Podcast
Questions and Answers
What are the primary regions that make up the structure of lymphocyte antigen receptors?
What are the primary regions that make up the structure of lymphocyte antigen receptors?
Which hypervariable region of an antibody contains the greatest variability and significantly contributes to antigen binding?
Which hypervariable region of an antibody contains the greatest variability and significantly contributes to antigen binding?
Which type of chains participate in the binding and neutralization of microbes and toxins, but do not take part in effector functions?
Which type of chains participate in the binding and neutralization of microbes and toxins, but do not take part in effector functions?
What are the sections of an antibody that allow for independent movement of antigen-binding sites?
What are the sections of an antibody that allow for independent movement of antigen-binding sites?
Signup and view all the answers
How is the vast diversity of receptor structures in the lymphocyte repertoire primarily generated?
How is the vast diversity of receptor structures in the lymphocyte repertoire primarily generated?
Signup and view all the answers
What is the concept of the affinity of interaction in the context of antigen-antibody binding?
What is the concept of the affinity of interaction in the context of antigen-antibody binding?
Signup and view all the answers
Which of the following types of immunoglobulin heavy chains is NOT one of the five classes?
Which of the following types of immunoglobulin heavy chains is NOT one of the five classes?
Signup and view all the answers
What distinguishes conformational epitopes from linear epitopes?
What distinguishes conformational epitopes from linear epitopes?
Signup and view all the answers
What does a lower dissociation constant (Kd) indicate about an antibody's affinity for an antigen?
What does a lower dissociation constant (Kd) indicate about an antibody's affinity for an antigen?
Signup and view all the answers
Which process is crucial for the activation of T Cell Receptors (TCR)?
Which process is crucial for the activation of T Cell Receptors (TCR)?
Signup and view all the answers
What role does IL-7 play in T lymphocyte development?
What role does IL-7 play in T lymphocyte development?
Signup and view all the answers
What is the primary consequence of positive selection in T lymphocyte development?
What is the primary consequence of positive selection in T lymphocyte development?
Signup and view all the answers
What is an implication of the cross-reaction phenomenon in antibody interactions?
What is an implication of the cross-reaction phenomenon in antibody interactions?
Signup and view all the answers
Why do mouse monoclonal antibodies induce immune response when injected into humans?
Why do mouse monoclonal antibodies induce immune response when injected into humans?
Signup and view all the answers
What aspect of T cell receptor (TCR) structure is most variable?
What aspect of T cell receptor (TCR) structure is most variable?
Signup and view all the answers
What is the primary purpose of negative selection in T cell development?
What is the primary purpose of negative selection in T cell development?
Signup and view all the answers
What is the role of Bruton’s tyrosine kinase (Btk) in B cell maturation?
What is the role of Bruton’s tyrosine kinase (Btk) in B cell maturation?
Signup and view all the answers
How does the pre-BCR complex influence Ig gene rearrangement?
How does the pre-BCR complex influence Ig gene rearrangement?
Signup and view all the answers
Which selection process allows mature B cells to express complete antigen receptors?
Which selection process allows mature B cells to express complete antigen receptors?
Signup and view all the answers
What occurs as a result of negative selection in immature B cells?
What occurs as a result of negative selection in immature B cells?
Signup and view all the answers
What is the significance of the double-negative T cell stage in T cell differentiation?
What is the significance of the double-negative T cell stage in T cell differentiation?
Signup and view all the answers
What defines the transition from double-negative to double-positive T cells?
What defines the transition from double-negative to double-positive T cells?
Signup and view all the answers
What is the consequence of a mutation in Bruton’s tyrosine kinase (Btk) for boys?
What is the consequence of a mutation in Bruton’s tyrosine kinase (Btk) for boys?
Signup and view all the answers
What occurs during the process of allelic exclusion in B cells?
What occurs during the process of allelic exclusion in B cells?
Signup and view all the answers
What are the gene segments present in the antigen receptor gene loci?
What are the gene segments present in the antigen receptor gene loci?
Signup and view all the answers
During Ig heavy-chain expression, what is the order of gene rearrangement?
During Ig heavy-chain expression, what is the order of gene rearrangement?
Signup and view all the answers
Which proteins make up the VDJ recombinase essential for somatic recombination?
Which proteins make up the VDJ recombinase essential for somatic recombination?
Signup and view all the answers
What constitutes the pre-B cell receptor (pre-BCR)?
What constitutes the pre-B cell receptor (pre-BCR)?
Signup and view all the answers
What type of lymphocytes express VDJ recombinase?
What type of lymphocytes express VDJ recombinase?
Signup and view all the answers
Which statement is true about the arrangement of Ig light chains and TCR chains?
Which statement is true about the arrangement of Ig light chains and TCR chains?
Signup and view all the answers
What is the purpose of junctional diversity in antigen receptors?
What is the purpose of junctional diversity in antigen receptors?
Signup and view all the answers
What happens to the DNA breaks during somatic recombination?
What happens to the DNA breaks during somatic recombination?
Signup and view all the answers
Study Notes
Antigen Recognition in the Adaptive Immune System
- Lymphocyte antigen receptors recognize diverse antigens and transmit activating signals to cells.
- B cell and T cell antigen receptors have different recognition properties.
- Receptor diversity in lymphocytes is generated through various mechanisms.
Antigen Receptors of Lymphocytes
- Variable (V) regions of receptors recognize antigens.
- Constant (C) regions are conserved in receptors.
- Complementarity-determining regions (CDRs) are short stretches in variable regions that contribute to antigen receptor function.
- B cell receptors (BCR) complexes and T cell receptors (TCR) complexes contain sets of plasma membrane antigen receptors and signaling molecules.
- They function in antigen recognition, signal transduction, cell division, differentiation, and effector function.
Antibodies
- Antibodies have three hypervariable regions (CDRs) located at the junction of V and C regions. CDR3 has the greatest variability and contributes most to antigen binding.
- The fragment, antigen-binding (Fab), contains the light chain and the V and first C domains of a heavy chain.
- The Fc (fragment, crystalline) region is in the constant heavy chain domains and is responsible for the biologic activity and effector function of antibodies.
- The hinge region links the Fab and Fc regions.
- Antibodies have different classes (isotypes) of heavy chains (μ, δ, γ, ε, and α) with distinct functions and plasma concentrations.
- Two types of light chains (κ and λ) are present. κ or λ remains fixed throughout the life of each B cell clone.
- Light chains do not participate in effector functions, except for binding and neutralizing microbes, and toxins.
Binding of Antigens to Antibodies
- Epitopes are parts of antigens recognized by antibodies. Antigens can be linear or conformational.
- The strength of interaction is called affinity and is determined by dissociation constant (Kd). The lower the Kd, the higher the affinity.
- Affinity maturation is an increase in antigen-binding strength during an immune response.
- Antibodies against one antigen can cross-react with other structurally similar antigens.
Generation of Hybridomas and Monoclonal Antibodies
- Monoclonal antibodies are used in therapeutics and diagnostics.
- Mouse monoclonal antibodies induce human immune responses.
- Recombinant DNA technology generates monoclonal antibodies of desired specificity using gene technology.
T Cell Receptors for Antigens
- T cell receptors have variable regions (CDRs) that enable antigen recognition. CDR3 has the largest variability.
- TCRs interact with both the MHC molecule and the peptide presented.
- TCR activation requires CD3 and ζ chains, and CD4 or CD8 coreceptors.
Features of Antigen Recognition
- Immunoglobulins (Igs) have three CDRs in VH and three CDRs in VL. Heavy chain class switching changes the function and secretion of Igs. Igs have low Kd.
- T cell receptors (TCRs) also have three CDRs in Va and three CDRs in Vb. TCRs have high Kd.
Development of T and B Lymphocytes
- Lymphocytes with distinct specificities develop before antigen encounter.
- Growth factors and stroma cells promote survival and proliferation in bone marrow and thymus.
- Positive selection ensures that cells survive if they can partially recognize MHC molecules.
- Negative selection eliminates cells with high affinity for self-peptides that are presented by self MHC.
Production of Diverse Antigen Receptors
- Hematopoietic stem cells contain Ig and TCR genes.
- Receptor gene loci contain V, J, and C gene segments (V, D, J).
- Variable regions are highly variable. One or a few constant regions are present.
Somatic Recombination and Expression of Immunoglobulin
- Ig heavy chain expression involves D-J joining followed by V-DJ joining.
- Recombined genes are transcribed to give rise to precursor mRNA and translated to create protein chains.
- Recombination of light chains and T cell receptors follows similar mechanisms. D regions are not part of light chain recombination.
- V gene recombines directly with a J gene segment.
Diversity in Antigen Receptors
- Somatic recombination is mediated by V (D) J recombinase.
- Recombination activating genes (RAG)1 and RAG2 proteins bring together gene segments.
- Combinatorial diversity and junctional diversity increase the total potential diversity of receptors.
- DNA breaks are repaired to generate complete recombinations.
Maturation and Selection of B Lymphocytes
- Large pre-B cells survive and proliferate if their heavy chain genes rearrange properly and a pre-BCR assembles.
- Small pre-B cells engage in light-chain rearrangements.
- Immature B cells assemble complete membrane IgM receptors.
- Mature B cells simultaneously express IgD.
B-Cell Differentiation
- Heavy μ chains of IgM accumulate in cytoplasm and combine with short Ig-a and Ig-β chains to form pre-B cell receptors.
- Pre-BCR signaling allows for the expression of the light chains and for functional IgM to be produced.
- Subsequent differentiation occurs as the B cells encounter antigens.
Role of the Pre-BCR Complex
- Pre-BCR activation involves Bruton's tyrosine kinase (Btk), a protein encoded on the X chromosome.
- Btk activation delivers signals from the pre-BCR and mediates B cell survival, proliferation, and maturation.
- Mutations in Btk cause X-linked agammaglobulinemia (XLA), a disease resulting from the failure of pre-B cells to survive and develop into mature B cells.
- Allelic exclusion ensures that each B cell expresses only one heavy-chain gene.
Mature B-Cells
- Positive selection results in the expression of complete antigen receptors.
- Negative selection assures that mature B cells that bind self-antigens are eliminated.
Maturation and Selection of MHC-Restricted T Lymphocytes
- Pro-T cells are double-negative cells that increase in number through thymic IL-7 influence.
- TCR beta chain is first expressed at the double-negative pre-T cell stage and is mediated by VDJ recombinase.
- TCR beta is then expressed with a pre-T protein in association with an invariant protein (pre-Ta).
- Double-positive cells mature and develop to single-positive CD4+ or CD8+ T-cell.
- Cells that do not express antigen receptors die through apoptosis.
T-Cell Differentiation: Double-Negative (DN) Stage
- Thymocytes rearrange genes coding for the beta chain of the T-cell receptor.
- Gene segments are selected and joined to produce a unique antigen-binding site.
T-Cell Differentiation: Double-Negative (DN) Stage
- Alpha and beta chains recognize antigen.
- Six other chains (in three pairs) assist with intracellular signaling.
Positive and Negative Selection of Thymocytes
- Positive selection creates cells that recognize self-MHC.
- Negative selection eliminates cells that bind self-antigens too strongly.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Explore the intricacies of antigen recognition in the adaptive immune system, focusing on lymphocyte antigen receptors. Learn the differences between B cell and T cell receptors, and understand the mechanisms behind receptor diversity and antibody structure.
