Practice 5 structured short- and long-answer medical questions on Weekly Year 2: Cellular Immunology Exam - May 15, 2026 (Sections B & C). Review model answe...
Answer: Th1 cells are characterized by the production of cytokines such as IFN-γ and IL-2. Their primary role is to activate macrophages and promote cell-mediated immunity, important for clearing intracellular pathogens like viruses and bacteria. Th2 cells, on the other hand, produce cytokines like IL-4, IL-5, and IL-13. They are crucial for B cell activation and differentiation, leading to the production of antibodies, and are important for defense against extracellular parasites like helminths.
Answer: Immunological tolerance refers to the acquired ability of the immune system to prevent an immune response against self-antigens. Central tolerance is established during lymphocyte development in primary lymphoid organs (thymus for T cells, bone marrow for B cells). Two mechanisms for central T cell tolerance are: 1. Negative selection (clonal deletion): T cells that strongly recognize self-antigens presented by MHC molecules in the thymus undergo apoptosis. 2. Receptor editing (in B cells, but conceptually similar for T cells encountering strong self-reactivity with self-MHC-peptide complexes where some T cell receptors can be re-expressed with altered specificity, though less common for T cells compared to B cells. A more accurate second mechanism for T cells would be anergy induced by weak recognition of self-antigens without co-stimulation).
Answer: Innate immunity is the first line of defense, characterized by rapid, non-specific responses. Key characteristics include: 1. Pre-existing cells and molecules: It relies on cells like phagocytes (neutrophils, macrophages) and NK cells, and molecules like complement proteins, that are ready to act immediately. 2. No immunological memory: It does not improve with repeated exposure to a pathogen. Adaptive immunity develops over time and is highly specific, characterized by: 1. Specificity: It recognizes and targets particular antigens. 2. Immunological memory: It generates long-lasting immunity, with faster and stronger responses upon re-exposure to the same pathogen.
Answer: Antigen-presenting cells (APCs) are specialized cells that capture, process, and present antigens to lymphocytes, primarily T cells. Their essential roles include: 1. Antigen processing and presentation: APCs engulf pathogens or foreign material, break them down into smaller peptides, and display these peptides on their surface bound to Major Histocompatibility Complex (MHC) molecules. 2. T cell activation: APCs present antigen-MHC complexes to naive T cells. Crucially, they also provide co-stimulatory signals (e.g., B7 molecules binding to CD28 on T cells) which are essential for full T cell activation, proliferation, and differentiation. Without co-stimulation, T cells may become anergic.
Answer: The immune system's ability to recognize an almost limitless array of foreign antigens relies on the generation of immense diversity in its antigen receptors: T cell receptors (TCRs) and B cell receptors (BCRs). This diversity is primarily achieved through somatic recombination of variable (V), diversity (D), and joining (J) gene segments, and in some cases, constant (C) gene segments, which encode the variable regions of the receptor chains. For both TCRs and BCRs, the process involves a series of steps mediated by the V(D)J recombination machinery, including RAG1 and RAG2 enzymes. First, specific V, D, and J segments are selected and joined together. This joining event is imprecise, creating junctional diversity. Junctional diversity arises from several mechanisms: 1. **Nucleotide additions:** Terminal deoxynucleotidyl transferase (TdT) can randomly add non-templated nucleotides (N-nucleotides) at the junctions between gene segments. 2. **Exonucleolytic trimming:** The DNA ends at the joining sites can be trimmed by exonucleases, further altering the sequence. The combination of different V, D, and J gene segments, coupled with the random addition and trimming of nucleotides at the junctions, creates a vast combinatorial diversity. For example, if there are 100 V genes, 20 D genes, and 6 J genes for a particular chain, the number of possible combinations is 100 x 20 x 6 = 12,000. When considering both chains of a receptor (e.g., alpha and beta for TCR; heavy and light for BCR), the total repertoire size is exponentially larger (e.g., (V x D x J) x (V x J) for TCRs). Furthermore, for BCRs, the diversity is amplified by the random combination of different heavy and light chains, and by somatic hypermutation, a process that introduces point mutations into the variable regions of rearranged immunoglobulin genes after B cell activation. This allows for fine-tuning of antigen affinity. This immense receptor diversity is crucial for mounting an effective adaptive immune response against novel pathogens. However, it also poses a challenge: the potential for generating lymphocytes that recognize self-antigens. The immune system employs mechanisms to eliminate or inactivate these potentially self-reactive lymphocytes through central and peripheral tolerance. Central tolerance, occurring during lymphocyte development in primary lymphoid organs, involves negative selection (clonal deletion) where lymphocytes with high affinity for self-antigens are eliminated. Peripheral tolerance mechanisms exist to control self-reactive lymphocytes that escape central tolerance.