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Course: MCAT > Unit 2

Lesson 3: Foundation 3: Organ Systems
Test prep
MCAT
Practice Passages: Biological and Biochemical Foundations of Living Systems
Foundation 3: Organ Systems
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Immune system: T cell activation

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Problem

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.
Which processes are required for the activation of naive T cells into effector cells?
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