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Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
Cutaneous Immunology
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  • 1. CUTANEOUS IMMUNOLOGY นพ . สุรสฤษดิ์ ขาวละออ 9/9/2009
  • 2. CONTENTS
    • Normal skin structure
    • Cutaneous immunology
      • -innate immunity
      • -IL-1
      • -complement activation
      • -PRRs
      • -Langerhans’ cell & dermal DC
      • -acquired immunity
      • -role of T & B cell
  • 3. 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 )
  • 4. NORMAL SKIN STRUCTURE
    • 1 Epidermis
    • 2 Dermis
    • 3 Subcutis
    • 4 Hair follicle
    • 5 Sebaceous gland
    • 6 Sweat gland
  • 5. 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
  • 6. NORMAL SKIN STRUCTURE
  • 7. 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
  • 8. 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
  • 9. 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
  • 10. 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
  • 11. 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
  • 12. 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
  • 13. 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
  • 14. 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
  • 15. 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
  • 16. 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
  • 17. 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
  • 18. 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
  • 19. 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
  • 20. 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
  • 21. 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
  • 22. 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
  • 23. 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
  • 24. 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
  • 25. 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
  • 26. NORMAL SKIN STRUCTURE B.Spellberg.Life Sciences 2000;67:477-502
  • 27. 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
  • 28. 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
  • 29. 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
  • 30. 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
  • 31. 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
  • 32. 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
  • 33. 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
  • 34. 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
  • 35. 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
  • 36. 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
  • 37. INNATE IMMUNITY Murphy JE. J Invest Dermatol 2000; 114:602-608
  • 38. 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
  • 39. 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
  • 40. 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
  • 41. 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
  • 42. 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
  • 43. 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
  • 44. 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
  • 45. 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
  • 46. 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
  • 47. 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
  • 48. 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
  • 49. 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
  • 50. 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
  • 51. 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
  • 52. 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
  • 53. 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
  • 54. 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
  • 55. INNATE IMMUNITY B.Spellberg.Life Sciences 2000;67:477-502
  • 56. INNATE IMMUNITY B.Spellberg.Life Sciences 2000;67:477-502
  • 57. 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
  • 58. 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
  • 59. 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
  • 60. 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
  • 61. 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
  • 62. 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
  • 63. 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
  • 64. 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
  • 65. 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
  • 66. 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
  • 67. 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
  • 68. 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
  • 69. 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
  • 70. 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
  • 71. 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
  • 72. 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
  • 73. ACQUIRED IMMUNITY B.Spellberg.Life Sciences 2000;67:477-502
  • 74. ACQUIRED IMMUNITY B.Spellberg.Life Sciences 2000;67:477-502
  • 75. SUMMARY N Franklin. Middleton’s allergy 7th edition 2009
  • 76. 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)
  • 77. 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

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