Antigen Processing & Presenting Flashcards
Qualifications to be a professional Ag-presenting cell
- Express MHC II
- Present Ag to CD4 T-cells
- Activate CD4 T-cells
Professional Ag-Presenting Cells
ONLY use MHC II
Types of Professional Ag-Presenting Cells
Myeloid Dendritic Cells (DCs)
Macrophages
B-cells
Types of Dendritic Cells
- Myeloid
2. Follicular
Function of Myeloid Dendritic Cells
capture Ags & present to CD4 cells
Location of Myeloid Dendritic Cells
diffuse lymphoid, connective tissue, epithelia
Function of Follicular Dendritic Cells
retain Ags for B cells
T-cell & dendritic cell interactions
T-cells sample the Ags DCs present to see if the DCs have something the T-cells can respond to.
they are NOT just idly sitting around waiting for things to “bump” into them.
Methods of Getting Exogenous Antigens
Phagocytosis
Pinocytosis
Receptor-Mediated Endocytosis
After the Ag has been internalized by an Ag-specific B-cell and fragmented, it…
is presented on the membrane at a HIGH density.
Ag pathway with M cells
M cells endocytose and phagocytose Ag and transport it across cell for release at basal surface where Ag binds to DCs that then go activate T-cells
Antigenic peptide (T cell epitope)
only one side of the peptide chain is presented to the T-cell
TCR contacts…
Ag and MHC molecule.
Why is MHC an important determinant of transplant tissue success?
Each MHC molecule has different conformities (b/c of polymorphism) than the resident T-cells normally see, SO the T-cells view them as Ags.
“Non-professional” APCs…
can be induced to express MHC II by exposure to cytokines like IFN-gamma
Myeloid Dendritic Cells Ag uptake (exogenous Ags)
phagocytosis
pinocytosis
receptor-mediated endocytosis
Macrophages present Ags primarily to…
effector CD4 and CD8
memory CD4 and CD8
B Lymphocyte Ag uptake (exogenous Ag)
receptor-mediated endocytosis
Myeloid Dendritic Cells present Ag primarily to…
naive CD4 & CD8
effector CD4 & CD8
memory CD4 & CD8
Macrophage Antigen uptake (exogenous Ag)
phagocytosis
pinocytosis
receptor-mediated endocytosis
B Lymphocytes present Ags primarily to…
effector CD4 Tfh
memory CD4 Tfh
Activated Myeloid DCs…
Langerhans cells (DCs) uptake Ag in skin & leave it to enter lymphatic system. The mature Langerhans enters lymph node & transfers Ags to resident DCs. B7-positive DCs stimulate naive T-cells
Dendritic Cells Activated by…
PAMPs, DAMPs, IL-1, TNF-a, IFN-a, IFN-beta
Activated DCs actions =
- migrate to diffuse lymphoid tissues
- present Ag to T-cells (signal 1)
- deliver signal 2 to T-cells
- deliver signal 3 to T-cells
Adjuvants in vaccines
enhance immune response
How do adjuvants enhance the immune response?
- enhance presentation of Ags to Helper T-cells
- induce inflammation
- depot effect
How do adjuvants induce inflammation?
incorporate PAMPs, mimic DAMPs, and have irritant properties
What is the depot effect?
Ag retained at inoculation site and released slowly
Effect of the depot effect
lymphocyte stimulation is prolonged resulting in a stronger immune response.
Dendritic cell MHC expression
low on immature DCs
high on DCs in lymphoid tissue
DC location
throughout the body
Effect of Ag uptake by DCs
activation of naive T-cells
Macrophage MHC expression
inducible by bacteria & cytokines
Macrophage location
lymphoid tissue, connective tissue, body cavities
Effect of Ag uptake & MHC expression on Macrophages
macrophage activation
B cell Ag uptake
Ag-specific receptors (immunoglobulins)
B-cell MHC expression
constitutive and increases on activation
B-cell location
lymphoid tissue
peripheral blood flow
Effect of Ag uptake and MHC expression
delivery of help (Tfh) to B-cell
MHC I loading of endogenous Ags
peptides transported to rER
MHC II loading of exogenous ags
phagosome fuses with vesicles containing MHC II molecules
Endogenous antigenic peptides formed by…
proteasomes in cytoplasm break down the Ag proteins
Exogenous antigenic peptides formed by…
phagosomal & lysosomal enzymes break down Ag proteins
