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Chapter 3
Immunologie




Cara Mestdag
KU Leuven
Chapter 3

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Inhoudsopgave

The induced responses of innate immunity:
How phagocytic cells of the innate immune system inititate the induced innate immune response, leading to an
inflammatory reaction that recruit new phagocytic cells and circulating effector molecules tot he site of infection

Pathogen recognition by cells
of the innate immune system
 Adaptive immune system's antigen recognition capacity
is well-established.
 Innate immune receptors recognize conserved molecular
features, known as pathogen-associated molecular
patterns (PAMPs)1.
 PRRs 2recognize PAMPs, ensuring the innate immune
system's capacity to recognize various microorganisms.
o Specificities of PRRs are genetically encoded and
inherited through the germline.
o Evolution has shaped PRR specificities to recognize PAMPs, crucial for microbial fitness.
o Cells (macrophages, neutrophils, dendritic cells) express multiple PRRs (nonclonal expression),
allowing a broad response to different pathogens. ><clonal expression in the adaptive immune
system.
o Ligands for PRRs do not occur in healthy host cells, ensuring immune responses target microbes.
(there are exceptions)
 PAMPs are conserved, invariant features shared by related groups of microbes.
 Innate immune system recognizes the consequences of infection, such as cellular perturbations and DAMPs
(damage-associated molecular patterns)3.
 Innate immune receptors categorized into four groups based on cellular localization and function.
 Coördination relies on various types of pattern recognition receptors
o Ficolins and histatins: free receptors in serum


1
Molecules specifically associated with groups of pathogens that are recognized by cells of the innate immune system
2
Attern-recognition receptors = receptors of the innate immune system that recognize common molecular patterns on pathogen
surfaces
3
Molecules specifically associated with groups of pathogens that are recognized by cells of the innate immune system

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o Membrane-bound receptors like chemotactic receptors (guide cells to infeciton sites) and Toll-like
receptors (TLRs)
o Membrane bound phagocytic receptors: signal for phagocytosis of recognized microbes
o Cytoplasmic receptors.

After entering tissues, many microbes are recognized, ingested and
killed by phagocytosis
When a microorganism crosses an epithelial barrier and begins to replicate in the host's tissues, it is typically
promptly identified by resident phagocytic cells. The primary phagocytic cells in the innate immune system include
macrophages and monocytes4, granulocytes, and dendritic cells.
1) Macrophages: a major population of phagocytes in normal tissues at homeostasis
o Can originate from progenitor cells entering tissues during embryonic development, self-renewing
throughout life, or circulating monocytes(  During infection or inflammation they can arise from
monocytes (develop in the bone marrow) that leave from the circulation to enter into tissues).
o Are particularly abundant in connective tissues, such as the submucosal layer of the gastrointestinal
tract, submucosal layer of the bronchi, lung interstitium (around air sacs/alveoli), certain liver blood
vessels, and throughout the spleen, where they eliminate senescent blood cells.
o Historically, macrophages in different tissues were given distinct names,
 Microglial cells in neural tissue
 Kupffer cells in the liver
 The self-renewal of these cells relies on the cytokine interleukin-34 (IL-34), produced in the
respective tissues, acting on the same receptor as macrophage-colony stimulating factor
2) Monocytes circulating are classical monocytes that express CD14 (co-receptor for PRR) and fuction during
infecting by entering tissues and differentiating into activated inflammatory monocytes or macrophages.
3) Granulocytes, which include neutrophils, eosinophils and basophils  Neutrophils have the greatest
phagocytic activity and are the most immediately involved in innate immunity against infectious agents 
also called PMNs (polymorphonuclear neutrophilic leukocytes) or polys
4) Dendritic cells reside in lymphoid organs and in peripheral tissues
o Two types: conventional dendritic cells (cDCs) 5and plasmacytoid dendritic cells (pDCs) 6
o Both originate from progenitor cells in the bone marrow and migrate via the bloodstream to tissues
and peripheral lymphoid organs
o Ingest and break down microbes
o Unlike macrophages and neutrophils, the primary role of dendritic cells isn't the direct large-scale
killing of microbes.
o cDCs process ingested microbes to generate peptide antigens capable of activating T cells and
inducing an adaptive immune response.
 produce cytokines upon microbial recognition (via PRRs) to activate other cell types against
infections.
 are considered a bridge between innate and adaptive immune responses.
o pDCs can produce substantial amounts of type I interferons (antiviral interferons 7) are considered
part of innate immunity.
5) Macrophages and neutrophils express cell-surface PRRs
o C-type lectin-like family (Dectin-1 recognizes beta-(1,3)-linked glucans = component of fungal cell
walls) (Mannose receptor recognizes various mannosylated ligands on fungi, bacteria and viruses;
clears host glycoproteins such as beta-glucuronidase and lysosomal hydrolases)

4
Type of white blood cell with a bean-shaped nucleus; it is a precursor of tissue macrophages
5
The lineage of dendritic cells that mainly participates in antigen presentation to, and activation of, naive T cells
6
A distinct lineage of dendritic cells that secrete large amounts of interferon on activation by pathogens and their products via
receptors such as Toll-like receptors
7
Interferons (IFNs): several related families of cytokines originally named fort heir interference with viral replication. IFN-alfa and
IFN-beta are antiviral in their effects; IFN-gamma has other roles in the immune system