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Tuesday, 4 October 2022

Immunology Q&A

Antigen capture & Presentation to lymphocytes.

1. De ne MHC restriction.
Answer: MHC restriction means that the T lymphocytes are only able to recognize peptides of
antigens when these peptides are on the MHC molecules.

2. What are APCs?


Answer: APCs are antigen presenting cells, which capture the antigens, and present them to
lymphocytes.

3. What are MHC molecules? What are their functions?


Answer: MHC molecules - Major Histocompatibility complex, are molecules present in APCs, which
bind to the peptides. They’re function is to bind to the peptide and present it to the lymphocytes.

4. How are Dendritic cells activated?


Answer: Dendritic cells are antigen presenting cells. Dendritic cells upon interaction with the
microbe, engulf them. At the same time other innate immune system cell receptors TLRs are also
stimulated by these microbes which results in production of the cytokines, like tumor necrosis factor
and this activates dendritic cells.

5. What is CCR7?
Answer: CCR7 is a receptor which is expressed on the dendritic cells after activation. CCR7 is
attracted to chemokines that are produced by lymphoid tissue at the sites where are T lymphocytes
in the lymph nodes. This is important so that dendritic cells carry captured antigens to the T
lymphocytes.

6. What are the di erences between MHC class I and MHC class II?
Answer: There are several di erences between class I MHC and class II:

MHC class I MHC class II

* Found on all nucleated cells on mammals. * Mainly found on APCs.

* Composed of three alpha domains and one * Composed of two alpha and two beta
beta domain. domains.

* Present antigens to cytotoxic T cells (CD8+). * Present antigens to the T helper cells (CD4+).

* Responsible for cytosolic antigens. * Responsible for extracellular antigens.


7. What is HLA?
Answer: Genes in MHC complexes, that help in encoding of proteins of MHC complexes.

8. What is processing and how is it di erent in MHC I and MHC II?


Answer: Processing is getting the antigen peptides ready for presentation to the lymphocytes.

* In MHC class I, processing involves ubiquitin - proteasome pathway: intracellular antigen proteins
are unfolded, and covalently bound to ubiquitin, then taken to the proteasome, where we have
proteolytic enzymes and this enzymes turn proteins into peptides, so that these peptides can t
into the MHC class I molecule.

* In MHC class II, processing starts with phagocytosis of the extracellular proteins. Then these
proteins are in the APCs and degraded to the peptides by lysosomal enzymes.

9. What is Cross presentation of internalized antigens?


Answer: Normally, most internalized proteins are presented to CD4+ cells by the MHC II molecules.
Cross-presentation occurs when the infected cells are not able to express enough signals for T-cell
activation and dendritic cells are not in the area. Well, specialized dendritic cells are able to take
antigens from such places and take them to the lymph nodes, where the T cells are, but these
dendritic cells express MHC class I molecules and can present to CD8+ cells, an that is what
happens.

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Tuesday, 4 October 2022
10. How are peptides bound to the MHC molecules?
Answer: This process is somewhat di erent for both MHC class molecules:

* MHC class I are always produced in the ER, whereas the peptides are in the cytosol, to solve this
problem, TAP bind the peptides and pumps into the ER. New MHCs bind to a protein tapasin,
which binds MHC I to TAP and MHC I easily binds to the peptides which were brought by TAP.

* MHC class II are also always produced in the ER of APCs. Each new MHC II carries invariant
protein, which is bound to the peptide binding cleft of the MHC II molecule. MHC class II go from
the ER to the Golgi clefts and then to the endosomes where the proteins are being degraded into
peptides. Here we have MHC II-like molecule called the MD, which takes the invariant protein and
frees the peptide binding cleft of MHC, so the MHC II is able to bind the peptide.

11. What is immunodominant peptide of an antigen?


Answer: Immunodominant peptide is the peptide that is able to bind the MHC molecules, when
proteins are degraded many peptides are produced, but only those can be presented to lymphocytes
that are able to bind with the MHCs.

12. Describe the MHC I pathway of antigen presentation.


Answer:

* Production of proteins in the cytosol.

* Proteolytic degradation of proteins (proteasome).

* Transport of peptides from cytosol to ER.

* Assembly of peptide class I MHC complexes in the ER.

* Surface expression of peptide - class I complexes.

* CD8+ cells recognize the peptide - class I complexes.

13. Describe the MHC II pathway of antigen presentation.


Answer:

* Phagocytosis by APCs

* Processing of internalized proteins in endosomal/lysosomal vesicles.

* Biosynthesis and transport of class II MHC molecules from ER to the endosome.

* Association of MHC molecules to the peptides.

* Expression of the peptide - class II complexes on the cell surface.

* CD4+ recognize the peptide - class II complexes.

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