Antigen Capture and Presentation Flashcards
TLRs recognize _____
PAMPs
What are the 2 signals that allows the innate immune system to initiate the adaptive immune response?
Process and present antigens to T lymphocytes
Generation of surface molecules that function as costimulatory signals with antigen to activate B and T cells
What are Major Histocompatibility Complexes Type I and II? Where are each found?
MHC I and II are complexes found on cells that present processed antigens to naive T cells
MHC I is found on all nucleated cells
MHC II is found on APCs: Dendritic cells, Macrophages, B lymphocytes, and thymocytes
What are MHC molecules AKA?
HLA- Human Leukocyte Antigen
Why do we need MHC/HLA receptors to recognize antigens?
T lymphocytes do not recognize free or soluble antigens
What are the 3 classes of MHC/HLAs?
Class I**- B, C, and A (Found on all nucleated cells)
Class II- DP, DQ, DR (Found on APCs)
Class III- Cytokines and complement proteins
Note that class I has 1 letter and class II has 2 letters
What is an MHC/HLA Haplotype?
The total set of MHC/HLA alleles that are present on each chromosome.
Most humans have 2 MHC/HLA haplotypes- one from mom and one from dad
What is the goal during transplantation?
To find the best match possible between recipient and donor for both class I and class II genes
Where on all nucleated cells are class I MHC molecules found? What is its function? (Note that it has 2 functions)
On membrane bound glycoproteins
Function is to present antigens to CD8+ Cytotoxic T lymphocytes
It is also an inhibitory receptor to NK cells
Describe the structure of class I MHC/HLA receptors.
Heterodimer of 2 proteins:
Alpha chain (alpha 1, 2, 3)
Beta2- Microglobulin- associates noncovalently with the alpha chain
What kind of antigen molecules bind to MHC class I receptors? Where do they bind?
Peptides with 8-10 amino acids
They bind to the peptide groove between alpha1 and alpha 2. Note that the conformation of this groove dictates what peptides can bind.
Where are MHC class I and II receptors synthesized?
In the Endoplasmic Reticulum
Note that how the antigen finds the MHC receptors is different for both. Will get to this in later note cards
Where are MHC class II receptors found on APCs? What is their function?
Membrane bound glycoproteins
Function is to present antigen to CD4+ T-lymphocyte
Describe the structure of MHC class II receptors. Describe the binding site.
Composed of two proteins- alpha and beta chains. Both encoded by the HLA-D gene.
Alpha1 and Beta1 form the peptide groove where antigens bind.
How does the peptide binding groove of MHC class II differ from MHC class I?
It allows for larger peptides to bind (13-18 amino acids)
For MHC Class I and MHC Class II, which regions of the receptors have the greatest amount of polymorphisms?
MHC Class I- alpha 1 and alpha 2
MHC Class II- alpha 1 and beta 1
Note that these are the peptide binding groove for each MHC
What is the dual recognition system that is critical for T-lymphocyte function?
The ability of T-lymphocytes to recognize antigens when associated with the organism’s own MHC/HLA Haplotype.
What is the function of MHC class II receptors on Dendritic cells?
To allow dendritic cells to present antigens to naive T cells to allow for “priming” of the T cells
What is the function of MHC class II receptors on Macrophages?
For antigen presentation to CD4+ effector T cells in the cell-mediated immune response
What is the function of MHC class II receptors on B lypmhocyte cells?
Antigen presentation to CD4+ Helper T cells in the humoral immune response (T cell - B cell interactions)
What are the costimulators for MHC class II receptors on APCs such as dendritic cells, macrophages, and B lymphocytes?
CD40-CD40L
Antigens entering via the periphery are filtered by the ____.
Antigens in the blood are filtered by the _____.
Ags from periphery are filtered by lymph nodes
Ags from the blood are filtered by the spleen
When dendritic cells are activated, they lose adhesion markers allowing them to travel to lymph nodes unaffected. What is the marker they up regulate to allow entry into the lymph nodes?
when they are in the lymph nodes what receptor is up regulated to allow costimulation with T cells?
CCR7
CD80 on the Dendritic cells are upregulated to bind to CD86 on T cells (costimulation) and allow presentation to T lymphocytes
Differentiate between the types of pathogens Class I and Class II MHC receptors are used to kill?
MHC class I kills intracellular pathogens
MHC class II kills extracellular pathogens
Describe the pathway of MHC class II synthesis.
Exogenous proteins are ingested and degraded in a lysosome and endosome. From the endosome the ER synthesizes MHC class II and the antigen is further degraded in the lysosomes where MHC from the ER migrates to and binds with CLIP.
In the lysosome, CLIP is removed which allows for the processed antigen to enter the MHC class II.
MHC class II with the antigen from the lysosome migrates to the surface of the cell to allow for binding with T cells
Describe the pathway of MHC class I synthesis.
Cytosolic antigens are processed in the proteasome via ubiquitin. From the proteasome, the processed antigen enters the ER using TAP and binds to MHC class I.
MHC class I + antigen migrate to the golgi and then to the exocytic vessicle and then leaves the cell to bind to CD8+ T lymphocytes.
Describe what cross presentation is?
Extracellular pathogens are taken up and end up getting processed by the proteasome therefore allowing them to be expressed on MHC class I receptors and bind to CD8+ Cytotoxic T lymphocytes
T/F: Even in the absence of infection, protein degradation and peptide transport occur constinuously
True
What is a major factor that determines the success of transplantation?
HLA/MHC matching from patient to donor
Which HLA associated disease occurs in 88% of individuals that express the HLA-B27 allele?
Ankylosing Spondylitis- inflammation of the spine
Describe the issue with a rheumatic fever from streptococcus pyogenes and how it causes an HLA associated disease.
The generation of antibodies against the streptococci cross react with cardiac tissue. Patients with the HLA-D4 allele are more prone to develop rheumatic fever.
This is what grandma had
What disease occurs from down regulation of the TAP protein, which is used to transport antigens into the ER for MHC class I presentation?
Human Neuroblastoma
What are the molecules that are involved in the transport of proteins and loading of MHC class I receptors? Essentially asking what allows for the antigens to move into the ER for each MHC class…
What about for MHC class II receptors?
TAP- MHC Class I
Invariant chain- MHC class II
