Lymphocyte development and diversity: Flashcards
What is clonal selection?
- Clonal selection- process by which an antigen will find the right lymphocyte that recognizes it and therefore select the clone
o Allows initiation of adaptive immune response
What is clonal expansion and how does it happen?
- Clonal expansion- when a specific lymphocyte proliferates to deal with specific microbial expansion
o How this expansion happens is that the antigen receptor generates signals which leads to mitotic division of the cell
o Therefore, clonal expansion leads to an increase in the number of lymphocytes specific to the microbe-> the expanded lymphocytes eradicate the microbes
How are clonal selection and clonal expansion linked?
o Clonal selection (binding of the microbe to a lymphocyte receptor) leads to clonal expansion (proliferation)
What are the challenges that the adaptive immune system must overcome to mount a specific response to a microbe
o Lymphocytes must search an enormous amount of physical space to locate microbes that bind their specific receptors
o Microbes can multiply extremely rapidly, potentially outpacing the immune system
o There are only a few lymphocytes with receptors specific for any given microbe
What is the diversity of lymphocytes that exist before infection?
- Before infection, there exists a large and diverse library of lymphocytes with different specificities
o Specificities based on antigen receptors of each lymphocyte clone
o Almost any possible molecule will be recognized by some of these lymphocyte receptors, but very few lymphocytes of any one specificity exist
Where do blood cells descend from?
- All blood cells descend from hematopoietic stem cells (from bone marrow)
What provides food for the hematopoietic stem cells?
o Fat cells/adipocytes provide food for hematopoietic stem cells
What happens when hematopoietic stem cells divide?
- Hematopoietic stem cells (HSC) are self-renewing
o When hematopoietic stem cells divide, they produce two cells:
An exact copy of themselves
A differentiated cell (a lymphoid progenitor cell)
What are 2 pathways that hematopoietic stem cells can go through?
-Common myeloid progenitor
-Common lymphoid progenitor
What cells does common myeloid progenitor produce?
Can lead to megakaryocytes which turn into platelets (for blood clotting)
Can lead to red blood cells (oxygen delivery)
Precursor to monocytes, macrophages and dendritic cells
Precursor to neutrophils, basophils and eosinophils
What cells does common lymphoid progenitor produce?
o Another precursor cell called the common lymphoid progenitor which gives rise to lymphocytes in blood
Gives rise to B cells and T cells (both CD4+ and CD8+ T cells)
Gives rise to innate lymphoid cells-> gives rise to Natural Killer/NK cell
What is the differentiation process for B cells?
- B cells mature primarily in the bone marrow
o HSC-> common lymphoid progenitor cell-> pro-B cell-> pre-B cell produces an antibody heavy chain (checkpoint)-> immature B cells with full surface Ig molecules-> immature B cell moves into other tissue where maturation happens (lymph nodes, spleen and mucosal associated lymphoid tissues
What is the differentiation process for T cells?
- T cells mature primarily in the thymus
o Start with HSC in the bone marrow-> common lymphoid progenitor cell in bone marrow-> pro-T cell in bone marrow-> pro-T cell migrates to the thymus-> differentiates into a pre T cell (double negative cell) that makes the beta chain of the T cell receptor, TCR (checkpoint)-> double positive cell with full TCR ( cells express CD4 and CD8 and TCR cells)-> mature T cells only express CD4 OR CD8: to do full maturation they travel to secondary lymphoid organs like lymph node or spleen
What are major histocompatibility complex molecules?
- Major Histocompatibility Complex (MHC) molecules-> transmembrane proteins that bind to peptides and display them to T cells
What is the difference between B and T lymphocyte mechanisms for recognition of antigens?
- B cells can recognize virtually any structure
o Leads to distraction-> they can’t see everything at once
o Antibodies can see everything - T cells can only recognize peptide-MHC complexes displayed on the surface of cells
o T cells are uniquely capable of recognizing infected cells
o T cells are virtually blind- they can ignore everything
What is V(D)J recombination?
- V(D)J recombination is the genetic shuffling process that generates receptor diversity
What makes up antibody and T cell receptor genes?
- V,D and J segments make up antibody and TCR (T cell receptor) genes
What is the Dreyer and Bennett hypothesis?
o The Dreyer and Bennett hypothesis: antibody genes must come in pieces which could create an enormous amount of diversity because of mixing and matching different segments into one cell, as well as deleting or adding stuff in between segments of the cells
Gene rearrangement
What contributes to the diversity in the generation of lymphocyte receptor genes?
V(D)J recombination, combinatorial diversity and junctional diversity
* Combinatorial diversity and junctional diversity contribute to an enormously diverse repertoire of lymphocyte receptors
What is junctional diversity?
o Junctional diversity- type of diversity caused by variability in the sequences that join the gene segments
What are treatments for psoriasis?
- Topical steroid creams
- Topical vitamin D creams
o Calcipotriene - Methotrexate (immunosuppressive small molecule drug)
- Cyclosporine (immunosuppressive small molecule drug)
- UV light therapy
What is the mechanism of methotrexate and the side effects?
- Methotrexate (immunosuppressive small molecule drug)
o Oral medication taken once a week
o Targets lymphocytes
o Led to infections and PGs for the patient
o Side effects
Increased risk of infection
Affect the liver
Need to avoid excess alcohol use
Affects bone marrow/suppresses production of blood cells - Folic acid metabolism
What is the mechanism of cyclosporine and what are its side effects?
- Cyclosporine (immunosuppressive small molecule drug)
o One year drug: but can go on it for several years
o Inhibits lymphocytes
o Side effects:
Increased blood pressure
Affect kidneys
Blood cell counts
What is the mechanism of UV light therapy for psoriasis treatment?
- UV light therapy
o Focused wavelengths of UV light (narrow band UV-B) is used to treat inflammatory diseases of the skin/psoriasis
o Light penetrates upper layer of the skin which turns down lymphocyte function
