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DEPARTMENT OF IMMUNOLOGY Chair of Histology and Immunology Medical University of Gdańsk

DEPARTMENT OF IMMUNOLOGY Chair of Histology and Immunology Medical University of Gdańsk. Research group Head: Jolanta Myśliwska, MD, PhD Professor of immunology Joanna Więckiewicz, M. Sc. Dominik Rachoń, MD Łukasz Hak, M. Sc. Monika Mlotkowska, M.Sc. Katarzyna Zorena, PhD

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DEPARTMENT OF IMMUNOLOGY Chair of Histology and Immunology Medical University of Gdańsk

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  1. DEPARTMENT OF IMMUNOLOGYChair of Histology and ImmunologyMedical University of Gdańsk Research group Head: Jolanta Myśliwska, MD, PhDProfessor of immunology Joanna Więckiewicz, M. Sc. Dominik Rachoń, MD Łukasz Hak, M. Sc. Monika Mlotkowska, M.Sc. Katarzyna Zorena, PhD Hanna Suchanek, MD, PhD

  2. RESEARCH PROBLEMS • AGE-RELATED CHANGES OF IMMUNE RESPONSE • HORMONAL MODULATION OF IMMUNE RESPONSE • IMMUNOLOGICAL ASPECTS OF CARDIOVASCULAR DISEASE

  3. PREVIOUS AND CURRENT

  4. AGE-RELATED CHANGES OF IMMUNE RESPONSE ROLE OF NATURAL KILLER CELLS IN AGEING • We found that successful healthy ageing is associated with a shift towards high cytotoxic activity of Natural Killer cells. The high values of NK-associated parameters may be preserved until very old age. • Healthy elderly people have an increased number of the regulatory NK cells with intra-cellular IFN . • This status correlates with anti-viral immune response in the elderly what we observed on the natural model of vaccination against influenza.

  5. Myśliwska J, et al. (1997) Gerontology, 43, 158-167. • Myśliwska J, et al. (2000) Acta Biochem. Pol., 47, 1-11. • Kmieć Z, et al. (2001) Gerontology, 47, 282-288. • Brydak LB, et al. (2003) J. Clin. Immunol., 23:214-222. • Myśliwska J, et al. (2003) Clin Exp. Immunol., accepted

  6. PRO-INFLAMMATORY STATE IN THE ELDERLY • We found that ageing process is accompanied by an enhanced expression of pro-inflammatory cytokines. • Low immune response to vaccination in the elderly, who stayed apparently healthy, is associated with an increased expression of genes of such inflammatory cytokines as; Interleukin 1, TNF, Interleukin 6, Interleukin 12. • Enhanced expression of pro-inflammatory cytokines was associated with carrier status of latent CMV infection in the elderly low responders to influenza vaccination. Myśliwska J, et al. (1999) Mech. Ageing Dev. ,107: 1-14. Myśliwska J, et al. (2000) Eur. Cytokine Net. ,11:397-406. Trzonkowski P, et al. (2002) Mech. Ageing Dev. ,123, 1283-1293. Trzonkowski P, et al. (2003) Vaccine , 21:3826-3836.

  7. HORMONAL MODULATION OF IMMUNE RESPONSE ESTROGENS DOWN-REGULATE PRO-INFLAMMATORY AND UP-REGULATE ANTI-INFLAMMATORY CYTOKINES

  8. Non-stimulated ex vivo monocytes of healthy postmenopausal women express the TNF gene 883bp b-actin 800bp 692bp 501bp TNF 420bp 404bp 1 2 3 4 5 6 (-) (+) pUC • This may be the effect of estrogen deprivation

  9. Non-stimulated ex vivo monocytes of healthy postmenopausal women express the IL-6 gene 883bp b-actin 800bp 692bp IL6 628bp 501bp 1 2 3 4 5 6 (-) (+) pUC • This may be the effect of an exaggerated TNF expression which in turn stimulates IL-6 gene expression Rachoń D, Myśliwska J, et al. (2002) J Endocrinol.,172, 387-395.

  10. Non-stimulated PBMC of postmenopausal women produce more bioactive TNF and IL-6 compared to young controls

  11. In vitro effects of 17b-estradiol on the spontaneous TNF and IL-6 production by PBMC of postmenopausal women

  12. In vivo effects of 17b-estradiol treatment on the spontaneous TNF and IL-6 production by PBMC of postmenopausal women

  13. Non-stimulated PBMC of postmenopausal women produce less IL-10 compared to young controls

  14. In vitro effects of 17b-estradiol on the IL-10 gene expression in the PBMC of postmenopausal women

  15. IMMUNOLOGICAL ASPECTS OF CARDIOVASCULAR DISEASE CURRENT RESEARCH

  16. Polymorphism of the human Interleukin 6 (IL6) gene at position –174G/C in coronary heart disease (CHD) patients

  17. Polymorphism of the human atrial natiuretic peptide (ANP) gene in coronary heart disease (CHD) patients • Polymorphism is analysed in CHD patients with different cardiac arrhythmias occurring in (or without) association with cardiac surgery. • The A2A2 allele combination carriers constitute 55% of the whole group of CHD patients and seem to be protective from atrial fibrillation.

  18. 21 bp 67 bp 96 bp 111 bp 117 bp 147 bp 213 bp 190 bp 234 bp 242 bp

  19. INFECTIONS WITH CMV AND CHLAMYDIA PNEUMONIAE IN CHD PATIENS 185 bp sample of mononuclear cells positive control

  20. Analysis of function of CD14+CD16+ monocytes detection of monocyte populations by cytophotometric technique tests revealing presence of intra-cytoplasmic cytokines in CD14+CD16+ monocytes in vitro cultures analysing an effect of Lovastatin on spontaneous and LPS-induced synthesis of intra-cytpolasmic IL6 ROLE OF CD14+CD16+ BLOOD MONOCYTES IN CORONARY HEART DISEASE

  21. CD14+CD16+ BLOODmonocytes in CORONARY HEART DISEASE and controls

  22. LPS-induced IL-6 production Spontaneous IL-6production 90 80 80 70 70 ____*____ 60 60 50 50 _____*_____ 40 40 30 30 20 20 10 10 0 Mediana 0 Min.-Maks. Mediana 14+16+ Min.-Maks. 14+16- 14+16+ 14+16- CD14+ CD16+ 90 80 70 ___*____ 60 50 ____*____ 40 30 20 10 Mediana 0 Min.-Maks. Control Lova LPS LPS + Lova CD14+ CD16- 90 80 70 60 50 40 30 20 10 Mediana 0 Min.-Maks. Control Lova LPS LPS + Lova

  23. Human cytokine array system– expression profile of multiple cytokines • In serum of the patients with coronary heart disease, with CCS 3 and 4 grade of the angina pectoris, we found an expression of 18 new cytokines positive control positive control

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