REACTIVE OXYGEN SPECIES INDUCES IMMUNO-SUPPRESSION: THERAPEUTIC STRATEGIES TO IMPROVE IMMUNE STATUS IN AUTOIMMUNITY AND CHRONIC PATHOPHYSIOLOGICAL STRESS

BY

OYEBAMIJI, DEBORAH BUKOLA [email: bukolaoyebams@yahoo.com]

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OUTLINE
INTRODUCTION SOURCES AND CONSEQUENCES OF INCREASE REACTIVE OXYGEN SPECIES

IMMUNE SYSTEM
ROS AND IMMUNOSUPPRESSION ROS AND AUTOIMMUNITY ROS AND CHRONIC PATHOPHYSIOLOGICAL STRESS THERAPEUTIC STRATEGIES TO IMPROVE IMMUNE STATUS IN AUTOIMMUNITY AND CHRONIC PATHOPHYSIOLOGICAL STRESS CONCLUSION

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INTRODUCTION
Reactive oxygen species (ROS) Antioxidant Oxidative stress Immunity Immunosuppression Autoimmunity Chronic stress

(Al-Mamun et al., 2007)

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ILLUSTRATIONS

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(Holt 2003)

SOURCES AND CONSEQUENCES OF INCREASED ROS GENERATION

The mitochondrial respiratory chain Exogenous factors such as ultraviolet light, ionizing radiations and chemical reactions. Respiratory Burst Transition metals ions (Trifunovic and Larsson, 2008)
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 Consequences: lipid peroxidation

Oxidative damage to cellular components results in altered cellular function compromised tissue and organ function death

DNA damage
Oxidation of protein. (Devi et al., 2007)

(Rahman, 2007)

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THE IMMUNE SYSTEM

The immune system is made up of a vast and highly complex network of cells, tissues and organs that all work in unison all of the time to protect the body from harm. A key element of immunity is the recognition of self and of nonself. (MRI, 2009)
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CELLS OF THE IMMUNE SYSTEM

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Jim Johnson, 2006 8

ROS AND IMMUNOSUPPRESSION

Immunosuppression could result from; Ageing Diseases Stress Malnutrition UV radiation
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ROS AND IMMUNOSUPPRESSION

Immune cell have high polyunsaturated fatty acids (PUFA) content. Immune cells are at risks of lipid peroxidation by ROS. Lipid peroxidation decreases membrane fluidity.

Loss of membrane fluidity has been related directly to the decreased ability of lymphocytes to respond to challenges to the immune system 8/13/2012 (Bendich et al., 1990) 10

ROS AND AUTOIMMUNITY

Environmental factor (Stejskal et al., 1999). Genetic predisposition Infections via cross-reactivity between foreign and host antigens. (Dixit et al., 2001) Inefficient clearance of apoptotic cells (Casiano et al., 2006). Exaggerated B cell proliferation Quantitative or qualitative abnormalities of regulatory T cells and natural killer (NK) T cells. Malnutrition (Vit. D deficiency) (Ritterhouse ,2011).
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ROS AND AUTOIMMUNITY

ROS are physiologic activators of transcription factors(activator protein -1 and nuclear factor-kB) for pro-inflammatory cytokines ROS can modulate the expression of a variety of immune and inflammatory molecules leading to inflammatory processes, exacerbating inflammation and can lead to tissue damage (Sukkar et al., 2004) )
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ROS AND CHRONIC PATHOPHYSIOLOGICAL STRESS

Chronic stress could arise from Disease Anxiety Past experience Psychosocial Environmental factors Work pressure Interpersonal conflict Bereavement 8/13/2012

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Thomas Guilliams and Lena Edwards 2010

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 Chronic stress is associated with increased ROS production

ROS AND CHRONIC PATHOPHYSIOLOGICAL STRESS

The persistent production of large amounts of ROS may induce changes in signal transduction and gene expression determining a chronic stress condition .

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(Droge, 2002)
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Relationship between ROS and Immune system

ROS CELL DAMAGE AUTOIMMUNITY

CPS

IMMUNE SUPRESSION

Therefore any mechanism that will reduce ROS may serve as a thetaspeutic strategy to improve immune status autoimmunity and chronic pathophysiological stress 8/13/2012 16

THERAPEUTIC STRATEGIES
Antioxidant Protection System
Endogenous Antioxidants Thiols, e.g glutathione, lipoic acid, N-acetyl cysteine Enzymes: Copper/zinc and manganese- dependent superoxide dismutase (SOD) Iron-dependent catalase Selenium-dependent gluathione peroxidase Dietary Antioxidants Vitamin C Vitamin E Beta carotene and other carotenoids e.g. lycopene Polyphenols e.g flavonoids, flavones,
MARK PERCIVAL ,1996
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 Vitamin A supports healthy immune function (immunity booster)

Lycopene and -carotene possess antioxidant, anti-infection, anti-proliferative and anticancer activity in humans

(Dahan et al., 2008)

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 Vitamin C is a powerful antioxidant acting to alleviate, the deleterious effects caused by ROS.
It works synergistically with vitamin E to quench free radicals and also regenerates the reduced form of vitamin E

(Arulmozhi et al., 2010)

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 Vitamin E -tocopherols via its interaction with lipids, stabilize membranes, and scavenges ROS and lipid soluble byproducts of oxidative stress

Vitamin E has been shown to reduce several different markers of inflammation in the body, including inflammatory cytokines
Vitamin E helps stabilize membranes of lysosomes, or immune cells that contain destructive enzymes used to fight intruders. (Shao et al., 2008)
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 The antioxidant enzymes metabolize oxidative toxic intermediates and require micronutrient cofactors for optimum catalytic activity.
Glutathione peroxidase selenium Catalase iron

Superoxide dismutase (SOD) - copper, zinc, and manganese (Corpas et al., 2006)
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Antioxidant enzymes
ROS, the primary antioxidant enzymes and antioxidants. Abbreviations are indicated in the text. GPx, glutathione peroxidase; GR, glutathione reductase; GSH, glutathione; GSSG, glutathione disulphide; MPO, myeloperoxidase; NADPH oxidase, nicotinamide adenine dinucleotide phosphate oxidase; Prx, peroxiredoxin;
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SOD, superoxide dismutase; TR, thioredoxin reductase; Trx, thioredoxin; Trx-S-S-Trx, thioredoxin disulfide.

The British Journal of Radiology, 80 (2007), S23S31 22

 Lipoic acid and its reduced form, dihydrolipoic acid (DHLA), are capable of quenching free radicals in both lipid and aqueous domains and as such has been called a universal antioxidant. Lipoic acid may also exert its antioxidant effect by chelating with pro-oxidant metals. Lipoic acid has a sparing effect on other antioxidants as it protect against the symptoms of vitamin E or vitamin C deficiency. ( Packer et al., 1995)
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 Supplementation with N-acetylcysteine support the bodys antioxidant systems by increasing levels of glutathione, the bodys major antioxidant Polyphenols can be classified into phenolic acids, flavonoids, stilbenes and lignans possess antioxidant activity

(Atawodi et al., 2009)

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 Vitamin D intervenes in the process of autoimmunity by tilting the properties of T- and B-cells towards "tolerance" of self tissues.
Vitamin D exerts multiple actions at the cellular level to balance the population of effector cells and regulatory cells

(Bruce 2011)
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THERAPEUTIC HERBS
Ginkgo biloba contains flavonoids and terpenoids, which are antioxidants (Muir 2002). Pine bark extract reduce oxidative stress (Stefanescu 2001). Curcumin antioxidant, anti-cancer, and antiinflammatory clinical properties (Kurien 2010).

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NEEM

ECHINACEA

GINSENG GINKGO BILOBA

PINE BARK

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CAYENNE PEPPER

GARLIC BULB

ONION BULB

ROSE MARY CURCUMIN

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HORSERADISH

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Others include: Echinacea Cayenne pepper Garlic bulb Onion bulb Horse radish Rosemary Ginseng Neem

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 Hematopoietic stem cell transplantation (HSCT) (Sykes et al., 2005). Monoclonal antibodies (Thanou-Stavraki 2011). Immune System Modulators called immunosupressives (Goekoop et al, 2005; Walsh 2007; Shun 2011; Hahn 2011). Anti-Inflammatory Drugs Corticosteroids (Ben-Zvi 2011; Chang 2011; Yildirim-Toruner 2011)

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Therapeutic Options For Stress

Regular sleep, relaxation and non-competitive exercise

Learning to perceive and respond to stressful situations in ways that do not stimulate the HPA axis Mediterranean like balanced diet. (Sofi et al 2008) Supplement with soluble and fermentable fibers Increase phytonutrients (Kurien 2010).
Supplementing with Dehydroepiandrosterone DHEA (Coates 2010). 8/13/2012 31

CONCLUSION
In conclusion, maintaining adequate antioxidant status may provide a useful approach in attenuating ROS mediated cell injury and dysfunction observed in some inflammatory/ autoimmune disorders and chronic Pathophysiological stress

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