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DEPARTMENT OF IMMUNOLOGY Chair of Histology and Immunology Medical University of Gda ń sk DEPARTMENT OF IMMUNOLOGY Chair of Histology and Immunology Medical.

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Presentation on theme: "DEPARTMENT OF IMMUNOLOGY Chair of Histology and Immunology Medical University of Gda ń sk DEPARTMENT OF IMMUNOLOGY Chair of Histology and Immunology Medical."— Presentation transcript:

1 DEPARTMENT OF IMMUNOLOGY Chair of Histology and Immunology Medical University of Gda ń sk DEPARTMENT OF IMMUNOLOGY Chair of Histology and Immunology Medical University of Gda ń sk Research group Head: Jolanta My ś liwska, MD, PhD Professor of immunology Joanna Wi ę ckiewicz, M. Sc. Dominik Racho ń, MD Ł ukasz Hak, M. Sc. Monika Mlotkowska, M.Sc. Katarzyna Zorena, PhD Hanna Suchanek, MD, PhD

2 RESEARCH PROBLEMS AGE-RELATED CHANGES OF IMMUNE RESPONSEAGE-RELATED CHANGES OF IMMUNE RESPONSE HORMONAL MODULATION OF IMMUNE RESPONSEHORMONAL MODULATION OF IMMUNE RESPONSE IMMUNOLOGICAL ASPECTS OF CARDIOVASCULAR DISEASEIMMUNOLOGICAL 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.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 .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.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. (1997) Gerontology, 43, 158-167. Myśliwska J, et al. (2000) Acta Biochem. Pol., 47, 1-11.Myśliwska J, et al. (2000) Acta Biochem. Pol., 47, 1-11. Kmieć Z, et al. (2001) Gerontology, 47, 282-288.Kmieć Z, et al. (2001) Gerontology, 47, 282-288. Brydak LB, et al. (2003) J. Clin. Immunol., 23:214-222.Brydak LB, et al. (2003) J. Clin. Immunol., 23:214-222. Myśliwska J, et al. (2003) Clin Exp. Immunol., acceptedMyśliwska J, et al. (2003) Clin Exp. Immunol., accepted

6 We found that ageing process is accompanied by an enhanced expression of pro-inflammatory cytokines.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.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.Enhanced expression of pro-inflammatory cytokines was associated with carrier status of latent CMV infection in the elderly low responders to influenza vaccination. PRO-INFLAMMATORY STATE IN THE ELDERLY My ś liwska J, et al. (1999) Mech. Ageing Dev.,107: 1-14. My ś liwska 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  -actin TNF 1 2 3 4 5 6 (-) (+) 883bp 501bp 800bp pUC 420bp 404bp 692bp Non-stimulated ex vivo monocytes of healthy postmenopausal women express the TNF gene This may be the effect of estrogen deprivationThis may be the effect of estrogen deprivation

9  -actin IL6 692bp 883bp 501bp 800bp pUC 628bp Non-stimulated ex vivo monocytes of healthy postmenopausal women express the IL-6 gene 1 2 3 4 5 6 (-) (+) This may be the effect of an exaggerated TNF expression which in turn stimulates IL-6 gene expressionThis 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 17  -estradiol on the spontaneous TNF and IL-6 production by PBMC of postmenopausal women

12 In vivo effects of 17  -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 17  -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.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. The A2A2 allele combination carriers constitute 55% of the whole group of CHD patients and seem to be protective from atrial fibrillation.

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

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

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

22 CD14+CD16+ BLOOD monocytes in CORONARY HEART DISEASE and controls

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

24 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

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