1. Free radicals and antioxidants.
Cell and biochemical mediators
involved in allergy,
immunomodulation and inflammation.
BY
Mahender.K
M.Pharm 1st yr 1st sem.
Srikrupa institute of pharmaceutical sciences,
Velkatta,kondapak,medak.
Andhra pradesh.
Under the guidance of
Dr. T.Shivaraj gouda M.pharm.,PhD
H.O.D. (Pharmacology)

2. Free radicals and
antioxidants

3. Free radicals:
Free radicals are atoms or groups of atoms with an odd
(unpaired) number of electrons these are also known as
Reactive Oxygen Species (ROS) and these compounds are
formed when oxygen molecules combine with other
molecules.
Once formed these highly reactive radicals can start a chain
reaction, like dominoes. Their chief danger comes from the
damage they can do when they react with important
cellular components such as DNA, or the cell membrane.
Cells may function poorly or die if this occurs. To prevent
free radical damage the body has a defense system of
antioxidants.

4. Where do these free
radicals come from?

5. • An oxygen molecule with paired electrons is stable;
however oxygen with an unpaired electron is reactive.
The radicals are likely to take part in chemical
reactions, taking electrons from vital components and
leaving them damaged.
• Radicals also play an important role in combustion,
atmospheric chemistry, polymerization, biochemistry,
and many other chemical processes, including human
physiology

8. Antioxidants:
Antioxidants are molecules which can safely interact with
free radicals and terminate the chain reaction before vital
molecules are damaged.
Although there are several enzyme systems within the body
that scavenge free radicals, the principle micronutrient
(vitamin) antioxidants are vitamin E, beta-carotene, and
vitamin C.
Additionally, selenium, a trace metal that is required for
proper function of one of the body's antioxidant enzyme
systems, is sometimes included in this category.
The body cannot manufacture these micronutrients so they
must be supplied in the diet.

9.  Hopefully we have enough antioxidants to "fight off" the Free
Radicals!
 Unfortunately, free radicals are not just formed through
breathing and other normal bodily processes, but we have
many outside influences and factors that dramatically further
produce free radicals in our cells. (stress, toxins, chemicals,
etc.)
 Then there are many things that deplete our antioxidant
supply.(medication, cigarette smoke, Tylenol, etc.)
 So, not only do we have more stresses in our life that create
more free radicals than even just 30 years ago, but we have
also become dependant on drugs, surgeries and medication
that deplete our natural antioxidant supply.

10. Now, more than ever we need to eat antioxidant rich foods
and take antioxidant supplements.
Free radicals in our cells are like little fires. Once a free
radical is formed that “small fire” begins to grow just like a
real fire.
If this fire is not put out by antioxidants then these fires
cause serious damage to our cells, tissues, and then organs.
Free radicals will damage our cell membranes, enzymes,
blood lipoprotein, unsaturated fatty acids in our cell
membranes and even damage our chromosomes and DNA.
All of this damage will eventually lead to premature aging
and disease.

11. Functions of antioxidant:
The most important and well characterised natural
antioxidants in the animal body are vitamin E and C.
Four possible mechanisms have been suggested (John,
1989) by which antioxidants function to reduce the
rate of oxidation of fats and oils. These are:
Hydrogen donation by the antioxidant.
Electron donation by the antioxidant.
Addition of the lipid to the antioxidant.
Formation of a complex between the lipid and
antioxidant.

12. The Best Natural
Antioxidants:
 Beans - High in folate, fiber and antioxidants, beans can help
lower cholesterol and scavenge free radicals
 Blueberries - Blueberries have one of the highest levels of
antioxidants than any fruit or vegetable. They have a wide variety
of different beneficial phytonutrients as well.
 Broccoli - Broccoli helps promote eye health
 Spinach - Spinach Contains iron, and is packed with carotenoids
which help your eyes
 Sweet Potatoes - These boost your immune system
 Walnuts - These are one of the few plant sources that are high in
omega-3 fatty acids. They also have some of the best antioxidants
known for fighting cancers, as well as amino acids that can reduce
the risk of heart attack.
 Salmon - Salmon is another excellent source of omega three fatty
acids that reduce the risk of heart disease and heart attack.

13. • Vitamin E : d-alpha tocopherol. A fat soluble vitamin
present in nuts, seeds, vegetable and fish oils, whole grains
(esp. wheat germ), fortified cereals, and apricots. Current
recommended daily allowance RDA{Recommended Dietary
Allowance}is 15 IU{International Unit} per day for men and
12 IU per day for women.
• Vitamin C : Ascorbic acid is a water soluble vitamin present
in citrus fruits and juices, green peppers, cabbage, spinach,
broccoli, kale, cantaloupe, kiwi, and strawberries. The RDA
is 60 mg per day. Intake above 2000 mg may be associated
with adverse side effects in some individuals.
• Beta-carotene is a precursor to vitamin A (retinol) and is
present in liver, egg yolk, milk, butter, spinach, carrots,
squash, broccoli, yams, tomato, cantaloupe, peaches, and
grains. Because beta-carotene is converted to vitamin A by
the body there is no set requirement. Instead the RDA is
expressed as retinol equivalents (RE), to clarify the
relationship. (NOTE: Vitamin A has no antioxidant
properties and can be quite toxic when taken in excess.)

14. CONCLUSION:
• Antioxidant plays a very important role in the body
defense system against reactive oxygen species.
• Vegetable oils contain natural antioxidants.
• Lipid peroxidation is the introduction of a functional
group containing two catenated oxygyen atoms into
unsturated fatty acids in a free radical reaction.
• Antioxidant enzymes are an important protective
mechanism ROS.

15. ALLERGY

16. An allergy is a hypersensitivity disorder of the immune
system.
Allergic reactions occur when a person's immune system
reacts to normally harmless substances in the environment.
A substance that causes a reaction is called an “allergen”.
Allergic reactions are distinctive because of excessive
activation of certain white blood cells called mast cells and
basophils by a type of antibody called Immunoglobulin E
(IgE).
This reaction results in an inflammatory response which
can range from uncomfortable to dangerous.

17. Origin of the Word “Allergy”
The word allergy is a combination of two Greek words:
“Allos” - other and
“Ergos” - action
 Some Allergic Conditions & Symptoms
• Some serious allergic diseases are: asthma, dermatitis,
bee sting allergy, food allergy, conjunctivitis, and
severe systemic anaphylaxis
• Some common symptoms of allergy are: nose itching,
sneezing, burning sensation, production of watery or
mucous excretion, and possibly altered condition of
other organs

19. The Allergy
Pathway

20. Allergy degranulation
processes

21. Cells Involved In Allergic
Reactions
CD4+ T cells play the central role in allergic
inflammation.
Two types of CD4+ :
 T helper-1 (Th1) - Produces IL-2, TNF-, and interferon- (IFN-
). Antagonize the allergic response.
 T helper-2 (Th2): Produces IL-4, IL-5, IL-6, IL-9, IL-10, and IL-
13. IL-4 and IL-13 play the main role in allergic response.
 Histamine which causes the 5 symptoms of allergic
inflammation:heat, pain, swelling, redness and itchiness.
 IL-4, affects more B cells to differentiate into plasma cells and
produce more IgE and thus the vicious cycle continues.

22. Types of Allergy:
There are four types of allergic reactions:
Type-1 allergic reaction (immediate, anaphylactic): Develops
when the allergen stimulates the organism to produce IgE. It is also
known as IgE mediated, immediate or anaphylactic reaction
Type-2 allergic reaction (cytotoxic): Develops when the allergic
reaction is accompanied by the appearance of IgG or IgM class
immunoglobulins. These antibodies react with allergens on the
surface of the blood cells or bone marrow cells membranes and
causing them to undergo lysis
Type-3 allergic reaction: Develops when allergen reacts with IgG,
IgM, IgA or IgE forming immune complexes that are deposited in
tissues and initiate inflammations
Type-4 allergic reaction: It is also known as a delayed or cellular
reaction. T lymphocytes play main role in this type of allergic
reaction when they encounter specific allergen, by secreting
cytokines triggering inflammatory reaction in tissues.

23. Types of Allergen
There are 2 types of Allergens:
(a) Allergens from the natural environment:
• These are of high-molecular weight compounds, molecular
weight higher than 10 kDa. Most of these allergens have an
enzymatic function in their natural state.
• Few examples are: pollen of different plants, mould fungi
spores, bacteria, house dust mites, epidermis of house pets,
insect venom, some food proteins, etc.
(b) Allergens from a chemical environment:
• These are usually low-molecular chemical compounds, less
than 1 kDa. They usually bind with a large protein and exert
allergenic effect.
• Few examples are: metals, drugs, additives to food products,
latex, aldehydes.

24. Medication
Several antagonistic drugs are used to block the action of
allergic mediators, or to prevent activation of cells and
degranulation processes.
These include antihistamines, glucocorticoids, epinephrine
(adrenaline), theophylline and cromolyn sodium. Anti-
leukotrienes, such as Montelukast (Singulair) or Zafirlukast
(Accolate), are FDA approved for treatment of allergic
diseases.
Anti-cholinergics, decongestants, mast cell stabilizers, and
other compounds thought to impair eosinophil chemotaxis,
are also commonly used. These drugs help to alleviate the
symptoms of allergy, and are imperative in the recovery of
acute anaphylaxis, but play little role in chronic treatment
of allergic disorders.

25. Inflammation:

26.  Inflammation is part of the complex biological
response of vascular tissues to harmful stimuli, such as
pathogens, damaged cells, or irritants.
 Inflammation is a protective attempt by the organism to
remove the injurious stimuli and to initiate the healing
process.
 Inflammation is not a synonym for infection even in
cases where inflammation is caused by infection.
 Although infection is caused by a microorganism,
inflammation is one of the responses of the organism to
the pathogen.
 However, inflammation is a stereotyped response, and
therefore it is considered as a mechanism of innate
immunity as compared to adaptive immunity, which is
specific for each pathogen.

28. Cellular Components of inflammation:
Granulocytes:
• Polymorphonuclear cells( neutrophils)
• Basophils
• Eosinophils
Lymphocytes:
• B cells and humoral immunity,
• T cells and cell mediated immunity,
• Natural killer cells.
Monocytes and macrophages.
• Endothelium
• Fibroblasts
• Smooth muscle cells
• Mast cells

29. Chemical Mediators:
• Chemical substances synthesised or released which
mediate the changes in inflammation.
• Histamine by mast cells - vasodilatation.
• Prostaglandins – Cause pain & fever.
• Bradykinin - Causes pain.
• Products of the complement system
• Lymphokines released by sensitized T cells

31. Inflammatory disorders
 Inflammatory abnormalities are a large group of
disorders which underlie a vast variety of human
diseases.
 The immune system is often involved with
inflammatory disorders, demonstrated in both allergic
reactions and some myopathies, with many immune
system disorders resulting in abnormal inflammation.
 Non-immune diseases with etiological origins in
inflammatory processes include cancer,
atherosclerosis, and ischaemic heart disease.

33. Examples of disorders associated with inflammation
include:
• Acne vulgaris
• Asthma
• Autoimmune diseases
• Hypersensitivities
• Inflammatory bowel diseases
• Pelvic inflammatory disease
• Reperfusion injury
• Rheumatoid arthritis

34. Treatment : Anti-inflammatory
• Steroids
• Non-steroidal anti-inflammatory drugs
• Immune Selective Anti-Inflammatory Derivatives
(ImSAIDs)
• Herbs
• Ice treatment
• Food

35. Immunomodula
tion

36. immunomodulator?
• An immunomodulator is any substance that helps to
regulate the immune system.
• This "regulation" is a normalisation process, so that an
immunomodulator helps to optimise immune response.
• Give an immunomodulator to someone with a low
immune system, and it can help raise that immunity;
• Give a modulator to someone with a healthy immune
system, and it will have little effect in the body; and
• Give a modulator to someone with an overactive immune
system, and can help to normalize that overactive immune
system.
• So immunomodulators do not tend to boost immunity, but
to normalize it.

37. How do they work in
the body?
How immunomodulators work in the body is still largely a
mystery. Part of their benefit appears to be their ability to
naturally increase the body's production of messenger
molecules, such as cytokines, which mediate and regulate
the immune system.
Some of them, like Biobran, can also decrease the
production of inflammatory cytokines. Overall, the effect is
a more efficient immune system.
Most people using substances like Biobran MGN-3 do so
because they have low immune systems.
 Increasing cytokine production in this case can
significantly help raise the immune response. This site
focuses, therefore, on the effect of immunomodulators in
helping to increase immune function.

38. A Standard Immunomodulatory
Response:
• After a period of time on a
particular dose, this typical
modulator modulates the
immune system to a
characteristic level that is
independent of dosage .
• The difference between dosages
is that higher doses tend to
modulate quicker, and although
the difference might only be
small, as in this case, it is very
significant to those who are
seriously unwell and need
immune system help as fast as
possible.

39. Types :
There are two types of effects
1. Immunostimulation:
• Increase the immune response, useful in infections,
immunodeficiency (for example, AIDS) and cancers.
2. Immunosuppression:
• Inhibits immune response in organ transplantation
and autoimmune diseases.

40. Immunostimulant drugs
 Levamisole:
 An antihelmintic drug that also restores functions of B lymphocytes, T lymphocytes,
monocytes and macrophages, Causes agranulocytosis. Hence it has been used in colon
cancer along with 5-FU.
 Thalidomide. Different effects of this old drug have been utilized in
conditions such as:
• Erythema nodosum leprosum: Anti-inflammatory effect
• Multiple myleoma: Anti-angiogenesis
• Rheumatoid arthritis: Anti TNF effect.
 BCG(Bacillus Calmitte Guerin): Used in carcinoma bladder.
 Recombinant cytokines.
• Interferons: In tumors and chronic hepatitis B and C
• Interleukin 2 (aldeslukin): has been used in renal cell carcinoma and
melanoma

41. Immunosuppressant
drugs:
These drugs have major role in organ transplantation
and auto immune diseases. The drugs are:
 Calcineurin inhibitors (Specific T-cell inhibitors).
Cyclosporine (Ciclosporin), Tacrolimus
 Antiproliferative drugs (Cytotoxic drugs).
Azathioprine, Cyclophosphamide, Methotrexate,
Chlorambucil, Mycophenolate mofetil (MMF)
Glucocorticoids. Prednisolone and others
 Antibodies. Muromonab CD3, Antithymocyte globin
(ATG), Rho (D) immuneglobin, Efalizumab

42. Conclusion:
• Immunomodulators are going to be a central part of
medicine. Helping the body help itself by optimising
the immune system is of central importance in a
society so stressed, unhealthily nourished and exposed
to toxins that most of us are likely to have
compromised immune systems.
• Immunomodulation, however, is a normalizing
process, and it is important to bear this in mind when
choosing doses over time and comparing different
products.

43.  Most immunomodulatory drugs are suppressants
◦ Cause problems as it makes patients more susceptible to
infection
◦ Most are somewhat toxic.
 Tolerance is a great concept but not yet fully realized.
 Stimulants are helpful to boost the immune system.
 Immunization has been a proven tool against fighting
infectious diseases.

44. NEVER GIVE UP FACE ANY
STRUGLE IN UR LIFE TO
REACH UR DESTINATION