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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

Presented By: Anika Ramos


Outline
OUTLINE adhesion molecules by circulating T lymphocytes in psoriasis

  • 1. Introduction

  • 2. What is psoriasis

  • 3. What causes it?

  • 4. T-cells…

  • 5. Genetically Predisposed?

  • 6. Cytokines

  • 7. Article Presentation


What is psoriasis
What is Psoriasis? adhesion molecules by circulating T lymphocytes in 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
What causes Psoriasis? adhesion molecules by circulating T lymphocytes in 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
Function of Normal T Cells adhesion molecules by circulating T lymphocytes in psoriasis

  • 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
What Happens in Psoriasis? adhesion molecules by circulating T lymphocytes 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
What type of T-cells are involved? adhesion molecules by circulating T lymphocytes in psoriasis

  • The CD4+ T cells predominate in the dermis

  • The CD8+ T cells localize to the epidermis


Is psoriasis a disease with genetic predisposition
Is Psoriasis a Disease With Genetic Predisposition? adhesion molecules by circulating T lymphocytes in psoriasis

  • 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
The Role of Cytokines in the Pathogenesis of Psoriasis adhesion molecules by circulating T lymphocytes in 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
Cytokines… adhesion molecules by circulating T lymphocytes in psoriasis

  • 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
Background… Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
Purpose of experiment Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
A reminder… Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
“Radiation” Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
Adhesion molecules… Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
E-Selectin… Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
So what’s important for the spread of psoriasis? Adhesion Molecules by Circulating T lymphocytes in 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
Materials and Methods… Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
Treatment… Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
What is PASI? Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
Materials and Methods continued… Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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… Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
Monoclonal Antibodies… Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
Isolation of Mononuclear blood lymphocytes Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
Immunofluorescence staining and flow symmetry…. Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
Stimulation of lymphocytes Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
Statistical analysis… Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • Significance was determined by the paired t-test

  • P< 0.05 was considered significant


Results
Results… Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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 Adhesion Molecules by Circulating T lymphocytes in Psoriasis


Figure 11
Figure 1 Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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 Adhesion Molecules by Circulating T lymphocytes in Psoriasis


Figure 21
Figure 2 Adhesion Molecules by Circulating T lymphocytes in Psoriasis

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


Discussion
Discussion Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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
Controls vs. experimental Adhesion Molecules by Circulating T lymphocytes in Psoriasis


Before after
Before/After Adhesion Molecules by Circulating T lymphocytes in Psoriasis


Conclusion
Conclusion Adhesion Molecules by Circulating T lymphocytes in Psoriasis

  • 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????? Adhesion Molecules by Circulating T lymphocytes in Psoriasis


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