Introduction effect on microbial commensals which badly affect

Introduction

Is it necessary to live in too clean environment
? using of various types of sensitizer, cleaning soaps? or just like that
live  naturally without any fear of  that expectant opportunistic creatures that
may invade our bodies with all their deleterious weapons!  Over use of such means may be simply two
edges sword. This is the premise of the puzzle (hygiene hypothesis),our
environment is too clean and our immune systems are no longer as heavily taxed
with fighting off germs and bacteria. Increased rates of  allergies and other conditions like asthma
partly attributed to deviation in immune response because of poor immune
response towards the infectious agents might be caught by normal contact with
them.

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So, simply living and interacting with
natural micro living components of the environment leads to more activating of
neutralizing potency  represented by the
presence of our fascinating body armor (immune system) with all its types
natural active and passive means.   

The decreased fighting ability of our immune
system is also due to the emergence and overuse  of antibiotics and vaccines. The immune system
is no longer as challenged and becomes dependent on these products to assist in
fighting off even the most common bacterial infections. Antibiotics ,
particularly those with broad spectrum do not target invading microorganism
only but also have deleterious effect on microbial commensals which badly
affect future response to later on infections.

One of such immune overreactions is Eczema; a
common skin disorder, Researchers recently reviewed 20 studies of first year of
age and prenatals antibiotic use in connection with later skin problems. The
results of these studies showed that risk for the disease was increased by up
to 40% in children who had been exposed to antibiotics in their first year of
life.

The Early  Beginning

this hypothesis was originally postulated by a lecturer in
epidemiology. Where he used very big sample of population represented by British
children born during the same week in 1958 and followed them up to age 23 years
their number was 17414 , he came out with three results he further investigated
first: self reported “hay fever d            during
the past 12 months” at age 23; second: parental report of “hay fever
or allergic rhinitis in the past 12 months” at age 11; third: parental
recall of “eczema in the first year of life” occurred when the child
was at 7 years old(Strachan,1989) .

the conclusion of that study was that the
children in larger families had more exposure to pathogens than smaller
families this will make them less possibility to get hay fever , asthma or
other atopic diseases(Umetsu, 2012; Okada et
al., 2012; Benn et al., 2004;
Tulic et al., 2004)

the association between the decreased
exposure to microbial  agents during
early infancy and increased allergic diseases later in life  has been expanded to include also increased
autoimmune diseases such as  inflammatory
diseases and type 1 diabetes mellitus.(Azad
et al.,2013)

examples of tangible clues supporting the hygiene hypothesis

1-in Kilimanjaro increased delayed hypersensitivity
to Candida is related with early life infection (Wander et al.,2012)

 2-Variation
of microflora of gut support healthy immune system lowering predisposing to
autoimmune diseases including T1D, the HEV infection could suppress the
genetically driven autoimmune disease by activating immune system(Azad et al., 2013)

3-Using Eschericha coli in
infecting mice led to decrease of  some
parameters mediating the allergic response represented by allergic airway
disease ( AAD)   (Pang et al., 2013)

4- an inverse link between getting infected
with Helicobacter pylori  and
allergic asthma (Matsushima and Nagai, 2012)

5-Hepatitis- A Virus was inversely linked
with incidence of hay fever.(Umetsu,2012)

6-Other relationship is based on the mild
intracellular living pathogens like Mycobacteria  mainly from soil and Salmonella , in
other words those were ingested with food would protect from atopic diseases
through the development of  immune
response further(Matricardi,2010)

7-The
hygiene hypothesis is thought to be a significant supporter to the growing
incidence of inflammatory bowel disease (IBD) around the world(Koloski et al., 2008)

 

Immunological Mechanisms underlying the
hygiene hypothesis

 

All immature T-cells contain CD3 designated
as CD3+ and after differentiation are subdivided into two subsets, first
effector T-cells which are characterized by the presence of CD8 having
cytotoxic functions and so the name cytotoxic T-cells. These cells are capable
of killing tumor cells, allografts, and viral infected cells. Second subset are
the regulator T-cells also named helper T-cells characterized by their
possession of CD4 , which further subdivided into two types called the T
helper-1 (T h-1), and T helper -2 (T h-2) cells. The first produce interleukin
-2 (IL-2)which stimulate cytotoxic activity in the CD8+ cytotoxic T-
cells , while production of  IL-2 and
interferon -?(IFN- ?) will stimulate delayed type hypersensitivity response by
macrophage.(Th-2) cells produce IL-4, IL-5 that stimulate B- cells to be plasma
cells antibody producing cells

The atopic diseases that hypothesized to be
correlated with lowered exposure to microbes in early immune system development
is caused by antibody mediated immunity whereas the immune response against
pathogens  especially those in gastrointestinal
tract is cellular mediated  immunity.
(Levinson, )

The most famous elaboration was that the
poor early exposure to infectious agents would lead to an immunological  deviation towards Th-2 mediated immune
response away from the Th1- immune response. (Martinez and Holt,1999)

 

Other explanations focusing on that the
invariant natural killer T-cells can directly respond to some of bacterial glycolipids  like that derived from H. pylori which
leads to expand cell subset of suppressor iNKT-cells preventing the development
of experimentally designed asthma in mice (Chang et al.,2011)

other correlates the immune regulation by T-regulator
cells by cytokines produced by other cells (Pang et al., 2013)

in short the hypothesis needs for more
researches that focusing on various aspects of the immunological disorders
associated with the modern life style in order to modulate it in the way
providing more protection against such disorders in the future.

References

 

·        
 

Azad,M.B., Konya, T., Maughan, H., Guttman, D., Field, C., Sears,
M., Becker, A.,  Scott2, J.,  Kozyrskyj, A., and CHILD Study
Investigators.( 2013).
Infant gut microbiota and the hygiene hypothesis of allergic disease: impact
of household pets and siblings on microbiota composition and diversity.
Allergy, Asthma & Clinical Immunology . 9:15

·        
 

Benn ,C.S., Melbye,
M., Wohlfahrt J, et al. Cohort study of sibling effect, infectious
diseases, and risk of atopic dermatitis during first 18 months of life. BMJ
2004;328:1223–7

·        
 

Chang YJ, Kim HY, Albacker LA, etal.(2011).  Influenza infection in suckling mice
expands an NKT cell subset that protects against airway hyperreactivity. JClin
Invest . 121:57-69.

·        
 

 Koloski, N., Bret, L., and
Radford-Smith G.(2008). Hygiene
hypothesis in inflammatory bowel disease: A critical review of the
literature. World J Gastroenterol . 14(2): 165-173

·        
 

Levinson,W.(2004). Review of Medical Microbiology
and Immunology. 9th ed.Lange Medical Books.

·        
 

Martinez, F.D., and Holt, P.G. (1999) .Role of microbial burden
in aetiology of allergy and asthma. Lancet 354: SII12–SII15

·        
 

Matsushima, K., and  Nagai,
S.(2012). Unraveling
the mystery of the hygiene hypothesis
through Helicobacter pylori infection. Clin Invest. 122(3):801–804.

·        
 

Okada, H., Kuhn, C., Feilletand H. Bach J.-F. (2010). The
‘hygiene hypothesis’ for autoimmune and allergic diseases: an update.
British Society for Immunology, Clinical and Experimental Immunology,
160: 1–9 1

·        
 

Pang, W., Wang, H., Shi, L., Sun,Y., Wang, X., Wang, M., Li, J.,
Wang, H., and Shi, G.(2013). Immunomodulatory Effects of Escherichia coli
ATCC 25922 on Allergic Airway Inflammation in a Mouse Model. PLOS ONE .8 (3):
e59174

·        
 

Strachan, D.,P.(1989).
Hay fever, hygiene, and household size. Br. Med. J. 299:1259-60
 

·        
 

Tulic, M.K., Fiset, P-O., Manoukian, J.J., et al.(2004).
Role of toll-like receptor 4 in protection bacterial lipopolysaccharide in
the nasal mucosa of atopic children but not adults. Lancet.363:1689–97

·        
 

Umetsu, D.(2012). Early exposure to germs and the Hygiene Hypothesis.
Cell Research (2012) 22:1210-1211.

·        
 

 Wander, K., O’Connor, K.,
Shell-Duncan,
B.(2012). Expanding the Hygiene Hypothesis:
Early Exposure to Infectious Agents Predicts Delayed-Type Hypersensitivity to
Candida among Children in Kilimanjaro. PLoS ONE. 7( 5) :37406

Introduction

Is it necessary to live in too clean environment
? using of various types of sensitizer, cleaning soaps? or just like that
live  naturally without any fear of  that expectant opportunistic creatures that
may invade our bodies with all their deleterious weapons!  Over use of such means may be simply two
edges sword. This is the premise of the puzzle (hygiene hypothesis),our
environment is too clean and our immune systems are no longer as heavily taxed
with fighting off germs and bacteria. Increased rates of  allergies and other conditions like asthma
partly attributed to deviation in immune response because of poor immune
response towards the infectious agents might be caught by normal contact with
them.

So, simply living and interacting with
natural micro living components of the environment leads to more activating of
neutralizing potency  represented by the
presence of our fascinating body armor (immune system) with all its types
natural active and passive means.   

The decreased fighting ability of our immune
system is also due to the emergence and overuse  of antibiotics and vaccines. The immune system
is no longer as challenged and becomes dependent on these products to assist in
fighting off even the most common bacterial infections. Antibiotics ,
particularly those with broad spectrum do not target invading microorganism
only but also have deleterious effect on microbial commensals which badly
affect future response to later on infections.

One of such immune overreactions is Eczema; a
common skin disorder, Researchers recently reviewed 20 studies of first year of
age and prenatals antibiotic use in connection with later skin problems. The
results of these studies showed that risk for the disease was increased by up
to 40% in children who had been exposed to antibiotics in their first year of
life.

The Early  Beginning

this hypothesis was originally postulated by a lecturer in
epidemiology. Where he used very big sample of population represented by British
children born during the same week in 1958 and followed them up to age 23 years
their number was 17414 , he came out with three results he further investigated
first: self reported “hay fever d            during
the past 12 months” at age 23; second: parental report of “hay fever
or allergic rhinitis in the past 12 months” at age 11; third: parental
recall of “eczema in the first year of life” occurred when the child
was at 7 years old(Strachan,1989) .

the conclusion of that study was that the
children in larger families had more exposure to pathogens than smaller
families this will make them less possibility to get hay fever , asthma or
other atopic diseases(Umetsu, 2012; Okada et
al., 2012; Benn et al., 2004;
Tulic et al., 2004)

the association between the decreased
exposure to microbial  agents during
early infancy and increased allergic diseases later in life  has been expanded to include also increased
autoimmune diseases such as  inflammatory
diseases and type 1 diabetes mellitus.(Azad
et al.,2013)

examples of tangible clues supporting the hygiene hypothesis

1-in Kilimanjaro increased delayed hypersensitivity
to Candida is related with early life infection (Wander et al.,2012)

 2-Variation
of microflora of gut support healthy immune system lowering predisposing to
autoimmune diseases including T1D, the HEV infection could suppress the
genetically driven autoimmune disease by activating immune system(Azad et al., 2013)

3-Using Eschericha coli in
infecting mice led to decrease of  some
parameters mediating the allergic response represented by allergic airway
disease ( AAD)   (Pang et al., 2013)

4- an inverse link between getting infected
with Helicobacter pylori  and
allergic asthma (Matsushima and Nagai, 2012)

5-Hepatitis- A Virus was inversely linked
with incidence of hay fever.(Umetsu,2012)

6-Other relationship is based on the mild
intracellular living pathogens like Mycobacteria  mainly from soil and Salmonella , in
other words those were ingested with food would protect from atopic diseases
through the development of  immune
response further(Matricardi,2010)

7-The
hygiene hypothesis is thought to be a significant supporter to the growing
incidence of inflammatory bowel disease (IBD) around the world(Koloski et al., 2008)

 

Immunological Mechanisms underlying the
hygiene hypothesis

 

All immature T-cells contain CD3 designated
as CD3+ and after differentiation are subdivided into two subsets, first
effector T-cells which are characterized by the presence of CD8 having
cytotoxic functions and so the name cytotoxic T-cells. These cells are capable
of killing tumor cells, allografts, and viral infected cells. Second subset are
the regulator T-cells also named helper T-cells characterized by their
possession of CD4 , which further subdivided into two types called the T
helper-1 (T h-1), and T helper -2 (T h-2) cells. The first produce interleukin
-2 (IL-2)which stimulate cytotoxic activity in the CD8+ cytotoxic T-
cells , while production of  IL-2 and
interferon -?(IFN- ?) will stimulate delayed type hypersensitivity response by
macrophage.(Th-2) cells produce IL-4, IL-5 that stimulate B- cells to be plasma
cells antibody producing cells

The atopic diseases that hypothesized to be
correlated with lowered exposure to microbes in early immune system development
is caused by antibody mediated immunity whereas the immune response against
pathogens  especially those in gastrointestinal
tract is cellular mediated  immunity.
(Levinson, )

The most famous elaboration was that the
poor early exposure to infectious agents would lead to an immunological  deviation towards Th-2 mediated immune
response away from the Th1- immune response. (Martinez and Holt,1999)

 

Other explanations focusing on that the
invariant natural killer T-cells can directly respond to some of bacterial glycolipids  like that derived from H. pylori which
leads to expand cell subset of suppressor iNKT-cells preventing the development
of experimentally designed asthma in mice (Chang et al.,2011)

other correlates the immune regulation by T-regulator
cells by cytokines produced by other cells (Pang et al., 2013)

in short the hypothesis needs for more
researches that focusing on various aspects of the immunological disorders
associated with the modern life style in order to modulate it in the way
providing more protection against such disorders in the future.

References

 

·        
 

Azad,M.B., Konya, T., Maughan, H., Guttman, D., Field, C., Sears,
M., Becker, A.,  Scott2, J.,  Kozyrskyj, A., and CHILD Study
Investigators.( 2013).
Infant gut microbiota and the hygiene hypothesis of allergic disease: impact
of household pets and siblings on microbiota composition and diversity.
Allergy, Asthma & Clinical Immunology . 9:15

·        
 

Benn ,C.S., Melbye,
M., Wohlfahrt J, et al. Cohort study of sibling effect, infectious
diseases, and risk of atopic dermatitis during first 18 months of life. BMJ
2004;328:1223–7

·        
 

Chang YJ, Kim HY, Albacker LA, etal.(2011).  Influenza infection in suckling mice
expands an NKT cell subset that protects against airway hyperreactivity. JClin
Invest . 121:57-69.

·        
 

 Koloski, N., Bret, L., and
Radford-Smith G.(2008). Hygiene
hypothesis in inflammatory bowel disease: A critical review of the
literature. World J Gastroenterol . 14(2): 165-173

·        
 

Levinson,W.(2004). Review of Medical Microbiology
and Immunology. 9th ed.Lange Medical Books.

·        
 

Martinez, F.D., and Holt, P.G. (1999) .Role of microbial burden
in aetiology of allergy and asthma. Lancet 354: SII12–SII15

·        
 

Matsushima, K., and  Nagai,
S.(2012). Unraveling
the mystery of the hygiene hypothesis
through Helicobacter pylori infection. Clin Invest. 122(3):801–804.

·        
 

Okada, H., Kuhn, C., Feilletand H. Bach J.-F. (2010). The
‘hygiene hypothesis’ for autoimmune and allergic diseases: an update.
British Society for Immunology, Clinical and Experimental Immunology,
160: 1–9 1

·        
 

Pang, W., Wang, H., Shi, L., Sun,Y., Wang, X., Wang, M., Li, J.,
Wang, H., and Shi, G.(2013). Immunomodulatory Effects of Escherichia coli
ATCC 25922 on Allergic Airway Inflammation in a Mouse Model. PLOS ONE .8 (3):
e59174

·        
 

Strachan, D.,P.(1989).
Hay fever, hygiene, and household size. Br. Med. J. 299:1259-60
 

·        
 

Tulic, M.K., Fiset, P-O., Manoukian, J.J., et al.(2004).
Role of toll-like receptor 4 in protection bacterial lipopolysaccharide in
the nasal mucosa of atopic children but not adults. Lancet.363:1689–97

·        
 

Umetsu, D.(2012). Early exposure to germs and the Hygiene Hypothesis.
Cell Research (2012) 22:1210-1211.

·        
 

 Wander, K., O’Connor, K.,
Shell-Duncan,
B.(2012). Expanding the Hygiene Hypothesis:
Early Exposure to Infectious Agents Predicts Delayed-Type Hypersensitivity to
Candida among Children in Kilimanjaro. PLoS ONE. 7( 5) :37406

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