immunology skin
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Immunology of Dermatologic
YUFRI ALDI
FARMASI UNIVERSITAS ANDALAS
2016
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Invading
microbes
pathogens)
External defenses -1
ST
Line
Skin
Mucous membranes
Secretions
INNATE IMMUNITY Aktif)
Rapid responses to a
broad range of microbes
ADAPTI
Slo
sp
Internal defenses - 2
nd
Line
Phagocytic cells
Inflammatory response
Hum
an
Antimicrobial peptides
Natural killer cells
Cell
cyt
lym
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http://en.wikipedia.org/wiki/File:Antigen_presentation.jpg -
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http://en.wikipedia.org/wiki/File:Cytotoxic_T_cell.jpghttp://en.wikipedia.org/wiki/File:Antigen_presentation.jpg -
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Education of T lymphocytes
Sel T menjalani transformasi pada thymus melalui seleksi positif dan nMereka diajarkan perbedaan antara molekul diri sendiri dan asing dtersebut mereka untuk mencapai toleransi imunologi.
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T Cells
Sel T mengembangkan dan matang dalam thymus setelah migrasi dari sel-sel indutulang.
Pada thymus hanya sel T yang dapat mengenali antigen asing dan tidakkompleks MHC (Major Histocompatibility Complex) untuk mendapatkan skelangsungan hidup (seleksi positif) dan lolos ke sirkulasi dan kelenjar geta
Mereka yang tidak memiliki afinitas terhadap antigen akan menerima sinapoptosis (seleksi negatif) sehingga tidak ada serangan auto.
Mereka yang gagal memiliki afinitas terhadap antigen diri menerima sinyapoptosis (seleksi negatif) sehingga tidak ada serangan auto.
Seleksi positif dan negatif memungkinkan kelangsungan hidup hanya sel-sel T yangasing (tapi tidak "diri") peptida dalam konteks "diri" molekul MHC dan dengan demuntuk pertahanan kekebalan tubuh tanpa menyebabkan auto-serangan
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Types of T cells
1. Immature T cells:Express both CD4 and CD8 molecules.
2. Mature T cells:Later with the development of the T-cell receptor (TCR), they eitherexpress:
a) CD4 and become T helper cell that binds antigens in MHCII
b) CD8 molecule and becomes T cytotoxic cell that binds antigens onMHCI.
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Ag Presentation to T-Cells
APC ke sel B dan sel T tidaksama.
Sel T hanya mengidentifikasiantigen ketika diolah menjadi peptida terikadengan molekul permukaan tertentu pada APC.
Sel B dapat mengidentifikasiseluruh antigen oleh antibodi padapermukaannya
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Dendritic cells (DC)
Didefinisikan sebagai APC profesional yang menampilkan kemampuanyang luar biasa untuk merangsang sel-sel T untuk memulai respon imunprimer.
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LNGERHANS CELLS
Sel dendritit dari epidermis, berasal dari sumsum tulang
Mengekspresikan :
1. Birbeck granules
2. Langerin
3. MHC class II.
4. CD1, berguna sebagai penanda LC(Langerhans Cell), padaepidermis (normal atau meradang) itu secara eksklusif diekspada LC.
5. S100 ptn
6. Vimentin
7. FcRI
Turunan dari sumsum tulang dari sel prekursor CD34.
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LNGERHANS CELLS
LC tidak dapat diidentifikasi dengantetap dan bagian yang bernodapada histologis; Pemastian ini membutuhkan mikroskop elektron atauanalisis histokimia
Jumlah LC berkurang dengan mengikuti :1. usia.
2. Paparan UV kronis.
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Langerhans cells can be visualized by staining using an antibodyagainst MHC class II molecules.
Note: the dendritic shape of Langerhans cells.
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Gambar : sel Langerhans dilihat menggunakan Mikroskop ElektPanah menunjukkan Granul Birbeck, organel berbentuk batang yang kh
Langerhans.
Mereka dikatakan menyerupai raket tenis
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Ag Presentation to T-Cells
T-sel mengidentifikasi proses keterikatan antigen - MHC pada permukaan
T helper CD4 , sel T mengidentifikasi antigen terikat MHC II sementara;
Cytotoxic CD8 sel T sitotoksik mengidentifikasi sel-sel T antigen terikat MHC
Eksogen dan endogen penampilan antigen.
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http://en.wikipedia.org/wiki/File:TCR-MHC_bindings.png -
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TYPES OF AP to T-cells
1. Exogenous antigens:ditelan oleh APC, diproses dan disajikan dalam hubungan dengan MHC II CD1.
2. Endogenous antigens:(VIRUS & TUMOURS) diproses dan disajikan dalam asosiasi dengan MHC I CD8
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TCR SIGNALLING
CD3 is an important part of TCR responsible for
transmission of the signal to the cell thatencodes for the cytokine needed to stimulate
the required response for that particular
antigen.
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Costimulatory molecules
Signaling through the TCR complex alone does not suffice to activate T cells. presence of costimulatory signals is needed for T cells to undergo antigen-speexpansion.
Development of a productive T-cell immune response requires exposure of that least two types of stimuli.
The first signal is the interaction of the TCR with peptideMHC complexesby APCs, which determines the specificity of the immune response.
The second signal involves surface molecules and cytokines, which detclonal expansion of specific T cells and their differentiation into effector acells.
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Costimulatory molecules
B7 FAMILY e.g. B7-1 (CD80) and B7-2 (CD86) induced by cytokines (TNF, IL1) or by various TLR ligands
Cytokines, especially inflammatory mediators like IL-1, IL-6 and TNF-, alsoprovide costimulatory signals by themselves and, in addition, upregulatecostimulatory molecules.
Are very important for completion of the T-cell response other wiseANERGY (non-reactivity) and failure of T-cell stimulation occurs.
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Criteria of Skin T cells
Majority are:
In the dermis.
CD4 OR CD8.
/ TCR.
memory phenotype CD45RO+/CD45RA-
Skin homing receptor CLA(cutaneous lymphocyte associatedantigen).
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Memory T cells
1. CENTRAL MEMORY T CELLS [TCM]:express lymph node homing receptors and thus stay in the lymph nodes.CD45RO+CD45RA- CCR7+ Have no effector function. They stimulate dendritproduce IL-12 upon secondary stimulation and differentiate into CCR7- cells
2. EFFECTOR MEMORY T CELLS [TEM]:CD45RO+CD45RA- CCR7- develop receptors to migrate to the inflamed tis
CLA in the skin). express receptors for migration to inflamed tissues and haveeffector function.
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Effector T cell function
After recognition of the antigen
CD4: T helper cells (Th):activate the immune system to combat the antigen including both T and cells.
CD8: T cytotoxic cells (Tc):
Antiviral and anti-tumor responses
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Cytotoxic T cells (CD8+ T cells)
Direct killing of the organism or the abnormal or infected cells.
TC1 and TC2 in cytokine patterns (functional roles still remain to be determined.
Viral and anti-tumor activities.
Cytotoxic T cells with CD8 surface protein are called CD8+ T cells.
Three different pathways of killing:
a) Perforin which forms pores in the target cell's plasma membrane this causwater to flow into the target cell, making it expand and eventually lyse ththat can enter target cells via the perforin-formed pore and induce apop
b) Tc cells activate the death receptor Fas on the target cell by expressing tdeath ligand FasL. The activated Fas also triggers apoptosis.
c) Cytokines, including TNF- and IFN-, which are released as long as TCR scontinues. These mediators can affect distant cells as well as the target c
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Terima Kasih
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References
Dr Samia Esmat Professor of Dermatology Cairo University
Bolognia: Dermatology, 2nd &3rd ed.
Immense Immunology Insight
Immunity and the immune system Dr. Angelo Smith WHPL
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