IMMUN SCIENTIFIC LECTURE

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Nutrition and the Immune System


Functions

Defence against infections

Involved in tisssue regeneration

Destruction of tumor cells

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Functions of the immune system


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Nonspecific defence Neutrophil granulocytes • phagocyting cells • are eliminated during immune defence (Æ pus)

Macrophages (called monocytes in the blood) • phagocytosis and lysosomal digestion

Natural killer cells • specific large lymphocytes • produce perforins • defence against viruses, bacteria and tumor cells

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• involved in specific defence (antigen presentation)


Specific defence T Lymphocytes: Helper T Cells ("Cellular managers of the immune system") • recognize foreign substances at the MHC receptor of antigen-presenting cells • produce interleukins

Natural Killer T Cells • cytotoxic cells • destroy body's own cells and dedifferentiated tumor cells

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• give the starting signal for natural killer T cells and the production of the majority of antibodies


Specific defence B Lymphocytes: • precursors of antibody-producing plasma cells • antigen specifity Æ production of specific antibodies

Antibodies • IgA, IgD, IgE, IgG, IgM • released into plasma and surrounding body fluid • labelling of target cells for nonspecific defence (so-called opsonization)

T and B memory cells • responsible for acquired immunity

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• activation of the complement system


Complement system and cytokines Complement System • consists of more than 20 different plasma proteins • effects Æ lysis of bacteria Æ triggering of local inflammatory response

Cytokines: "transmitters and regulators" • interferons • interleukins

• colony-stimulating factors • chemokines • transforming growth factors

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• tumor necrosis factors


Defence against infection • epithelial integrity (mucous membranes, skin)

• activity of immune cells

• antioxidant protection

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• production of immune cells


Micronutrients and infections Contribution to immune response • such as phagocytosis, activity of lymphocytes • vitamins C, E, beta-carotene, zinc, selenium

Involvement in energy metabolism

Epithelial integrity • vitamin A

Antioxidant protection • vitamins C, E, carotenoids, bioflavonoids, selenium, zinc

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• B vitamins


Major ROS and their origins Mitochondrial respiratory chain Xenobiotic intoxication

Pharmaceuticals UV irradiation

Catecholamine oxidation Endogenous sources

Smoking

Exogenous sources

Purine metabolism Eicosanoid metabolism

Ozone

Smog

Radical pool in the body

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Granulocytes


Freie Radikale Key role of free radicals

Preferably attack lipids in cell walls

Change of body structures

Dysfunction

Impairment of function; degradation

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Why are free radicals dangerous?


Antioxidants: collaboration at molecular level Non-enzymatic Micronutrients: • vitamin C • vitamin E • caroteoids • polyphenol • coenzym Q10 Enzymatic

ROO˙ Free radical

Vitamin E Alpha-tocopherol Alpha-tocotrienol

ROOH Reduced radical

Dehydroascorbate

Ascorbate

Trace elements involved: • selenium • copper • manganese • zinc

Biesalski HK, Grimm P, Nowitzki-Grimm S. Taschenatlas der Ernährung. 1. Aufl. Stuttgart: Thieme; 2002; S. 199.

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Vitamin- E-Radical


Features and characteristics Example: Vitamin C • high concentrations in granulocytes (in part 50-fold increased concentration compared with plasma level) • high ascorbic acid concentrations stimulate granulocytes to migrate to the inflammation site (chemotaxis) • supplementation of ascorbic acid lead to enhanced phagocytosis and

• supplementation of 1-10 g ascorbic acid per day increases the proliferation of activated T cells in humans

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intracellular killing of microorganisms


Answer 2 Place

Question

Place

1. What is a duty of the immune system?

help to think more positiv

help regenerate tissue

2. What is the positive function of free radicals?

destroying fungus and bacteria

making the blood fluid

from birth

from the first birthday

4. Why is it necessary to strengthen the epithelia?

to be protected against injury

bacteria can´t settle down on the epithelia

5. Which Vitamin protects the epithelia?

Coenzym Q10

Vitamin A

6. Which Vitamin group is involved in energy production?

the Vitamin B complex

all antioxidants

7. Which micronutrient degenerates Vitamin E?

Vitamin C, Coenzym Q10

Vitam A, magnesium

8. Where is Vitamin C higher concentrated?

granulocytes

plasma

9. Wich source of free radicals can we influence?

endogenous

exogenous

3. Since when is our nonspecific defence active?

Obst

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Answer 1


Vitamins + trace elements: role for common colds in the elderly Objective:

To assess the effect of micronutrients on immune status and incidence of infections in the elderly

Design:

placebo-controlled, double-blind; 96 independently living, healthy individuals (>65 years) were randomly assigned to receive a vitamin plus trace-element supplementation or placebo for 12 months; immunological variables were assessed at baseline and at 12 months; frequency and course of infections were recorded.

Results:

higher number of T cells and natural killer cells, increase of IL-2 production, enhanced activity of natural killer cells

Number of days with use of antimicrobials

Distribution pattern of infectionrelated colds in elderly patients No. patients

with micronutrients (n=41)

Days per year

with micronutrients (n=41)

Annual infection-related days with symptoms

Chandra RK. Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet 1992;340(8828):1124-7.

wĂ­thout micronutrients (n=49)

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wĂ­thout micronutrients (n=49)


Effect of micronutrient supplement on infection and quality of life 100% 90% 80%

93 %

89 %

70% 60% 50% Placebo (n=67)

40% 30%

Active group (n=63)

17 %

10%

0%

0% Frequency of infection (p<0,001)

Days of sick leave (p=0,002)

Barringer TA, Kirk JK, Santaniello AC, et al. Effect of multivitamin and mineral supplement on infection and quality of life. Ann Intern Med 2003;138(5):365-71.

Duration: 12 months

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20%


Respiratory tract infection and micronutrients Intervention: Age >65 years Participants (%)

Duration: 183 days

None Days with symptoms Control group n=18

Control group: isoenergetic control product

Active group n=16

Langkamp-Henken B, Bender BS, Gardner EM, et al. Nutritional formula enhanced immune function and reduced days of symptoms of upper respiratory tract infection in seniors. J Am Geriatr Soc 2004;52(1):3-12.

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Active group: supplementation of antioxidants, selenium, zinc + selected energy carriers


Respiratory tract infection and micronutrients Conclusion:

Æ After influenza vacciation, investigators observed an enhanced immune response: y41% control vs. 87% active: ≥4-fold increase of antibody titer to Influenza type A / Beijing yincreased lymphocyte proliferation (active vs. controls)

Langkamp-Henken B, Bender BS, Gardner EM, et al. Nutritional formula enhanced immune function and reduced days of symptoms of upper respiratory tract infection in seniors. J Am Geriatr Soc 2004;52(1):3-12.

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Æ The micronutrient combination reduced the symptoms of upper respiratory tract infection significantly: 50% less days of symptoms (active vs. controls; p=0.08)


Taking vitamins before surgical intervention? - Better prognosis with antioxidants

... he [Prof. Biesalski] recommended, especially for elderly patients who had to undergo surgery, to start a combination treatment with vitamin E plus vitamin C four weeks prior to the surgical intervention. [...] At least a vitamin C dose of 2.5 times as much as vitamin E should be use, for example 200 mg vitamin E plus 500 mg vitamin C.

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Medical Tribune 2004;39(May 25):5.


Intervention trial: micronutrient supplementation in winter I

Hofmeister M J. Auswirkungen von alimentären Ergänzungsmitteln auf die Gesundheit. Ernähr Med 2005;20(3):115-22.

Control without supplementation (n=27) © Copyright Orthomol 2008

C-reactive protein

NK cells

T cells

Intervention: Orthomol® Immun powder every day 4 months: Dec. to March (n=27) Monocytes

Percent increase or decrease in the intervention group

Laboratory parameters after 4-month supplementation


Intervention trial: micronutrient supplementation in winter II

Intervention: Orthomol® Immun powder every day 4 months: Dec. to March (n=27)

Æ Decrease in frequency of common colds by 48.6% in the group with micronutrient supplementation Hofmeister M J. Auswirkungen von alimentären Ergänzungsmitteln auf die Gesundheit. Ernähr Med 2005;20(3):115-22.

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Common colds -48.6%

Supplementation group

Common colds (%) in the supplementation group vs. previous years


Phytonutrients Characteristics: • occur only in small amounts, and in specific plants • are synthetized by plants as anti-agents against pest attack and diseases, as growth regulators and pigment • as scents or essences, determine food selection of men

• Today's focus is on multiple protective, health-promoting properties

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• in the past, especially the health-damaging or toxic effects of phytochemicals were considered (e.g., cyanide, solanine) Æ antinutritive agents


Bioactive agents and their potential effects Evidence for the following effects:

A Phytochemicals Carotenoids Phytosterols Saponins Glucosinolates Polyphenols Protease inhibitors Monoterpenes Phytoestrogens Sulfides Phytic acid Dietary fibers Agents in fermented foods A = anticarcinogenic B = antimicrobial C = antioxidative D = antithrombotic E = immunomodulating

X X X X X X X X X X X X

B

C

D

X X X X

E

F

G

X

I

J

X X X X

X X X

H

X

X

X

X

X

X X X

X

X

X

X X

X

X X X

X F = antiinflammatory G = influencing blood-pressure H = cholesterol-lowering I = influencing blood glucose J = digestion promoting

X X X

X X X

X

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Bioactive agents


Phytonutrients

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OrthomolÂŽ Immun contains: Citrus bioflavonoids Mixed carotenoids (beta-carotene, lutein und lycopene)


Further uses

• Asthma • COPD

• ...

http://healthguide.howstuffworks.com/non-small-cell-lung-cancer-in-depth.htm

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• Respiratory disorders due to ozone / fine particulate air pollution


... antioxidants should be administered prior to cancer therapy or between therapy courses (therapy-free intervals). Also higher doses (even exceeding the recommended allowances) can be used in order to achieve the frequently described "stimulation" of the immune system and to optimize the supply of normal tissues. Biesalski HK, Lambert C, Frank J. Antioxidative Mikronährstoffe als Zusatzstoffe in der Onkologie. Onkologe 2004;10(3):230-43.

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Antioxidant micronutrients as additives in oncology.


Role of micronutrients in wound healing Micronutrient

Effect on wound healing

Protein

• Revascularization

I

• Fibroblastic proliferation • Collagen synthesis Carbohydrate

• Energy metabolism

Fat

• Energy metabolism • Component of cell membranes

Vitamin C (ascorbic acid)

• Collagen synthesis

Vitamin A (retinol)

• Modulates collagenase activity

Vitamin D

• Bone growth • Healing of fractures

Vitamin E

• Interferes with collagen synthesis

Vitamin K

• Blood coagulation

Trujillo EB. Effects of nutritional status on wound healing. National Meeting of the Society for Peripheral, Vascular Nursing. Cambridge (MA), June 2, 1991.

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• Cell growth


Role of micronutrients in wound healing Micronutrient

Effect on wound healing

B vitamins:

• Co-factors for cell growth

II

(thiamin, riboflavon, niacin / nicotinamide) Folic acid

• Maturation of red and white blood cells

Pyridoxin

• Cellular immunity

Zinc

• Protein synthesis

Iron

• Hydroxylation of proline and lysine (collagen synthesis)

Copper

• Component of lysyl oxidase (collagen synthesis)

Trujillo EB. Effects of nutritional status on wound healing. National Meeting of the Society for Peripheral, Vascular Nursing. Cambridge (MA), June 2, 1991.

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• Component of metalloenzymes (regulating DNA and RNA synthesis)


answer answe question 1. What is the important for a good long- intake during at least go to sleep after the term effect? three month intake you have a tasty drink every day T-cells and natural killer cells don´t need fruits any more

you are half as often ill than the others c-reactive protein reduced nessity of antimicrobials young, dynamic people, with no infections

7. What function have phytonutrients in plants primary?

elderly patients with eating problems one dose of Vitamin E too 2.5 dose of Vitamin C anti agents against pest attack and UV beams

8. What are two other indications of Orthomol immun?

after cancer therapy, for healing wounds

good and coulerful looking part of a stress therapy, against depression

9. Can you use Orthomol immun by COPD?

No

Yes

5. Who could profit more? 6. How should be the proportion of Vitamin E to Vitamin C?

the same concentration

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2. What happens if you take trace elemant supplementation? 3. Which blood components rise under micronutriens supplementation? 4. What is a side effect of taking supplements?


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