Natural killer (NK) cells and killer T cells are two types of cytotoxic lymphocytes that serve vital roles in the immune system. At first glance, they may seem quite similar – they are both capable of killing infected or cancerous cells. However, NK cells and killer T cells actually have a number of important differences.
What are NK cells?
NK cells are a type of innate lymphoid cell that provide rapid, nonspecific immune responses. Some key facts about NK cells:
- NK cells are granular lymphocytes that contain cytotoxic granules in their cytoplasm.
- They make up 10-15% of all circulating lymphocytes in human blood.
- NK cells do not need to recognize a specific antigen in order to kill a target cell. Instead, they recognize stressed, infected, or cancerous cells by the altered expression of MHC class I molecules.
- NK cells kill cells by releasing perforin and granzymes from their cytotoxic granules. Perforin forms pores in the target cell membrane while granzymes enter the cell and trigger apoptosis.
- In addition to their cytotoxic activity, NK cells secrete cytokines like interferon-gamma to regulate immune responses.
Overall, NK cells provide a rapid first-line defense against viruses, intracellular bacteria, and tumor cells through their natural cytotoxicity. They do not need activation to perform effector functions.
What are killer T cells?
Killer T cells, also known as cytotoxic T lymphocytes (CTLs), are a subset of T cells that kill infected or cancerous cells. Key facts about killer T cells:
- Like all T cells, killer T cells develop from hematopoietic stem cells in the bone marrow and mature in the thymus.
- Killer T cells make up about 5-20% of circulating T cells in the human body.
- They express T cell receptors (TCRs) on their surface that can recognize specific antigens presented on MHC class I molecules.
- Once activated, killer T cells release perforin, granzymes, and other cytokines to induce apoptosis of the target cell.
- Memory killer T cells persist after an infection is cleared and facilitate faster secondary responses.
Therefore, killer T cells are a key component of adaptive immunity and provide antigen-specific responses against pathogens and cancer cells. They must be activated to perform effector functions.
Differences between NK cells and killer T cells
Despite their similar roles as cytotoxic lymphocytes, NK cells and killer T cells have a number of key differences:
| Characteristic | NK cells | Killer T cells |
|---|---|---|
| Type of immunity | Innate immunity | Adaptive immunity |
| Antigen specificity | Do not recognize specific antigens | Recognize specific antigens via the TCR |
| Activation | Do not require activation | Require activation by antigen presentation |
| MHC restriction | Recognize altered MHC class I | Recognize antigen presented on MHC class I |
| Persistence after infection | Do not form memory cells | Form memory cells after primary infection |
To summarize, NK cells provide rapid, nonspecific cytotoxicity as part of the innate immune system. Killer T cells have antigen-specific cytotoxicity and memory as part of the slower, adaptive immune response.
Development of NK cells and killer T cells
NK cells and killer T cells also differ in their developmental pathways:
NK cell development
- Develop from common lymphoid progenitor cells (CLPs) in the bone marrow
- Differentiate directly into mature NK cells under the influence of cytokines like IL-15
- Do not undergo clonal selection in the thymus
Killer T cell development
- Develop from CLPs that migrate from the bone marrow to the thymus
- Undergo positive and negative selection to establish central tolerance
- Mature into CD8+ cytotoxic T cells that express diverse TCRs
Therefore, NK cells have an earlier developmental pathway compared to killer T cells, which must undergo selection in the thymus.
Mechanisms of action
Both NK cells and killer T cells induce target cell death through similar cytotoxic mechanisms:
- Release of perforin and granzymes – These cytotoxic granules induce apoptosis in the target cell.
- Fas/Fas ligand interactions – Fas ligand expression on the cytotoxic cell triggers apoptosis by binding to Fas on the target.
- Secretion of cytokines like IFN-gamma and TNF-alpha – These stimulate inflammatory responses against infected cells.
However, the regulation of these pathways differs between NK cells and killer T cells:
- NK cells constitutively express perforin and granzymes within their cytoplasmic granules, allowing immediate cytotoxicity when an abnormal cell is detected.
- In contrast, killer T cells only produce these cytotoxic granules after activation by a specific antigen.
Overall, both cell types induce apoptosis of target cells through cytotoxic granule contents and death receptor pathways. But NK cells are ready to kill abnormal cells immediately, while killer T cells require prior antigen-induced activation.
Target recognition by NK cells and killer T cells
NK cells and killer T cells identify target cells in very different ways:
NK cell target recognition
- Do not recognize specific antigens
- Detect abnormal MHC class I expression using killer cell immunoglobulin-like receptors (KIRs)
- Normal cells express intact MHC class I, blocking NK cell attack
- Stressed cells often downregulate MHC class I, activating NK cells
- NK cells also express other activating/inhibitory receptors like NKG2D which bind ligands upregulated by infected cells
Killer T cell target recognition
- Express TCRs specific for antigens presented on MHC class I
- Recognize infected cells presenting foreign antigen peptides via MHC class I
- Memory killer T cells are pre-activated and readily respond to secondary antigen exposure
In summary, NK cells are activated by altered MHC class I on abnormal cells, while killer T cells recognize specific antigen peptides presented by intact MHC class I.
Conclusion
NK cells and killer T cells are both cytotoxic lymphocytes capable of inducing apoptosis in infected or cancerous cells. However, NK cells provide rapid, innate, nonspecific immunity while killer T cells mediate slower, adaptive, antigen-specific immunity. Key differences between them include MHC restriction, memory formation, activation requirements, and mechanisms of target recognition. Understanding these distinctions provides insight into the complementary roles of innate and adaptive immunity.
