Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Dec 18;8(Suppl 1):20.
doi: 10.1186/s40635-020-00309-z.

Role of the adaptive immune response in sepsis

Jack Brady  1   2 , Shahd Horie  1   2 , John G Laffey  3   4   5
Affiliations
Review

Role of the adaptive immune response in sepsis

Jack Brady et al. Intensive Care Med Exp. .

Abstract

Sepsis is a syndrome of shock and dysfunction of multiple vital organs that is caused by an uncontrolled immune response to infection and has a high mortality rate. There are no therapies for sepsis, and it has become a global cause for concern. Advances in patient care and management now mean that most patients survive the initial hyper-inflammatory phase of sepsis but progress to a later immunosuppressed phase, where 30% of patients die due to secondary infection. Deficits in the adaptive immune response may play a major role in sepsis patient mortality. The adaptive immune response involves a number of cell types including T cells, B cells and dendritic cells, all with immunoregulatory roles aimed at limiting damage and returning immune homeostasis after infection or insult. However, in sepsis, adaptive immune cells experience cell death or exhaustion, meaning that they have defective effector and memory responses ultimately resulting in an ineffective or suppressed immune defence. CD4+ T cells seem to be the most susceptible to cell death during sepsis and have ensuing defective secretory profiles and functions. Regulatory T cells seem to evade apoptosis and contribute to the immune suppression observed with sepsis. Preclinical studies have identified a number of new targets for therapy in sepsis including anti-apoptotic agents and monoclonal antibodies aimed at reducing cell death, exhaustion and maintaining/restoring adaptive immune cell functions. While early phase clinical trials have demonstrated safety and encouraging signals for biologic effect, larger scale clinical trial testing is required to determine whether these strategies will prove effective in improving outcomes from sepsis.

Keywords: Immune homeostasis; Immune suppression; Sepsis.

PubMed Disclaimer

Conflict of interest statement

None

Figures

Fig. 1
Fig. 1
The time course of immune events in Sepsis. Adapted and reprinted from Macmillan Publishers Ltd: Hotchkiss et al. [15]. Nature Review Immunology, Copyright 2013
Fig. 2
Fig. 2
The normal functional state of adaptive immune cells
Fig. 3
Fig. 3
Adaptive immune cell function is dysregulated in sepsis
Fig. 4
Fig. 4
Promising targets for sepsis therapies
See this image and copyright information in PMC

References

    1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche J-D, Coopersmith CM. The third international consensus definitions for sepsis and septic shock (Sepsis-3) Jama. 2016;315:801–810. doi: 10.1001/jama.2016.0287. - DOI - PMC - PubMed
    1. Vincent J-L, Marshall JC, Ñamendys-Silva SA, François B, Martin-Loeches I, Lipman J, Reinhart K, Antonelli M, Pickkers P, Njimi H. Assessment of the worldwide burden of critical illness: the intensive care over nations (ICON) audit. Lancet Respir Med. 2014;2:380–386. doi: 10.1016/S2213-2600(14)70061-X. - DOI - PubMed
    1. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020;395:200–211. doi: 10.1016/S0140-6736(19)32989-7. - DOI - PMC - PubMed
    1. Torio CM, Andrews RM, (2006) National inpatient hospital costs: the most expensive conditions by payer, 2011: statistical brief# 160 - PubMed
    1. Iwashyna TJ, Cooke CR, Wunsch H, Kahn JM. Population burden of long-term survivorship after severe sepsis in older Americans. J Am Geriatr Soc. 2012;60:1070–1077. doi: 10.1111/j.1532-5415.2012.03989.x. - DOI - PMC - PubMed