Journal of Medicinal Plants Research Vol. 6(7), pp.

1100-1105, 23 February, 2012

Available online at http://www.academicjournals.org/JMPR
DOI: 10.5897/JMPR11.1401
ISSN 1996-0875 ©2012 Academic Journals

Review

Autoimmune diseases and immunomodulant plant

M. M. Akram1, M. Saim Jamil1, Zahid Mehmood2, Khan Usmanghani1, Iqbal Azhar4,
Muhammad Akram5, H. M. Asif3 and Umar Iqbal1
1
Shifa ul Mulk Memorial Hospital, Hamdard University, Karachi, Pakistan.
2
Department of Chemistry and Biochemistry, University of Agriculture, Faisalabad, Pakistan.
3
Department of Pharmacy, The Islamia University of Bahawalpur, Pakistan.
4
Department of Pharmacognosy, University of Karachi, Pakistan.
5
Department of Pharmacy, University of Sargodha, Pakistan.
Accepted 4 November, 2011

The immune system in general responds appropriately to the presence of foreign antigens. Body
immune system protects the body against invading organisms. In an autoimmune disease, immune
system attacks healthy cells in body by mistake. Autoimmune diseases can affect many parts of the
body. Various plants are used to strengthen the immunity due to their immunomodulatory activities. In
this article, autoimmune diseases, description of autoimmune diseases, and plants used as
immunomodulant agent has given.

Key words: Autoimmune diseases, immunomodulatory activity, medicinal plants, research study.

INTRODUCTION

Autoimmune disorders are disorders in immune
regulation resulting in antibody or cell mediated immunity
against the host’s own tissues (Table 1). Autoimmune
disorders may or may not result in injury to the host.
Autoimmune disorders are disorders in which persons
are normally unresponsive to self antigens due to
tolerance; however, B-cell clones do exist in persons with
idiotypes reacting with self antigens. Autoimmune
diseases include systemic lupus erythematosis (Ruiz-
Irastorza, 2010; Hahn et al., 2008), primary central
nervous system (CNS) vasculitis, rasmussen's
encephalitis, autoimmune peri-pheral neuropathy,
autoimmune cerebellar degeneration, autoimmune
thrombocytopenia (Segal et al., 2006), gait ataxia with
late age onset polyneuropathy, stiff person syndrome,
chronic inflammatory demyelinating poly-neuropathy,
myasthenia gravis and multiple sclerosis. Hashimoto’s
thyroiditis is a chronic autoimmune disease characterized
by immune destruction of the thyroid gland and
hypothyroidism. Grave‘s disease is autoimmune disease
characterized by production of immunoglobulin G (IgG)
*Corresponding author. E-mail: makram_0451@yahoo.com.
Tel: 92 021 6440083. Fax: 92 021 6440079.
auto-antibodies to the thyroid stimulating hormone (TSH)
receptor. Addison‘s disease occurs due to destruction of
adrenal cortex leading to a deficiency of glucocorticoids,
mineralocorticoids and androgens. Rheumatoid arthritis
(RA) is a systemic chronic and inflammatory disease
characterized by progressive arthritis, production of
rheumatoid factor and extra-articular manifestation. It is
thought to be caused by an autoimmune reaction
triggered by an infectious agent in a genetically
susceptible individual (Meroni et al., 2010; Fritzler, 2011).
Myasthenia gravis is an autoimmune disease
characterized by autoantibodies against the
neuromuscular junction, resulting in muscular weakness.
Vitiligo is characterized by irregular, completely
depigmented patches. It may affect any race. Insulin
dependent diabetes mellitus is thought to be caused by
an autoimmune reaction triggered by an infection
(Coxsakie B virus) in a genetically susceptible individual.
It represents 10% of cases of diabetes. It affects children
and adolescents usually younger than 20. Asparagus
racemosus have also shown immunopotentiating effects
in cyclophasphamide treated mouse with ascetic
sarcoma (Diwanay et al., 2004). Kalita and Dutta (1999)
reported that maternal antibody was persistently found in
sera samples tested against ND virus during the first
week of age in broilers. This was attributed to transfer of
 Akram et al. 1101

Table 1. Autoimmune classification.

Disease Antibody against

Juvenile insulin-dependent diabetes Pancreatic islet cells
Pernicious anemia Gastric parietal cells
Addison's disease Adrenal cells
Idiopathic hypoparathyroidism Parathyroid cells
Autoimmune hemolytic anemia Erythrocytes
Idiopathic thrombocytopenic purpura Platelets
Idiopathic neutropenia Neutrophils
Vitiligo Melanocytes
Chronic active hepatitis Nuclei of hepatocytes
Goodpasture's syndrome Basement membranes
Rheumatoid arthritis Gamma globulin, virus-related antigens
Sjogren's syndrome Nuclei and centromeres
Systemic lupus erythematosus Nuclei, DNA, RNA, erythrocytes, etc.
Myasthenia gravis Acetylcholine receptors
Grave’s disease Thyroid-stimulating hormone receptor
Thyroiditis Thyroid
Insulin-resistant diabetes Insulin receptor
Asthma Beta-2 adrenergic receptors

natural passive immunity in young chicks as (multiple myeloma).

demonstrated by Hellar (1975).
Central nervous system
EXPLANATORY THEORIES FOR AUTOIMMUNE 1. Allergic encephalitis,
DISORDERS 2. Multiple sclerosis,
1. Microbial antigens cross reacting with host tissues 3. Myasthenia gravis.
induce an immune response against self,
2. Host antigen previously sequestered from fetal Endocrine
tolerance-inducing mechanism are released and become
immunogenic, 1. Chronic thyroiditis,
3. Alteration of host molecules, exposing new antigenic 2. Grave’s disease,
determinants unavailable at the time of induction of fetal 3. Diabetes mellitus.
tolerance,
4. Attachment of foreign hapten to self molecule, forming
Gastrointestinal tract
a hapten carrier complex,
5. Depletion of suppressor cells. 1. Pernicious anemia,
2. Ulcerative colitis,
SYSTEMIC AUTOIMMUNE DISORDERS 3. Crohn disease,
4. Chronic active hepatitis.
1. Systemic lupus erythematosis,
2. Rheumatoid arthritis,
DISEASES INVOLVING PRIMARILY ONE TYPE OF
3. Sjogren’s syndrome,
CELL OR ORGAN
4. Polyarteritis nodosa.
Myasthenia gravis
ORGAN SPECIFIC AUTOIMMUNE DISORDERS
This acquired condition is characterized by weakness
Blood and fatigability of proximal limb, ocular and bulbar
muscles. The heart is not involved. The cause is un-
1. Autoantibodies reacting with blood cells, known. IgG antibodies to acetylcholine and acetylcholine
2. Malignant transformation of a single plasma cell clone receptor proteins are found. Immune complexes (IgG and
1102 J. Med. Plants Res.
complement) are deposited at the postsynaptic mem-
branes causing interference with and latter destruction of
the acetylcholine receptor. The prevalence is about 4 in
100,000. It is twice as common in women as in men, with
a peak incidence around the age of 30 years.
Occurrence
It occurs in one of 20, 000 persons.
Causes
It is caused by antibodies directed against the ach-
receptors of the muscle fibers of sarcolemma. The
antibodies are bind to receptors and hinder the
attachment of ach to the receptors. As the disease
progresses, more neuromascular junctions become
affected.
Clinical features
This disease is more common in females between the
ages of 20 to 50 years. The muscles of the face and neck
are mostly involved. Initial symptoms include a weakness
of the eye muscles and difficulty in swallowing. Later, the
individual has difficulty in chewing and talking. Eventually,
muscles of the limbs may become involved. Death may
result from the paralysis of respiratorymuscles.
Treatment
Anticholinesterase drugs such as neostigmine and
pyriodostigmine derivates of physostigmine are advised
to be used.
Antibodies
These are substance made in response to antigenic
stimuli. They are found in plasma and are developed from
small lymphocytes.
Sites of antibodies production central lymphoid
system
These are lymphoid tissue of the thymus gastroinal tract
(peyer’s patches, tonsils, appendix).
Peripheral lymphoid organs
Lymph nodes and spleen have lymphocytes and plasma
cells.
Formation of antibodies by plasma cell
All Ig are made and secreted actively by plasma
cells (Dormant B- lymphocytes in lymphoid tissue). Each
plasma cell makes 2000 molecules of antibodies
(gamma-globlins).
Production of antibodies
Antigens stimulate proliferation of lymphoid cells,
resulting in the production of antibodies.
Nature of antibodies
These are gamma-globulins or 1 g found free in serum
and on the surface of lymphocytes. In plasma cells, they
are found inside the cells.
Major functions of antibodies: They neutralize the
toxins viruses, and also opsonize bacteria, making them
easier to phagocytize.
Concentration (normally): It is normally 1.6 gm/100 ml
of blood.
Molecular weight: It is between 150,000 to 900,000
(unit) structures of a typical 1g molecule four polypeptide
chains.
Two heavy chains: Molecular weight, 20,000 (unit);
Each chain has 450 amino acids.
Major groups: They are 1Gg, 1Gm and 1gA.
Minor groups: They are 1 gE, 1 gD and 1 gD.
Graves’s disease
Graves’ disease accounts for about 85% of all
hyperthyroidism. It occurs most frequently in young
women, although it can occur in either sex at any age.
Susceptibility is certainly multigenic but has been
associated with the human leukocyte antigen (HLA)-DR3
haplotype in the major histocompatibility complex (MHC)
locus. It is generally characterized by hyperthyroidism
and diffuse thyroid enlarement and the presence of
circulating antibodies directed against the TSH receptor
on the membrane of the thyroid gland. Three types of
antibodies may be found.
Diabetes mellitus
This form of diabetes is immune-mediated in over 90% of
cases and idiopathic in less than 10%. The rate of
pancreatic B cell destruction is quite variable, being rapid
in some individuals and slow in others. Type I diabetes is
usually associated with ketosis in its untreated state. It
occurs at any age but most commonly arises in children
and young adults with a peak incidence before school

age and again at around puberty. It is a catabolic disorder
in which circulating insulin is virtually absent, plasma
glucagon is elevated, and the pancreatic B cells fail to
respond to all insulinogenic stimuli. Exogenous insulin is
therefore required to reverse the catabolic state, prevent
ketosis, reduce the hyperglucagonemia, and reduce
blood glucose.
DISEASES INVOLVING MULTIPLE ORGANS
(SYSTEMIC DISEASES)
Systemic lupus erythematosus (SLE) rheumatoid
arthritis (RA) and other collagen vascular diseases
These disorders feature vasculitis and collagen
degeneration, plus a variety of focal inflammatory lesions
and the presence of autoantibodies against many
different self antigens. For example, antibodies to
deoxyribonucleic acid (DNA) are found in SLE and
antibodies to IgG (rheumatoid factor) occur in rheumatoid
arthritis.
In Goodpasture‘s syndrome, antibodies are formed
against the basement membranes of the pulmonary
alveoli and the renal glomeruli. In these diseases,
complement is activated by the antigen-antibody
complexes, and neutrophils are attracted to the site.
Neutrophils release various enzymes and oxygen
radicals that damage the tissues. Although, in most
patients, the immune stimulus that initiates these
disorders is unknown, typical cases have followed
sensitization by and foreign proteins.
Other diseases in this category include ankylosing
spondylitis, which is very common in people carrying the
HLA-B27 gene; polymyositis- dermatomyositis, sjogren’s
syndrome and Reiter’s syndrome.
Rheumatic fever (RF)
Rheumatic fever (RF) is a febrile disease, affecting
connective of the throat by group A beta haemolytic
strptococci. Although RF is not a communicable disease,
it results from a communicable disease (streptococcal
pharyngitis). RF often leads to rheumatic heart disease
(RHD) which is a crippling disease. The consequences of
RHD include continuing damage to the heart; increasing
disabilities, repeated hospitalization and premature death
usually at the age of 35 years even earlier. RHD is one of
the most readily preventable chronic diseases.
Reiter’s syndrome
This syndrome consists of the triad of a seronegative
reactive arthritis, non specific urethritis and conjunctivitis.
The male to female ratio is 20:1 and most cases occur in
young adults. HLA-B27 is present in about 60% of cases.
The diagnosis in these conditions is entirely clinical; there
Akram et al. 1103
are no diagnostic blood tests. The erythrocyte
sedimentation rate (ESR) is raised in the acute stage.
Tests for rheumatoid factor and other autoantibodies are
negative; 60% of patients are HLA-B27 positive. X-rays
are of no value in the acute stage of the disease, though
signs of sacroiliitis may appear with the development of
ankylosing spondylitis.
Aspirated synovial fluid is inflammatory in nature with a
high polymorphonuclear leucocyte count; the fluid is
sterile.
Treatment of autoimmune diseases
The conceptual basis for the treatment of autoimmune
diseases is to reduce the patient’s immune response
sufficiently to eliminate the symptoms. Corticosteroids,
such as prednione, are the mainstay of treatment, to
which antimetabolites (such as azathioprine and
methotrexate) can be added. The latter are nucleoside
analogues that inhibit DNA synthesis in the immune cells.
Immunosuppressive therapy must be given cautiously
because of the risk of opportunistic infections.
Anti-inflammatory agents
Nonsteroidal anti-inflammatory drugs have been used
since 1800s when salicin extracted from willow bark
(1828), sodium salicylate (1875) and aspirin (1899) were
synthesized. A large numbers of these drugs, which
either selectively or non-selectively inhibit the enzyme
cyclo-oxygenase (a synthetic enzyme for pros-taglandins)
are currently in use to treat inflammatory disease.
Anti-malarial
Anti-malarial drugs have been used for the treatment of
SLEq and RA since early 1900s. The precise mechanism
of action remains uncertain, but they have been shown to
inhibit cytokine (IL-1 and IL-6) production in vitro. The
anti-malarial pass freely through cell membranes at
neutral PH, but in acidic environments such as
endosomes, they become protonated and can no longer
diffuse freely.
Anticytokine agents
The development of tumour necrosis factor-α (TNF-α)
inhibitors in the 1990s ushered in a new era of therapy of
autoimmune disease using biological capable of
interfering with the interactions between cytokines and
their receptors.
Methotrexate
Methotrexate is a folic acid analog used extensively for
1104 J. Med. Plants Res.

Table 2. Research study.

Plant/title Activity
Ginseng In one study, it has been evaluated that ginseng polysaccharide decreases the expression of TNF-α and
interferon-gamma (IFN-γ), and regulate the function of lymphocytes in enteric mucosal immune system in
collagen-induced arthritis (CIA) rats. This study indicates that ginseng polysaccharide could be used in the
treatment of autoimmune disease (Hongyan et al., 2011)

O. basilicum It has been studied that aqueous extract of O. basilicum is a powerful natural immunomodulatory spice
influencing various types of immune-responses and have potential health effects (Tsai1 et al., 2011).

T. cordifolia It has been studied that T. cordifolia has immunomodulatory properties, and is used for the treatment of
jaundice, skin diseases, diabetes and anemia (Chopra et al., 1982).

In one study, it has been evaluated that T. cordifolia improves the phagocytic and bactericidal activities in
patients suffering from polymorphism in surgical jaundice (Thatte et al., 1989). In one study, effect of
feeding T. cordifolia has been observed in broiler birds which were immunosuppressed with
cyclophosphamide, and found a significant rise in antibody titer against ND virus with augmentation of
inflammatory reaction to skin contact sensitivity test (Kolte et al., 2007). Rege et al. (1989) and Bishavi et al.
(2002) have proved the hepatoprotective effect of T. cordifolia.

W. somnifera Akram et al. (2010) studied the immunomodulant effect of W. somnifera.

Ocimum sanctum Modulates humoral immune response (Kujur, 2001; Krishnamohan et al., 1997; Kumar, 2003).
A. racemosus Stimulates both humoral and cell mediated immune responses (Kuttan et al., 1992).

the treatment of RA. Autologous hematopoietic stem cell transplantation

(HSCT)

Anti-T-lymphocyte therapy
T-cells play a key role in the pathogenesis of type IV
autoimmune reactions and also, they are critical for
generating the T-cell dependent autoantibodies mediating
type lll autoimmune diseases.
Anti-B-lymphocyte therapy
Hematopoietic stem cells are the earliest progenitor cells
of the immune system and give rise to B and T-
lymphocytes as well as antigen-presenting cells
(monocytes, macrophages and dendritic cells). The
rationale for HSCT as a therapy for autoimmune disease
is based on the concept that the peripheral expansion of
auto-reactive T- and B-cell clones is central to the
pathogenesis of autoimmunity.

Rituximab is a cytotoxic chimeric human- mouse DISCUSSION

monoclonal antibody with a high affinity for CD20, a pan-
B-cell surface antigen. It was developed originally for the
treatment of B-cell lymphomas.
Intravenous immunoglobulin
Intravenous immunoglobulin (IVIG) is a preparation of
human immunoglobulin pooled from thousands of healthy
individuals. It was originally developed for replacement
therapy in humoral immunnodeficiency syndromes but
has more recently become an important therapeutic
modality in severe autoimmune disorders, such as
thrombocytppenic purpura, autoimmune haemolytic
anaemia (AIHA), neuroimmunological diseases such as
Guillain-Barre syndrome, SLE, certain forms of vasculitis,
and polymyositis dermatomyositis.
An autoimmune disease occurs when the immune
system fails to recognize the body‘s own tissues as self
and mounts an attack on them. Disorders include RA,
juvenile (insulin-dependent) diabetes, thyroiditis and
multiple sclerosis. Illnesses are divided into those that
affect much system. Autoimmune diseases are mostly of
unknown aetiology although genetic, hormonal,
microbiological and environmental factors are known to
be implicated in their manifestation and severity.
Many herbal plant preparations are prescribed to
strengthen host resistance (Thatte and Dahanukar, 1986)
due to their immunomodulatory activities (Table 2).
Body’s immune system protects from disease and
infection (Damian et al., 2008). In an autoimmune
disease, immune system attacks healthy cells in your
body by mistake. Autoimmune diseases can affect many

parts of the body. These diseases tend to run in families.
There are more than 80 types of autoimmune diseases,
and some have similar symptoms (Xiao et al., 1997).
Several studies have demonstrated the effects of herbal
extracts on the immune system (Martino et al., 2010).
Natural medicinal products have been traditionally used
for the treatment of various complications in eastern
countries, particularly China, India and Iran since the
immemorial time (Ram et al., 2009). In a healthy body,
circulating antibodies attack and destroy pathogenic
invaders by means of humoral or cell-mediated immunity.
In autoimmune disease, circ-lating antibodies seek attack
and destroy self-antigens found in healthy tissue.
Immunomodulator is a substance which stimulates or
suppresses the components of immune system including
both innate and adaptive im-mune responses (Agarwal
and Singh, 1969). Tinospora cordifolia increases
leukocyte count (Manjrekar et al., 1999). Ocimum
sanctum has been reported to modulate humoral immune
response by releasing mediators for hypersensitivity
reactions (Kujur, 2001; Krishnamohan et al., 1997;
Kumar, 2003). Withania somnifera exhibits
immunomodulatory activities and is usually used for the
treatment of gouty arthritis (Akram et al., 2010). A.
racemosus stimulates both humoral and cell mediated
immune responses in Swiss albino mice by Kuttan and
Kuttan (1992). A. racemosus extracts increase
phagocytic activities of macrophages in vitro (Rege and
Dahanukar, 1993).
Conclusion
Autoimmune diseases may be greatly improved by
strengthening the immune system with nutritional
supplements and by making healthy lifestyle changes in
diet and stress reduction. The protocols needed may
include prescription drugs as well as the following
supplements. Extracts of several plants have shown
impressive spectrum of biological activities as well as
immunomodulatory effects (Martino et al., 2010).
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