Antigen Presentation and the MHC Flashcards
Define antigen presentation.
The process of displaying antigen by MHC molecules is called antigen presentation.
When we refer to antigen presenting cells, what are we specifically talking about?
Specialized cells displaying antigen and class II MHC molecules are referred to as antigen presenting cells (APCs), even though all nucleated cells express MHC class I molecules and can present antigen via these molecules.
Which are the major professional antigen presenting cells (APCs)?
Describe their action. How can they take up an antigen?
APCs take up antigen, either by surface receptors or by phagocytosis and then present it to immunologically competent lymphocytes. MHC class II expression is to a large extent confined to APCs, which are: - Mononuclear Phagocytes (macrophages) - Dendritic Cells - B Lymphocytes.
For the following cell types, provide the location, whether or not it is phagocytic, and whether or not it is Class II.
Mononuclear phagocytes (macrophages)
dendritic cells
B lymphocytes
macrophages- blood, liver, spleen tissues, it is phagocytic and class II
dendritic cells- skin, lymphoid tissues, phagocytic, Class II
B lymphocytes- lymphoid tissues, sites of immune reactions, NOT phagocytic, Class II
What are mononuclear phagocytes localized in tissues referred to as? Mononuclear phagocytes that line the sinusoids of the liver? Brain?
tissues-macrophages
sinusoids of liver- Kupffer cells
brain-microglial cells
What are Langerhans’ cells? What do they form/where? What do they do?
Skin APCs are Langerhans’ cells, which form a continuous cellular sheet at the junction of
the dermis and epidermis. These cells are capable of migrating via the afferent lymphatics into the paracortex of the draining lymph node. Within the paracortex, they interdigitate with T lymphocytes, presenting antigen carried from the skin to immune responsive cells.
Where are follicular dendritic cells found? What do they do?
Follicular dendritic cells are found in B lymphocyte areas of lymph nodes and spleen. These
cells present antigen to B lymphocytes.
There are two distinct lineages of dendritic cells. Describe.
conventional
and plasmacytoid
Plasmacytoid dendritic cells produce large quantities of interferon in response to viral infections.
Describe dendritic cell maturation in Figure 3.
Scanning electron micrographs are in the right panels and show
maturation from immature at the top to mature dendritic cells at the bottom. In the left panels, green fluorescence depicts MHC class
II molecules and red fluorescence depicts lysosomal protein. When the two colors occupy the same cellular locale they appear as yellow. The top panel depicts highly phagocytic immature
dendritic cells and the bottom panel depicts non-phagocytic
mature dendritic cells that present large quantities of peptide in the context of MHC class II molecules.
Describe B lymphocytes. When is B lymphocyte antigen presentation most important?
B lymphocytes are also rich in surface class II molecules and have been shown to process and present antigen, particularly when the B lymphocyte is immunologically specific for the antigen.
B lymphocyte antigen presentation is most important during secondary antibody
responses.
Name some cells that express Class II MHC molecules.
Macrophages, Langerhans’ cells, interdigitating dendritic cells, and B lymphocytes all
express Class II MHC
Describe antigen processing (the steps).
What must happen to complex antigens before they can be recognized by T lymphocytes?
When does the actual association of the antigen take place for Class I vs Class II?
- Complex antigens (e.g. cells, proteins) are degraded or processed into small antigenic
fragments that are recognizable by T lymphocytes. - These fragments are peptides that associate with either MHC class I (see Figure 5) or class II molecules (see Figure 6).
- The actual association of the antigenic fragments takes place following cytoplasmic
production (Class I) of the antigen or alternatively following phagocytosis or endocytosis (Class II) of the antigen.
Describe MHC Class I antigen presenting pathway.
virus infects cell
viral proteins synthesized in cytosol
peptide fragments of viral proteins bound MHC class I in ER
Bound peptides transported by MHC Class I to cell surface
Figure 5 p 5 or slide 8.
Describe MHC Class II antigen presenting pathway. (cytosol and B-cell)
antigen is taken up from the extracellular space into intracellular vesicles
in early endosomes of neutral pH, endosomal proteases are inactive
acidification of vesicles activates proteases to degrade antigen into peptide fragments
Vesicles containing peptides fuse with vesicles containing MHC Class II molecules
B cell:
antigen specific B cell binds antigen
specific antigen efficiently internalized by receptor-mediated endocytosis
high density of specific antigen fragments presented
Slide 9
What are MHC class I molecules typically derived from?
How are these antigens degraded?
Antigenic peptides that bind to MHC class I molecules are typically derived from viruses that take over the biosynthetic machinery of the cell, resulting in the production of viral proteins (foreign antigens).
These viral proteins are degraded by the host cell’s proteasomes [long
cylindrical structures, comprised of subunits LMP2 and LMP7 that contain multicatalytic proteases] into small peptide fragments.