Immunology 2 Flashcards
How does the immune system generate diversity in T cell and B cell receptors to recognize a wide range of antigens?
• B cells: Diversity is generated through recombination of gene segments (V, D, J) in the heavy and light chains, leading to diverse immunoglobulins.
• T cells: Similar recombination of V, D, and J segments occurs in T cell receptors (TCRs), creating diversity in antigen specificity.
• CDRs: Complementarity-determining regions (CDRs), especially CDR3, play a crucial role in antigen binding specificity.
What is V(D)J recombination, and how does it contribute to immune diversity?
V(D)J recombination is the process where B and T cells randomly recombine gene segments (V, D, J) to create diverse antigen receptors. This increases the combinatorial diversity of antibodies and TCRs, enabling recognition of a vast range of antigens.
What is the disadvantage of V(D)J recombination?
Inefficiency: 1/3 of recombination events are wasteful and non-functional.
- Self-recognition risk: Random recombination can lead to antibodies or TCRs that mistakenly recognize self-proteins, leading to autoimmunity.
What is allelic exclusion, and how does it ensure specificity in B and T cells?
Allelic exclusion ensures that each B or T cell expresses only one receptor specificity. Each TCR gene has two alleles, but only one is rearranged, ensuring that the receptor recognizes a single antigen.
How is central tolerance achieved for self-reactive B cells?
Central tolerance tests B cells for self-reactivity in the bone marrow. Self-reactive B cells undergo:
• Death
• Anergy (non-responsive)
• Gene editing to alter specificity.
How do T cells undergo positive and negative selection in the thymus?
Positive selection: T cells must bind MHC molecules, but not self-peptides. If they weakly bind MHC and do not react strongly to self-antigens, they survive.
• Negative selection: Strong binding to self-peptides results in apoptosis (self-reactivity).
What is immune privilege, and why was the CNS thought to be isolated from the immune system?
• Immune privilege refers to certain tissues (e.g., brain, eye) being less susceptible to immune responses due to anatomical barriers. This protects vital, irreplaceable tissues.
• The CNS was considered isolated because immune cells were thought to be restricted from entering, due to the blood-brain barrier.
Why is the concept of immune privilege now challenged, and what examples support this?
• Cross-talk between the immune system and CNS has been demonstrated, with immune cells like microglia residing in the brain.
• Additionally, immune responses such as inflammation can occur in the brain in diseases like Parkinson’s and multiple sclerosis, showing that the CNS is not completely isolated from immune activity.
Q9: What is the role of microglia in the CNS immune response?
Microglia are resident immune cells in the CNS that function in immune surveillance, clearing debris, and responding to injury or infection. They contribute to the inflammatory processes seen in neurological diseases.
Q10: What is the relationship between autoimmune disease and failure of tolerance mechanisms?
Autoimmune diseases arise when the immune system fails to recognize self-antigens properly, either through breakdown of central tolerance (in the thymus or bone marrow) or peripheral tolerance mechanisms (e.g., failure of regulatory T cells or anatomical barriers).
Q11: What is the role of regulatory T cells in maintaining peripheral tolerance?
Regulatory T cells (Tregs) actively suppress self-reactive T cells and maintain peripheral tolerance by preventing autoimmune responses. They play a key role in controlling autoimmune diseases.
How does Parkinson’s disease have an immune component?
Parkinson’s disease involves the accumulation of misfolded alpha-synuclein, forming Lewy bodies that induce inflammation.
• Both innate and adaptive immune responses are activated, leading to increased immunoglobulins and a decrease in Tregs, suggesting a breakdown of self-tolerance in the disease.
Q13: What is the concept of “danger signals” in immune activation, and how does it relate to autoimmunity?
Danger signals are indicators of infection or tissue damage that trigger an immune response. In autoimmunity, self-reactive T and B cells may be activated in the absence of these signals, leading to an inappropriate immune response against the body’s own tissues.
Q14: Give examples of neurological diseases with an immune component.
Multiple sclerosis: Autoimmune attack on myelin in the CNS.
- Parkinson’s disease: Inflammation and immune activation linked to the accumulation of alpha-synuclein.
- Alzheimer’s disease: Microglial activation and neuroinflammation are involved in disease progression.
What role do peripheral tolerance mechanisms play in preventing autoimmune diseases?
Peripheral tolerance controls auto-reactive T and B cells that recognize self-antigens. It is maintained through factors like the absence of innate immune signals, active suppression by Tregs, or anatomical barriers to immune cell access.
