Antigen processing and presentation Flashcards
what is antigen processing and presentation
It is the process by which antigen-presenting cells digest antigens acquired from inside or outside the cell and display the resulting antigenic fragments on cells surface MHC molecules for recognition by T lymphocytes
what cells are involved in the process of antigen processing and presentation
- Antigen-presenting cells (APC)
- they digestion (processing) and display (presentation)
- Later, T lymphocytes recognize the presented antigens and get activated to initiate a cellular immune response
What are the 3 professional antigen-presenting cells
- Dendritic cells
- Macrophages
- B lymphocytes
what is the function of Dendritic cells as professional antigen-presenting cells
Present antigen to naive CD4+ and CD8+ T lymphocytes, so they initiate T-cell responses
what is the function of Macrophages cells as professional antigen-presenting cells
present antigens to differentiated CD4+ T lymphocytes in the effector phase of cell-mediated immunity
what is the function of B lymphocytes cells as professional antigen-presenting cells
present antigens to helper T cells (CD4+) during humoral immune response
what other cells can act as non-professional antigen presenting cells
all other nucleated cells when they become infected, particularly with virus
how is MHC-2 expression on macrophage
Low levels: introduced by PAMPs, DAMPs, and cytokines
how is MHC-2 expression on DC
always expressed
how is MHC-2 expression on B cell
always expressed, inducible on activation
how are antigen types and presentation by MHC with macrophages
Extracellular antigens: presentation via MHC 2
how are antigen types and presentation by MHC with DC
Intracellular and extracellular antigens: presentation via MHC 1 and MHC 2
how are antigen types and presentation by MHC with B cell
Extracellular antigen binds to specific Ig receptors: presentation via MHC 2
Location of macrophages
Lymphoid tissue connective tissue body cavities
Location of DC
Lymphoid tissue connective tissue Epithelium
Location of B cells
lymphoid tissue Blood
the responses of antigen specific T-cells to proteins requires the participation of ________________, which capture, digest and display the antigens to T-cells
the responses of antigen specific T-cells to proteins requires the participation of Antigen Presenting cells (APCs), which capture, digest and display the antigens to T-cells
Two important functions of antigen presenting cells
- they convert protein antigens to peptides and they display peptide MHC complexes for recognition by T-cells
- conversion of proteins to peptides within APCs is called antigen processing
- APCs provide stimulus to T-cells, the stimulus is called co-stimulation
what does antigen presentation begin with
antigen presentation begins with antigen processing
the pathway of antigen processing convert protein antigens derived from the ___________ or the ____________ and load these peptides into MHC molecules for display to lymphocytes
the pathway of antigen processing convert protein antigens derived from the extracellular space or the cytosol into peptides and load these peptides into MHC molecules for display to lymphocytes
Protein antigens present in acidic vesicular compartments of APCs generate_________ whereas antigens present in the cytosol generate___________
Protein antigens present in acidic vesicular compartments of APCs generate MHC class 2 associated peptides whereas antigens present in the cytosol generate MHC class I-associated peptides
what is the sequence of events for processing of endocytosed antigens for MHC class 2-associated presentation: sequence of events
- uptake: of extracellular proteins into vesicular compartments of APCs
- Processing: of internalized proteins in endosomal and lysosomal vesicles
- Biosynthesis and Transportation of MHC class 2 molecules: to endosomes
- Association: of processed peptides with MHC class 2 molecules in vesicles
- Expression: of peptide-class 2 complexes on the APC surface
what happens to the material once internalized
the uptaken material is localized in vesicles called endosomes
what are endosomes
endosomes are acidic compartments that contain proteolytic enzymes
what happens when the endosomes communicate with lysosomes
form phagolysosomes or secondary lysosomes, where further degradation of engulfed material takes place
Internalized proteins are degraded _________ in _________ and lysosomes
Internalized proteins are degraded enzymatically in Late endosomes and lysosomes
what is created when the proteins are degraded
about 14-20aa long peptides are generated that bind to the peptide-binding clefts of class 2 MHC molecules
what are the most important proteolytic enzymes involved in protein degradation
Cathepsins
how are the MHC 2 bio synnthesised and transport
- The alpha and beta chains of the MHC class 2 molecule are synthesized and associated with each other in the endoplasmic reticulum (ER)
- Upon synthesis in the ER, MHC class 2 molecules are transported to the Golgi apparatus and to endosomes with an associated invariant chain (I)
- In endosomes, the I dissociates and the antigenic peptides are associated with MHC class 2 molecules
- Stable peptide-MHC class 2 complexes are delivered to the surface of the APC, where they are displayed for recognition by CD4+ T lymphocytes
what are the sequence of events for processing of cytosolic antigens for MHC class 1 associated presentation
- Cytosol location of foreign proteins
- Proteolytic degradation of cytosolic proteins in the proteosome
- Transport of peptides from the cytosol to the ER
- Assembly of peptide MHC class 1 complexes in the ER
- Surface express of peptides MHC class 1 complexes
Sources of cytosolic antigens
- Proteins that are found in the cytosol are endogenously synthesized in nucleated cells
- Cytosolic proteins may originate from viruses or other intracellular microbes that infect cells
- Sometimes even endocytosed antigens may be presented through MHC class 1 molecules
what happens to the proteins that are synthesized in the cytosol
proteins synthesized in the cytosol are ubiquitinated thus destined for proteosomal degradation
what are proteosomes
large multienzyme complex found in the cytoplasm of most cells and has a broad range of proteolytic activity
how are peptides derived from cytosolic protein antigens
by proteolysis in the proteosome
How are the peptides generated in the proteosome transported to the ER
The main transporting system is the “transporter associated with antigen presentation (TAP)
where is TAP located
in the membrane of the ER
what is the function of TAP
it mediates the transport of peptides into the ER
what happens to the proteins in the assembly of peptide MHC class 1 complexes in the ER
Peptides translocated into the ER bind MHC class 1 molecules that are attached to the TAP dimer
how are the MHC class 1 peptide complex surface expressed
- MHC class 1 peptide complexes move through the Golgi complex and are delivered to the cell surface
- MHC class 1 molecules with bound peptides are structurally stable and are expressed on the cell surface
- once expressed on the cell surface, complexes may be recognized by peptide antigen-s[ecific CD8+ t lymphocytes
