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CD4 Proteins & Antigen presenting cells

CD4 Proteins & Antigen presenting cells


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If Helper T-Cells express CD4+ proteins on their surface to bind to MHC Class ll proteins on antigen presenting cells, why do antigen presenting cells also have CD4+ Proteins?


Adhesion Molecules and Alcohol Consumption

Abbreviations

Intercellular adhesion molecule-1,2,3

Leukocyte function associated antigen-1

Monocyte chemotactic peptide-1

Macrophage inflammatory protein-1 β

Neural cell adhesion molecule-1

Peripheral blood mononuclear cells

Platelet derived growth factor

Platelet endothelial cell adhesion molecule-1

Transforming growth factor β-1

Tissue-type plasminogen activator

Urokinase-type plasminogen activator

Vascular cell adhesion molecule-1

Vascular endothelial growth factor

Very late activation antigen

Very late activation antigen-3

Very late activation antigen-4

Very late activation antigen-5


Antigen-presenting cells look within during influenza infection

During viral infections, antigen-presenting cells (APC) have traditionally been thought to recruit and activate CD4 + T cells by presenting fragments of viral proteins captured from the extracellular environment. A new study indicates that the material the APCs need to present is much closer: in fact, APCs need to make it themselves.

Humans—even immunologists—like to make sense of the world's complexity by establishing simple, and if possible, binary categories. For example, the discovery that the processing of extracellular antigens for presentation by major histocompatibility class II (MHC II) molecules takes place in endosomal compartments 1 , whereas antigens presented by MHC I molecules are produced by the cells themselves and processed in the cytosol 2,3 , led to the establishment of a simple, now 30-year-old paradigm: the antigens presented by MHC I are endogenous (synthesized by the cells performing the presentation) and those presented by MHC II are exogenous (synthesized by other cells). This is a rule stated in most immunology textbooks and frequently reiterated in the introductions of primary research papers on antigen presentation. But it is a gross simplification. Cross-presentation—the process whereby exogenous antigens are presented via MHC I—has long been known to represent an important departure from the paradigm 4 , but it took three decades for its physiological role to be widely accepted 5 . In this issue of Nature Medicine, Miller et al. present data indicating that, at least in the mouse influenza model studied, induction of robust CD4 + T cell responses requires MHC II presentation of endogenous antigens produced by infected APCs 6 . This paradigm shift has important implications for our understanding of antiviral immunity and vaccine development.

The confusion about the origins of antigens presented via MHC I as compared to II is partly semantic. The most accurate criterion to categorize the type of antigens presented by each molecule is the site of peptide production: the cytosol for MHC I and endosomal compartments for MHC II. The problem is that the term 'cytosolic' is often used interchangeably with 'endogenous' and the term 'endosomal' as synonymous with 'exogenous'. It is true that, except in the few cell types capable of cross-presentation, the vast majority of cytosolic proteins are endogenous. However, the content of endosomal compartments is always both endogenous (membrane proteins, endosomal components, cytosolic proteins delivered to endosomes by autophagy) and exogenous (endocytosed from the extracellular environment). Because the proteases that produce MHC II ligands cannot distinguish exogenous from endogenous proteins, MHC II molecules end up presenting peptides derived from both 7 . However, this conflation of endosomal with exogenous helped cement a common misconception in the field: that the APCs that activate CD4 + T cells by presenting antigens via MHC II—namely, dendritic cells (DCs)—must have obtained this antigen from an exogenous source. In the case of viral infection, this exogenous source would correspond to virions or to cells infected with the virus (Fig. 1). In this scheme, the location of the viral antigen within the infected cell is irrelevant what matters is that the antigen has been produced by a different cell from the one performing the presentation.

(a) Dendritic cells (DCs) can capture these exogenous antigens by endocytosis (left). The DCs process the antigens in endosomal compartments and present them via MHC II to CD4 + T cells. The repertoire of viral peptides presented, and the magnitude of presentation, are relatively small, so the antiviral CD4 + T cell response elicited is limited. (b) IAV can also infect DCs, which produce viral proteins. These endogenous antigens access endosomal compartments by endocytosis (membrane proteins) or autophagy (cytosolic proteins) and are also presented via MHC II to CD4 + T cells. The viral peptides presented by this pathway are more diverse and their presentation is more efficient, leading to more vigorous antiviral CD4 + T cell responses. MHC II presentation of endogenous viral antigens by the infected DCs may involve accessory molecules that are not used by DCs performing presentation of exogenous antigens.

Miller et al. put this assumption to the test using mouse models in which the influenza A virus could infect either only non-DCs or both DCs and non-DCs. Their conclusion is that only when DCs are infected, enabling presentation of viral antigens produced by the DCs themselves, does an efficient CD4 + T cell response develop 6 . Next they explored the role of known components of the MHC II presentation machinery 8 in the presentation of endogenous viral antigens in DCs. Regardless of the mechanism used to access endosomes, it is assumed that the conversion of proteins into peptides capable of binding to MHC II will be carried out by proteases and other enzymes located in the endocytic route. For example, the endosomal reductase GILT would be expected to assist proteolysis by breaking disulfide bonds contained in the antigen. Binding of the peptide antigens to MHC II molecules should be dependent on the endosomal chaperone H-2M. However, Miller et al. found that the presentation of most viral peptides derived from endogenous sources did not require H-2M or GILT. Even more surprisingly, presentation of some peptides required the proteasome and the transporter TAP, molecules involved in MHC I, not MHC II, presentation. A role for MHC I presentation machinery in MHC II presentation is not without precedent 9 , but its contribution in the setting of infection is not clear additional work is needed to clarify the precise role of MHC I machinery in this process.

The conclusions of this paper raise important considerations for future studies. For example, when assessing the role of different APCs in priming CD4 + T cells against viruses, it will be important to take into account the susceptibility of each APC subtype to infection. Specializations amongst APC may also be based on differential capacity to present endogenous viral antigens via MHC II 10 . These new results also point to potential strategies that might be exploited by viruses to impair the induction of neutralizing antibody responses, which require B cells to present antigens to the same helper CD4 + T cells that were primed by DCs 11 . If the viral antigens are presented only by the endogenous route, and the offending virus infects DCs but not B cells, the helper CD4 + T cells and B cells would not interact productively, and antibody production would be blunted.

Finally, there is a practical and rather unsettling implication of the conclusions of Miller et al. 6 : 'dead' or inactivated viruses used in vaccine preparations may not be capable of inciting robust and protective virus-specific CD4 + T cell responses because, unlike live viruses, inactivated viruses will not productively infect DCs and produce endogenous antigens. To what extent are these implications correct? To how many and which viruses do they apply? These are questions that viral immunologists will now have to address by seeking the truth not only outside but also inside the APCs.


Ribosomal versus non-ribosomal cellular antigens: factors determining efficiency of indirect presentation to CD4+ T cells

Proteins released from dying cells can be taken up and presented by antigen-presenting cells (APC) to T cells. While the presentation of such self antigens may lead to beneficial anti-tumour responses, in autoimmune disease it leads to pathological immune responses. The sub-set of self proteins targeted in autoimmune disease is circumscribed, and certain cellular components such as ribonucleoprotein (RNP) complexes are often targeted. Although explanations for this antigen selectivity have been proposed, there has been little direct testing of these hypotheses. We and others previously showed that ribosomal proteins, targeted in autoimmune disease, are also targets of anti-tumour T-cell responses. We asked whether particular properties of ribosomal proteins such as incorporation into RNP complexes or sub-cellular localization enhance ribosomal protein presentation by APC to CD4(+) T cells. Ribosomal protein antigens within purified intact ribosomes or free of the ribosomes were equally well taken up and presented by APC, demonstrating that inclusion of ribosomal proteins into an RNP complex does not confer an advantage. However, antigens localized to ribosomes within apoptotic cells were less efficiently taken up and presented by APC than the same antigens localized diffusely throughout the cell. This suggests that presentation of ribosomal proteins is somehow down-regulated, possibly to facilitate presentation of other less-abundant intracellular proteins. Consequently, the explanation for the frequent targeting of ribosomal proteins by both autoimmune and anti-tumour T-cell responses is not at the level of uptake from apoptotic cells and must be sought elsewhere.

Figures

Model proposed to explain the…

Model proposed to explain the preferential presentation of ribosomal proteins antigens from apoptotic…

(a) CD4 + T-cell stimulation assay. Antigen in the form of purified ribosomes,…

A bacterial expression system to…

A bacterial expression system to test T-cell stimulation by enhanced green fluorescence protein…

Antigens localized to the ribosome…

Antigens localized to the ribosome do not stimulate as well as non-localized antigens.…

E antigen localized by mutated…

E antigen localized by mutated ribosomal proteins does not stimulate as well as…

(a) Specific antigen must compete…

(a) Specific antigen must compete with irrelevant intracellular proteins for presentation to CD4…


Discussion

In the study we have investigated the effect of inhibiting PI3Kδ on the ability of CD4 + T cells to form productive conjugates with APCs.

To our initial surprise, we found Rac activity to be intact, or even enhanced, in p110δ D910A T cells after stimulation with anti-CD3. This contrasts to observations in neutrophils where PI3K has been shown to positively regulate Rac activity via the protein P-Rex1, which catalyses the exchange of GDP for GTP on Rac using its GEF domain. 37 However, in subsequent studies, no effect of P-Rex1 deficiency on lymphocyte function was found 38 (our unpublished data). Vav1 is a key regulator of Rac activity in T cells and its capacity to regulate Rac is dependent on the ability of the Vav-PH domain to bind PtdIns(4,5)P2 or PIP3. 39 However, as the Vav1 PH domain does not discriminate effectively between PIP3 and its much more abundant precursor PtdIns(4,5)P2, it is unlikely that Vav1 is acutely regulated by PI3Ks. The Rac GEF Dock2 has also been considered to bridge PI3K signalling to Rac activation. Rac activity is reduced in Dock2 −/− T cells stimulated via the TCR or through chemokines. 40 , 41 , 42 During the activation of CD8 + T cells, actin is cleared from the immune synapse to facilitate the delivery of cytotoxic granules. 41 , 43 Le Floc'h and colleagues noted reduced cell spreading and depletion of actin at the centre of the immune synapse in CD8 + T cells, lacking Dock2 or that had been inhibited with IC87114. 41 Our data are consistent with this study with regards to cell spreading and impaired actin reorganisation, but we cannot conclude that this is simply a consequence of impaired Rac activation. Inactivation of Rac is mediated by GAP, which stimulates the intrinsic hydrolysis activity of small GTPases. ArhGAP15 is regulated in a PIP3-dependent manner and ArhGAP15 −/− neutrophils and macrophages show enhanced Rac activity, which is antagonised by PI3K signalling. 44 , 45 Although TCR-dependent Rac activity in ArhGAP15 −/− T cells is unperturbed (Garçon F, Costa C, Hirsch E, Okkenhaug K, manuscript in preparation), these results indicate that Rho-family GAPs as well as Rho-family GEFs need to be taken into account when considering the effect of PI3K inhibition on Rac activity in different cell types and downstream of distinct receptors. Indeed, during phagocytosis, the activation of up to three different PI3K-dependent Rac-GAPs is required for actin clearance in a manner reminiscent of that observed during CTL activation by antigen. 46 We propose that impaired actin reorganisation in p110δ D910A CD4 + T cells is a consequence of altered dynamics in the cycling between the GTP- and GDP-bound states of Rac, which can be affected both by PIP3-dependent GEFs and GAPs.

Rap1 activation was reduced in p110δ D910A T cells stimulated with anti-CD3, and binding of ICAM-1 to LFA-1 was also impaired suggesting that PI3Kδ could regulate LFA-1 activation through Rap1. The capacity of LFA-1 to interact with its ligand ICAM-1 is regulated by two processes: conformational change, leading to higher affinity binding, and clustering, leading to increased avidity. 20 Although activated Rap1 has been reported to regulate both the avidity and the affinity of LFA-1, a constitutively active mutant of Rap1 preferentially increased LFA-1 avidity in primary T cells. 26 , 47 Our results suggest that PI3Kδ regulates the affinity rather than the avidity of LFA-1, as PI3Kδ inhibition suppressed binding of LFA-1 on T cells to a soluble ligand without affecting capping of LFA-1 on the T cells. If the main effect of activated Rap1 is to increase LFA-1 clustering, then this would explain the failure of a constitutively active form of Rap1 (Rap1V12) to rescue the binding to ICAM-1 by LFA-1 expressed by p110δ D910A T cells. This may also explain why in a previous study we found that p110δ D910A T cells bound normally to ICAM-1 plate-based adhesion assay. 10 The plate-based adhesion assay used in that study cannot discriminate between affinity- and avidity-mediated changes in adhesiveness. The present study shows that although p110δ D910A T cells were able to cap LFA-1 at the surface and bind plate-bound ICAM-1, they failed to spread and had a very small surface of contact.

Contrary to our initial hypothesis, the reduction of Rap1 activity we observed when PI3Kδ was inhibited is not in itself sufficient to explain the reduced binding of LFA-1 to ICAM-1. In addition to regulating integrin affinity, Rap1 is also required for cell spreading and actin dynamics. 48 Rap1 does so by promoting the dephosphorylation and activation of the actin-severing protein cofilin. Cofilin phosphorylation is also increased via Rac upon TCR/CD28 engagement. 27 Our data show that PI3Kδ inhibition suppressed cofilin dephosphorylation and dynamic actin reorganisation required for cell shape modification and productive interactions with APCs, which may be another consequence of reduced Rap1 activity. How the reduced Rap1 activation and increased Rac1 activity in p110δ D910A T cells is integrated to regulate cytoskeletal rearrangements and integrin activation still remains to be fully elucidated, however.

Interestingly, Rap1 activity was also reduced when Akt was inhibited. Inhibition of Akt also led to a small decreased binding to ICAM-1 but not as strong as that observed in p110δ D910A T cells or T cells treated with the PI3Kδ inhibitor IC87114. These results implicate Akt in the regulation of integrins, but also suggest that PI3K effectors other than Akt mediate PI3K-dependent integrin activation. Which other PIP3-binding proteins could contribute to Rap1 activation and increased LFA-1 affinity? SKAP1 is composed of a unique NH2-terminal region followed by a PH and a SH3 domain. 49 , 50 Upon TCR engagement, SKAP1 is recruited to an ADAP-SLP-76 complex via the interaction of its SH3 domain with a proline-rich region in ADAP and then interacts with RapL and allows its recruitment to Rap1 and LFA-1. 50 Like p110δ D910A mice, SKAP1-deficient mice are impaired in forming T-cell–APC conjugates in vitro and in vivo. 50 , 51 A mutation R131M in the PH domain, which is predicted to uncouple SKAP1 from regulation by PIP3 inhibits the ability of SKAP1 to enhance LFA-1 activation in a cell line. 49 , 52 Kindlin-3, a key LFA-1 co-activator deleted in leukocyte-adhesion deficiency-III, also possesses a PIP3-specific PH domain in its FERM domain F2. 53 Kindlin-3 is required for induction of the high-affinity conformation of LFA-1. 54 Moreover, the PH domain of Kindlin-3 is essential for LFA-1-mediated regulation of lymphocyte adhesion and migration. 55 The intermediate affinity conformation of LFA-1 requires Talin-1, whereas further conformational changes associated with the high-affinity state are Kindlin-3 dependent. 54 Further work will help delineate how different PIP3-binding proteins co-ordinate the regulation of LFA-1 affinity and avidity. These studies may be facilitated using human T cells as antibodies that distinguish between low-, medium- and high-affinity forms of human LFA-1 are available.

T-cell activation within the spleen or lymph nodes occurs through multiple stages over a period of up to 30 h, starting with transient contacts that allow T cells to scan a large number of APCs and then proceeding to longer-lasting interactions once an APC-bearing cognate peptide antigen is encountered. 33 , 56 , 57 Although shorter interactions can stimulate T-cell proliferation and cytokine production, sustained dynamic interactions are thought to be required to initiate differentiation programs and for immunological memory. 21 , 22 Consistent with previous results, 36 , 58 we found that PI3K inhibition did not affect the basal motility of T cells moving through lymph nodes in absence of antigen. However, when presented with antigen, p110δ D910A T cells failed to establish stable conjugates with APCs. This defect is likely to be a contributing factor to the impaired T-cell responses to antigen in p110δ D910A mice.


The Class II Pathway

Class II histocompatibility molecules consist of

All three components of this complex must be present in the endoplasmic reticulum for proper assembly.

But antigenic peptides are not transported to the endoplasmic reticulum, so a protein called the invariant chain ("Ii") temporarily occupies the groove.

  • The two chains of the class II molecule are inserted into the membrane of the endoplasmic reticulum.
  • They bind (in their groove) one molecule of invariant chain.
  • This trimolecular complex is transported through the Golgi apparatus and into vesicles called lysosomes.
  • Foreign antigenic material is engulfed by endocytosis forming endosomes.
  • These also fuse with lysosomes.
  • The antigen is digested into fragments.
  • The invariant (Ii) chain is digested.
  • This frees the groove for occupancy by the antigenic fragment.
  • The vesicles move to the plasma membrane and the complex is displayed at the cell surface.
  • The complex can be bound by a T cell with
    • a receptor (TCR) able to bind the peptide and flanking portions of the histocompatibility molecule (the hot dog in the bun) and
    • CD4 molecules that bind the CD4 receptor (shown above as a yellow triangle) found on all class II histocompatibility molecules.

    Role of Cd4 + T Cells in Anti-Tumor and Anti-Viral Adaptive responses

    Growing evidences in the literature indicate that CD4 + T cells have direct roles in anti-tumor and anti-viral responses without contribution of CD8 or B cells. Several effector mechanisms have been described depending on the experimental models and the investigated Th subsets. Quezada et al. have demonstrated that transfer of tumor-specific CD4 + cells in lymphopenic mice resulted in rejection of melanoma tumors (37). In this study, CD4 + T cells had a Th1-like phenotype, produced granzyme B and displayed a MHC class II-dependent cytotoxic activity. In another mouse adoptive transfer model, Th17-polarized T cells were also capable of rejecting melanoma tumors via an IFN-γ dependent mechanism (38). Nevertheless, Th17 cells can also have a protumor effect by inducing angiogenic factors (39).

    More recently, several studies highlighted anti-tumor properties of IL-9 producing CD4 + T cells (40). Purwar et al. have found in the B16 melanoma mouse model that tumor growth was accelerated in IL-9 receptor-deficient mice while injection of recombinant IL-9 prevented tumor progression in wild-type mice (41). Other studies reported that anti-cancer effects of Th9 cells were mediated by production of IL-21 and their cytolytic activity (42).

    CD8 + T cells are considered as the main effector cells of cancer and virus immunosurveillance, capable of killing tumors or infected cells and secreting immunostimulatory cytokines. Nevertheless, CD4 + T cell help is critical for maintaining CD8 + T cell functions during anti-tumor response and chronic infection (2, 43, 44). Indeed, CD4 + T cells are required to fully activate and “license” DCs which can effectively prime CD8 + T cells. CD40L-CD40 interactions between activated CD4 + T cells and DCs, respectively, are crucial to increase DC antigen-presentation and costimulation capacities (45). However, primary CD8 + T cell responses could be induced in a T cell help independent manner by microbial pathogen infections that provide potent inflammatory stimuli. Additionally, cognate interactions between activated CD4 + T cells and DCs lead to the production of chemokines that facilitate the recruitment of naïve CD8 + T cells toward antigen-bearing APCs in the secondary lymphoid organs (46). Although there is a consensus on the requirement of T cell help for the generation of long-lived memory CD8 + T cells, it is still discussed whether CD4 + T cells deliver a differentiation program during the priming phase or subsequently at later stages during the CD8 + T cell memory maintenance (47�). Production of IL-2 by Th cells during the priming phase is crucial for an effective secondary CD8 + response (50). However, it has been shown that “licensed” DCs may provide signals that enable autocrine secretion of IL-2 by memory CD8 + T cells (51). CD4 + helper T cells also stimulate IL-15 production by DCs that favors induction of long-lived CD8 + T cells by increasing expression of anti-apoptotic molecule Bcl-xL (52). In the context of viral chronic infection, IL-21 is an essential component of CD4 + T cell help by avoiding clonal deletion and maintaining CD8 + T cell function (53). Regulation of activation-induced cell death (AICD) by CD4 + T cells is a putative mechanism for the maintenance of CD8 + T cell response. It has been reported that CD8 + T cells primed in the absence of CD4 + T cells could undergo AICD-mediated by TNF-related apoptosis-inducing ligand (TRAIL) signaling (54). However, other studies using TRAIL-deficient mice, do not confirm this mechanism (55). Furthermore, recently, CD4 + T cells have been shown to upregulate the expression of CD70 on DCs, a costimulatory molecule that triggers CD27 receptor on CD8 + T cells. CD70-CD27 interactions result in the delivery of a help program that amplifies CTL functions and downregulates inhibitory receptors, such as PD-1 (56).

    Neutralizing antibodies are a central component of adaptive immune responses against microbial pathogens. In the previous decade, Tfh cells characterized by the expression of CXCR5 have been identified as the main providers of B cell help. CD40L on Tfh cells is the most prominent costimulatory molecule to promote survival and proliferation of CD40-expressing B cells. Cytokines IL-4 and IL-21 are necessary for the formation of germinal centers and differentiation of B cells into long-lived plasma cells (57). Recently the role of Tfh in anti-tumor immunity was underlined by several reports. In colorectal cancer, gene expression and tissue microarray analyses of tumor biopsies showed that tumor infiltrating Tfh and B cells were correlated with patient disease-free survival (58). The authors also found that chemokine CXCL13 and IL-21 were key factors of adaptive immunity in tumor environment. Infiltration of CXCL13-producing CD4 + Tfh cells was also associated with a better disease-free survival or preoperative response to chemotherapy (59).


    Wiskott–Aldrich syndrome protein controls antigen-presenting cell-driven CD4 + T-cell motility by regulating adhesion to intercellular adhesion molecule-1

    Correspondence: Loïc Dupré, INSERM U1043, Purpan University Hospital, 31300 Toulouse, France.

    INSERM, U1043, Toulouse, France

    Université Toulouse III Paul-Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France

    CNRS, U5282, Toulouse, France

    Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil

    INSERM, U1043, Toulouse, France

    Université Toulouse III Paul-Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France

    CNRS, U5282, Toulouse, France

    INSERM, U951, Généthon, Evry, France

    INSERM, U1043, Toulouse, France

    Université Toulouse III Paul-Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France

    CNRS, U5282, Toulouse, France

    INSERM, U1043, Toulouse, France

    Université Toulouse III Paul-Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France

    CNRS, U5282, Toulouse, France

    Correspondence: Loïc Dupré, INSERM U1043, Purpan University Hospital, 31300 Toulouse, France.

    Summary

    T-cell scanning for antigen-presenting cells (APC) is a finely tuned process. Whereas non-cognate APC trigger T-cell motility via chemokines and intercellular adhesion molecule-1 (ICAM-1), cognate APC deliver a stop signal resulting from antigen recognition. We tested in vitro the contribution of the actin cytoskeleton regulator Wiskott–Aldrich syndrome protein (WASP) to the scanning activity of primary human CD4 + T cells. WASP knock-down resulted in increased T-cell motility upon encounter with non-cognate dendritic cells or B cells and reduced capacity to stop following antigen recognition. The high motility of WASP-deficient T cells was accompanied by a diminished ability to round up and to stabilize pauses. WASP-deficient T cells migrated in a normal proportion towards CXCL12, CCL19 and CCL21, but displayed an increased adhesion and elongation on ICAM-1. The elongated morphology of WASP-deficient T cells was related to a reduced confinement of high-affinity lymphocyte function-associated antigen 1 to the mid-cell zone. Our data therefore indicate that WASP controls CD4 + T-cell motility upon APC encounter by regulating lymphocyte function-associated antigen 1 spatial distribution.


    Functions of T Cells

    Helper T Cells

    Helper T cells play a central role in the adaptive immune response, but they don’t directly attack pathogens. Instead, they secrete cytokines that activate and coordinate other immune cells (such as macrophages, B cells, and cytotoxic T cells) to launch an attack against foreign invaders.

    Cytotoxic T Cells

    Cytotoxic T cells are also known as ‘killer’ T cells, as they directly attack and destroy pathogens and virus-infected host cells. When they find an abnormal cell, these lymphocytes release cytotoxic granules containing perforin and granzymes, two proteins that work together to destroy the infected cell. Perforin causes pores to develop in the target cell membrane, and granzymes enter the cell through these holes. Once inside, the granzymes trigger apoptosis, killing the host cell and any viruses living inside.

    Memory T Cells

    Memory T cells are cytotoxic T cells that remain in the body once an infection has been cleared. Once activated, cytotoxic T cells will proliferate rapidly and migrate to the infected part of the body. The number of cytotoxic T cells typically peaks around 7 days after the initial infection, after which it rapidly declines in a mass die-off known as the contraction phase.

    Any cytotoxic T cells that survive the contraction phase stay in the body long-term as memory T cells. They ‘remember’ the pathogen, and will quickly respond in the event of re-infection.



Comments:

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