Cutaneous Immunology
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Cutaneous Immunology Cutaneous Immunology Presentation Transcript

  • CUTANEOUS IMMUNOLOGY นพ . สุรสฤษดิ์ ขาวละออ 9/9/2009
  • CONTENTS
    • Normal skin structure
    • Cutaneous immunology
      • -innate immunity
      • -IL-1
      • -complement activation
      • -PRRs
      • -Langerhans’ cell & dermal DC
      • -acquired immunity
      • -role of T & B cell
  • NORMAL SKIN STRUCTURE
    • Three functional layers
    • -epidermis 150 µm
    • thick
    • -horny layer
    • -clear layer
    • -granular layer
    • -basal layer
    • -basal membrane
    • -dermis or corium
    • 2,800 µm thick
    • -subcutis
    • (hypodermis )
  • NORMAL SKIN STRUCTURE
    • 1 Epidermis
    • 2 Dermis
    • 3 Subcutis
    • 4 Hair follicle
    • 5 Sebaceous gland
    • 6 Sweat gland
  • NORMAL SKIN STRUCTURE
    • 1 Horny layer
    • (stratum corneum)
    • 2 Clear layer
    • (stratum lucidum)
    • 3 Granular layer
    • (stratum granulosum)
    • 4 Prickle-cell layer
    • (stratum spinosum)
    • 5 Basal layer
    • (stratum basale)
    • 6 Basal membrane
  • NORMAL SKIN STRUCTURE
  • NORMAL SKIN STRUCTURE
    • Dendritic cells in cutaneous immunity
    • The Langerhans’ cells(epidermal DC)
    • -LC arise in BM
    • -controversy about whether LC
    • descended from myeloid or lymphoid
    • progenitor but evidence suggest
    • myeloid origin
    Carole L. Berger.IJBCB 2006;38:1632-1636
  • NORMAL SKIN STRUCTURE
    • The Langerhans’ cells(cont.)
    • -can differentiate from monocytes or
    • CD34 precursors(CD34=precursors of
    • hemopoietic cells/endothelium in high
    • endothelial venules)
    • -mediators of LC differentiation from
    • peripheral monocytes include TGF- β ,
    • GM-CSF, IL-4 and Notch ligand δ -1
    Carole L. Berger.IJBCB 2006;38:1632-1636
  • NORMAL SKIN STRUCTURE
    • The Langerhans’ cells(cont.)
    • -keratinocyte secrete TGF- β , GM-CSF
    • and δ -1
    • - LC express CCR6 Rc for MIP-3 α
    • (CCL20) by keratinocytes
    • - LC that endocytosed Ag and be
    • activated by inducible innate response
    • may directly present Ag to skin-resident
    • memory T cells or exit skin via lymph
    • vessels
    N Franklin. Middleton’s allergy 7th edition 2009
  • NORMAL SKIN STRUCTURE
    • The Langerhans’ cells(cont.)
    • - in LN  LC process and present Ag
    • peptide to naïve T cells initial step to
    • develop acquired immunity
    • - LC can induce tolerance to self-Ag if
    • take up apoptotic material through
    • stimulation of T-regulatory cells which
    • inhibit immune responses
    Carole L. Berger.IJBCB 2006;38:1632-1636
  • NORMAL SKIN STRUCTURE
    • Dermal dendritic cells
    • two types of DDC
    • 1.interstitial DDC
    • -dermis compose of extracellular matrix
    • (ECM) and contain fibroblasts,DC,M Ø,
    • infiltrating T lymphocytes
    • -dermal DC present in ECM & also
    • called type-I dendrocytes
    J.Valladeau.Seminars in Immunology 2005;17:273-283
  • NORMAL SKIN STRUCTURE
    • Dermal dendritic cells(cont.)
    • -expression MHC class II, scavengerRc
    • (CD36), coagulation factor XIIIa
    • these 3 markers can find in MØ
    • - expression of lectin DC-SIGN/CD209
    • distinguishes DDC from other dermal
    • cellular populations
    J.Valladeau.Seminars in Immunology 2005;17:273-283
  • NORMAL SKIN STRUCTURE
    • Dermal dendritic cells(cont.)
    • 2.plasmacytoid DC
    • -pDC lymphoid origin
    • -natural IFN-  /  -producing cells
    • -present in skin in atopic dermatitis,
    • contact dermatitis, psoriasis, SLE
    • -immature pDC also described in situ in
    • primary melanoma
    • - normal skin  very low frequency
    J.Valladeau.Seminars in Immunology 2005;17:273-283
  • NORMAL SKIN STRUCTURE
    • Dermal dendritic cells(cont.)
    • plasmacytoid DC(cont.)
    • -more sensitive than myeloid skin DC
    • to danger signals  produce typeI-IFN
    • via TLRs
    • -little is know about pDC trafficking in
    • vivo
    J.Valladeau.Seminars in Immunology 2005;17:273-283
  • NORMAL SKIN STRUCTURE
    • Dermal dendritic cells(cont.)
    • plasmacytoid DC(cont.)
    • -mechanism for recruitment into skin
    • 1.1.pDC express CCR6(Rc of CCL20 that
    • responsible for homing of LC to skin
    • 1.2.pDC express CXCR3 whose ligrands
    • highly expressed in inflammatory skin
    • 1.3.pDC express ChemR23 binds chemerin
    • expressed on dermal inflamed vessels
    J.Valladeau.Seminars in Immunology 2005;17:273-283
  • NORMAL SKIN STRUCTURE
    • Migration of cutaneous DCs
    • 1.TNF-  & IL-1 induce migration of
    • LC out of epidermis
    • 2.CCR6 control migration from
    • blood/dermis to epidermis
    • 3.CCR7 control migration from
    • epidermis to regional lymphatics
    • (CCR7=Rc of SLC)
    J.Valladeau.Seminars in Immunology 2005;17:273-283
  • NORMAL SKIN STRUCTURE
    • Migration of cutaneous DCs(cont.)
    • 4.trafficking is controlled at level of cell
    • adhesion
    • -LC down-regulate some adhesion
    • molecules to exis epidermis and
    • up-regulate other to migrate across
    • dermal ECM & home to T cell area
    • of region lymphoid tissue
    J.Valladeau.Seminars in Immunology 2005;17:273-283
  • NORMAL SKIN STRUCTURE
    • Migration of cutaneous DCs(cont.)
    • -key role of CD44 &  6 integrins in
    • LC migration was demonstrate
    • -down-regulation of E-cadherin also
    • key event in LC migration
    • 5.expression of matrix metalloproteinases-9
    • & -2 (MMP) are necessary both for
    • migration of LC & DDC
    J.Valladeau.Seminars in Immunology 2005;17:273-283
  • NORMAL SKIN STRUCTURE
    • -cutaneous DC Ag presentation involve
    • interaction of
    • -MHC class II-antigenic pepetide
    • -MHC class I-antigenic peptide
    • -via CD1 molecules(non-peptide
    • microbial antigen presented)
    N Franklin. Middleton’s allergy 7th edition 2009
  • NORMAL SKIN STRUCTURE
    • Epidermis lymphocyte
    • -about 1% in epidermis
    • -close proximity to basement membrane
    • -majority of T cells are memory cell
    • (CD45RO + ) most express CD8 receptor
    • -50% of epidermal T cell express CLA
    • (cutaneous lymphocyte Ag) :
    • Sialyl Lewis-X glycoprotein serve as
    • ligand to endothelial cell adhesin
    • (E-selectin)
    B.Spellberg.Life Sciences 2000;67:477-502
  • NORMAL SKIN STRUCTURE
    • Epidermis lymphocyte(cont.)
    • -T cell do not enter epidermis by
    • random migration, rather epidermal
    • T cells are special population of
    • memory cells, which have specific set
    • of instruction to selectively home to
    • epidermis
    • -human αβ -T cell : γδ -T cell = 10:1
    B.Spellberg.Life Sciences 2000;67:477-502
  • NORMAL SKIN STRUCTURE
    • Nerve
    • - numerous free nerve endings, consist
    • of dendrite branching of slow
    • conducting nerve fibers
    • -afferent sensory, unmyelinated,
    • terminate at epidermal surface of
    • basement membrane
    B.Spellberg.Life Sciences 2000;67:477-502
  • NORMAL SKIN STRUCTURE
    • Nerve(cont.)
    • -nerve ending can be found between
    • keratinocytes through Stratum
    • Granulosum
    • - able to elaborate neuropeptides which
    • modulate local immunologic function
    B.Spellberg.Life Sciences 2000;67:477-502
  • INNATE IMMUNITY
    • keratinocyte express epidermal
    • growth factors : amphiregulin
    • -induce inflammatory-immune
    • reaction
    • -recent finding expression amphiregulin
    • by Th2 important mechanism to clear
    • intestinal helminth infestation through
    • epithelial shedding
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • epidermal γδ -T cells , like B cell, capable
    • directly binding to small phospate
    • containing Ag with their receptors
    • -do not require Ag presentation in context
    • of MHC or CD1
    • -serve as primitive, immediate response
    • element, recognizing conserved
    • phosphoprotein or phospholipid Ag of
    • microbes & necrotic human tissues
    B.Spellberg.Life Sciences 2000;67:477-502
  • NORMAL SKIN STRUCTURE B.Spellberg.Life Sciences 2000;67:477-502
  • CUTANEOUS IMMUNOLOGY
    • Innate immunity
    • - first-line defense mechanism
    • -two separate categories
    • -constitutive innate immunity
    • -anatomic barrier -physiologic barrier
    N Franklin. Middleton’s allergy 7th edition 2009
  • CUTANEOUS IMMUNOLOGY
    • -inducible innate immunity
    • -acute inflammation
    • -cellular infiltration
    • -both do not demonstrates acquired
    • specificity or memory for invading
    • pathogen
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • 1.cutaneous constitutive innate
    • immunity consist of
    • 1.1.normal skin flora
    • 1.2.cornified keratinocytes
    • 1.3.antimicrobial polypeptides/lipids
    • 1.4.low pH
    • 1.5.normal body temperature
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • Normal flora of skin
    • -coryneforms and staphylococci
    • -mush lesser extent, fungi (primarily
    • Malassezia)
    • Compete with other pathogenic organisms
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • Cornified keratinocytes
    • -form impenetrable surface
    • -outward growth and shedding of
    • cornified keratinocytes  eliminate
    • superficially bound pathogens
    • -reduced water content & lipid layers of
    • stratum corneum reduce relative
    • humidity  bad environment
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • Antimicrobial polypeptides
    • -β-defensin-1 and -2, dermcidin,
    • iron-binding proteins, lysozyme, RNases,
    • DNases, and natural IgM on skin
    • from sweat and from keratinocytes
    • Reduce skin surface pH
    • -exhibit antibacterial activity
    • -lactic acid excreted in eccrine sweat
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • Normal body temperature
    • -inhibits growth of some pathogens
    • 2.Inducible innate immunity
    • Acute inflammation
    • 2.1.performed IL-1 α stored in cytoplasm
    • of keratinocyte,released from
    • itch/scratch
    • 2.2.TNF- α
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • IL-1
    • - 2 forms : α and β
    • -31 kDa molecules
    • -IL-1 β must be cleaved by ICE
    • (IL-1 β converting enzyme : caspase-1)
    • -produced by monocyte, MØ, langerhans
    • cells, dendritic cells
    • -IL-1 α biologically active predominates in
    • epithelial cells (keratinocytes, etc)
    Murphy JE. J Invest Dermatol 2000; 114:602-608
  • INNATE IMMUNITY
    • -receptors
    • -IL-1R1 can bind both IL-1 α & IL-1 β
    • -IL-1ra(IL-1 receptor antagonist)
    • bind to this Rc but does not induce
    • signaling
    • -mice defcient in IL-1ra show
    • exaggerated & persistent
    • inflammatory responses
    Murphy JE. J Invest Dermatol 2000; 114:602-608
  • INNATE IMMUNITY
    • -IL-1R2
    • -short cytoplasmic domain
    • -bind IL-1 α & IL-1 β efficiently
    • -but not IL-1ra
    • -serves to inhibit IL-1 responses
    • -expression can be upregulated by
    • corticosteroids & IL-4
    Murphy JE. J Invest Dermatol 2000; 114:602-608
  • INNATE IMMUNITY Murphy JE. J Invest Dermatol 2000; 114:602-608
  • INNATE IMMUNITY
    • -important among this cascade of events is
    • induced expression inflammatory cytokine,
    • chemokine, mediators(eicosanoids,
    • histamine, neuropeptides, ROS)
    • -contribute to classic signs of acute
    • inflammation : redness, heat, swelling, pain
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • IL-1 α induce molecules of typical
    • cutaneous inflammatory response
    • include : TNF- α , IL-8(CXCL-8),
    • nitrous oxide synthase,
    • PG-producing cyclooxygenase,
    • postcapillary venule endothelial
    • cell expression of ICAM-1,
    • VCAM-1, E-seletin
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • -Moreover,IL-1 α & other induced
    • molecules activate most cell types of skin,
    • alerting and preparing them for further
    • host defense functions including cytokine
    • and chemokine secretion, wound repair,
    • release of antimicrobial products,
    • phagocytosis, initiation of acquired
    • immune responses
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • 2.3.inducible pathogen-targeted soluble
    • molecules
    • -inducible antimicrobial polypeptides
    • -complement-activating a/o opsonin
    • proteins
    • -complement proteins
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • Inducible antimicrobial polypeptides
    • - β -defensin-2 and -3, cathelicidin LL-37
    • -produced by keratinocytes
    • -IFN- α , IFN- β , IFN-k another class of
    • antimicrobial polypeptides
    • (IFN- α produced by plasmacytoid DC,
    • mononuclear phagocytes)
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • - IFN- β produced by many cell ; fibroblasts
    • sometimes called fibroblasts IFN)
    • -protective activities related to antiviral
    • effect on host cells rather than diract toxic
    • to pathogen
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • 2.4.complement activating/opsonin molecules
    • -members of acute phase proteins
    • (C-reactive protein, serum amyloid
    • protein)
    • -members of collectin(mannan-binding
    • lectin)
    • -ficolin lectin families
    • -C3b fragment, natural IgM
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • 2.4.complement activating/opsonin molecules
    • - acute phase protein produced by liver &
    • supply to skin via blood
    • -increase serum concentration in response
    • to IL-1, IL-6, TNF- α from activated MØ
    • - collectins & ficolins recognize
    • carbohydrates on bacteria, fungi, viruses
    • then mark them for destruction
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • - opsonin C3b target pathogen : phagocytosis
    • - C3a, C5a(anaphylatoxins) : keratinocyte
    • activating, chemoattractant, mast cell
    • degranulating functions)
    • - C5b, C6, C7, C8, C9 : MAC(lethal pore)
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • 2.5.PRRs host molecules recognize
    • -PRRs host molecules recognize PAMPs
    • -PAMPs include
    • -unmethylated CpGs of bact. DNA
    • -dsRNA(e.g.influenza)
    • -mannans
    • -gram+ bact. lipoteichoic acids
    • -gram- bact. LPS
    • -bacterial peptidoglycan
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • 2.5.PRRs host molecules recognize(cont.)
    • -N-terminal formyl-methionine
    • -parasitic phosphoglycans
    • -fungal glucans/zymosan
    • - M Ø & DC ,activated during cutaneous
    • inflammatory response, first phagocytic
    • host cells utilizing their cell-surface PRRs
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • -inflammation-ass increase chemotactic
    • factors (chemokines) , produced by
    • keratinocytes stimulated via their TLRs
    • and postcapillary venule endothelial cell
    • adhesion molecules (P- & E-selectin,
    • ICAM-1, VCAM-1) synergiscally mediate
    • integrin-dependent extravasation of
    • PRR-expressing leukocytes
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • -cellular infiltration
    • - neutrophils earliest infiltrating
    • leukocytes(due to neutrophil
    • active CXC : IL-8)
    • -later, monocyte begin extravasate
    • into inflam. site
    • - assist in phagocytosis &
    • intracellular destruction of
    • pathogen with lysozyme, defesins, ROI
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • - eosinophil less phagocytic than
    • neutrophil, produce ROS at plasma
    • membrane surface, not intracellularly
    •  readily degranulate & deposit toxic
    • cationic proteins onto surface of
    • parasites
    • -furthermore : basophils, blood Dc,
    • mast cell, T cells, B cell, NK-T cell,
    • NK cells
    N Franklin. Middleton’s allergy 7th edition 2009
  • INNATE IMMUNITY
    • -local defenses are quickly augmented by
    • recruitment of dermal M Ø , just beneath
    • basement membrane
    • -lymphocyte-/keratinocyte-derived IFN &
    • growth factors across basement membrane
    • initiates priming MØ to produce IL-12
    B.Spellberg.Life Sciences 2000;67:477-502
  • INNATE IMMUNITY
    • -epidermal-derived cytokine & Ag stimuli
    •  MØ mobilize their cytoskeletons to
    • become mobile & secrete metalloproteinases
    • and degradative enzymes  allow them to
    • slice through collagen and other structural
    • components of basement membrane  cross
    • into epidermis
    B.Spellberg.Life Sciences 2000;67:477-502
  • INNATE IMMUNITY
    • - M Ø use ligands expressed on activated
    • keratinocytes, such as E-cadherin/ICAM-1,
    • to pull themselves through epidermis and
    • crawl to danger site by following chemokine
    • gradient to its source
    B.Spellberg.Life Sciences 2000;67:477-502
  • INNATE IMMUNITY B.Spellberg.Life Sciences 2000;67:477-502
  • INNATE IMMUNITY B.Spellberg.Life Sciences 2000;67:477-502
  • ACQUIRED IMMUNITY
    • -inflammation state that continues beyond
    • 24-36 hr induces onset of adaptive immunity
    • -IFN- γ in epidermis stimulates leukocytes,
    • fibroblasts to express CC chemokines,
    • particular MCP-1, MIP-1, RANTES
    • while suppress production of CXC
    • chemokines such as IL-8
    B.Spellberg.Life Sciences 2000;67:477-502
  • ACQUIRED IMMUNITY
    • -MIP-1 α : CCL20;induce chemotaxis of
    • neutrophil and lymphocytes
    • -MCP-1 : chemotactic for monocytes
    • & lymphocytes
    • -RANRES : selectively pro-inflammatory
    • Th1 lymphocytes, not
    • inflammatory-suppressive
    • Th2 cells
    B.Spellberg.Life Sciences 2000;67:477-502
  • ACQUIRED IMMUNITY
    • -Th1 have RANTES Rc : CCR5
    • -Th1 produce IFN- γ which drive RANTES
    • production by lymphocytes and MØ 
    • selectively summon additional Th1 cells
    • to area of danger
    B.Spellberg.Life Sciences 2000;67:477-502
  • ACQUIRED IMMUNITY
    • - endothelial cell adhesins critical to
    • selection of leukocyte extravasation
    • - several hour after stimulation  lower
    • their expression of E-selectin(CD62E),
    • upregulate their ICAM-1 expression,
    • begin express VCAM  diminish neutrophil
    • across vascular lumen  L & Mo are
    • recruited into area
    B.Spellberg.Life Sciences 2000;67:477-502
  • ACQUIRED IMMUNITY
    • -exposure to IFN- γ  endothelium express
    • MHC class II
    • then presence of IFN- γ , microvascular
    • endothelial cells capable acting as
    • professional APC to circulating T cells
    B.Spellberg.Life Sciences 2000;67:477-502
  • ACQUIRED IMMUNITY
    • -keratinocytes unable to express sufficient
    • costimulatory molecules to drive T cell
    • activation  result in T cell anergy/deletion
    • -keratinocytes able to abort adaptive
    • response by competing with phagocytes
    • for presentation of Ag to T cells
    B.Spellberg.Life Sciences 2000;67:477-502
  • ACQUIRED IMMUNITY
    • -In presence in skin of IFN- γ , IFN- α ,
    • TNF- α , microbial particles
    • (LPS, gram+ cell wall fractions, prokaryotic
    • DNA)  induces M Ø & DC produce IL-12
    • -IL-12 induces newly activated T cell to Th1
    B.Spellberg.Life Sciences 2000;67:477-502
  • ACQUIRED IMMUNITY
    • -if stimulus initiating danger response is
    • too bulky(hyphal fungi, helminths, large
    • foreign bodies,etc)  leukocytes initiate
    • “ frutrated phagocyte complex ” this
    • induce production of IL-10 prefentially
    • over IL-12  favoring antibody-based Th2
    B.Spellberg.Life Sciences 2000;67:477-502
  • ACQUIRED IMMUNITY
    • -antibody production stimulated by Th2
    • response  allow leukocytes to damage
    • large organisms via ADCC
    • -eosinophil, neutrophil, NK, monocyte/M Ø
    • able to use this mechanism
    B.Spellberg.Life Sciences 2000;67:477-502
  • ACQUIRED IMMUNITY
    • - B cell other key cell for acquired immunity
    • -B cell recognize relatively intact Ag
    • (contrast T cells)
    • -plasma cell, memory B cell development,
    • Ig class switching, somatic hypermutation
    • all occur in secondary lymphoid geminal
    • center of skin-draining LN
    N Franklin. Middleton’s allergy 7th edition 2009
  • ACQUIRED IMMUNITY
    • -absence of cutaneous B cells suggests a
    • need for Ag that enter skin to be
    • transported to B cell as opposed to B cell’s
    • migrating to Ag in skin(but mechanism of
    • B cell activation remains unclear)
    • -five classes of Ig have been detected in
    • normal human sweat
    N Franklin. Middleton’s allergy 7th edition 2009
  • ACQUIRED IMMUNITY
    • -sIgA arise from secretory epithelia of
    • eccrine glands, sebum also contain IgA
    • -exact source of cutaneously secreted
    • Ig remains unresolved
    • -IgG1 & IgA capable to clear pathogenic
    • organisms from skin via Fc γ Rc-mediated
    • immune response(ADCC, complement
    • fixation) and sIgA-coating of bacteria
    N Franklin. Middleton’s allergy 7th edition 2009
  • ACQUIRED IMMUNITY
    • -in human IgE & IgG4 produced by type 2
    • cytokine (IL-4, IL-13)
    • -most antigen-specific IgE supplied via
    • blood(except respiratory mucosa , local
    • IgE production appear posible)
    • -IgE can bind to Fc ε RI-bearing cells(LC,
    • mast cell, infiltrating basophils)  contribute
    • to various allergic skin dz
    N Franklin. Middleton’s allergy 7th edition 2009
  • ACQUIRED IMMUNITY
    • -Ab specific for Fc ε RI may contribute to
    • cutaneous dz such as urticaria, Ab against
    • desmosomal and hemidesmosomal protein
    • provoke immunobullous dz
    N Franklin. Middleton’s allergy 7th edition 2009
  • ACQUIRED IMMUNITY
    • -impact of innate to acquired immunity
    • -chemotactic activity of β -defesin-2
    • & C5a for DC a/o T cells
    • -tissue injury danger signals or
    • engagement of PRRs (LPS Rc,
    • mannose binding Rc, TLRs, CD1a)
    • expressed on cutaneous APC such as
    • Langerhans’ cells, dermal DC, MØ
    N Franklin. Middleton’s allergy 7th edition 2009
  • ACQUIRED IMMUNITY
    •  increase co-stimulatory molecule
    • expression (CD80 & CD86) & modulate
    • cytokine expression patterns
    • -LPS bind to cell surface CD14 of M Ø
    • induces IL-12  favor Th1 development
    • -mast cell-produced cytokines such as IL-4,
    • histamine, keratinocyte-derived thymic
    • stromal lymphopoietin(TSLP)  acquire
    • immune response Th2 profile
    N Franklin. Middleton’s allergy 7th edition 2009
  • ACQUIRED IMMUNITY B.Spellberg.Life Sciences 2000;67:477-502
  • ACQUIRED IMMUNITY B.Spellberg.Life Sciences 2000;67:477-502
  • SUMMARY N Franklin. Middleton’s allergy 7th edition 2009
  • TAKE HOME MESSAGE
    • -Various constitutive and inducible
    • innate immune mechanisms function in
    • skin to fight infection and to direct
    • acquired immunity – these include
    • keratinocyte– derived molecules such
    • as IL-1, antimicrobial pe ptides   
    • -Immune functions attributed to
    • cutaneous mast cells and dendritic
    • cells (DCs)
  • TAKE HOME MESSAGE
    • -Langerhans' cells, dermal DCs, and
    • DCs infiltrating during inflammatory
    • disease are increasing in number and
    • being redefined -Skin homing of memory, effector,
    • and regulatory T-cell subtypes is
    • programmed by skin-derived DCs
    • and prominently directed by CLA,other
    • types of chemokines