Innate immunity

• Characterization of innate immunity

• Lines of defenses in innate immunity
• Cells of Innate immunity
• Receptors for Innate immunity

Characterization of innate immunity

 Early protection from infection
 The innate immune defenses are all present at birth;
 Activated very soon after pathogen exposure or opportunistic microbe reactivation
 They have a very limited diversity for antigen, & attack microbes with the same
basic vigor no matter how many times they have seen the same pathogen.
Lines of defenses in innate immunity
First line of defense
Anatomical & physiologic barrier
• Skin & epithelial layers insulate the interior of the body from outside
pathogens
• Epithelial layers of mucosal tracts & secretory glands produce a variety of
protective substances, including acidic pH, enzymes, binding proteins,
antimicrobial proteins & peptides.

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• Due to its size & critical roles as barriers, many call the skin is the most imp.
immunological organ in the body.

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Second line of defense (Cellular innate response)

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Monocytes/MQs:
Monocytes circulate in blood, become MQs in tissues, characterized by:
• Phagocytosis
• Prolonged defense.
• Produce cytokines that initiate & regulate inflammation.
• Professional antigen presenting cell (APC), Clear dead tissue & Initiate tissue
repair
• Macrophages will develop along one of 2 different pathways
1. M1 (Classical)
• Induced by innate immunity (TLRs, IFN-γ)
• Phagocytosis & initiate inflammatory response
2. M2 (Alternative)
• Induced by IL-4, IL-13
• Tissue repair & control of inflammation

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 Receptors for Innate immunity
• Antigen presenting cells (APCs) recognize conserved microbial components,
pathogen-associated Molecular patterns (PAMPs) such as bacterial LPS &
peptidoglycans, as well as viral ssRNA & dsRNA.
• These PAMPs serve as ligands for a broad array of protein families referred to as
pattern recognition receptors (PRRs).
• PAMPs can be expressed by microbes whether or not they are pathogenic, hence
they are sometimes referred to as microbe-associated molecular patterns
(MAMPs).
• PRRs recognize MAMPs that are common to whole classes of microbes.
• Some PRRs are also capable of recognizing molecules released by damaged,
dying, or dead host cells, referred to as damage-associated molecular patterns
(DAMPs).
• Until now, there are Five families of PRRs; Toll-like receptors (TLRs), C -type
lectin receptors (CLRs), NOD-like receptors (NLRs), RIG-1-like receptors
(RLRs), & AIM-2-like receptors (ALRs).

• A single innate immune cell may express multiple types of innate receptors, &
many innate cells can express same PRRs. This means that every antigen that is
capable of binding to a particular innate receptor can be bound immediately by
many cells.

Receptor name Cellular Location (s) Pathogen target Downstream effect

Toll-like Extracellular Microbial CHO, Production of

Receptor (Plasma mem.) lipoproteins, fungal mannans, antimicrobials,
(TLRs) Intracellular bacterial flagellin, viral RNA, antivirals, & cytokines;
TLR-1 to 13 (endosomes & self-components of damaged Inflammation
Lysosomes) tissues, etc.
C-type lectin Extracellular CHO components of fungi, Phagocytosis,
Receptor (Plasma mem.) mycobacteria, viruses, production of
(CLR) parasites, & some Allergens antimicrobials &
cytokines;
NOD-like Intracellular Fragments of intracellular or Production of
Inflammation
Receptors (cytosol) extracellular bacteria cell wall antimicrobials &
(NLRs) peptidoglycans cytokines;
Inflammation
RIG-like Intracellular Viral RNA IFN production &
Receptors (cytosol) cytokines
(RLR)
AIM-like Intracellular Viral and bacterial DNAs Production of IFNs &
Receptor (cytosol & Nucleus) cytokines
(ALR)

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• In addition, many different cell types express PRRs, including keratinocytes,
epithelial cells, & even B and T lymphocytes.
• After PRRs recognize a specific of ligands as PAMP & DAMP & they trigger
signaling pathways which activate a variety of genes encoding proteins that
contribute to innate & inflammatory responses.
• After PRRs recognize a specific of ligands as PAMP & DAMP & they trigger
signaling pathways which activate a variety of genes encoding proteins that
contribute to innate & inflammatory responses.
These genes, including those for
• Antimicrobial peptides,
• Type 1 interferons (IFNs),
• Cytokines & chemokines &
• Enzymes that help to generate antimicrobial & inflammatory responses.
Cytokines

• Cytokines function as the hormones of immune system, produced in response

to stimuli & acting on a variety of cellular targets. Major proinflammatory
cytokines induced by PRR activation during innate immune responses are IL-
1, TNF-α, and IL-6.

• They act locally on blood vessels to increase vascular permeability & also on
other cells, including lymphocytes, to recruit & activate them at sites of
infection.
• They also have systemic effects, including inducing fever & feeding back on
BM hematopoiesis to enhance production of neut., & other myeloid cells that
will contribute to pathogen clearance.

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Chemokines
• Chemokines are small protein chemoattractants recruit cells into, within, &
out of tissues.
• Some chemokines are responsible for homeostatic migration of white blood
cells throughout body.
• Other chemokines, produced in response to PRR activation, have key roles in
the early stages of immune & inflammatory responses in that they attract cells
such as IL-8 and that they contribute both to clearing infection or damage & to
amplifying response.
Enzymes
• Two enzymes produced in response to PRR-activated signaling pathways,
inducible nitric oxide synthase (iNOS) & cyclooxygenase-2 (COX2) have
key roles in generation of antimicrobial & proinflammatory mediators.
• iNOS enzyme catalyzes an important step in formation of nitric oxide, which
kills phagocytosed microbes.
• COX2, whose produced by monocytes, MQs, neut., & mast cells, is key to
converting lipid intermediate arachidonic acid to prostaglandins, potent
proinflammatory mediators.

Dr. Dekra El-Aghbary

Associate Professor of Immunology