T cell activation
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T cell activation
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[post_date] => 2024-12-23 18:36:05
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[post_content] => Practice Passage (Question 1-6)
*This passage is the property of Khan Academy and has been reformatted into an AAMC-style interface in their entirety by MedLife Mastery. MedLife Mastery does not endorse and is not an affiliate of Khan Academy.
T cell activation is an antigen-dependent process leading to the proliferation and differentiation of naive T cells into effector cells. This process requires primary and coactivating signals including those referred to here as Signal 1 and Signal 2:
- Signal 1 occurs when the T cell receptor (TCR) binds fragments of foreign antigenic proteins that are loaded onto the major histocompatibility complex (MHC) molecule. MHC is displayed on the surface of an antigen-presenting cell (APC) or a target cell. A T cell coreceptor (CD4 or CD8) also binds the MHC molecule on the APC or target cell.
- Signal 2 occurs when co-activating molecules on the T cell bind costimulatory proteins on the APC or target cell, the most important of which is the B7 protein. B7 binding by T cell costimulatory proteins results in T cell activation, whereas a lack of binding results in apoptosis of the cell. Because most native cells do not possess B7, this system prevents T cells from reacting to the host’s own proteins.
Figure 1 Overview of T cell activation; adapted from Sharma et al. Nature Reviews Cancer 11, 805-812 (November 2011)
The combination of Signals 1 and 2 determines the nature of the T cell’s response to the antigen. Activation of cytotoxic (CD8) T cells via MHC Type I binding results in the direct lysis of target cells, whereas activation of helper (CD4) T cells via MHC Type II binding causes multiple downstream effects including synthesis of important proinflammatory molecules (cytokines) such as tumor necrosis factor, enhancement of antibody secretion by B cells, and enhanced killing by cytotoxic CD8 cells.
CD4 T cells play a crucial role in regulating a broad range of immune responses essential for normal immune function, and defects in CD4 cells underlie a variety of diseases. For example, retroviral infection with human immunodeficiency virus (HIV) impairs CD4 cells, rendering the affected individuals susceptible to opportunistic infections. Conversely, when CD4 cells become overactive, they may excessively secrete inflammatory cytokines, leading to inflammatory diseases like lupus.
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[question] => Which processes are required for the activation of naive T cells into effector cells?
[value] => Array ( [answer] => 2 [description] =>Reason for the Correct Answer:
Antibody binding is not a component of T cell activation. Antibody production results from the activation of CD4 T cells.
The binding of MHC Type I or II is necessary for activation, but this is not the only requirement.
According to the passage, the most accurate answer here is T cell binding to BOTH the MHC (Signal 1) and costimulatory proteins (Signal 2).
) [answers] => Array ( [0] => Array ( [each_answer] =>A. Costimulatory antibody and B7 binding by T cells
) [1] => Array ( [each_answer] =>B. MHC and costimulatory protein binding by T cells
) [2] => Array ( [each_answer] =>C. MHC Type I and MHC Type II binding by T cells
) [3] => Array ( [each_answer] =>D. MHC Type I and B7 binding by T cells
) ) ) [1] => Array ( [quiz_unique_key] => 3873426850 [question] =>Which of the following best describes the mechanism of T cell tolerance to host proteins?
[value] => Array ( [answer] => 2 [description] =>Reason for the Correct Answer:
It is important to remember that Signal 1 provides specificity. When the T cell receptor binds the antigen–MHC complex and the coreceptor binds MHC, the T cell will adequately recognize the antigen.
Signal 2 results from binding of the T cell to costimulatory molecules on antigen-presenting cells or target cells.
If the costimulatory molecule is not present on a presenting cell, it will not activate the T cell, and the T cell will have “tolerance” for that protein.
) [answers] => Array ( [0] => Array ( [each_answer] =>A. The T cell receptor binds costimulatory molecules but fails to bind antigen/MHC.
) [1] => Array ( [each_answer] =>B. The T cell binds antigen/MHC but not costimulatory molecules.
) [2] => Array ( [each_answer] =>C. The T cell receptor binds antigen/MHC but the coreceptor fails to bind antigen.
) [3] => Array ( [each_answer] =>D. The T cell binds antigen and costimulatory molecules but fails to bind MHC.
) ) ) [2] => Array ( [quiz_unique_key] => 83407773 [question] =>Which statement about CD4 cells is NOT accurate?
[value] => Array ( [answer] => 3 [description] =>Reason for the Correct Answer:
CD4 cells are indeed activated by binding to Type II MHC; Type I MHC binding results in activation of CD8 cells (this information is found in the passage.)
CD4 cells are involved in multiple critical immune functions including the enhancement of antibody production by B cells and the production of important cytokines. According to the passage, they also promote “enhanced killing by cytotoxic T cells.”
However, CD4 cells do not directly kill target cells – this is the role of CD8 cells. This is why CD4 cells are called “helper” T cells, not “cytotoxic” T cells.
) [answers] => Array ( [0] => Array ( [each_answer] =>A. They are activated by binding to Type II MHC.
) [1] => Array ( [each_answer] =>B. They secrete important inflammatory cytokines.
) [2] => Array ( [each_answer] =>C. They are involved in the direct killing of target cells.
) [3] => Array ( [each_answer] =>D. They enhance antibody production by B cells.
) ) ) [3] => Array ( [quiz_unique_key] => 2261298308 [question] =>A 25-year-old woman with lupus has been taking medication that inhibits the effect of CD4-secreted cytokines, specifically tumor necrosis factor (TNF). She comes to her physician’s office with a fever and a cough that has lasted for weeks. Based on her medical history, which of the following is this patient at the greatest risk of developing?
[value] => Array ( [answer] => 2 [description] =>Reason for the Correct Answer:
Inhibiting TNF would decrease the effect of CD4 cell signaling.
This could, in turn, have the effect of decreasing, not increasing, the activity of other immune cells.
This could make the patient more susceptible to certain types of infection.
The only side effect that fits with this is impairment of normal inflammatory response with resultant tuberculosis.
) [answers] => Array ( [0] => Array ( [each_answer] =>A. Excessive inflammatory response due to medication, resulting in an asthma-like reaction
) [1] => Array ( [each_answer] =>B. Impairment of normal inflammatory response with resultant tuberculosis
) [2] => Array ( [each_answer] =>C. Lung cancer due to abnormally high levels of tumor necrosis factor
) [3] => Array ( [each_answer] =>D. Overcompensation by cytotoxic CD8 cells, causing sterile bronchitis
) ) ) [4] => Array ( [quiz_unique_key] => 2261298308 [question] =>Which of the following would be a potential explanation for T cell-mediated autoimmune disease?
[value] => Array ( [answer] => 3 [description] =>Reason for the Correct Answer:
Overexpression, not underexpression, of inflammatory cytokines contributes to autoimmune disease.
CD8 cytotoxic cells play less of a role in autoimmune disease than CD4 helper cells.
According to the passage “B7 binding by T cell costimulatory proteins results in T cell activation, whereas a lack of binding results in apoptosis of the cell”. Therefore, a failure of apoptosis of T cells that recognize self-antigens is the most likely explanation for many autoimmune diseases.
) [answers] => Array ( [0] => Array ( [each_answer] =>A. Underexpression of cytokines by T cells
) [1] => Array ( [each_answer] =>B. Excessive apoptosis of self-recognizing T cells
) [2] => Array ( [each_answer] =>C. Failure of apoptosis of self-recognizing T cells
) [3] => Array ( [each_answer] =>D. Failure of differentiation of naive T cells into CD8 cytotoxic cells
) ) ) [5] => Array ( [quiz_unique_key] => 2261298308 [question] =>HIV infection eventually leads to acquired immunodeficiency disorder (AIDS) if left untreated or inadequately managed. Which of the following would NOT be a helpful therapy for patients with HIV infection or AIDS?
[value] => Array ( [answer] => 3 [description] =>Reason for the Correct Answer:
HIV is a retrovirus. Retroviruses enter host cells and use specific enzymes, including reverse transcriptase and integrase, to incorporate their genes into the DNA of the host cell.
https://commons.wikimedia.org/wiki/File:Hiv_gross.png
Therefore, drugs that block the entry of the virus and drugs that inhibit the integrase enzyme are effective treatment options.
Antibiotics would also be useful to help combat the frequent infections that result from dysfunctional CD4 T cells in patients with HIV.
However, chemotherapy drugs that target CD4 T cells would NOT be helpful, as they would further reduce the number of viable CD4 T cells, worsening the side effects of HIV/AIDS.
) [answers] => Array ( [0] => Array ( [each_answer] =>A. Inhibitors of the integrase enzyme
) [1] => Array ( [each_answer] =>B. Antibiotics to treat opportunistic infections
) [2] => Array ( [each_answer] =>C. Chemotherapy drugs that target CD4 T cells
) [3] => Array ( [each_answer] =>D. Drugs that block the entry of HIV into CD4 T cells
) ) ) ) [total_question] => 6 [correct_answers] => Array ( [554846|1] => B [554846|2] => B [554846|3] => C [554846|4] => B [554846|5] => C [554846|6] => C ) [hide_display_feedback_settings] => [hide_solutions] => )