An antigen was injected into a mouse. Macrophages and antigen primed TH cells were isolated from this mouse to perform the following in vitro experiments: A. Macrophages were treated with the antigen for an hour and then incubated with TH cells. B. Macrophages were treated with paraformaldehyde first and then treated with the antigen for an hour. These macrophages were then incubated with T H cells. C. Macrophages were treated with paraformaldehyde first then treated with the digested (proteolytically cleaved) antigen for an hour. These macrophages were then incubated with T H cells. D. Macrophages were treated with the antigen for an hour and then treated with paraformaldehyde. These macrophages were then incubated with TH cells. Which of the above experiments would lead to TH cells proliferation?
A, C and D only
Antigen Presentation and TH Cell Proliferation
To understand which experiments would lead to TH cell proliferation, we need to consider how TH cells are activated. T helper (TH) cells are a type of T cell that play a central role in the adaptive immune response. They require activation by antigen-presenting cells (APCs), such as macrophages.
The process of TH cell activation involves:
- Macrophages engulf and process antigens.
- The processed antigen is broken down into peptides.
- These peptides bind to MHC class II molecules inside the macrophage.
- The MHC class II-peptide complexes are transported to the macrophage cell surface.
- TH cells recognize the specific peptide presented by the MHC class II molecule on the macrophage surface using their T cell receptor (TCR).
- This recognition, along with co-stimulatory signals, leads to TH cell activation and subsequent proliferation.
Paraformaldehyde is a fixative that cross-links proteins, essentially killing the cells and preventing further cellular processes like antigen processing or internal trafficking of molecules. However, it can preserve existing structures and surface molecules.
Analyzing the Antigen Experiments
Let's analyze each experiment described:
Experiment A: Macrophages treated with Antigen then incubated with TH cells
- In this experiment, macrophages are live and functional when exposed to the antigen.
- They can take up the antigen, process it into peptides, and load these peptides onto MHC class II molecules.
- The MHC class II-peptide complexes are then presented on the macrophage surface.
- When incubated with antigen-primed TH cells, these TH cells can recognize the presented antigen peptides.
- This recognition should lead to TH cell activation and proliferation.
Conclusion for A: TH cell proliferation is expected.
Experiment B: Macrophages treated with Paraformaldehyde first, then with Antigen
- Macrophages are treated with paraformaldehyde before being exposed to the antigen.
- Paraformaldehyde fixes and kills the cells, preventing them from actively processing the antigen.
- Although antigen is present, the fixed macrophages cannot efficiently internalize, process, or load the antigen peptides onto MHC class II molecules.
- Without proper antigen processing and presentation, TH cells will not receive the necessary signal for activation.
Conclusion for B: TH cell proliferation is unlikely.
Experiment C: Macrophages treated with Paraformaldehyde first, then with Digested Antigen
- Macrophages are fixed with paraformaldehyde first, so they cannot process antigen themselves.
- However, they are then treated with *digested* antigen, meaning the antigen has already been broken down into peptides.
- Even though the macrophages are fixed, pre-processed peptides can often still bind to available MHC class II molecules, particularly those already on the cell surface or accessible within the fixed cell structure.
- If MHC class II-peptide complexes form and are presented on the surface, antigen-primed TH cells can recognize them.
Conclusion for C: TH cell proliferation is expected because processed peptides are provided externally and can likely bind to MHC II on fixed cells.
Experiment D: Macrophages treated with Antigen, then with Paraformaldehyde
- Macrophages are treated with antigen for an hour *before* fixation.
- This allows the live macrophages time to take up and process the antigen into peptides and load them onto MHC class II molecules.
- After this processing and presentation have likely occurred, the macrophages are fixed with paraformaldehyde.
- The fixation preserves the MHC class II-peptide complexes that are already present on the cell surface.
- When incubated with antigen-primed TH cells, these TH cells can recognize the stable MHC-peptide complexes on the fixed macrophage surface.
Conclusion for D: TH cell proliferation is expected because antigen processing and presentation happen before fixation, preserving the presentation signal.
Summary of Experiment Outcomes
Based on the analysis:
- Experiment A: Leads to TH cell proliferation.
- Experiment B: Does not lead to TH cell proliferation.
- Experiment C: Leads to TH cell proliferation.
- Experiment D: Leads to TH cell proliferation.
Therefore, experiments A, C, and D would lead to TH cell proliferation.
Important Questions from Immune System
Bacterial infections are generally divided into two broad classes: intracellular and extracellular bacterial infections. Given below are some of the properties which are applicable for bacterial infections.
A. Humoral immune response is the main protective response against extracellular bacteria.
B. Innate immunity is not effective against intracellular bacterial pathogens.
C. Bacterial endotoxins do not induce an innate immune response.
D. Intracellular bacterial infections generally induce a cell-mediated immune response resulting in secretion of cytokines which activate macrophages.
Which one of the following combination of statements is correct?
The immunoglobulin heavy-chain that is rearranged first and is displayed on the surface of early stages of B-cell development is associated with:
Dr. Ralph M. Steinman was awarded Nobel Prize for his discovery on:
Which one of the following systems forms a chemical mediator that is involved in the mechanism of pain during inflammation?
Suresh was bitten by a poisonous snake and was immediately treated with anti-venom human immunoglobulin and was saved. A year later he was bitten by the same type of snake second time. Predict his response to the venom from second bite from the following:
