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The effects of ultraviolet B treatment on the expression of adhesion molecules by circulating T lymphocytes in psoriasis PowerPoint PPT Presentation


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The effects of ultraviolet B treatment on the expression of adhesion molecules by circulating T lymphocytes in psoriasis. Presented By: Anika Ramos. OUTLINE. 1. Introduction 2. What is psoriasis 3. What causes it? 4. T-cells… 5. Genetically Predisposed? 6. Cytokines

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The effects of ultraviolet B treatment on the expression of adhesion molecules by circulating T lymphocytes in psoriasis

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The effects of ultraviolet B treatment on the expression of adhesion molecules by circulating T lymphocytes in psoriasis

Presented By: Anika Ramos


OUTLINE

  • 1. Introduction

  • 2. What is psoriasis

  • 3. What causes it?

  • 4. T-cells…

  • 5. Genetically Predisposed?

  • 6. Cytokines

  • 7. Article Presentation


What is Psoriasis?

  • Psoriasis is a chronic (long-lasting) inflammatory dermatitis

  • It affects approximately 2% of the population(5.5 million people)

  • It is characterized by red, scaly skin and patches that are usually found on the scalp, elbows, and knees


What causes Psoriasis?

  • Recent research indicates that psoriasis is a disorder of the immune system

  • The immune system includes a type of white blood cell, called a T cell.

  • T cells usually protect the body against infection and disease

  • However, in psoriasis an abnormal immune system causes negative activity by T cells in the skin


Function of Normal T Cells

  • There are two types of white blood cells

    1. T- cells

    2. B- cells

  • When T –cells identify a foreign material or organism, they attack it

  • When B-cells identify a foreign material, they secrete special chemicals called antibodies.

  • These antibodies stick on the foreign material and destroy it


What Happens in Psoriasis?

  • Psoriasis causes abnormal immune system activity of T-cells in the skin

  • These T-cells cause the skin to become inflamed and reproduce excessively

  • It is therefore called a T-cell mediated disease


What type of T-cells are involved?

  • The CD4+ T cells predominate in the dermis

  • The CD8+ T cells localize to the epidermis


Is Psoriasis a Disease With Genetic Predisposition?

  • Psoriasis is a heterogeneous disease in its clinical expression

  • Both genetic and environmental factors are thought to contribute to the pathogenesis

  • There is a higher than average incidence of psoriasis in relatives of people with psoriasis, indicating “familial tendency”


The Role of Cytokines in the Pathogenesis of Psoriasis

  • T-cells as well as cytokines are of major importance in the pathophysiology of psoriasis

  • Cytokines are a unique family of growth factors.

  • Secreted primarily from leukocytes,

  • cytokines stimulate cellular immune responses, as well as the activation of phagocytic cells.


Cytokines…

  • Basically, the over expression of these proinflammatory cytokines is considered to be responsible for initiation, maintenance, and recurrence of psoriatic skin lesions

  • What happens is that in contrast to the overexpression of proinflammatory cytokines, there is a relatively low level of expression of the antiinflammatory cytokines

  • What results is an insufficient counterregulatory capacity in psoriasis


The Effects of Ultraviolet B Treatment on the Expression of Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • Presented by Anika Ramos


Background…

  • T lymphocytes are believed to play a role in the pathogenesis of psoriasis

  • More than 80% of T lymphocytes that infiltrate psoriatic lesions express the surface glcoprotein called:

  • Cutaneous Lymphocyte Associated Antigen (CLA) CLA is a 200 kDa cell-surface glycoprotein

  • This compares with expression in the blood which is less than 20%


Purpose of experiment

  • The purpose of this study was to compare the effects of UVB treatment of psoriasis on the expression of CLA and several other surface markers expressed by circulating T lymphocytes.


A reminder…

  • T- lymphocytes are thought to have an important role in the pathogenesis of psoriasis, and agents that act selectively on T cells have a potent antipsoriatic effect


“Radiation”

  • Exposure to ultraviolet B is a common and effective treatment for psoriasis.

  • UVB radiation suppresses their proliferative responses to allogenic cells and mitogens

  • High UVB doses act both on T cells and antigen presenting cells

  • Lower doses selectively affect T cells, including suppression of their cytokine production and expression


Adhesion molecules…

  • Several adhesion molecules are involved in the migration of T cells from the blood into tissues

  • T cells that infiltrate the skin express a unique skin homing determinant called:

  • Cutaneous Lymphocyte Associated antigen (CLA):

  • It is a carbohydrate epitope interacting with endothelial E-selectin that facilitates the targeting of T cells to inflamed skin


E-Selectin…

  • The expression of E-selectin is low in normal skin

  • In psoriatic skin the expression of E-selectin increases dramatically

  • Therefore, causing a large attraction for T cells in the skin


So what’s important for the spread of psoriasis?

  • A large amount of localized T cells

  • Expressing the CLA antigen

  • The very late antigen (VLA)-4

  • And its cell adhesion molecule


Materials and Methods…

  • Seven patients with active chronic plaque psoriasis were included in the study:

  • 4-men

  • 3-women

  • Age (17-65)

  • The patients were not on ant other treatment except for moisterizing ointments


Treatment…

  • They were treated daily with narrow-band (312 nm) UVB

  • Initial dose: 0.1 mJ cm

  • Gradually increased during the 4 weeks to

  • Max dose: 1.7 mJ cm

  • The patients were all evaluated for a PASI score


What is PASI?

  • PASI stands for:

  • Psoriasis Area and Severity Index score

  • Doctors use this type of scoring method to indicate the severity of the psoriasis in any given area of the body


Materials and Methods continued…

  • Blood was drawn simultaneously from all seven patients at the beginning of treatment and weekly thereafter.

  • This blood was to be tested for several factors


Antigens…

  • Antigens are macromolecules that elicit an immune response in the body. The most common antigens are proteins and polysaccharides.

  • Antigens were added to the blood samples

  • they are associated with the T cell antigen receptor.

  • Required for cell surface expression of and signal transduction by TCR.

  • Specific antigen added was:

  • Streptococcal antigen


Monoclonal Antibodies…

  • Humans (and mice) have the ability to make antibodies able to

  • recognize (by binding to) virtually any antigenic determinant (epitope)

  • to discriminate between even similar epitopes.

  • Antibodies used:

  • Anti-CD4, Anti-CD8, Anti CD4/PE, Anti CD8/PE, and a couple more


Isolation of Mononuclear blood lymphocytes

  • Peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood by a density gradient

  • The cells were washed and resuspended


Immunofluorescence staining and flow symmetry….

  • The (PMBC) blood cells were double-stained with solutions containing the monoclonal antibodies

  • The stained cells were immediately submitted to flow symmetry analysis using a special machine called a FACScan, used specifically for this purpose

  • Analysis of unstimulated and stimulated cells was performed usin a light scatter that included both small and large T lymphocytes.

  • Mean fluorescence intensity was assessed by flow symmetry using the soft ware


Stimulation of lymphocytes

  • After the correct T-cells were recovered, they were cultured together with 1000 ng mL of the streptococcal superantigens

  • Cultured lymphocytes were pulsed with tritiated thymidine

  • Proliferation was determined by thymidine incorporation as measured by spectroscopy

  • They were also stained for surface marker expression


Statistical analysis…

  • Significance was determined by the paired t-test

  • P< 0.05 was considered significant


Results…

  • The mean PASI score had decreased from 13.4 to 3.5 (P= 0.006)\

  • This correlated closely with a significant decrease in the intensity of CLA and VLA-4 expression by the T cells( P=0.016 and 0.015)

  • A corresponding but less marked decrease in the frequency of CLA T cells was observed

  • The frequency of VLA-4 T cells did not decrease during the treatment


Figure 1


Figure 1

  • The mean PASI score decreases from 13.4 to 3.5 after 2 weeks of treatment

  • This correlated closely with a progressive and linear decrease in the intensity of CLA expression by the T cells


Figure 2


Figure 2

  • As in the previous explanation, the expression of VLA-4 by T cells also decreased in correlation with the PASI score


Discussion

  • In this study they demonstrated a marked decrease in the expression by circulating T cells of the skin molecules CLA and VLA-4 during the first 2 weeks of UVB treatment

  • No decrease was observed in the expression of ICAM – 1 activation markers

  • Also lymphocyte responses to streptococcal antigens and superantigens remained unchanged


Controls vs. experimental


Before/After


Conclusion

  • Treatment with narrow band UVB has been reported to deplete dermal T cells in psoriasis and to induce T-cell apoptosis in vivo

  • In view of this, the reduced expression of CLA and VLA-4 that was observed may be due to an elimination of T cells within the UVB exposed skin

  • It is an interesting possibility that sustained remission that is obtained after UVB treatment is due to apoptosis of T cell clones that are specific for autoepitopes in the skin


  • Questions?????


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