Immunology - T cells
What are the 3 types of T Cells?
Helper T cells are CD4+. They recognize antigens that are presented by phagocytic cells. They produce cytokines, activate phagocytic cells to become more active. Cytotoxic T lymphocytes are CD8+ recognize microbes and infected cells. Kill cellular reservoirs of infection intracellular bacteria, fungi, protozoa virus. Regulatory T cells modulate immune response, can turn off responses.
What happens to T Cells if they bound moderately well to MHC I?
If T cell bind well to MHC I, they lose CD4+ and keep CD8+ become Cytotoxic T cell.
What happens if T cells cannot assemble alpha and beta cells?
If T cells cannot assemble A & B cells, it will assemble gamma & delta lymphocytes.
How are autoreactive T Cells regulated in the Thymus? What are their fates when they mature? How are matured T cells activated, specifically, what stimulus do they react to?
If immature T cells react to self molecules it would die in thymus. Then we have development of matured T regs that go into periphery that downregulate continually autoimmune diseases. T Cells are MHC restricted - only activated by foreign peptides presented on MHC molecules.
What happens to T Cells if they bound moderately well to MHC II?
If the T cell can bind moderately well to MHC II, they keep CD4+ lose CD8+ and become Helper T cell.
How are CD4 and CD8 T cells get Activated?
1) Naïve T cells never see antigen. They differentiate and expand and become effector T cells after seeing antigen from APCs. Clonal expansion occur. 2) They produce cytokines, interact with B cells, allowing B cells to switch isotypes and produce antibodies of different class. 3) After B cells interact with T Helper cells and switch isotypes, starts to make IgG or IgM depending on cytokines they receive from T Helper cells. 4) T helper cells produce cytokines that induce macrophage, activate granulocytes to induce inflammation, induce neutrophils. 5) Cytotoxic T lymphocytes adhere, mature to cytotoxic T cells, migrate to lymphoid organs (nodes) where interaction would occur, in cortical regions where B and T cells interact in lymph nodes. 6) From there, cell could go into circulation and go to site of infection, produce cytokines induce phagocytosis and produce cytokines to induce cells to come and fight. 7) Some turn into memory T cells.
T cells with Gamma-Delta receptors lack what glycoproteins on their membranes?
CD4 and CD8 They are CD4 negative and CD8 negative
T Cells with Alpha-Beta receptors have what glycoproteins on their membranes? What are they important for?
CD4+ and CD8+ Important for antigen-MHC binding
Describe Positive Selection. -Initially T cells are double positive CD4 CD8, after MHC selection, what happens to their double positive status? What does this mean? -What happens when a T cell with TCR cannot bind MHC?
First, positive selection. They are still double positive CD4+ CD8+ and they have randomly assembled TCR, which has configuration that can bind MHC. After MHC selection, which means it can bind to MHC peptide with moderate affinity, they can go from ++ to + If T cell with TCR can't bind MHC, it dies
What are the functions of T cells?
Lyse. Upregulate immune response. Activate macrophage and receive signals from macrophage. Produce cytokines. Downregulate immune response.
What happens in Negative Selection of T Cells? What is Central Tolerance?
Medullary thymus epithelial cells (MTEC) express and present AIRE, unique protein autoimmune regulator, allow medullary cells to express a LOT of self molecules. Negative Selection (central tolerance) occurs when T cells with high affinity to self-MHC molecules are deleted. This ensures self tolerance .
What are other means of activating NKCs?
NK cells (have FC receptors on them) can be linked to target cells by antibody molecule bridging it. NK FC receptors can be bound to antibody molecule that's bound to antigen. IgG binds to Fc receptors bridging, recruit inflammatory cells and phagocytes.
What are the two lineages of T Cell Receptors and what glycoprotens are expressed on them?
T Cells with alpha-beta receptors express CD4+ and CD8+ glycoproteins T Cells with gamma-delta receptors and are CD4- and CD8- for glycoproteins
What is the general process that occur in Thymus for T Cells?
T cells develop in thymus (cortex to medulla) from bone marrow. In there, they express CD4 and CD8. Assembling TCRs, select those that can recognize MHC, and come out as effector T cells.
TCRs overall structure resemble what structure on Antibodies?
The Fab fragment
What do NKCs express, what activates them and what do they release?
They don't have AG specific receptors like T and B lymphocytes. They get recognized and activate in a different manner. They cover scenario when MHC molecules presenting antigen to Cytotoxic T cells get deactivated. NK cells fill in the gap and perform regulatory jobs by producing cytokines: interferons. They can lyse target cells like NK cells.
How do NKCs recognize targets?
They work by Missing Self action. They have inhibitory receptors and activating receptors. It's a balance.
Describe the CD4 & CD8 expression process.
1) They are CD25+ first as precursor going into thymus, no CD4 or CD8+ first. There is molecule that turns them into T cells. Initially, they are double negative for CD4/CD8. 2) Then T cells start assembling TCRs beta chain, then alpha chain, become TCR-AB or if not TCR-YD. 3) T cells with TCR expressed will be CD4+ and CD8+. Begin travel through cortex. 4) In cortex, encounter antigen and begin selection. After selection, come out with CD4 or CD8 on there. Post delivery, they are CD4 or CD8+. 5) CD4 T cells will have helper functions and CD8 T cells will have cytotoxic functions.
Describe the properties of gamma-delta TCR lymphocytes. - Do they have single or double positive stage? - True or False: gamma-delta TCR lymphocytes are involved in innate immunity as well as adaptive immunity. - True or False: gamma-delta TCR can undergo thymic education and can interact with MHC but is of a lesser reactivity. -What types of molecules do they recognize?
Comes out early stage of development. Important at young age. They do not have double positive stage. Part of innate immunity. DOES NOT GO THROUGH THYMIC EDUCATION LIKE ALPHA AND BETA TCR LYMPHOCYTES. THEY CANNOT INTERACT WITH MHC or antigens and protein molecules. They recognize lipids and heat shock proteins..
Describe MHC selection. - What does MHC bind - Compare MHC specificity to B and T Cells. - What happens if cells are bound strongly to self MHC complexes? -What happens if cells are bound just right to MHC complexes?
MHC have group for binding peptides, can bind self and foreign peptides. Very promiscuous unlike B and T lymphs. Immature cells under go - and + selection based on how strong they bind MHC. If T cells bound to strongly to self MHC complexes = apoptosis If T cells bound not too strong, just nicely, they will mature in peripheral tissues.
Describe NKC's balance of inhibitory vs. activating receptor action.
NORMAL: In a normal cell, it would be the ligand that engage activating and inhibitory receptors. Healthy normal cells have MHC class I. NK cells would be engaged to that MHC by inhibitory receptors. It would have activating receptors that bind to ligand also but inhibitory receptors are higher in concentration and would not activate the activating. ABNORMAL: When virus comes in and downregulate MHC class I, inhibitory receptors are gone. Then balance towards activation. NKCs would activate and produce lytic enzymes.
How do T Cells recognize antigens? How does this differ or is similar to B cells?
T cells do not recognize antigen as 3D foreign structure like B cells but recognize antigens processed by APCs, which generate a peptide and present to T cells. MHC has groove carrying fragment of peptide and TCR come in and interact with structure.
Describe Regulatory T Cells development through the CD Selection process in the Thymus. What are Regulatory T Cells' importance in the immune system?
T reg also express Alpha Beta receptors. Going through CD4/CD8 selection and they are CD4+. They go into periphery and downregulate autoimmune disease and respond to self molecule in periphery. In case clone for some reason that's auto reactive, this T reg will downregulate that in the periphery. Important in immune disease regulation
Compare and contrast the biochemical structure of TCR to BCR.
TCR can be assembled from a,b,y,d, forming two types of A-B and Y-D receptors with disulfide bonds. -Similar to BCR, it has light chains kappa and lambda, and 5 isotypes for the heavy chains. Each peptide has Variable and constant region.
What do cytotoxic T lymphocytes (CTL) do? -How do they bind a target? -What do they secrete? -What are the effects of their secretions?
Use TCR to bind to target, which is presenting the viral antigen it has through MHC I molecules through CD 8 T lymphocytes. Adhesion molecules facilitate interaction, activating CTL Reoriented cytoskeleton that secrete granules that include perforin, like C9. They produce cytokines such as IFN-Y and TNF-B. This interferon would inhibit virus from enter and replicate. TNF and granzymes would also kill target cell.
What is the Antigen Recognition Site of T Cell composed of? What determines it's specificity properties?
Within variable region, we have hypervariable region or complementarity-determining regions CDRs 1-2-3 for each a, b, y, d chains, closest with antigen that are presented through MHC. The amino acid residues in hypervariable region determine specificity. Not y shape. Not divalent but MONOVALENT.
