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Pathogens(such as bacteria,fungi, and viruses)
INNATE IMMUNITY(all animals)
Rapid response
Recognition of traits sharedby broad ranges ofpathogens, using a small
set of receptors
Recognition of traitsspecific to particularpathogens, using a vastarray of receptors
Slower response
Barrier defenses:SkinMucous membranesSecretionsInternal defenses:
Phagocytic cellsNatural killer cellsAntimicrobial proteinsInflammatory response
Humoral response:
Antibodies defend againstinfection in body fluids.
Cell-mediated response:Cytotoxic cells defendagainst infection in body cells.
ADAPTIVE IMMUNITY(vertebrates only)
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Roles of the Skin
The skin or integumentary system has four roles It acts as a barrier against infection and injury It helps to regulate body temperature It removes waste products from the body Provides protection against UV radiation from the sun
It also serves as a way through which sensations aretransmitted to the nervous system
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The immune system protects organisms with layereddefenses of increasing specificity
Most simply, 1. physical barriers prevent pathogens such as bacteria and viruses from entering the bodyIf a pathogen breaches these barriers, the 2. innate immunesystem provides an immediate, but non-specific response Innate immune systems are found in all plants and animalsIf pathogens successfully evade the innate response, vertebrates
possess a third layer of protection, the 3. adaptive immunesystem Here, the immune system adapts its response during an infection to improve
its recognition of the pathogen
This improved response is then retained after the pathogen has beeneliminated, in the form of an immunological memory, and allows theadaptive immune system to mount faster and stronger attacks each time this
pathogen is encountered
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Innate Immune Features of the Skin
Cells Phagocytes: Macrophages, neutrophils, NK
cells Mast cells
Circulating chemicals Complement
Locally produced chemicals Cytokines, histamine
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Mast CellsBone marrow-derivedDermal residentPerivascularMediators Preformed (histamine, e.g.) Newly synthesized (cytokines,
e.g.)
Various stimulimediator release Immunologic: IgE binding antigen Nonimmunologic: Physical,
drugs, complement
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Cells of the Cutaneous Adaptive
Immune Response
Langerhans cell Dermal dendrocytesKeratinocytesT-cellsEndothelial cells
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Langerhans Cells
Bone marrow-derived Monocyte lineage
Transient epidermal cellsDendritic cell Cell surface molecules: CD1a, MHC II,
ATPase, Fc receptor for IgG, C3 receptor,
B7, several CAMsElectron microscopy: Birbeck granules,convoluted nucleus
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Langerhans Cells:
Epidermal TransientsMigration and maturationBone marrow Blood Epidermis (LC)
Afferent lymph Lymph nodeFunctions
Antigen capture and processing
Presentation of antigen Costimulation of nave T-cells Produce activating cytokines
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LangerhansCell Migration
Antigen
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Keratinocytes AsImmune Cells
Old view : Keratinocytes...Are passive barrier cellsAre passive victims of immune attack
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Keratinocytes AsImmune Cells
Newer view : Keratinocytes...
Produce cytokines e.g., IL-1, TNF- , Chemokines
Respond to cytokines
e.g., IFN, IL-1Upregulate ICAM-1Present antigen
Antimicrobial peptide
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Endothelial Cells &
Cutaneous InflammationIncrease permeabilityWhen activated, endothelial cells... cell surface expression of P-selectin
for enhanced leukocyte margination synthesis & expression of E-selectin
for selective T-cell (CLA +) homing tothe skin
expression of VCAM-1 & ICAM-1to stop leukocytes and allow diapedesis
Immune response amplified
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Cutaneous Lymphocyte Antigen
(CLA)Specific skin homing marker on T-cellsCLA+ lymphocytes are memory/effector cells(CD45RO +)Cell adhesion to endothelial cell E-selectin is ligand
With cutaneous inflammation, E-selectin up-regulated, CLA+ cells selected
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The Skin Immune System
Components1. APCs: Langerhans cells, dermal
dendrocytes, dermal macrophages2. Keratinocytes3. Endothelial cells
4. Skin-homing T-cells5. Draining regional lymph vessels and
nodes
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