Immunogenetics and Transplants

Questions and Answers

What is the primary purpose of developing an immune system during evolution?

To provide a defense against microorganisms and mutated cells. (correct)

To create adaptive behavior in multicellular organisms.

To evolve complex genetic structures for cellular replication.

To enhance the growth and reproduction of multicellular organisms.

Which of the following correctly describes the relationship between innate and acquired immunity?

Innate immunity responds only to foreign antigens while acquired doesn't.

Acquired immunity is dependent on prior exposure to specific antigens for its response. (correct)

Innate immunity is less effective than acquired immunity due to lack of specificity.

Acquired immunity is an evolutionary adaptation that occurs before innate immunity.

Which cells are primarily involved in the innate immune response?

Macrophages, Basophils, and Monocytes. (correct)

T lymphocytes, B lymphocytes, and dendritic cells.

Dendritic cells, NK lymphocytes, and T lymphocytes.

Neutrophils, Eosinophils, and NK lymphocytes.

How do dendritic cells communicate with lymphocytes in the adaptive immune response?

By presenting antigens to lymphocytes for recognition. Signup and view all the answers

What characteristic of T and B lymphocytes is significant in the recognition of antigens?

Each lymphocyte possesses a unique antigen receptor. Signup and view all the answers

What is a major limitation of the first layer of defense in the immune system?

It may present vulnerabilities such as permeable mucous membranes. Signup and view all the answers

What is the primary role of memory in the immune response?

To remember the first encounter with an antigen for a faster response Signup and view all the answers

How do T-lymphocytes recognize antigens differently from B-lymphocytes?

T-lymphocytes require antigen processing and presentation by an antigen-presenting cell. Signup and view all the answers

What is a key factor that contributes to the diversity of lymphocyte recognition of different antigens?

The ability of lymphocytes to rearrange their genes during maturation Signup and view all the answers

What does the term 'MHC molecule' refer to in the context of T-lymphocyte antigen recognition?

A histocompatibility complex that presents processed peptides to T-lymphocytes. Signup and view all the answers

In which environment does the maturation of B-lymphocytes primarily occur?

Bone marrow Signup and view all the answers

What did Tonegawa's experiment demonstrate regarding the genomic arrangement of lymphocytes?

Mature lymphocytes exhibit genomic diversity due to gene rearrangement. Signup and view all the answers

What defines the specificity of an antigen receptor on a B-lymphocyte?

The variable regions located on the receptor that bind to specific antigens. Signup and view all the answers

Which types of cells do class I MHC molecules present antigens to?

T-lymphocytes Signup and view all the answers

What is the significance of HLA compatibility in organ transplants?

It plays a role in preventing organ rejection. Signup and view all the answers

Which type of stem cell is capable of differentiating into any cell type?

Totipotent stem cells Signup and view all the answers

Ethical principles in organ transplantation prioritizes which aspect?

Allocating organs based on the potential for success Signup and view all the answers

Which future perspective is aimed at addressing the donor shortage in transplants?

Tissue engineering Signup and view all the answers

What type of cells are hematopoietic stem cells known to produce?

Blood cells Signup and view all the answers

Which factor is NOT considered in the allocation criteria for heart transplants?

Body weight of the donor Signup and view all the answers

From which source can totipotent stem cells be obtained?

Embryo only Signup and view all the answers

What is a critical requirement for a transplant candidate's HLA compatibility?

HLA A, B, and DR must match Signup and view all the answers

What is a notable advantage of stem cells obtained from umbilical cord blood?

They are easier to obtain and less controversial Signup and view all the answers

What is the primary goal of nuclear transfer reprogramming?

To generate embryonic stem cells from oocytes without using embryos. Signup and view all the answers

Which of the following describes a significant limitation of the nuclear transfer approach?

It requires a vast number of cells to achieve successful reprogramming. Signup and view all the answers

What ethical concern is associated with the nuclear transfer approach?

Utilization of an excessive number of oocytes from donors. Signup and view all the answers

What is a major risk associated with induced pluripotent stem (iPS) cells?

They can inherit genetic defects from the donor cells. Signup and view all the answers

What was a key factor that led the scientific community to question Hwang's research on nuclear transfer?

He was found to have conducted unethical experiments on a large number of eggs. Signup and view all the answers

What type of cells are utilized to prevent Graft versus Host disease?

Mesenchymal stem cells. Signup and view all the answers

Which of the following best describes the contributions of Yamanka and Gurdon within the stem cell field?

They contributed to the development of induced pluripotent stem cell technology. Signup and view all the answers

What potential issues are involved with the use of viruses in iPS cell technology?

Viruses might induce genetic rearrangements leading to mutations. Signup and view all the answers

What is the consequence of a mutation in the RAG 1 or RAG 2 genes?

Rearrangement failure leading to immunodeficiency Signup and view all the answers

Which step in the genetic rearrangement mechanism involves recognizing double strand breaks in DNA?

DNA damage recognition Signup and view all the answers

What type of transplant involves genetic material from the same individual?

Autograft Signup and view all the answers

Which proteins are crucial for the formation of the VJ recombination complex?

RAG 1 and RAG 2 Signup and view all the answers

What characterizes class I and class II HLA molecules?

They have specific polymorphic sites in the peptide-binding region. Signup and view all the answers

Which of the following is NOT a factor aiding in the rearrangement of DNA during VJ recombination?

Visualizing antigen receptors Signup and view all the answers

What results from the genetic barrier experiments involving different genotype donors and recipients?

An identical genotype results in allograft acceptance. Signup and view all the answers

In the context of the human leukocyte antigen (HLA) system, what does MHC stand for?

Major Histocompatibility Complex Signup and view all the answers

What happens to the DNA segment cut out during the VJ recombination process?

It is maintained as a circular piece before being lost. Signup and view all the answers

How does the structure of the skin contribute to the organism's first layer of defense against pathogens?

The skin serves as a continuous, elastic, and resistant barrier, primarily protecting against physical and biological threats. Signup and view all the answers

In what way do dendritic cells function as a link between innate and acquired immunity?

Dendritic cells engulf exogenous antigens and present them to T lymphocytes, facilitating the adaptive immune response. Signup and view all the answers

What role do the invariant receptors of NK cells play in the immune response?

Invariant receptors allow NK cells to recognize and respond quickly to infected or cancerous cells without prior sensitization. Signup and view all the answers

What significance does genetic diversity in T and B lymphocyte receptors have on the adaptive immune response?

It enhances the immune system's ability to recognize a vast array of antigens, allowing for a more effective adaptive response. Signup and view all the answers

How did the evolutionary development of innate immunity precede the establishment of acquired immunity?

Innate immunity provided immediate, non-specific defense mechanisms that were necessary before the evolution of specific, adaptive responses. Signup and view all the answers

What is the significance of clonal selection theory in the context of lymphocyte maturation?

Clonal selection theory explains how lymphocytes recognize specific antigens and maintain memory for future encounters, allowing for a more efficient immune response. Signup and view all the answers

Describe the difference in antigen recognition between B-lymphocytes and T-lymphocytes.

B-lymphocytes recognize antigens in their native form, while T-lymphocytes recognize processed antigens presented by antigen-presenting cells in conjunction with MHC molecules. Signup and view all the answers

How do mutations in genes affect the maturation of lymphocytes?

Mutations in key genes essential for lymphocyte ontogenesis can lead to immunodeficiencies, disrupting normal cell maturation and function. Signup and view all the answers

What was Tonegawa's major contribution to our understanding of immunoglobulin gene rearrangement?

Tonegawa demonstrated that immunoglobulin genes undergo rearrangement during B-lymphocyte maturation, providing evidence that these cells have diverse antigen receptors. Signup and view all the answers

Explain the role of MHC molecules in the recognition of antigens by T-lymphocytes.

MHC molecules present processed peptide fragments of antigens on the surface of antigen-presenting cells, enabling T-lymphocytes to recognize and respond to those antigens. Signup and view all the answers

What are the roles of RAG 1 and RAG 2 proteins in the mechanism of VJ recombination?

RAG 1 and RAG 2 proteins are essential for forming the VJ recombination complex, recognizing recombination signals, and initiating the DNA cleavage necessary for rearrangement. Signup and view all the answers

Explain how the arrangement of HLA molecules contributes to the diversity of antigen recognition in humans.

HLA molecules are highly polymorphic, especially in the peptide antigen binding sites, allowing for a wide variety of antigen presentation and recognition by T cells. Signup and view all the answers

Describe the significance of the circular DNA piece that is formed during VJ recombination.

The circular DNA piece is a byproduct containing the sequenced DNA between the V and J genes, which is lost during cell division, ensuring that only rearranged genes are expressed. Signup and view all the answers

How do the results of transplantation genetic barrier experiments inform the understanding of MHC compatibility?

These experiments demonstrated that MHC compatibility is critical for successful allografts, as mismatches can lead to graft rejection. Signup and view all the answers

What is the function of terminal deoxynucleotidyl transferase (TDT) in the DNA repair phase during VJ recombination?

TDT adds nucleotides at the junctions of the rearranged V and J segments, increasing the diversity of antigen receptors. Signup and view all the answers

What are the two types of MHC molecules and their primary expression locations?

MHC class I molecules are expressed on all nucleated cells, while MHC class II molecules are primarily expressed on antigen presenting cells. Signup and view all the answers

What are the key HLA types that show compatibility in organ transplants?

The key HLA types are A, B, and DR, with HLA DQ and DP having additional benefits for kidney transplants. Signup and view all the answers

Why is HLA compatibility critical in the transplantation process?

HLA compatibility is critical because it reduces the risk of transplant rejection and enhances the chances of successful integration of the transplanted organ. Signup and view all the answers

What ethical principles must be considered when allocating organs for transplantation?

The ethical principles include justice, equity, and maximizing the gain in terms of both lifespan and quality of life for transplant candidates. Signup and view all the answers

What is the significance of stem cells in addressing transplant shortages?

Stem cells hold the potential for generating tissues and organs, which could alleviate the donor shortage for transplants. Signup and view all the answers

How are embryonic stem cells differentiated into specific cell types?

Embryonic stem cells can be differentiated into specific cell types using chemicals and culture techniques after isolation from the inner cell mass of the blastocyst. Signup and view all the answers

What limitations are associated with using embryonic stem cells for research?

Limitations include ethical concerns regarding the source of the cells and regulatory restrictions in various countries. Signup and view all the answers

What criteria are considered when evaluating recipients for organ transplants?

Criteria include ABO blood group compatibility, HLA compatibility, the absence of specific anti-tissue antibodies, age, and the severity of illness. Signup and view all the answers

What type of stem cells are found in adult bone marrow and their potential?

Adult bone marrow contains hematopoietic stem cells, which can produce various blood cell types, and mesenchymal stem cells, which produce bone cells. Signup and view all the answers

Study Notes

Immunogenetics Overview

Immunogenetics combines immunology and genetics to understand immune system evolution and function.
The immune system evolved to protect multicellular organisms from microorganisms, mutated cells, and foreign nucleic acids.
Three defense strategies evolved: physical barriers (shell), innate immunity, and adaptive (acquired) immunity.

Structure of Immune System

The first layer of defense includes continuous, elastic barriers dependent on chemical, physical, and biological mechanisms.
Weaknesses exist in membranes (e.g., gastrointestinal, respiratory, genital), making them vulnerable to pathogens.
Innate immunity includes cells like neutrophils, eosinophils, basophils, monocytes/macrophages, and dendritic cells that engulf foreign material.

Acquired Immunity

Dendritic cells bridge innate and acquired immunity by presenting antigens to NK, B, and T lymphocytes.
T and B lymphocytes develop specific antigen receptors through genetic mechanisms leading to diversity in immune response.
Memory cells retain information about prior encounters with antigens, enabling faster responses upon re-exposure.

Autoimmune Response Features

Specificity for antigens (epitopes), diversity of antigen recognition, distinction between self and non-self cells, and immune memory are crucial characteristics.
Clonal Selection Theory, proposed in the late 1950s, anticipates these immune characteristics.

Maturation of Lymphocytes

Ontogenesis and lymphocyte maturation can be studied via cancer cell lines, bone marrow analysis, and knockout mice models.
Immunodeficiencies can reveal insights about the maturation steps affected by genetic mutations.

Genetic Rearrangement in Lymphocytes

Genetic rearrangement involves variable regions (V regions) and conserved regions (C regions) in B-lymphocyte immunoglobulin genes.
Tonegawa's Nobel Prize-winning research demonstrated unique genomic arrangements in mature versus immature lymphocytes through hybridization techniques.

Mechanisms of Genetic Rearrangement

Three steps: initiation of DNA damage, recognition of double-strand breaks, and DNA repair.
RAG1 and RAG2 proteins are crucial for the recombination process, influencing antigen receptor diversity.
Errors in these rearrangements can lead to severe immunodeficiencies.

Transplantation Genetics

Transplant categories include autograft (same individual), isograft (identical twins), allograft (same species), and xenograft (different species).
MHC complex (HLA in humans) is a genetic barrier critical for transplant acceptance/rejection.
Genetic experiments identified how MHC compatibility influences graft success, highlighting the importance of HLA-A, HLA-B, and HLA-DR in organ transplants.

HLA Structure and Function

HLA molecules come in Class I and Class II forms; Class I presents antigens from intracellular sources, and Class II is involved in external antigen processing.
The HLA locus, located on chromosome 6, exhibits high polymorphism affecting antigen binding capabilities.

Transplant Criteria and Allocation

Successful transplants depend on HLA compatibility, blood group (ABO) matching, absence of anti-tissue antibodies, and recipient's age.
Ethical considerations involve equitable organ allocation and maximizing patient outcomes based on predicted success.

Future Perspectives in Transplants and Regenerative Medicine

Challenges include donor organ shortages, prompting exploration in stem cells and tissue engineering.
Stem cells, capable of self-renewal and differentiation, can be unipotent, multipotent, or totipotent (only embryonic).
Techniques to derive stem cells from various sources, including embryos and adult tissues, face ethical considerations regarding embryo use.

Ethical and Research Considerations

Stem cell research has undergone legislative changes, with some countries allowing or restricting embryonic stem cell usage.
Adult stem cells are found in many tissues, including the heart and brain, which were previously considered non-regenerative.### Umbilical Cord Blood and Stem Cells
Umbilical cord blood provides a source of stem cells similar to mesenchymal stem cells but with a more differentiated and embryonic-like nature.
Stem cells can be reprogrammed from already differentiated cells through technological advancements.

Types of Reprogramming Technology

Nuclear Transfer Reprogramming:
- Involves injecting the nucleus of an adult cell into an enucleated oocyte, resulting in embryonic stem cells without using embryos.
- Successful in mice but no nuclear transfer-derived stem cells reported in humans.
Induced Pluripotent Stem Cells (iPS):
- Adult cells are reprogrammed back to pluripotent state using a gene set known as the "Yamanaka cocktail".
- Offers similar properties to embryonic stem cells but presents risks of genomic instability and potential tumorigenesis.

Notable Achievements and Challenges

Dolly the Sheep was the first mammal cloned via nuclear transfer in 1996, spurring interest in cloning other animals.
John B. Gurdon is recognized as a pioneer in nuclear transfer techniques.
Controversy arose when Hwang's research on nuclear transfer was found fraudulent, impacting the scientific community's focus on this method.
The Yamanaka group successfully derived iPS from both mouse and human cells, establishing an alternative to nuclear transfer.

Advantages and Disadvantages of iPS Technology

Pros:
- Cells can be genetically identical to the donor, reducing immune rejection risks.
- Avoids ethical concerns associated with embryo use.
Cons:
- Maintaining genetic defects from the donor, if present.
- Potential cancer gene involvement from pluripotency factors.
- Risk of mutations due to viral gene insertion during reprogramming.

Applications of Stem Cells in Medicine

Adult stem cells are used in therapies for hematological and immune diseases.
Hematopoietic and mesenchymal stem cells can mitigate Graft vs Host disease and aid in regenerating bone and cartilage.
Skin tissue engineering employs keratinocytes cultured from biopsies for burn treatment and epidermal renewal.

Tissue Engineering Innovations

Tissue engineering has enabled the creation of virtual replacements, such as in mandible reconstruction.
Efforts in cystoplasty have led to autologous engineered bladders using tissue engineering techniques.
Research in airway tissue regeneration has focused on tracheal transplantation using a specialized bioreactor.

Experimental Therapies Utilizing Stem Cells

Cardiac muscle regeneration is explored using stem cells, with tissue-engineered scaffolds developed to replace damaged myocardium.
Stem cells are also researched for treating brain and spinal cord injuries, enabling neurons and glial cells generation.
For Type 1 diabetes, ES cells are cultured to mimic insulin-producing pancreatic islets.

Ongoing Research and Future Perspectives

Significant research continues addressing heart disease, demonstrating promising scaffold applications for myocardial repair and function restoration.
Large in vivo studies are required before progressing to human applications to ensure safety.
Comprehensive scrutiny of stem cell therapy is essential due to historical abuses and public misinformation.

Ethical and Regulatory Considerations

Stem cell research and therapy often face ethical scrutiny, particularly regarding the use of embryos and cloned cells.
Misleading claims and fraud cases (like the "stamina case" in Italy) highlight the need for stricter regulations and monitoring in clinical stem cell applications.
Governments, such as the Chinese Ministry of Health, move to establish guidelines for stem cell treatments to curb unverified practices.