Lecture 13 The Respiratory System PT4 - Immune response Flashcards
- How is TCR Diversity Generated?
Answer: TCR diversity is generated through a process called V(D)J recombination, which occurs before a T cell encounters an antigen. Random recombination of V (variable), D (diversity), and J (joining) gene segments in the TCR β-chain and TCR α-chain allows for a wide variety of TCRs.
- What is Burnett’s Clonal Selection Hypothesis?
Answer: Burnett’s Clonal Selection Hypothesis suggests that each lymphocyte has unique receptors (TCRs/BCRs), and when a specific antigen binds to the receptor, the lymphocyte is selected to proliferate and form clones. This explains the specificity of the immune response.
- Steps in T Cell Maturation
Pro-T cells migrate from bone marrow to thymus.
TCR β-chain recombination occurs, creating Pre-T cells.
Pre-T cells express TCR α-chain, becoming double positive for CD4 and CD8.
Positive selection: T cells with functional TCRs that weakly bind MHC are selected.
Negative selection: Strongly self-reactive T cells are eliminated.
- What is Clonal Expansion and the Role of Memory Cells?
Answer: During an infection, antigen-specific T cells undergo rapid division, increasing by 10,000-fold to fight the infection. After the infection is cleared, most of these T cells die, but some survive as long-lived memory T cells, ready to respond quickly to future infections.
- Differences Between CD4 and CD8 T Cells
CD4 T cells: Recognize MHC-II (extracellular antigens), help other immune cells.
CD8 T cells: Recognize MHC-I (intracellular antigens), directly kill infected cells.
- Types of CD4 T Cells and Their Characteristics
Th1: Secrete IFN-γ, activate macrophages, fight intracellular pathogens.
Th2: Secrete IL-4, IL-5, IL-13, fight helminths.
Th17: Secrete IL-17, fight bacteria and fungi.
Tregs: Regulate immune responses, maintain tolerance to self-antigens.
- Other Types of T Cells and How They Differ from αβT Cells
Answer:
γδT cells: Have a different TCR structure (γ and δ chains) and are involved in early immune responses, particularly at mucosal sites.
NKT cells: Recognize lipid antigens presented by CD1d and have both T and NK cell characteristics.
- How Do T Cells and Innate Immune Cells Co-operate to Control Intracellular Bacterial Infections?
Activation of naïve T cells: Naïve T cells circulate between blood and lymph nodes, seeking APCs presenting the antigen. Co-stimulation ensures they are only activated by threats.
Th1 cells: Interact with macrophages, secreting IFN-γ and expressing CD40L to activate macrophages, enhancing their ability to kill bacteria.
CD4 and CD8 T cell cooperation: If bacteria escape into the cytosol, CD8 T cells kill the infected cell, while Th1 CD4 T cells help activate macrophages to kill phagocytosed bacteria.
- Control of Acid Secretion in the Stomach
Answer:
Parietal cells: Secrete HCl. Histamine, gastrin, and acetylcholine stimulate acid secretion.
Transporters: Proton pumps (H+/K+ ATPase) actively pump H+ into the stomach lumen.
Mucous cells: Secrete mucus to protect the stomach lining from the acid.
Pepsinogen secretion: Pepsinogen is secreted by chief cells and activated into pepsin by stomach acid, aiding protein digestion.
- Why is V(D)J recombination irreversible?
Answer: V(D)J recombination involves the permanent deletion of DNA segments during T cell receptor (TCR) and B cell receptor (BCR) gene rearrangement. Once specific V, D, and J segments are joined, the intervening DNA is excised and lost. This irreversible process ensures that each lymphocyte expresses only one unique antigen receptor, which is critical for specificity in immune responses.
- Will we use all the naïve T cells we make?
Answer: No, we will not use all the naïve T cells we make. A large number of naïve T cells never encounter their specific antigen. If a naïve T cell does not encounter its matching antigen during its lifespan, it will eventually undergo apoptosis (programmed cell death). Only a small subset of naïve T cells that recognize antigens will become activated, clonally expand, and differentiate into effector and memory T cells.
- As we age, our thymus shrinks. What effect do you think this will have?
Answer: The shrinking of the thymus with age is called thymic involution. This leads to a decrease in the production of new naïve T cells. As a result, the immune system relies more heavily on existing memory T cells to respond to infections and less on newly generated naïve T cells. This can contribute to a weakened immune response in older individuals, making them more susceptible to infections and reducing the ability to respond to new antigens.
- How will the ratio of naïve to memory T cells change as we age?
Answer: As we age, the ratio of naïve T cells decreases, and the ratio of memory T cells increases. This happens because the production of new naïve T cells declines due to thymic involution, while exposure to antigens over a lifetime leads to an accumulation of memory T cells. Therefore, older individuals have a larger proportion of memory T cells but fewer naïve T cells, which limits the ability to respond to novel infections.
- What is driving the chronic activation of macrophages and T cells in a granuloma?
Answer: Chronic activation of macrophages and T cells in a granuloma is typically driven by persistent pathogens, such as Mycobacterium tuberculosis, or other foreign substances that cannot be fully eliminated by the immune system. This leads to continuous immune stimulation. Th1 CD4+ T cells secrete IFN-γ, which activates macrophages to contain the pathogen, while macrophages produce pro-inflammatory signals that sustain T cell activation. The cycle of activation and recruitment continues, resulting in chronic inflammation and granuloma formation.
- Why does one subset of CD4 T cells inhibit the differentiation of other subsets?
Answer: Different CD4 T cell subsets secrete cytokines that not only promote their own differentiation but also suppress the differentiation of other subsets. For example:
Th1 cells secrete IFN-γ, which promotes Th1 differentiation but inhibits the development of Th2 and Th17 cells.
Th2 cells produce IL-4, which promotes Th2 differentiation but suppresses Th1 and Th17 differentiation.
This cross-regulation ensures that the immune response is tailored to the type of pathogen or threat, preventing inappropriate immune responses.
