Risposta immunitaria innata e adattativa

Le cellule mieloidi, come i granulociti, i monociti, le cellule NK e le cellule dendritiche contribuiscono al sistema immunitario innato nel riconoscere gli agenti patogeni e i danni tissutali. Queste cellule si attivano al contatto con microbi e di segnali di danno (PAMPs, DAMPs) innescando una robusta risposta infiammatoria e rilasciando vari mediatori pro-infiammatori come citochine, interferoni (IFNs) e marcatori cellulari specifici. Ciò costituisce la risposta immediata all'infezione, data dal sistema immunitario innato.

L'immunità adattativa, che è necessaria per la risposta a lungo termine, è attivata attraverso la classica interazione MHCI e II/TCR con le cellule dendritiche attivate. Gli interferoni agiscono anche come collegamento chiave tra la risposta immunitaria innata e l'attivazione della risposta immunitaria adattativa.Diagram showing the innate versus the adaptive immune response

CD64 (FCγ-RI)

  • Provide a first line of recognition and defense against infections
  • Bacterial infections, leads to release of type II IFN (IFNγ), which strongly induces the expression of CD64 on neutrophils.

CD169 (Siglec-1)

  • Adhesion receptor, recognizing sialylated glycoproteins and glycolipids of viral membranes
  • Viral infections, leads to release of type I IFNs (IFNα, β), which strongly induces expression of CD169 on monocytes

HLA-DR

  • MHC-Class II receptor mainly involved in viral antigen presentation to T cells
  • HLA-DR on monocytes is induced immediately after infection, slowly declining with exhaustion.

References:

  1. Crocker PR. Properties and distribution of a lectin-like hemagglutinin differentially expressed by murine stromal tissue macrophages. J. Exp. Med. 164(6), 1862–1875 (1986).
  2. Macauley MS, Crocker PR, Paulson JC. Siglec regulation of immune cell function in disease. Nat. Rev. Immunol. 14(10), 653–666 (2014).
  3. Pino M, Erkizia I, Benet S, et al. HIV-1 immune activation induces Siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells. Retrovirology 12(1), 1–15 (2015).
  4. Kim W-K, McGary CM, Holder GE, et al. Increased Expression of CD169 on Blood Monocytes and Its Regulation by Virus and CD8 T Cells in Macaque Models of HIV Infection and AIDS. AIDS Res. Hum. Retroviruses 31(7), 696–706 (2015).
  5. Bourgoin P, Biéchelé G, Ait Belkacem I, Morange PE, Malergue F. Role of the interferons in CD64 and CD169 expressions in whole blood: Relevance in the balance between viral- or bacterial-oriented immune responses. Immun Inflamm Dis. 2020;8(1):106-123. doi:10.1002/iid3.289.
  6. Kipfmueller F, Schneider J, Prusseit J, et al. Role of Neutrophil CD64 Index as a Screening Marker for Late Onset Sepsis in Very Low Birth Weight Infants. PLoS ONE 10(4), 1–15 (2015).
  7. Selvaraj P, Fifadara N, Nagarajan S, Cimino A, Wang G. Functional Regulation of Human Neutrophil Fc γ Receptors. Immunol. Res. 29(1–3), 219–230 (2004).
  8. Krensky, A.M. The HLA system, antigen processing and presentation. 1997, Kidney International, suppl. 58, 51, 2-7.
  9. Lee, J., Dupont, B.O. The HLA system: An introduction. 1990, "The HLA system: A new approach", Springer-Verlag, 1-26.
  10. Uckun, F.M. Regulation of human B-cell ontogeny. 1990, Blood, 76, 1908-1923.
  11. Kontny, E., Ryzewska, A. Surface markers on human activated T lymphocytes IV. Comparison of high-affinity E-rosette receptor expression with the expression of other activation markers (receptor for Interleukin 2, MHC class II (antigens). 1990, Archivum Immunologiae et Ther. Experimentalis, 38, 421-431.
  12. Venet F, Lukaszewicz AC, Payen D, Hotchkiss R, Monneret G. Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies. Curr Opin Immunol. 2013;25(4):477-483. doi:10.1016/j.coi.2013.05.006.