Download Tissue Histology

‫‪16th lecture‬‬
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16th lecture
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In many cases, the nature have provided
penetrating insights into the exact functions of
certain cells, tissues, and organs because of the
specific signs and symptoms shown by the
immuno-deficient individuals. The predominant
consequences
of
immunodeficiencies
are
recurrent, overwhelming infections, often with
opportunistic microbes. Immunodeficiencies fall
into two general categories:
primary diseases, present at birth (congenital) and
usually stemming from genetic errors
secondary diseases, acquired after birth and caused
by natural or artificial agents.
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Deficiencies affect both specific immunities such as
antibody production and less specific ones such as
phagocytosis. In many cases, the deficiency is due to an
inherited abnormality. Because the development of B cells
and T cells departs at some point, an individual can lack
one or both cell lines. It must be emphasized, however,
that some deficiencies affect other cell functions. For
example a T-cell deficiency can affect B-cell function
because of the role of T helper cells.
 In some deficiencies, the lymphocyte is completely
absent or is present at very low levels, whereas in
others, lymphocytes are present but do not function
normally.
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Genetic deficiencies in B cells usually appear as
an abnormality in immunoglobulin expression.
In
some
instances,
only
certain
immunoglobulin classes are absent; in others,
the levels of all types of immunoglobulins (Ig)
are reduced. A significant number of B cell
deficiencies are X-linked
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The term agammaglobulinemia literally means
the absence of gamma globulin, the primary
fraction of serum that contains immunoglobulins.
Because it is very rare for Ig to be completely
absent, some physicians prefer the term
hypogammaglobulinemia.
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Both sex-linked and autosomal recessive types of this
rare syndrome occur. In both cases, mature B cells are
absent, the level of antibodies is greatly reduced, and
lymphoid organs are incompletely developed. T-cell
function in these patients is usually normal. The
symptoms of recurrent, serious bacterial infections
(pyogenic cocci, Pseudomonas, and Haemophilus
influenza) usually appear about 6 months after birth.
Many Ig-deficient patients can have recurrent infections
with viruses and protozoa, as well. Patients often
manifest a wasting syndrome and have a reduced
lifespan. The current treatment for this condition is
passive immunotherapy with immune serum globulin
and continuous antibiotic therapy.
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The lack of a particular class of immunoglobulin is a relatively common condition. IgA
deficiency is the most prevalent, occurring in
about one person in 600.
Such persons have normal quantities of B cells
and other immunoglobulins, but they are
unable to synthesize IgA. Consequently, they
lack protection against local microbial invasion
of the mucous membranes and suffer recurrent
respiratory and gastrointestinal infections.
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Due to their critical role in immune defenses, a
genetic defect in T cells results in a broad
spectrum
of
disease,
including
severe
opportunistic infections, wasting, and cancer.
In fact, a dysfunctional T-cell line is usually more
devastating than a defective B-cell line, because T
helper cells are required to assist in most specific
immune reactions. The deficiency can occur
anywhere along the developmental spectrum,
from thymus to mature, circulating T cells.
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The most severe of the T-cell deficiencies involve the
congenital absence or immaturity of the thymus gland.
Thymic aplasia, or DiGeorge syndrome, results when the
embryonic third and fourth pharyngeal pouches fail to
develop. Some cases are associated with a deletion in
chromosome 22.
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The accompanying lack of cell-mediated
immunity makes children highly susceptible to
persistent infections by fungi, protozoa, and
viruses. Common, usually benign, childhood
infections such as chickenpox, measles, or mumps
can be overwhelming and fatal in these children.
Even vaccinations using attenuated microbes pose
a danger. Other symptoms of thymic failure are
reduced growth, wasting of the body, unusual
facial characteristics, and an increased incidence
of lymphatic cancer. These children can have
reduced antibody levels, and they are unable to
reject transplants. The major therapy for them is a
transplant of thymus tissue.
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Severe combined immunodeficiencies (SCIDs) are the most
dire and potentially lethal of the immunodeficiency diseases
because they involve dysfunction in both lymphocyte
systems. Some SCIDs are due to the complete absence of the
lymphocyte stem cell in the marrow; others are attributable to
the dysfunction of B cells and T cells later in development.
Infants with SCID usually manifest the T-cell deficiencies
within days after birth by developing candidiasis, sepsis,
pneumonia, or systemic viral infections.
This debilitating condition appears to have several forms. In
the two most common forms, agammaglobulinemia and
thymic a lymphoplasia, the numbers of all types of
lymphocytes are extremely low, the blood antibody content is
greatly diminished, and the thymus and CMI are poorly
developed.
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A rarer form of SCID is adenosine deaminase (ADA)
deficiency, caused by an autosomal recessive defect in
the metabolism of adenosine. Infants with ADA
deficiency are subject to recurrent infections and severe
wasting typical of severe deficiencies. A small number
of SCID cases are due to a developmental defect in
receptors for B and T cells. An X-linked deficiency in ILreceptors was responsible for the disease of David, the
child in the “plastic bubble’’. Another newly identified
condition, bare lymphocyte syndrome, is caused by the
lack of genes that code for class II MHC receptors.
Because of their profound lack of specific adaptive
immunities, SCID children require the most rigorous
kinds of aseptic techniques to protect them from
opportunistic infections.
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Some infants can benefit from fetal liver or bone
marrow grafts. Although transplanting compatible
bone marrow has been about 50% successful in curing
the disease, it is complicated by GVHD. The condition
of some ADA deficient patients has been partly
corrected by periodic transfusions of blood containing
large amounts of the normal enzyme. A more lasting
treatment for both X-linked and ADA types of SCID
has been found in gene therapy—insertion of a gene to
replace the defective gene.
Several children have apparently been cured by
transfecting their bone marrow stem cells with the
normal gene for ADA.
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Secondary acquired deficiencies are caused by one of four
general agents:
(1) Infection.
(2) Organic disease.
(3) Chemotherapy.
(4) Radiation.
 AIDS a syndrome caused when several types of immune
cells, including T helper cells, monocytes, macrophages,
and antigen presenting cells, are infected by the human
immunodeficiency virus (HIV). It is generally thought that
the depletion of T helper cells and functional impairment
of immune responses ultimately account for the cancers
and opportunistic protozoan, fungal, and viral infections
associated with this disease.
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infections can deplete immunities (measles,
leprosy, and malaria).
Cancers that target the bone marrow or lymphoid
organs can be responsible for extreme
malfunction of both humoral and cellular
immunity.
leukemia, the massive number of cancer cells
compete for space and literally displace the
normal cells of the bone marrow and blood.
Plasma cell tumors produce large amounts of
nonfunctional antibodies
thymus gland tumors cause severe T-cell
deficiencies.
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An ironic outcome of life-saving medical
procedures is the possible suppression of a
patient’s immune system. For instance, some
immunosuppressive drugs that prevent graft
rejection by T cells can likewise suppress
beneficial immune responses. Although
radiation and anticancer drugs are the first line
of therapy for many types of cancer, both
agents are extremely damaging to the bone
marrow and other body cells.
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