Practice 5 structured short- and long-answer medical questions on Weekly Year 2: Cellular Immunology Exam - June 12, 2026 (Sections B & C). Review model answ...
Answer: Toll-like Receptors (TLRs) are pattern recognition receptors (PRRs) expressed on innate immune cells. They recognize conserved molecular patterns (PAMPs) found on pathogens, such as lipopolysaccharide (LPS) or viral nucleic acids. TLRs are located on the cell surface (e.g., TLR4 for LPS) or within endosomes (e.g., TLR3 for viral dsRNA). Upon ligand binding, TLRs trigger intracellular signaling cascades (e.g., via MyD88 or TRIF pathways) that lead to the activation of transcription factors like NF-κB and IRFs. This results in the production of pro-inflammatory cytokines, chemokines, and type I interferons, orchestrating the innate immune response and bridging to adaptive immunity.
Answer: Primary lymphoid organs are where lymphocytes develop and mature, acquiring their antigen receptors and becoming immunocompetent. Examples include the bone marrow (site of B cell maturation and T cell progenitors) and the thymus (site of T cell maturation). Secondary lymphoid organs are sites where mature lymphocytes encounter antigens and initiate an adaptive immune response. Examples include lymph nodes, spleen, and mucosal-associated lymphoid tissue (MALT).
Answer: TCR repertoire selection occurs in the thymus to ensure that T cells are self-tolerant and can recognize foreign antigens presented by MHC molecules. Positive selection ensures that T cells can recognize self-MHC molecules. Thymocytes that fail to bind to self-MHC complexes undergo apoptosis. Negative selection eliminates T cells that have a high affinity for self-antigens presented by self-MHC molecules. This process prevents autoimmunity by removing self-reactive T cells. The combination of positive and negative selection shapes the functional T cell repertoire.
Answer: Th1 cells are characterized by their production of cytokines like IFN-γ and IL-2. They primarily promote cell-mediated immunity, enhancing the activity of macrophages and cytotoxic T lymphocytes (CTLs) to clear intracellular pathogens. Th2 cells are characterized by their production of cytokines like IL-4, IL-5, and IL-13. They primarily promote humoral immunity, supporting B cell differentiation into antibody-producing plasma cells and eosinophil activation, which are important for parasitic infections and allergic responses.
Answer: The activation of naive T cells is a multi-step process initiated by antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells. 1. **MHC Presentation (Signal 1):** Naive T cells recognize processed peptide antigens presented by MHC molecules on the surface of APCs. CD4+ helper T cells recognize peptides presented by MHC class II molecules, which are typically derived from extracellular pathogens or antigens taken up by endocytosis. CD8+ cytotoxic T cells recognize peptides presented by MHC class I molecules, which present antigens synthesized within the APC, often derived from intracellular pathogens or cellular proteins. The T cell receptor (TCR) on the T cell interacts with the TCR-peptide-MHC complex. This interaction provides the first signal for T cell activation. 2. **Co-stimulatory Signals (Signal 2):** Antigen recognition alone is insufficient for full T cell activation. APCs provide co-stimulatory signals, which are crucial for preventing T cell anergy and promoting full activation and proliferation. A key co-stimulatory pathway involves the interaction between CD28 on the T cell and B7 molecules (CD80/CD86) on the APC. This interaction is critical for providing the 'second signal' required for T cell survival, proliferation, and cytokine production. Other co-stimulatory molecules also play roles. 3. **Cytokine Signaling (Signal 3):** APCs also produce cytokines that influence the differentiation of activated T cells into specific effector subsets. The type of cytokine produced by the APC depends on the nature of the pathogen or stimulus encountered by the APC. For example, dendritic cells activated by microbial products will produce cytokines that polarize T cell differentiation. IL-12 produced by APCs drives Th1 differentiation, while IL-4 promotes Th2 differentiation. These cytokines bind to specific receptors on the T cell, initiating intracellular signaling pathways that activate lineage-specific transcription factors. **Outcome of T cell activation and differentiation:** The combination of these three signals dictates the fate of the activated T cell. * **Full Activation and Effector Function:** When all three signals are provided appropriately, naive T cells undergo robust proliferation, differentiate into effector T cells (e.g., Th1, Th2, Th17, CTLs), and develop effector functions required to combat the specific pathogen. For CD4+ helper T cells, this involves secreting cytokines to orchestrate immune responses. For CD8+ T cells, this involves acquiring cytotoxic capabilities to kill infected cells. * **Anergy:** If only Signal 1 is provided without sufficient co-stimulatory signals (Signal 2), the T cell can become anergic, a state of unresponsiveness. This is a critical mechanism for maintaining self-tolerance. * **Memory Cell Formation:** Following an effective immune response, a subset of effector T cells differentiates into long-lived memory T cells. These memory cells are primed to respond more rapidly and vigorously upon re-exposure to the same antigen, forming the basis of immunological memory. The signals received during initial activation, particularly cytokine milieu and duration of stimulation, influence the generation and maintenance of memory T cells. The balance between effector and memory cell generation is crucial for effective long-term immunity.