T Cell Biology and Cellular Immunology
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Questions and Answers

What is the primary condition affecting patients with defective RAG genes?

  • Excessive antibody production
  • Normal immune response
  • Autoimmune disorders
  • Non-functional B and T cells (correct)

Which syndrome is associated with partial function mutations in RAG genes?

  • Omen syndrome (correct)
  • Hyper-IgM syndrome
  • Ataxia-telangiectasia
  • Severe Combined Immunodeficiency

What prevalence rate is seen in males for SCID compared to females?

  • More prevalent in females
  • Twice as prevalent
  • Equally prevalent
  • Three times more prevalent (correct)

What immune response characteristic is seen in Omen syndrome?

<p>High IgE levels and eosinophilia (C)</p> Signup and view all the answers

What laboratory method is useful for analyzing T cell clones in tumor patients?

<p>Southern blot analysis (C)</p> Signup and view all the answers

What do T cell receptor gene rearrangements allow for?

<p>Diversity in T cell receptors (A)</p> Signup and view all the answers

What type of infections are SCID patients more prone to?

<p>Fungal and bacterial infections (C)</p> Signup and view all the answers

What is the primary consequence of gene recombination in T cells?

<p>Creation of unique T cell receptor clones (D)</p> Signup and view all the answers

What role do RAG1 and RAG2 play in T cell and B cell development?

<p>They facilitate somatic gene recombination in lymphocytes. (B)</p> Signup and view all the answers

What is the significance of the heptamer and nonamer sequences in T cell receptor formation?

<p>They act as recognition sites for RAG1 and RAG2 during recombination. (B)</p> Signup and view all the answers

How many distinct T cell receptors can potentially be found on a single T cell surface?

<p>$10^7$ (D)</p> Signup and view all the answers

What process contributes to additional diversity in T cell receptors beyond somatic recombination?

<p>P and N nucleotide diversification (C)</p> Signup and view all the answers

Which of the following is a key enzyme involved in the formation of random nucleotides during P and N nucleotide diversification?

<p>Terminal deoxynucleotidyl transferase (C)</p> Signup and view all the answers

What type of disease is associated with defects in RAG1 and RAG2?

<p>Severe combined immunodeficiency disease (A)</p> Signup and view all the answers

What components combine to form a T cell receptor?

<p>Alpha and beta chains, constant region genes, and spacer regions (B)</p> Signup and view all the answers

What is the primary purpose of somatic gene recombination in lymphocytes?

<p>To generate diversity of T and B cell receptors (B)</p> Signup and view all the answers

What do T cell receptors specifically recognize?

<p>MSC peptide complex (A)</p> Signup and view all the answers

What is the role of the invariant proteins in the T cell receptor complex?

<p>To aid in signal transduction (B)</p> Signup and view all the answers

What is the primary consequence of a receptor-ligand interaction in T cells?

<p>Gene transcription (D)</p> Signup and view all the answers

Which process is primarily involved in the mechanism of signal transduction?

<p>Phosphoridation and dephosphoridation (D)</p> Signup and view all the answers

What do T cell receptors lack that invariant proteins compensate for?

<p>Short cytoplasmic tail (B)</p> Signup and view all the answers

What is the term for molecules that facilitate communication within intracellular signaling in T cells?

<p>Second messengers (A)</p> Signup and view all the answers

Which part of the T cell receptor is referred to when mentioning the CD3 complex?

<p>The entire T cell receptor structure (D)</p> Signup and view all the answers

What happens to certain genes due to the receptor-ligand interaction in T cells?

<p>They are transcribed (C)</p> Signup and view all the answers

What occurs to thymocytes that cannot recognize MHC class one or class two molecules?

<p>They undergo programmed cell death. (A)</p> Signup and view all the answers

Which process eliminates thymocytes capable of responding to self-peptide antigens?

<p>Negative selection (D)</p> Signup and view all the answers

What type of T cells remain capable of recognizing self-peptide antigens after maturation?

<p>Mature naive CD4 and CD8 T cells (C)</p> Signup and view all the answers

Which characteristic is NOT associated with T regulatory (T reg) cells?

<p>Negative for FOXP3 (D)</p> Signup and view all the answers

What is the consequence of the absence of T reg cells?

<p>Development of auto-reactive T cells (D)</p> Signup and view all the answers

Which term describes the elimination of T cells that react strongly to self-antigens during maturation?

<p>Negative selection (B)</p> Signup and view all the answers

What distinguishes peripheral tolerance from central tolerance?

<p>It is a post-thymic mechanism. (C)</p> Signup and view all the answers

What happens to thymocytes that recognize MHC class molecules too avidly?

<p>They undergo apoptosis. (C)</p> Signup and view all the answers

What is the fate of auto-reactive T cells during negative selection?

<p>They are eliminated. (D)</p> Signup and view all the answers

What does the term 'self restricted' refer to in T cell development?

<p>T cells that are restricted to recognizing MHC class I molecules. (A)</p> Signup and view all the answers

During which selection process are thymocytes that successfully interact with MHC class I molecules recognized?

<p>Positive selection. (A)</p> Signup and view all the answers

At what stage in T cell development do progenitors begin rearranging their T cell receptor genes?

<p>At the subcapsular region of the thymus. (C)</p> Signup and view all the answers

What characterizes a single positive T cell?

<p>It expresses either CD4 or CD8, but not both. (D)</p> Signup and view all the answers

Which region of the thymus is involved in the later stages of T cell maturation, such as negative selection?

<p>Medulla. (B)</p> Signup and view all the answers

What happens to a thymocyte that recognizes an MHC class II molecule?

<p>It receives a different maturation signal and maintains CD4 expression. (A)</p> Signup and view all the answers

What is the role of high endothelial venules in T cell development?

<p>They allow T cell progenitors to enter the thymus. (A)</p> Signup and view all the answers

What happens to uncommitted progenitor cells as they differentiate in the thymus?

<p>They rearrange their genes and become double negative thymocytes. (A)</p> Signup and view all the answers

Which molecules are upregulated when progenitor cells become double negative thymocytes?

<p>CD2, CD5, CD127, and CD1A. (B)</p> Signup and view all the answers

What type of peptides do cortical epithelial cells present during the education process of T cells?

<p>Self-peptides. (D)</p> Signup and view all the answers

What state do T cells enter after becoming double positive?

<p>Single positive T cells. (D)</p> Signup and view all the answers

Why is the rare complex upregulated during the differentiation of thymocytes?

<p>For the initiation of recombination processes. (B)</p> Signup and view all the answers

What role do signaling molecules play during thymocyte differentiation?

<p>They activate transcription factors for lineage differentiation. (B)</p> Signup and view all the answers

Which stages are part of thymocyte differentiation?

<p>Double negative to double positive to single positive. (B)</p> Signup and view all the answers

Which of the following statements is true regarding T cell education in the thymus?

<p>It involves the selection of cells presenting self-peptides. (A)</p> Signup and view all the answers

Flashcards

T cell receptor (TCR)

The unique receptor on the surface of T cells that recognizes and binds to specific antigens presented by MHC molecules.

TCR complex

The complex of proteins that includes the TCR and the CD3 proteins, which are crucial for signal transduction.

MHC-peptide complex

A short sequence of amino acids derived from a protein that is presented on the surface of cells by MHC molecules. TCRs recognize specific MHC-peptide complexes.

Signal transduction

The process by which a cell converts an external signal (e.g., a TCR-ligand interaction) into an internal response (e.g., gene transcription).

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Ligand

A molecule, usually a protein, that binds to a receptor and initiates a cellular response. For T cells, the ligand is the MHC-peptide complex.

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CD3 proteins

A group of proteins that are involved in the TCR complex. They are important for signal transduction, amplifying the signal triggered by TCR-ligand interactions.

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Gene transcription

The process by which a cell changes its behavior or function in response to a signal.

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Cytokine

A type of signaling molecule that promotes or inhibits a specific cellular response. Many of these molecules are targeted by drugs.

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Somatic Gene Recombination

A process where segments of DNA within a lymphocyte's genome are rearranged, creating unique antigen receptors on the surface of each T cell.

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Heptamer and Nonamer Sequences

Specific DNA sequences on the variable region of T cell receptor (TCR) genes that are recognized by the RAG1 and RAG2 enzymes.

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RAG1 and RAG2 in Lymphocytes

The enzymes RAG1 and RAG2, essential for V(D)J recombination in lymphocytes, are only found in these cells.

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Recombination Immunodeficiency Disease

A disorder caused by defects in RAG1 and RAG2 genes, leading to impaired development of B and T cells and increased susceptibility to infections.

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P and N Nucleotide Diversification

A mechanism of increasing diversity in the antigen receptor repertoire by introducing random nucleotides during the joining of gene segments.

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Hyper-variable Region of TCR

The highly variable region of the TCR, directly contributes to the vast diversity of antigen recognition.

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Unique TCR on each T cell

Each T cell expresses a unique receptor on its surface, formed by the combination of different variable and constant region genes.

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Permutation and Combination for TCR Diversity

The process of combining different segments of DNA to generate diverse TCRs, ultimately resulting in a huge range of receptor diversity.

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Severe Combined Immunodeficiency (SCID)

A severe combined immunodeficiency (SCID) characterized by the inability to produce functional B and T cells, resulting in susceptibility to infections. It is caused by defects in RAG genes, essential for V(D)J recombination.

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Omen Syndrome

A genetic disorder characterized by partial or defective RAG genes, resulting in compromised V(D)J recombination and a weakened immune system. Patients often exhibit high IgE levels and eosinophilia.

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V(D)J Recombination

The process of rearranging antibody and T cell receptor genes by combining variable (V), diversity (D), and joining (J) gene segments, creating diverse immune receptors to recognize a wide range of antigens.

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Hyper IgE

The presence of high levels of immunoglobulin E (IgE) in the blood. This can be indicative of allergic reactions or parasitic infections.

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Eosinophilia

The abnormal increase in the number of eosinophils (a type of white blood cell) in the blood. Often associated with allergic reactions, parasitic infections, and some autoimmune diseases.

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Southern Blot

A specialized technique that separates DNA fragments of different sizes based on their electrophoretic mobility in a gel matrix. It is used to analyze DNA, including the presence of specific genetic markers.

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Clonal Expansion

Clonal expansion refers to the uncontrolled proliferation of a specific type of cell, often immune cells, resulting in an abnormal accumulation of those cells in the body. It can be a sign of infection, inflammation, or cancer.

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PCR (Polymerase Chain Reaction)

A technique used to multiply specific segments of DNA using the polymerase chain reaction (PCR). PCR is critical for molecular diagnostics, research, and forensic analysis.

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Uncommitted Progenitor Cells

Cells in the thymus that are not yet committed to becoming T cells. They lack expression of specific T cell markers like CD4 and CD8.

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Double Negative (DN) Stage

A stage in T cell development where the cell expresses neither CD4 nor CD8, marked by the upregulation of adhesion molecules and cytokine receptors.

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Double Positive (DP) Stage

A stage in T cell development where the cell expresses both CD4 and CD8, signifying successful gene rearrangement of the T cell receptor.

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Rare Complex

A rare complex of proteins crucial for initiating the process of gene rearrangement in T cells.

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Gene Rearrangement

The process by which T cell receptor genes are rearranged, selecting the specific antigen the T cell will recognize.

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Cortical Epithelial Cells

Cells in the thymus that present self-peptides to developing T cells, crucial for the selection process.

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Major Histocompatibility Complex (MHC)

Proteins that display peptide fragments to T cells for recognition. They play a vital role in the process of T cell selection.

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Signal Transduction Molecules

Proteins that activate specific signal transduction pathways within T cells, guiding their development and function.

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Negative Selection

A process where thymocytes that recognize MHC class I or II molecules too strongly are eliminated, preventing autoimmunity.

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Regulatory T Cell (Treg)

A type of T cell that helps maintain tolerance to self-antigens in the periphery, preventing autoimmune reactions.

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Thymic Selection

The process in the thymus where T cells undergo selection, ensuring only those capable of recognizing foreign antigens survive.

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Central Tolerance

Elimination of self-reactive T cells in the thymus, preventing autoimmune responses.

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Immune Tolerance

The ability of the immune system to tolerate self-antigens, preventing attacks on the body's own tissues.

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IPEX Syndrome

A rare genetic disorder characterized by severe autoimmune disease due to the absence of regulatory T cells.

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Peripheral Tolerance

The immune system's ability to tolerate self-antigens outside of the thymus, contributing to long-term immune homeostasis.

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CD4+ CD25+ FOXP3+ T Cell

A type of immune cell that plays a crucial role in suppressing autoimmune responses and maintaining immune tolerance.

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Negative Selection of T Cells

Process where T cells capable of binding tightly to self-antigens presented by APCs are eliminated to prevent autoimmunity.

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Positive Selection of T Cells

A stage of T cell development where T cells are tested for their ability to recognize MHC molecules and peptides.

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Single Positive (SP) T Cells

Mature T cells that can recognize and respond to specific antigens presented by MHC molecules. They are 'self-restricted' meaning they can only recognize antigens presented by MHC molecules of their own body.

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Thymus

A specialized organ where T cell precursors undergo maturation and develop into functional T lymphocytes.

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Self-Restriction

The process by which T cells acquire the ability to bind to MHC molecules of their own body, preventing them from attacking self-tissues.

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Self-Tolerance

The state of being tolerant to self-antigens, meaning the immune system doesn't attack its own tissues and organs.

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Double Positive (DP) T Cells

A stage in T cell development where precursor T cells express both CD4 and CD8 co-receptors, marking a significant step in their maturation process.

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T Cell Receptor Selection

A process that involves testing T cell receptor (TCR) and MHC molecule interactions, ultimately leading to the survival or elimination of T cells based on their specificities.

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Study Notes

Introduction to the Speaker

  • Speaker is Graduate Program Director, Professor, and Vice Chair of Education in PMI
  • Research interests in cancer biology
  • Has been involved in T cell biology for 30+ years

T Cell Biology

  • T cells are "time-must derived", meaning their development begins in a specific time period
  • Before this time period, T cells are similar to other cells
  • T cells are important for immune system function
  • Prior to this period, T cells are like other cells.
  • T cells have a different role in evolution.
  • T cells recognize processed antigens (proteins/peptides) in the context of MHC (major histocompatibility complex) peptide complexes

Cellular Immunology

  • Cellular immunology studies cell-based immune responses
  • Humoral immunity is associated with B cells
  • T cells have a receptor that binds ligands on other cells

T Cell Receptor

  • T cells recognize processed antigens (peptides) in the context of MHC molecules
  • T cells do not recognize whole proteins
  • Antigen processing and presentation are key components of T cell activation
  • Role of MHC and Peptides

Thymic Education

  • Thymocytes (immature T cells) are educated in the thymus
  • Thymic education involves two processes:
    • Positive selection: selecting T cells that can recognize self-antigens presented by MHC molecules without reacting to them excessively
    • Negative selection: eliminating T cells that react too strongly to self-antigens
  • These processes result in mature, self-tolerant T cells with diverse antigen specificities

Self and Non-Self Recognition

  • Crucial function of T cells is distinguishing self from non-self
  • Non-self refers to antigens that are not part of the body, thus foreign
  • Self refers to the body's own antigens

Types of T Cells

  • T cells have diversity, but each T cell has a single receptor for one type of antigen
  • MHC restriction is crucial for this process -Alpha-beta and Gamma-delta T cell receptors
  • Both have characteristic diversity within their receptors
  • Gamma-delta not MHC restricted

Receptor Diversity

  • Large repertoire of T cell receptors generated by gene recombination
  • The recombination process is orchestrated and not random
  • Receptor diversity is crucial for immune system function by enabling it to respond to a broad range of pathogens

Secondary Lymphoid Organs

  • These are sites of immune responses
  • Function as areas for T cells and B cells to interact and mount attacks
  • Distribution of these organs throughout the body aids in surveillance and immune defense

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T Cell Biology PDF

Description

Explore the fascinating world of T cell biology and cellular immunology. This quiz covers the development, function, and significance of T cells in the immune system, along with their unique interactions with antigens and MHC molecules. Test your knowledge on these essential components of the immune response.

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