm. viruses are intracellular and are hidden from antibodies. requires cytotoxic T lymphocytes to kill infected cells(MHCI)

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

3. extracellular bacteria- replicate outside the host cell. antibodies are soluble and reach them, and complement can neutralise them- MHC II(CD4)

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 membrane

• have peptide binding groove- where peptides bind

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

how do DC process and present on MHC II?

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 V-ATPASE acidification breaks down bacteria into small peptide fragments and removes most of the invariant chain leaving CLIP in the groove

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