Antigen Presenting and the MHC Lecture 7 Flashcards
What are the 3 professional APCs?
- Mononuclear Phagocytes (Macrophages) (phagocytic)
- Dendritic Cells (phagocytic)
- B Lymphocytes (not phagocytic)
What is the location of macrophages, dentritic cells and lymphocytes?
Macrophages=blood, liver, spleen tissues
Dendritic cells=skin, lymphoid tissues
B Lymphocytes= lymphoid tissues, sites of immune reactions
What do macrophages do and what are two types of macrophages?
- phagocytosis
- activation of bacterial mechanisms
- antigen prestation
- Liver-kupffer cells
- Brain-Microglial cells
Dendritic Cell function 3 types
- Antigen uptake in peripheral sites
- Antigen presentation in lymph nodes
- skin langerhans’s cells
- t lymphocyte area of lymph nodes- interdigitating dendritic cells
- b lymphocyte are of lymph nodes-follicular dendritic cells
What are the two distinct lineages of dendritic cells?
- conventional
2. plasmacytoid
What do plasmacytoid do in response to viral infections?
produce large quantities of interferon
Conventional dendritic cells undergo a maturation process, how do they mature?
immature-phagocytic mature-non phagocytic presenting witt MHC class 2 molecules
When is B lymphocyte antigen presentation most important?
during secondary antibody responses
When does the association of the antigenic fragment take place with class 1 and class 2?
class 1: takes place following cytoplasmic production of the antigen
class 2: takes place following phagocytosis or endocytosis of the antigen
How are antigenic peptides that bind MHC class 1 molecules typically derived? steps
- virus takes over the biosynthetic machinery of the cell
- production of viral proteins
- viral proteins degraded by the host cell’s proteasomes
- peptides are transported into the ER by TAP1 and TAP2
- newly synthesized MHC class 1 molecules in the ER associate with TAP1 and TAP2
- the peptides are then trimmed by ERAAP
- trimmed peptides bind to the MHC moleucle
- MHC-peptide complex leaves the ER and is transported through the golgi to the cell surface
What happens when an MHC class 2 molecules capture an antigen?
- antigens are degraded enzymatically, in endosomes and lysosomes into peptides
- MHC class 2 molecules are synthesized in the ER
- MHC class 2 molecules transported to an endosome with an associated protein=invariant chain (Ii)
- in the endosome the acification cleaves the Ii and leaves a short peptide fragment CLIP bound to the peptide binding grove of the MHC class 2
- Once the endosome fuses with a vesicle containing foreign antigen CLIP is removed by a peptide undloader/ loader=DM
- DM places the foreing peptide in the groove of the MHC class 2 molecules
- Peptide MHC complex then transits to the cells surface
what does the invariant chain do?
occupies the binding cleft of the newly synthesized MHC class 2 molecule
-degradation of Ii increases the mobility of antigen presenting cells
Under normal conditions what are MHC class 1 molecules loaded with?
self peptides derived from the normal degradation of self cellular proteins
Under normal conditions what are MHC class 2 molecules loaded with?
CLIP
CD4+ mediate what two responses?
- Macrophage activation
2. act as helper tcells in antibody response by secreting cytokines
What subset of CD4 T cells activate macrophage?
Th1
What subset of Cd4 T cells induce antibody synthesis?
Th2
What is the difference between mature and immature dendritic cells?
Mature dendritic cells are good at presenting antigens
- express large amounts of co-stimulatory molecules eg B7
- can produce large quantities of cytokines required for T lymphocyte proliferation and differentiation
What two signals does a niave T cell need to be activated
- Presentation of peptide by MHC
2. interaction between b7 on the APC and CD 28 on the membrane of the Tcell
What happens if there is an interaction with an antigen presenting cell that does not express T7 but has taken up an antigen?
- T cells that recognize the APC are stimulated to express CD 40 ligand (CD40L)
- CD 40L engages CD40 on the surface of the APC
- Signal induces APC to express B7
- CD28 ligation of B7 induces T cell proliferation and differentiation
What 6 steps lead to the B cells proliferating and differentiating into plasma cells that secrete antibody?
- B cells take up the antigen
- Display as MHC class 2
- Activates B cell to make B7
- T cells recognize MHC presented antigen and B7 costimulates CD 28 on T cell –>T cell activated
- Activation induces expression of CD40L which engages CD40 on the B cell
- This activates the T cell to produce cytokines allowing the B cell to proliferate and differentiate into plasma cells that secrete antibody
What does T cell proliferation require?
TCR engagement and signaling for many minutes or hours
What is a immunological synapse
specialized contact for the mechanism of sustained TCR engagement
- provide a mechanism for sustained TCR engagement and signaling
- provides a higher-order molecular mechanism of junction formation, MHC-peptide transport, and cluster stabilization
- central cluster with cocentric rings
What is the mature immunological synapse defined by?
a specific pattern of receptor segregation with a cluster of TCRs surrounded by a ring of adhesion molecules
What does the intermediate ring of the immunological synapse enriched in? What is one specific type of interaction?
Adhesion molecules that promote efficient TCR-MHC-peptide interation
-LFA-1(Tcell) —–ICAM1 (APC)
What does the inner circle contain?
TCR, CD4, and costimulatory molecules like CD28
