Where are naive, effector and memory T cells found
Naive T cells are always in the lymph nodes whereas effector T cells are always on the tissues. Memory T cell can be found both in the lymph nodes and in the skin and tissues.
What is the name of the dendritic cells in the skin
How are antigens present in the tissues and in the blood presented to the T cells
Dendritic cells phagocytose foreign matter in the tissues. They then move to the lymph nodes and present antigen to the T cells. On the other hand antigens present in the blood are filtered off in the spleen by APCs.
What are the 3 APCs
1. Macrophages 2. B cells 3. Dendritic cells
How do dendritic cells mature
Immature dendritic cells lie in the tissue, when they encounter an antigen, after they phagocytose a foreign particle, they get matured and activated by TLRs and cytokines. This maturation process induces the dendritic cells to move to the lymph nodes
What kind of ILs are important in viral infections
Type 1 ILs, so alpha and beta ILs
What are the 2 major types of dendritic cells and what are their functions
There are classical dendritic cells that we mostly talked about, they're the ones that make TNF and IL6 and then there are plasmacytoid dendritic cells that are important in viral infections since they make IL type 1
Explain the structure of the lymph node
Outside (green) is the B cell zone and then inside (red) is the region called T cell zone. The red stains are actually dendritic cells, they go to the T cell zone and interact with T cells in order to presnt the antigen.
From where does the dendritic cells and naive T cells enter the lymph nodes
Dendritic cells come from the afferent lymphatic vessel and leave from the efferent lymphatic vessel whereas the T cells come from HEVs or High Endothelial Venules
Explain the structure of the lymph nodes in detail
The B cell zone is called the cortex and the T cell zone is called the Paracortex. Medulla is where the B cells go when they are pumping out the antibodies. Follicles is where the B cells are assembled. Also the entire lymph node is covered in a capsule.
Histology of lymph node
The answer to this is C and she stated that sepsis usually is caused by bacterial infection with the bacteria invading in the blood. This will go unchecked if there is no spleen whereas if there is an uncontrolled viral infection, dendritic cells in that tissue will still be able to phagocytose, mature and move to the lymph nodes to present the antigen to the T cells
What does the CD4 and CD8 T cells respond to and how do they bind to MHC
CD4 cells only respond to MHC II whereas CD8 cells only respond to MHC I. They bind bind to the MHC complex by binding to the parts of MHC as well as by binding to the antigen that is being presented
What gene codes for MHCs and where is it found
The principle locus that determines grafts acceptance or rejection is found on chromosome 6 by the HLA genes. MHCs are coded by HLA genes (Human Leukocyte Antigens or HLAs). These HLAs or this locus, has coding for MHCs (I, II and III)
What is special in MHC gene
Theyre really polymorphic, this ensures some members of the population should be able to respond to some pathogens
Expalin the structure of HLA genes
MHC 1 genes have B, C and A whereas MHC 2 have DP, DQ, DR
How are HLA genes exressed
They are expressed in a codominant manner, genes from both of the parents are expressed
How does polymorphism and codominance help in antigen presentation
Due to codominance all of the B, C and A subunits from both of the parents are expressed. Since there are many polymorphisms found for this gene then it three subunits of HLA genes would be different which would allow six different MHC proteins to be expressed, allowing 6 different peptides to be presented altogether.
What does MHC haplotype mean
It means what kind of polymorphisms of MHC does the patient exhibit, it is usually something like B1, C2, A4 etc
Explain the difference in coding for MHC class 1 and 2
MHC class 1 is only identified by the CD8 cells whereas 2 is identified by the CD4 cells. For class 1, the HLA gene only codes for the alpha chain and the beta chain is coded somewhere else that binds to these alpha chains to complete it. For 2 both the alpha chain and the beta chain are coded by the HLA gene. On the top of both of the MHCs is the N terminus peptide binding region
Why does the CD8 cells only bind to MHC 1
They bind to the alpha chains and the TCR whereas CD4 only binds to the alpha chain in the MHC 2
What are the different kind of peptides that can go in MHC 1 and 2
MHC 1 takes shorter peptides that are 8-11 long whereas MHC 2 takes longer peptides which are 10 to 30 long
What are the 3 quick facts about MHCs
1. Each MHC can present several different peptides
2. MHCs only bind to peptides, hence T cells can only be activated by antigens
3. Peptide presentation by the MHC is necessary for the MHC to stay on the cell surface membrane
What is the associated of MHC and autoimmunity
Defect in discrimination between self and non self peptides presented on the MHCs can lead to autoimmunity, there is a strong associated between autoimmunity and certain MHC alleles
What cells represent MHC 1 and 2
MHC is expressed by all cells, MHC 2 is only by APCs, however MHC 2 presentation can be induced in other cells by making IFN gamma.
Also MHC 2 is expressed by thymus cells
How does a foreign antigen go inside the MHC 2
Foreign particles are phagocytosed by the APCs. Once they are in a phagocytic vessel, a lysozome fuses with the vessicle to form a phagosome where the foreign proteins are digested into peptides. These peptides are then held in lysozomes. MHC 2's alpha and beta chain are made in the ER. Once made in the ER, chaperon keeps them togehter. Then an invariant chain added between the newly synthesized MHC 2 to keep it from falling apart. Then this MHC 2 goes and into the cytosol and fuses with the lysozome where the peptides were held. Another protein called HLA DM cleaves the invariant chain so that peptides can be inserted into the MHC 2 which is the shown on the cell surface membrane
How are peptides placed in class 1 MHC
A little more detail is required here:
Usually peptides that go on 1 are from the cytosol. In case of a virus infection, viral proteins are made which like the cellular proteins are broken down by the proteosome into peptides. MHC 1 is also made in the ER where it is held together by chaperons called the CALRETICULIN and CALNEXIN. The peptides bind to the MHC by going to ER. In the ER, there is the TAP complex and TAPASIN comolecule which takes the peptides and puts them on the MHC 1 which is then shown on cell surface membrane.
TAP plays an important role in regulating the peptides that are shown on MHC 1 since MHC 1 only can have small peptides that are can only be 8-11 residues long.
What is cross presentation
A subset of DCs (dendritic cells) can engulf a virus infected cell and it can take the antigens that were presented in that infected cell and present it in the MHC 1. This phenomena is called cross presentation.
It is important to note that only a subset of DCs can do this.
What are super antigens
1. Potent activators of immune system
2. Staphylococcus aureus and streptococcus pyogenes
3. This develops due to excessive production of IL2, TNF alpha and IFN gamma
What is a fundamental biochemical difference between the detection of normal antigens and super antigens
Super antigens bind outside the MHC complex and it also stimulate the ligands which causes increased production of IL6, IFN gamma and TNF alpha
What are required to activate naive T cells
The answer is naive T cells require multiple signals to be activated. They also need ligands called CD28. We need to know that CD 28 binds to B7-1 and 2. B7-1 and 2 are also called CD 80 and CD 86. They also require cytokines
What is the difference in antigen presentation for T cells and B cells
B cells can detect wide variety of antigens such as proteins, polysaccharides, lipids and other chemicals whereas T cells can only detect peptides.
Also B cells can detect antigen on the microbe surface, so antien processing is not required and B cells can also detect solouble antigens
What cells present antigens to B cells
Follicular Dendritic Cells (FDCs) present antigens to B cells (FDCs are not related to the dendritic cells, they only look like dendritic cells).
Interesting thing to note is that FDCs have receptors for antigens. They just sit in the B cell zone and keep the antigen on display for B cells while they undergo somatic recombination to devise a suitable antibody to fight off the antigen
What are some other kinds of T cells that are important in immune response
NKT Cells! They detect antigens as lipids, in contrast to peptides for CD T cells. These NKT cells have an invariant TCR which detects lipids. These lipids are displayed on CD1d
What are some of the other T cells that play a role in the immune system
gamma delta T cells. They are not very well understood
What condition is associated with MHC class I and 2
Bare Lymphocyte Syndrome, it is a condition where there is a defect in one of the proteins that is associated with the synthesis, assmebly or transport of MHC to the surface membrane. There are 2 calssification of this syndrome.
Mutations are in TAP1, TAP2 or Tapasin
1. Type 1: when there is a lack of expression in the MHC class 1 which causes less CD8 T cells in the patient (MHC class 1 expression is required for the development and maturation of CD 8 T cells in the thymus).
2. Type 2: there is a lack of expression in the MHC class 2. Mutations are in CIITA, RFX5, RFXAP or RFXANK.