Adaptive Immunity and T-Cell Development Flashcards

Vocabulary flashcards covering T-cell development, positive and negative selection, dendritic cell antigen presentation, T helper cell subsets, cytotoxic killing mechanisms, memory T-cell subsets, and immunological assays from Lectures 16 and 17.

Positive Selection

The thymic maturation checkpoint in which cortical thymic epithelial cells present self-peptides on self-MHC molecules to developing T cells; weak or moderate recognition delivers a survival signal allowing continued maturation, whereas absent or insufficient recognition results in death by neglect.

Death by Neglect

The apoptotic death undergone by developing thymocytes that fail to receive a survival signal during positive selection due to absent or insufficient recognition of self-MHC molecules.

Negative Selection

The thymic process in which medullary thymic epithelial cells eliminate self-reactive T cells displaying strong recognition of self-peptides via clonal deletion, or divert them into regulatory T cells (Tregs), thereby preventing autoimmunity.

AIRE (Autoimmune Regulator)

A transcription factor expressed by medullary thymic epithelial cells (mTECs) that drives the ectopic expression of peripheral tissue-specific antigens (TSAs) in the thymus to facilitate central tolerance.

Tissue-Specific Antigens (TSAs)

Proteins normally restricted to specific peripheral organs (such as insulin produced by the pancreas) that are expressed by mTECs in the thymic medulla to purge self-reactive T cells during negative selection.

mTECs (Medullary Thymic Epithelial Cells)

Stromal cells located in the thymic medulla that express the AIRE transcription factor and present tissue-specific antigens to developing thymocytes; histological clusters of these cells form Hassall's corpuscles.

Naïve T Cell

A mature T lymphocyte that has completed thymic development and entered circulation or secondary lymphoid organs but has not yet interacted with its specific foreign antigen.

Dendritic Cell (DC)

A professional antigen-presenting cell residing in peripheral tissues that captures antigens upon activation by PAMPs, DAMPs, or proinflammatory cytokines, migrates via afferent lymphatics, and serves as the only cell capable of activating naïve T cells.

Signal 1 (T-Cell Activation)

The primary antigen-specific activation signal delivered to a T cell through the interaction between its T-cell receptor (TCR) and a specific peptide-MHC complex on an antigen-presenting cell.

Signal 2 (Co-stimulation)

The co-stimulatory survival signal delivered to a T cell when CD28 on the T-cell surface binds to B7 molecules (CD80/B7.1 or CD86/B7.2) expressed on the surface of an activated dendritic cell.

Signal 3 (Polarization)

The polarizing instruction provided by dendritic cell-derived cytokines (such as IL-6, IL-12, or TGF-$\beta$) and membrane molecules that dictates the differentiation pathway and effector character of an activated T cell.

MHC Class I Presentation

The antigen-processing pathway where intracellular or endogenous antigens (such as viral or tumor proteins) are degraded by the proteasome and displayed on MHC class I molecules to activate CD8+ cytotoxic T cells.

MHC Class II Presentation

The antigen-processing pathway where extracellular or exogenous antigens internalized into endosomes/MIIC compartments are loaded onto MHC class II molecules to activate CD4+ helper T cells.

Th1 Subset

A CD4+ T helper cell lineage polarized by IL-12 and IL-18 that produces IFN-$\gamma$ to activate macrophages for killing intracellular bacteria and viruses.

Th2 Subset

A CD4+ T helper cell lineage polarized by IL-4 that secretes IL-4, IL-5, and IL-13 to activate macrophages and drive the expulsion of parasitic worms.

T Follicular Helper (Tfh) Subset

A specialized CD4+ T helper cell subset polarized by IL-6 and IL-21 that produces IL-21 and IL-4 and expresses CD40L and ICOS to help B cells generate high-affinity, class-switched antibodies.

Th17 Subset

A CD4+ T helper cell lineage polarized by IL-6 and TGF-$\beta$ that produces IL-17 to recruit neutrophils and IL-22 to induce antimicrobial peptide production.

T Regulatory (Treg) Cell

An immunosuppressive CD4+ T cell lineage induced by TGF-$\beta$ and retinoic acid (or selected in the thymus) that inhibits immune responses using cell-surface molecules and inhibitory cytokines, including IL-10 and TGF-$\beta$.

Perforin and Granzymes

Cytotoxic effector proteins released by CD8+ T cells; perforin creates pores in the infected target cell's membrane, allowing granzymes (such as granzymes A and B) to enter and induce apoptotic cell death.

Natural Killer (NK) Cell Missing-Self Recognition

A non-antigen-specific cytotoxic mechanism where NK cells kill target cells lacking surface MHC class I molecules, which normally deliver an inhibitory signal to the NK cell's inhibitory receptor.

Central Memory T Cell ($T_{\text{CM}}$)$$

A long-lived memory T cell population that resides in and circulates through secondary lymphoid tissues, including lymph nodes and the spleen.

Effector Memory T Cell ($T_{\text{EM}}$)$$

A recirculating memory T cell population specialized to patrol peripheral tissues by circulating between the blood and non-lymphoid tissues.

Tissue-Resident Memory T Cell ($T_{\text{RM}}$)$$

A non-circulating, long-lived subset of memory T cells that takes up permanent residence directly within peripheral tissues at the prior site of insult or infection.

Memory T-Cell Reactivation

The ability of antigen-experienced CD4+ or CD8+ memory T cells to become reactivated through Signal 1 alone, without requiring co-stimulation (Signal 2), enabling a faster and stronger recall response.

ELISPOT Assay

A diagnostic method (used in tests such as the tuberculosis QuantiFERON assay) that measures the frequency of antigen-specific cytokine-secreting T cells by capturing secreted IFN-$\gamma$ onto antibody-coated plates in the presence of antigen and antigen-presenting cells.