Define these terms:
- pro-B cell
- nude mice
- T cells
- receptor editing
- toxic shock syndrome –
- CD3 –
- double positive thymocyte –
- anergic B-cell
- Ig isotypes
- Ig allotypes
- Ig idiotypes
Draw a picture of a T cell surface when it first becomes double positive. Label all the proteins you want me to grade.
Draw a picture of a Large pre-B cell surface Use colors as you see fit. Label all the receptor proteins you want me to grade.
Explain how a small pox vaccine works. Begin with what is injected and follow it through to the adaptive immune response.
How are recirculating T cells kept alive? In other words, describe the interactions that mature but naïve T cells use to avoid apoptosis.
The diversity of the Ig repertoire is generated by four main processes. Name each of them and briefly explain.
Where does an Anergic B cell die?
The frequency of mature naïve B- and T-cells that are specific for any given antigen are on the order of 1/10000 to 1/1,000,000. How then do activated TH cells manage to encounter B-cells with the specificity for the same pathogen? (Give details of both T- and B-cell activation)
Explain the final T cell outcome for this experimental conditions:
Thymectomized mouse with MHCbxc given donor thymus of genotype MHCc.
Table of Contents
Double positivity of T cell surface
Large pre-B cell surface
Working of Smallpox vaccine
Recirculation of T cells
Death of anergic B cell
Management of activated TH cells in encountering the B cells
Final T outcome of Thymectomized mouse with MHCbxc given donor thymus of genotype MHCc
Haplotype: Haplotypes are a particular group of alleles that are inherited together within a single parent from one of the two homologous chromosomes. Haplotype analysis is required in case of a gene-mapping experiment which involves intercross mating schemes and backcross. However, the particular mixing of MHC alleles on a single chromosome is called as MHC haplotype.
AP1: Activator protein or AP1 are transcription factors which regulates gene expression through a signaling pathway known as mutagen-activated protein kinases (Murphy & Weaver, 2016). Their primary role is to activate the expression of chemotactic factors and pro-inflammatory cytokines. It also regulates expression in response to different stimuli which includes stress, viral and bacterial infections and some growth factors.
JAKs: The Janus kinase (JAK) family is the signaling chains of some cytokine receptors belonging to hematopoietic family. This group of kinases is non-covalently linked with some proteins of tyrosine kinases and is classified into four division: Jak1, Jak2, Jak3 and Tyk2. JAK group phosphorylates on their receptors with the help of certain tyrosine residues.
Pro-B cell: The pro-B cells are said to be lineage committed. These cells occur when common lymphoid progenitor (CLP) are closely associated with B-cell lineages. It is a definitive B-cell stage which is induced by certain transcription factors known as E2A. The pro-B cell is also responsible for the rearrangement of the heavy-chain locus during the development of B-cell.
RAG-½: It is a recombination activating gene encoded by humans. Rag-½ is a complex that has the capability of recognizing the Recombination Signal Sequence (RSS) and later it nicks the DNA. As per the views of Rommel et al. (2017), RAG-1/2 also edges on the D, J and V regions in a gene coding for the light and heavy chains of an antibody.
TdT: TdT is a specific enzyme in a recombinase complex which randomly adds nucleotides in the ends of single stranded RNA. It is a lymphoid specifically enzyme which in other words known as Terminal Deoxynucleotidyl Transferase. The addition of this nucleotide normally takes place in any order, where there is no requirement of preceding the other (Murphy & Weaver, 2016).
VpreB: It is a light chain domain of V region located specifically at the terminal end of an amino acid. These proteins are also responsible for dimerization in other domains of an immunoglobulin. However, it is also responsible for the cross linkage on the cell surfaces of adjacent pre-B cell receptor.
Nude mice: Nude mices are laboratory mices that has been developed from a strain followed by a genetic mutation. This mutation has however resulted to an absent or a deteriorated thymus, thus resulting in an unnatural immune system causing a decrease in a number of T cells. According to Hiroshima et al. (2015), nude mices are responsible for responses of acute rejection.
NK: The natural killer cells or NK cells belong to the class of a lymphocyte and are also a constituent of an innate immune system. A distinctive granular cytoplasm is identified in this type of cells. They play a significant role in both viral infected cells and tumors by implementing the process of host rejection.
T cells: T cells or the T lymphocyte are identified by their receptor and are located in bone marrow especially in all white and red blood cells. These cells mature at the thymus and play an important role in a cell-mediated immunity (Murphy & Weaver, 2016). This T cell binds with the antigen-complexed MHC molecule II for its activation.
Receptor editing: It is a process of adaptive immune system which takes place while B cells are under maturation. An ongoing antibody gene which has a functional antigen receptor is rearranged in this editing process. This process involves apoptosis through cell death which further results in deleting the clone selection and induction.
Toxic shock syndrome: A toxic shock syndrome is a rare and potential fatal disease generally caused by a response caused by a huge production of cytokines through CD4 T cells. This syndrome occurs when the bacterial super antigen toxic shock syndrome toxin-1 or TSST-1 gets proliferated by secretion through Staphylococcus aureus or Staphylococcus pyogenes.
CD3: It is a multimeric protein complex consisting of four polypeptide chains; delta (δ), epsilon (ε), zeta (ζ) and gamma (γ). Chen et al. (2018) opines that all of these chains are linked as a disulfide bridge homodimer. This CD3 complex also known as T3 complex contains an immunoglobulin domain which functions as three pairs of dimers (εγ, εδ, ζζ).
Double positive thymocyte: Double positive thymocyte or double positive T generally expresses both CD8 and CD4 cells. This thymocyte is firstly responsible for proliferation, however some cells stops proliferation cycles (Murphy & Weaver, 2016). Cells accompanying this thymocyte die after it have failed a positive selection. However, the survived cells are responsible for maturation to a single positive T cells.
pTɑ: The pre-T alpha or pTɑ is a gene that encodes a protein which forms the newly expressed TCR beta chain with the pre-TCR during the early development of T cells. Based on the views of Galetto et al. (2015), it is an earliest marker of a lineage of T cell which helps to develop T cells at the checkpoint of selection.
Anergic B-cell: There are some B cells that are self-reactive which remains inactivated and enter across an environment of permanent unresponsiveness which is termed as anergy. This cells don’t die immediately and are not activated with specific antigen with the compliance from antigen specific T-cells. As per the views of Szodoray et al. (2016), this cell only rises when autoantigens are activated.
B-1: It is a part of B cell that is a major source of natural antibody and it takes part in innate immunity system during its development. These cells are reduced in their number within the second lymphoid organ and are basically found in adequate quantities. They are mainly present in pleural and peritoneal cavities (Murphy & Weaver, 2016).
TFH : T-follicular helper cells are a subset of CD4 T cells which has an interaction with B cells in regulating the antibody production while an immune response. This subsets main role is to act as a site of injury or infection in the adequate peripheral tissue or lymphoid tissue of a human body
Ig isotypes: Immunoglobulin isotype or Ig isotype is a class of protein which encodes antibodies resulting in the formation of B-cell receptor or B-cell antigen receptor. This receptor expresses the isotypic function of an antibody by a specific binding with the Fc receptor. Thus, Ig isotype is reflected through the maturation stage of B cells.
Ig allotypes: Immunoglobulin allotypes are those groups of allotypes that are responsible for genetic linkages in an individual. They are helpful in determining the allelic exclusion which depicts a linkage among the constant and the variable regions of a gene (Murphy & Weaver, 2016). Ig allotypes significantly shows that all heavy chains of a gene are closely linked.
Ig idiotypes: Ig idiotypes are uncommon determinants of an antigen which is located on an individual antibody molecule or certain molecules of a specific identity. This idiotypes have the exact number of hypervariable regions with a exact regulation of immune responses. Ig idiotypes plays an important role in treating B cells tumors and providing vaccination.
Fas: Fas is a special type of ligand which belongs to the family of tumor necrosis factor. It is actually a transmembrane protein of type-II function containing a death domain in its own cytoplasmic bounded tail, thus inducing death through apoptosis. Joyce & Fearon (2015) stated that Fas plays a crucial role in regulating the overall immune system.
AIRE: AIRE or autoimmune regulator is a long chain containing amino acid which triggers the mutation of cancerous cells. It is a transcription factor playing an efficient role with the help of thymic medullary epithelial cells (mTEC) in the ectopic expression of antigens related with specific tissues. These regulators are located on the chromosome number 21q22.
Granzymes: They are serine proteases which penetrate through the cell membrane by releasing some small cytoplasmic granules within the natural killer (NK) or cytotoxic T cells. Granzymes are responsible for cell death through apoptosis in their target cell, while deleting the infected or cancerous cells, viruses or bacteria (Murphy & Weaver, 2016).
Figure 1: Positiveness of T-cell surface
(Source: Joyce & Fearon, 2015)
Figure 1: Large pre-B cell surface
(Source: Szodoray et al. 2016)
A smallpox vaccine named as vaccinia helps an individual to develop immunity against the deadly viral disease smallpox. This vaccine is given on a person’s body using two-pronged needle through sudden punctures on the upper arm. Then the site of vaccine is covered with gauze to prevent the virus of the vaccine being transmitted to another part of the body or another person. On about 3 days, a red bump is seen on the vaccination site and on about 5 days, the bump is clearly filled with white fluid. By day 7, the fluid becomes cloudy white and increases to its largest attainable size by day 10. Over about 21 days, the vaccine site is back to normal with reducing smallpox rashes by falling off of dried pustule and undergoing normal skin reactions. These reactions are a positive sign that a body is developing an immune response to the smallpox virus. This are actually adaptive immune response which clears the localized vaccinia virus in the vaccination site and thus enhance the long-lived memory response which are capable of clearing and recognizing the smallpox infection.
Recirculation of T cells is alive due to the different mechanism of mature and naive T cells. The mature T cells live for about 6 months whereas 9 years for naive cells. Immunological memory can last for a long period of time by maintaining the division of existing memory T cells by recruiting the naive. Death mechanisms are different for both of the cells. However, the recirculation of T cells is alive in the automated process by anti apoptotic molecules.
Diversity of the Ig repertoire
The diversity of Ig repertoire is generated through four main processes:
Low resolution technique to identify cell types and analyze the index for overall repertoire: In this process, the analogy is to catalogue the animals based on their genus level other than species. Based on the views of Chen et al. (2018), it reflects on the diversity of other as being one. However, it can also take up specific losses in relation to their diversity
Looking at few subtypes and working on overall subtypes: According to this diversity process, one makes up a hundreth of the overall immune system consisting of 100 subtypes.
Locate a lot of individual cells and estimate the total number of subtypes: It takes a lot of effort in identifying the DNA sequences from genes but this process have become easier for future generation. Here it is possible to sequence thousands of genes with its blood type and samples.
Assessing clinical tests for determining the normal range of cell types: This process however gives the determination of the immune repertoire in compliance with the entire subset missing.
The anergic B cells usually die at the periphery where the spleen and lymph node is located. Szodoray et al. (2016) opines that this group of B cells quickly dies if the periphery has an absence of the existing foreign antigen which may be responsible for the reversibility caused by B cell anergy.
The development of T cell dependent antibodies needs the activation of B cells by T-helper cells for responding to the same specific antigen. This process is known as linked recognition. As per the views of Ito et al. (2016), a CD4 specific T cells is activated first to produce the selective armed helper T cells which helps to make induced B cells. However, this process occurs by interaction through antigen-presenting dendritic cells. The epitope recognizes the armed T helper cells to link with the recognizing B cells. Thus through recognizing a specific epitope in the cell body of a protein, the T helper cells can manage to encounter with the B cells for the specific pathogen.
Thymectomized mouse is challenged with sheep erythrocytes through an injection of live thoracic duct lymphocytes. Yamada et al. (2015) opines that injective is very effective and allogenic as this duct lymphocyte has the capability of reconstituting their own host. Elevation to response was not finally mitigated as achieving direct through bone marrow cells. The final T outcome has marked a redundancy in the restored capacity of neonatally thymectomized recipients affected with such sheep erythrocyte. However, it suggest that there are various cell types either in thoracic duct lymph or in thymus having the capacity to react spontaneously with antigen and also to induce differentiation to antibody forming cells.
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