module 12 questions & answers

what are double negative (DN) T-cells, and how are they classified?

they are early-stage T cells that lack detectable CD₄ & CD₈ markers. they are classified into four subsets (DN1-DN4) based on the presence or absence of specific cell surface molecules. they primarily express C-kit (CD117), CD44, & CD25

what happens during the transition from DN₄ to double positive (DP) thymocytes?

after proliferating in the DN4 stage, cells stop dividing and initiate alpha chain rearrangement, increasing the T-cell repertoire diversity. in the late DN4 stage, cells start expressing both CD4 & CD8, becoming double positive (DP) thymocytes. DP cells express T-cell receptors & associate w/ CD3

what is the process of positive & negative selection in T-cell development?

positive selection → thymocytes bearing receptors that bind with low affinity to self-MHC molecules are selected to survive, resulting in MHC restriction. this occurs primarily in the thymic cortex

negative selection → thymocytes bearing receptors with high affinity for self-MHC/self-peptide undergo apoptosis, ensuring self-tolerance. this occurs both in cortex & medulla 

what is the significance of the Zinkernagel experiment in understanding T-cell education?

demonstrated that thymic positive selection is responsible for self-MHC restriction. it showed that T-cells learn their own MHC type during development in the thymus, proving that MHC haplotype of the thymus determines MHC restriction of developing T-cells. 

how does the absence of MHC class I or II molecules affect T-cell positive selection?

in mice lacking class I molecules, CD8+ T-cells are absent b/c their TCRs cannot undergo positive selection with class I MHC. conversely, in mice lacking MHC class II molecules, CD4+ T-cells are absent for the same reason. highlights the necessity of TCR interaction w/ MHC molecules for positive selection

what are the signals required for naive T-cell activation?

signal 1: TCR/MHC peptide interaction along w/ co-receptor CD4 or CD8.

signal 2: co-stimulation by molecules like CD28 binding to CD80 or CD86 on APCs.

signal 3: cytokine binding to T-cell receptors, directing the T cell into distinct effector cell types.

what are the roles of co-stimulatory & co-inhibitory receptors in T-cell activation?

co-stimulatory receptors → CD28 on T-cells interacts w/ CD80/86 on APCs, leading to T-cell activation

co-inhibitory receptors → CTLA-4, expressed on activated T-cells, binds to CD80/86, acting as a brake on T-cell activation. PD-1 binds to PD-L1/2 and may be involved in T-cell tolerance

what is the role of checkpoint inhibitors in cancer immunotherapy?

checkpoint inhibitors, such as antibodies that block CTLA-4 or PD-1, prevent the inhibition of T-cell activation. this enhances T-cell activity against tumors, allowing the immune system to effectively target & kill cancer cells

what is clonal energy, and how is it induced?

state of unresponsiveness in T-cells due to lack of co-stimulatory signals (signal 2). it occurs when naive T-cells receive signal 1 (TCR engagement w/ MHC) without signal 2 (CD28 interaction w/ CD80/86), or through engagement of inhibitory receptors like CTLA-4

what are superantigens, and how do they activate T-cells?

viral or bacterial proteins that bind to all TCRs bearing a particular V beta sequence, regardless of antigen specificity. this strong binding activates T-cells en masse, leading to massive cytokine production & systemic toxicity

how do polarizing cytokines influence the differentiation of T-helper cell subsets?

polarizing cytokines, secreted by APCs or neighboring cells, interact w/ cytokine receptors on T-helper cells and induce the transcription of master genes. these genes regulate the expression of effector cytokines, guiding T-helper cells into specific subsets (Th1, Th2) with distinct function

what are the roles of Th1 & Th2 cells in the immune response?

Th1 cells: involved in cell-mediated immune responses against intracellular pathogens. they secrete IFN-gamma & TNF, enhancing APC activity, cytotoxic T-cell activity, & delayed-type hypersensitivity (DTH).

Th2 cells: protect against extracellular pathogens & parasites. they secrete IL-4, IL-5, & IL-13, promoting eosinophil activation and B-cell function, including class switching to IgE.

what is the role of T-regulatory (Treg) cells in the immune system?

treg cells maintain peripheral tolerance by suppressing autoimmune responses. they are characterized by the expression of CD4, CD25, and the transcription factor FoxP3. treg cells prevent autoimmune diseases by inhibiting the activity of self-reactive T-cells

how can Treg cells influence cancer & autoimmune diseases?

treg cells can suppress immune responses against cancer, allowing tumors to evade the immune system. conversely, depletion of treg cells can lead to autoimmune diseases. balancing treg activity is crucial for maintaining immune homeostasis and preventing both autoimmunity & cancer progression