Immuno Assignment #4 Flashcards
What molecules/cells link innate and adaptive immunity?
Cytokines, in conjunction with the presentation of foreign antigen by antigen presenting cells (aka dendritic cells)
how does a dendritic cell develop in vitro?
In vitro —> GM-CSF, IL-4 and FLT3 ligand stimulate production of dendritic cells from CD34+ stem cells.
how does a dendritic cell develop in vivo?
In vivo —> bone marrow derived precursors mobilize to the circulation where they differentiate into immature dendritic cells.
what cytokines are involved in the in vivo process of dendritic cell development?
GM-CSF, flt3 ligand, and M-CSF.
what is the role of an antigen-presenting cell in an immune response
Professional antigen presenting cells deliver antigen to CD4+ T cells.
what is needed on the antigen presenting cell for effective presentation?
an antigen fragment must be displayed within the groove of antigen presenting molecules, proteins encoded by the major histocompatibility complex (MHC).
In addition to dendritic cells what are two other cells that are considering antigen presenting cells?
Macrophages and B cells
why are dendritic cells called the “Gate-keeper” in peripheral tissues?
Capture antigens and carry them to secondary lymphoid tissues.
Dendritic cells are present on all lymphoid and non lymphoid tissues, except???
Brain
what molecules on a dendritic cell are critical for antigen presentation leading to activation of CD4+T cells?
HLA-Class II (MHC Class II)
B7-1/CD80 and B7-2/CD86
Describe general structure of a HLA-class II molecule
Heterodimer (two transmembrane polypeptide chains)
Bind antigenic fragments 15-30 AA long
Describe the properties of the molecules
- Only expressed on dendritic cells and all other APCs
- Normal APC expresses all three heterodimers
- Polymorphic in population
- Co-dominant expression
- IFNgamma up regulates expression of HLA class II
what are the three different isotopes that play a role in antigen presentation
DP, DQ and DR (Structurally similar and expressed on APC)
Number of different heterodimers that will be expressed on the dendritic cell if the parents are genetically unrelated?
minimum of six different class II molecules will be expressed on the cell surface (one copy of each HLA will be inherited per parent)
In this course MHC and HLA are used interchangeably, what is the reason for the different nomenclature?
In humans the MHC are referred to as HLA in recognition of the fact that the proteins are human leukocyte antigens
What is the reason for referring to MHC molecules as H2 molecules?
Class II MHC is for any species while H2 is for mouse.
list the Class II MHC molecules for the mouse
H2-mouse —> H2-IA, H2-IE
what is the advantage of polymorphism in the expression of MHC molecules?
advantageous for population survival because antigen fragments must associate with MHC molecules to be delivered to T cells, cells that are absolutely required for adaptive immunity.
what is the advantage of co-dominant expression of MHC molecules?
allows one to form 6 different stable heterodimers
what is the first step in the sequence of events that leads to the display of a microbial peptide with class II MHC on the cell surface?
When microbes penetrate the host’s physical defenses some of the microbes are endocytosed by antigen presenting cells.
what are subsequent steps in the antigen process and presentation
include the fusion of the endocytotic vesicle with lysosomes that release their contents into the endosome.
what is the second fusion process in the antigen process and presentation
the newly formed vesicle fuses with an endosome that contains the class II MHC, creating a chimeric endosome.
In creating a chimeric endosome, what complex is then exposed to lysosomal enzymes?
Class II MHC/Ii complex is exposed to lysosomal enzymes, the Ii chain is degraded, and an antigenic peptide binds in the newly exposed groove of the class II MHC.
What happens to the chimeric endosome?
migrates to, and fuses with, the cell membrane such that the antigen peptide/class II MHC complex is displayed in the surface of the antigen presenting cell.
