第一章：免疫细胞抵御病毒感染及杀灭异常细胞的过程概述
T cells develop in the thymus, where they undergo selection to ensure they can recognize antigen in the context of self-MHC but are not dangerously self-reactive. After exiting the thymus, they enter the circulation as naïve T cells. The journey from naïve to specialized effector or memory subsets depends on antigen encounter, cytokine environment, and repeated stimulation.
Below is the typical developmental flow after thymic maturation.
Characteristics:
Have not yet encountered their specific antigen.
Circulate between blood, lymph, and secondary lymphoid organs (e.g., lymph nodes).
Require strong co-stimulation to become activated.
Functionally:
They are “blank slates”—antigen-specific but inexperienced.
Transition trigger:
Encounter with antigen presented by dendritic cells along with co-stimulation (e.g., CD28 signals) and cytokines.
Upon recognizing their antigen with sufficient co-stimulation, naïve T cells:
Undergo clonal expansion (rapid proliferation).
Increase metabolic activity.
Upregulate activation markers (e.g., CD69, CD25).
Begin differentiating toward effector or memory fates, depending on signals from cytokines, antigen strength, and duration of stimulation.
Key point: “Activated” is a transitional functional state, not a terminal phenotype.
These are the frontline fighters generated during the acute immune response.
Produce perforin, granzyme B.
Kill infected or cancerous cells.
Produce inflammatory cytokines (e.g., IFN-γ).
Differentiate into subsets (e.g., Th1, Th2, Th17, Tfh), each directing different types of immune responses.
Fate:
Most effector cells die after the pathogen is cleared, but some survive and transition into memory subsets.
After the primary immune response, a portion of T cells transitions into long-lived memory subsets. These subsets differ in location, phenotype, and function.
Characteristics:
Considered the earliest and most primitive memory subset.
Have stem-like properties:
Long lifespan
Ability to self-renew
Capacity to regenerate all other memory and effector subsets
Retain many naïve markers but with enhanced functional potential.
Role:
Act as a reservoir that can generate new waves of effector and memory cells during future infections.
Characteristics:
Reside primarily in secondary lymphoid tissues.
Express lymphoid-homing molecules (e.g., CCR7, CD62L).
Respond rapidly to re-stimulation by proliferating and producing cytokines.
Function:
They are “poised responders”—ready to expand and differentiate into effectors upon re-exposure to antigen.
Characteristics:
Found primarily in the blood and non-lymphoid tissues.
Lack lymph node–homing receptors (e.g., CCR7⁻).
Readily produce effector cytokines.
Function:
They act as rapid-response sentinels, providing immediate protection in peripheral tissues.
Although not requested, it’s worth noting that another key memory lineage is Tissue-Resident Memory T cells, which permanently inhabit tissues like skin, lungs, and gut. They are often the first responders during reinfection.
Naïve T Cell ↓ (antigen encounter + activation)Activated T Cell ↙ ↘Effector T Cell Memory Precursors ↓ ┌───────────────────────────────┬───────────────────────┐Stem Cell Memory T Cell Central Memory T Cell Effector Memory T Cell
Naïve → Activated requires antigen and co-stimulation.
Activated → Effector occurs during immediate pathogen response.
Activated → Memory subsets occurs as the immune response resolves.
Memory subsets differ in homing behavior, longevity, and functional readiness.
The process of how T cells mature and differentiate in response to antigen is summarized as the following
Naïve T Cells: unexperienced, circulating.
Activated T Cells: triggered by antigen; proliferating.
Effector T Cells: perform immediate defense functions.
Stem Cell Memory T Cells: long-lived, highly regenerative.
Central Memory T Cells: lymphoid-homing, strong proliferative responses.
Effector Memory T Cells: peripheral-tissue sentinels with immediate effector function.
This dynamic differentiation allows the immune system to respond strongly to current threats while maintaining long-term protection.
Memory T cells need different co-sitmulatory molecules from Naive T cells.
Memory T cells have the property of recirculation, redistribute
Localization
Surface Marker Expression
CD44, CD62L and CCR-7
Potential of Reactivation
第二章：免疫细胞的衰竭及其对病毒感染的影响
