IMUNOLOGI "Cytokines and Chemokines"

Cytokines and Chemokines

 Sitokin Dasar
•Sitokin atau immunocytokine adalah nama generik yg digunakan utk menggambarkan grup berbeda dr protein yg larut atau peptida yang berperan sebagai pengatur humoral pada konsentrasi nano sampai picometer

•Sitokin mengatur aktifitas fungsional dari individu sel dan jaringan dibawah kondisi normal dan kondisi patologi

Cytokine Names 

•Interleukins - produced exclusively by leukocytes 

•Lymphokines - produced by lymphocytes 

•Monokines - produced exclusively by monocytes 

•Interferons - involved in antiviral responses 

•Colony Stimulating Factors - support the growth of cells in semisolid medias 

Chemokines  - promote chemotaxis 

Cytokine Basics

•Cytokines mempunyai sifat seperti hormon dimana berperan pada level sistemik, affecting,

inflammation, septic shock, acute phase reactions, penyembuhan luka dan jaringan

neuroimmun  

•Tidak seperti hormon, cytokines tidak dihasilkan oleh sel khusus atau kelenjar khusus -

 they have no single organ source  

 

 Cytokine Activity

•Cytokine actions may be characterized as:  

–Autocrine (self modulating) 

–Paracrine (modulating cells in the immediate surroundings) 

–Juxtacrine (modulating through cell membrane signaling) 

–Retrocrine (modulating to stop host defense )

SITOKIN

•Sitokin
Merupakan protein sistim imun yang mengatur reaksi antar sel dan memicu reaktifitas 
imun, baik pada imunitas nonspesifik maupun spesifik

Cytokine Basics

 

•Defining cytokines based only on their producer cells or target cells is inaccurate

•The historic cytokine concept of "one producer cell -one cytokine -one target cell" has been

falsified for almost every cytokine

• Hampir semua sitokin adalah pleiotropic effectors memperlihatkan aktifitas biologi yg  

banyak  

•Juga, multiple cytokines sering mempunyai aktifitas yg overlaping 

•Sel tunggal biasanya berinteraksi dengan multiple cytokines dengan respon yg identik  

Cytokine Transport

•Mediator sitokin dapat ditransport cepat ke daerah yg jauh pada organisme multiselular 

•Sitokin dapat menuju banyak target sel dan dapat dihancurkan cepat. Concentration 

gradients can be used to elicit specific responses

Cytokine - Regulation 

• Cytokines regulator penting baik positif dan negatif pada mitosis, differentiation,

 migration,cell survival, apoptosis, and transformation-oncogene   

Cytokines In Therapy

• The many specific activities of individual cytokines have been the basis for current

concepts of therapeutic intervention - particularly, hematopoietic malfunctions and tumor

therapy 

•Applications involve the support of chemo- and radiotherapy, bone marrow transplantation, 

and general immunostimulation  - adoptive immunotherapy

Cytokine Type I Subgroups

•Long-chain cytokines include:

–IL-6, IL-11

–Erythropoietin

–Thrombopoietin

–Leptin

–Leukemia inhibitory factor (LIF)

–Oncostatin M (OSM)

–Ciliary neurotrophic factor (CNTF)

– Cardiotrophin-1 (CT-1)

–Granulocyte colony-stimulating factor (G-CSF)

 

Cytokine Receptors

Cytokine Receptors

• The receptors for five different immunologically important cytokines, IL-2, IL-4, IL-7, IL-9, 

and IL-15, share the common cytokine receptor g chain, gc (CD132)

•These cytokines are all short-chain Type I cytokines 

 IL-2 Production 
 

•Mature IL-2 is a peptide 133 amino acids long

•Produced mainly by mitogen activated CD4+T-lymphocytes

•Originally called T-cell growth factor (TCGF)

•Transformed T-cells and B-cells, leukemia cells,LAK cells 

(Lymphokine-activated killer cells) and NK-cells also secrete IL-2

IL-2 Facts

•IL-2 damages the blood-brain barrier and the integrity of the endothelium of brain vessels

•IL-2 does not have a saturable transport system across the blood-brain barrier

•Electrophysiological alterations may cause neuropsychiatric side effects such as fatigue, 

disorientation, and depression, frequently observed under IL-2 therapy

IL-2 Summary

•IL-2 important actions: 

– It can increase immunoglobulin synthesis and J-chain transcription 

– Proliferation in B cells (with IL-4) 

– potently augment the cytolytic activity of natural killer (NK) cells 

– induce the cytolytic activity of lymphokine-activated killer (LAK) cells 

– Due to its effects on T-cells and B-cells IL-2 is a central regulator of immune response

IL-4 Production  
  

•IL-4, like IL-2, is produced principally by activated CD4+ T cells

•It is also produced by natural killer cells, and by mast cells and basophils

IL-7 Production 

•IL-7 is not a lymphokine but instead is produced by stromal cells

 •IL-7 is secreted constitutively into bone marrow stroma, and thymic cells 

•Murine and human keratinocytes have been shown also to express and secrete IL-7 

IL-7 Actions/Modulation

• IL-7 stimulates the proliferation of pre-B and pro-B-cells without affecting their  
differentiation

•IL-7 can replace murine bone marrow stromal cells in supporting the extended growth 
of both pre-B-cells and pro-B-cells

• It does not act on mature B-cells

  


 

IL-9

IL-9 Production

•IL-9 was originally described as a murine T-cell growth factor. Human and murine IL-9 are  

126 amino acids long

•IL-9 is produced by activated T-cells and supports the growth of T-helper (Th) clones but 

not CD8+ cytolytic clones

•In contrast to IL-2, its production is much more delayed, suggesting late/secondary 

signaling

•IL-9 can be isolated from culture of mitogen- or antigen-stimulated T helper cells

•In primary lymphocyte cultures it is produced predominantly by cells expressing CD4

•The synthesis of IL-9 can be induced by calcium ionophores (Ionomycin)  

•IL-9 can be isolated from culture of mitogen- or antigen-stimulated T helper cells

•In primary lymphocyte cultures it is produced predominantly by cells expressing CD4

•The synthesis of IL-9 can be induced by calcium ionophores (Ionomycin) 

IL-9 Actions/Modulation

•IL-9 stimulates the proliferation of a number of T helper cell clones in the absence of 

antigens or antigen-presenting cells 

•It does not promote the proliferation of freshly isolated T-cells or cytolytic T-cells 

•The activity as a growth factor seems restricted to a distinct subpopulation of cells or to a 

particular late activation state

 IL-15 Production 

•IL-15 is the most recently identified Type I cytokine 

•Although IL-15 messenger RNA (mRNA) is produced by a range of non-lymphocytic cell 

types, it is difficult to detect IL-15 protein production

IL-15 Actions/Modulation 

  

IL-15 receptors are widely expressed, and it is becoming more clear that IL-15 plays a  

major role related to NK cell development and cytolytic activity

Type I Cytokines

•IL-2, IL-4, IL-7, IL-9, and IL-15 collectively exhibit overlapping roles related to T cells, NK 

cells, B cells, and mast cells, and together would be expected to play vital roles in normal 

development and function of these cells  

Break
My friends, as a result of our experimentation, we have just lost a dear and valued colleague....
On. the other hand, we have just gained a publication.

kemokin

•Kemokin adalah sitokin yg berperan dalam kemotaksis sel-sel leukosit (limfosit, monosit 
dan neutrofil) ketempat infeksi atau kerusakan jaringan (sitokin kemotaktik) sehingga 
mempermudah interaksi antarsel. (Chemoattractant Cytokines)

•Small (8-10kd) secreted heparin-binding

•Promote recruitment and activation of leukocytes

•Can be divided into subclasses by virtue of structural properties

 Chemokine 

Chemokines

• Cell recruitment
• Th1/Th2 development
• Angiogenesis/angiostasis
• metastasis
• inflammation
• Wound healing
• Lymphoid organ development
• Lymphoid trafficking

Chemokine Function

•Recruitment of inflammatory cells to infection

•Provide immune homeostasis

•Important in host defense against bacteria, parasitic and viral infection

•Role in wound healing

•Role in hematopoesis and angiogenesis under study

•Chemokines promote chemotaxis in the direction of highest concentration 

 

Chemokine Effects 

•Chemokines promote shape change in cells

•Polymerization and breakdown of actin

•Breakdown of lamellipodia (cell anchoring arms/legs)

•Upregulate integrins causing cell adhesion in vascular endothelium

•Promote cell diapedesis

 

 

Chemokine Receptors

•Specific receptors bind specific chemokine

–CXCR1 binds IL-8

•There are also shared receptors

–CCR1 binds MIP-1a,RANTES, MCP-2 and MCP3

•Promiscuous receptors bind any class

•Viral encoded receptors

–Encoded by cytomegalovirus- CMV U28 binds CC chemokines

cc reseptors
ligands
cellular expression
 

   Questions?

"This composition was produced during the artist's 'Hay Fever' period, and is simply entitled 'The Sneeze'."