20 min of immunology for beginners
Régis JOSIEN, MD, PhD
Nantes University Medical School, Nantes, France
Regis.josien@univ-nantes.fr
The physiologic function of the immune system is defense against infectious microbes
1. The diversity of immune responses are linked to those of pathogens and their capacity to escape immune responses
Pathogens Exemples Effectors of the immune response
Extracellular bacteria Streptococcus An:bodies: IgG, A, M
Neisseria Complement
Phagocytes
ILC3
Th17
Intracellular bacteria and parasites Mycobacteria Th1 (IFNg)
Leishmania Macrophages
ILC1
Virus Influenza Natural killer cells
EBV Cytotoxic T cells
Worms Ascaris Antibodies: IgE, IgG
Schistosoma Eosinophils, mast cells
ILC2
Th2
2. Immune responses can cause tissue injuries: their magnitude and duration need to be tightly controlled by
immunoregulatory/inhibitory mechanisms
Immunoregulatory mechanisms Exemples
Molecules IL-10, IL-1RA, CTLA4, PD1
Cells Regulatory T cells (Treg)
The cellular players of the immune system
How do immune cells talk to each other - and to non immune cells?
Membrane mediators Soluble mediators
Activation Migration
Proliferation Activation
Differentiaton
Features of Innate and Adaptive Immunity
(all living species) (3-5% of living species)
(Recognized structure : 103)
(>109)
Pattern recognition receptors (PRR) are the sensors of innate immunity
PRR recognized:
• Products of microbes = Pathogen
associated molecular patterns
(PAMPs)
• Product of injured cells= Damage-
associated molecular patterns
(DAMPs)
Families of cellular PRR:
• Toll-like receptors (TLR)
• RIG-like receptors (RLR)
• NOD-Like receptors (NLR)
• C-type lectine like receptors (CLR)
• cDNA sensor (CDS)
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Upon triggering, some PRR instruct the immune system to mount a response
2 main types of
responses
Inflammation
+
TF Stimulation of
adaptive immunity
(activation of DCs)
TF
Anti-viral state
Created with BioRender.com
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Tissue macrophages exhibit both pro-inflammatory and homeostatic functions
Properties of tissue resident macrophages:
Pro-inflammatory functions of macrophages Ø Colonize developing tissues and participate to their developement
Ø Acquire functional specialization to tissue environment
Ø Various homeostatic and pathological functions: development, cell
renewal, elimination of apoptotic cells, inflammation, resolution of
inflammation and repair, metabolism
Ø Can be replaced by monocyte-derived Macs during inflammation
Functions of Natural Killer (NK) Cells in innate immunity
Features
• Lymphocyte
• Lack of antigen receptor
• Circulating and tissue resident
(liver, lung)
• Recognition of infected, injured
or tumor cells
• Functions: killing and cytokine
production
Innate lymphoid cells (ILCs) promote inflammation and innate immunity to
pathogens
• Lymphoid origin
• Lack of antigen receptors
• Enriched at mucosal sites
• Respond rapidly to environmental signals by producing cytokines
• Three subsets (ILC1, 2 and 3)
Sonnenberg and Artis, Nat Med 2015
The complement system is part of the humoral arm of the innate
immune response
The cellular players of innate and adaptive immunity
Humoral Immunity
(Antibodies)
Cellular Immunity
Phagocytosis,
Inflammation
Cell killing
Features of Innate and Adaptive Immunity
(most of the living species) (3-5% of living species)
(Recognized structure : 103)
(>109)
Development and maturation of lymphocytes
Primary lymphoid Secondary lymphoid
organs organs
Generation of
antigen receptors
Secondary lymphoid organs are highly organized and dynamic structures
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Phases of adaptive immune responses
Antigen recognition by lymphocytes
B lymphocytes T lymphocytes
Antigen recognition and activation of T lymphocytes
require specialize antigen-presenting cells (APCs) 17
Dendritic cells induce adaptive immunity through activation of naive T cells
18
Delves and Roitt. N Engl J Med. 343:37-49
The role of MHC molecules of in the presentation of antigenic peptides to T cells
Cytotoxic T
lymphocyte T helper
lymphocyte
19
Heath and Carbone. Nat Rev Immunol 2001. 1:126-135
Which signals are required to induce activation of naive T cells?
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Activation of naive and effector T cells by antigen
Classes of lymphocytes
Classes of effector T helper cells
Classes of lymphocytes
Classes of effector T helper cells
T cell activation is controlled by inhibitory receptors
CTLA4 PD-1
Main site of action SLO Non lymphoid tissues
Phase inhibited Induction phase Effector phase
Target cells CD4+ and CD8+ T cells CD8+> CD4+ T cells
Expression Treg, activated T cells Activated T cells
Ligands B7-1 & B7-2 PD-L1 & PD-L2
Main signals inhibited Compétition with Inhibition of
CD28 (binding to B7 intracellular activation
and internalisation of signals (phosphatase)
B7 from APC)
Role in the yes no
mechanisms of action
of Treg
Both PD-1 and CTLA4 are exploited by tumors to escape immune responses -> therapeutic targets (check point inhibitors)
Interplay between innate and adaptive immunity
Amplification
Confers
specificity
Innate Adaptative
immunity immunity
Induction
