Download Tissue Histology

‫‪15th lecture‬‬
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15th lecture
Type IV hypersensitivity involves primarily the T-cell
branch of the immune system. It has traditionally been
known as delayed hypersensitivity because the
symptoms arise one to several days following the
second contact with an antigen. In general, it result
when T cells respond to self tissues or transplanted
foreign cells (delayed allergic reactions to infectious
agents, contact dermatitis and graft rejection).
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Infectious Allergy
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A classic example of a delayed-type hypersensitivity is
tuberculin reaction is an acute skin inflammation at the
injection site appearing within 24 to 48 hours. Other
infections that use similar skin testing are leprosy, syphilis,
histoplasmosis, toxoplasmosis, and candidiasis.
This form of hypersensitivity arises from time-consuming
cellular events involving the TD class of cells. After these
cells receive processed microbial antigens from
macrophages, they release broad-spectrum cytokines that
attract inflammatory cells to the site particularly
mononuclear cells, fibroblasts, and other lymphocytes. In a
chronic infection (tertiary syphilis, for example), extensive
damage to organs can occur through granuloma formation.
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Contact dermatitis, is caused by exposure to resins in
poison ivy or poison oak, to simple haptens in
household and personal articles ( jewelry, cosmetics),
and to certain drugs. The allergen first penetrates the
outer skin layers, is processed by Langerhans cells (skin
macrophages), and is presented to T cells. When
subsequent exposures attract lymphocytes and
macrophages to this area, these cells give off enzymes
and inflammatory cytokines that severely damage the
epidermis in the immediate vicinity. This response
accounts for the intensely itchy papules and blisters that
are the early symptoms. As healing progresses, the
epidermis is replaced by a thick, horny layer within
week to 10 days.
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Common delayed-type reactions.
(a) Positive tuberculin test.
Intradermal injection of tuberculin extract
in a person sensitized to
tuberculosis yields a slightly raised red
bump greater than 10 mm in
diameter.
b) Contact dermatitis from poison oak,
showing various stages of involvement:
blisters, scales, and thickened patches.
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
Transplantation or grafting of organs and
tissues is a common medical procedure.
Although it is life-giving, this technique is
plagued by the natural tendency of
lymphocytes to seek out foreign antigens and
mount a campaign to destroy them. The bulk of
the damage that occurs in graft rejections can
be attributed to expression of cytotoxic T cells
and other killer cells.
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In general, the genes and receptors in MHC classes I
and II are extremely important in recognizing self and
in regulating the immune response. The MHC genes of
humans are inherited from among a large pool of
genes, so the cells of each person can exhibit variability
in the pattern of cell surface molecules. The pattern is
identical in different cells of the same person and can
be similar in related siblings and parents, but in the
more distant relationship, less likely that the MHC
genes and receptors will be similar.
When donor tissue (a graft) displays surface receptors
of a different MHC class, the T cells of the recipient
(called the host) will recognize its foreignness and react
against it.
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share
antigen A
identical HLA genes
The pattern of inheritance of MHC (HLA) genes. A simplified version of the
human leukocyte antigen (HLA) complex in a family. In this example,
there are two genes in the complex, and each parent has a different set of
genes (A/B and C/D). A child can inherit one of four different combinations. Out
of six children, two sets (3 and 5) have identical HLA genes and are good
candidates for exchange grafts. Children sharing one gene (for example, 1, 4,
and 6 share antigen A) are close matches, but two pairs of children (2 and 4, 3
and 6) do not match at all.
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Host Rejection of Graft When the cytotoxic T cells of a
host recognize foreign class I MHC receptors on the
surface of grafted cells, they release IL-2. Receipt of this
stimulus amplifies helper and cytotoxic T cells specific to
the foreign antigens on the donated cells.
The cytotoxic cells bind to the grafted tissue and secrete
lymphokines that begin the rejection process within 2
weeks of transplantation.
Late in this process, antibodies formed against the graft
tissue contribute to immune damage. A final blow is the
destruction of the vascular supply, promoting death of the
grafted tissue.
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15th lecture
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In certain severe immunodeficiencies, the host cannot or
does not reject a graft. But this failure may not protect the
host from serious damage, because graft incompatibility is
a two-way phenomenon. Some grafted tissues (especially
bone marrow) contain an indigenous population called
passenger lymphocytes. This makes it quite possible for
the graft to reject the host, causing graft versus host
disease (GVHD).
Since any host tissue bearing MHC receptors foreign to
the graft can be attacked, the effects of GVHD are widely
systemic and toxic. A skin rash is the most common
symptom. Other organs affected are the liver, intestine,
muscles, and mucous membranes.
GVHD occurs in approximately 30% of bone marrow
transplants within 100 to 300 days of the graft.
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Grafts are generally classified according to the genetic
relationship between the donor and the recipient
Autograft: Is tissue transplanted from one site on an
individual’s body to another site on his body (skin
replacement in burn repair and the use of a vein to fashion a
coronary artery bypass).
Isograft: tissue from an identical twin is used. Because
isografts do not contain foreign antigens, they are not
rejected.
Allografts: the most common type of grafts, are exchanges
between genetically different individuals belonging to the
same species (two humans)..
Xenograft is a tissue exchange between individuals of
different species (for temporary therapy only).
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Graft rejection can be lessened by directly comparing the
tissue of the recipient with that of potential donors.
Several tissue matching procedures are used. In the
mixed lymphocyte reaction (MLR), lymphocytes of the
two individuals are mixed and incubated.
If an incompatibility exists, some of the cells will become
activated and proliferate. Tissue typing is similar to blood
typing, except that specific antisera are used to disclose
the HLA antigens on the surface of lymphocytes. In most
grafts (one exception is bone marrow transplants), the
ABO blood type must also be matched. Although a small
amount of incompatibility is tolerable in certain grafts
(liver, heart, kidney).
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15th lecture
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Some sort of immunosuppressive therapy to
overcome rejection is usually required. Rejection
can be controlled with agents such as cyclosporin
A, methotrexate, prednisone, and a monoclonal
antibody OKT3.
Except for cyclosporin A, intervention with drugs
can be complicated by general suppression of the
immune system (especially T cells) and frequent
opportunistic infections. Cyclosporin A is a
polypeptide isolated from a fungus. It has
dramatically improved the survival rate of allograft
patients (kidney, heart, liver, and bone marrow)
and has reduced the incidence of fatal infections.
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Cyclosporin appears to block the activation of T
helper cells and interfere with the release of IL-2.
What makes this drug so valuable is that it does
not inhibit important lymphoid cells and
phagocytes, and the body is better able to ward
off infections. Its adverse effects of kidney toxicity
and increased blood pressure can be reduced by
adjusting the dose and monitoring blood levels of
the drug.
Because of its ability to inhibit undesirable T-cell
activity. Newer drugs aim to block the binding of
IL-2 on T cells.
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The most frequent transplant operations involve skin,
heart, kidney, coronary artery, cornea, and bone marrow.
The sources of organs and tissues are
 live donors (kidney, skin, bone marrow, liver).
 cadavers (heart, kidney, cornea)
 Fetal tissues.
we have witnessed some unusual types of grafts: For instance,
 the fetal pancreas has been implanted as a potential
treatment for diabetes,
 fetal brain tissues for Parkinson disease.
 Part of a liver has been transplanted from a live parent to a
child,
 parents have donated a lobe from their lungs to help restore
function in their children with severe cystic fibrosis.
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Bone marrow transplantation

is a rapidly growing medical procedure for patients with
immune deficiencies, aplastic anemia, leukemia and
other cancers, and radiation damage. This procedure is
extremely expensive, costing up to $200,000 per patient.
Before bone marrow from a closely matched donor can
be infused, the patient is pretreated with chemotherapy
and whole-body irradiation,(why??) a procedure
designed to destroy his own blood stem cells and thus
prevent rejection of the new marrow cells. Within 2
weeks to a month after infusion, the grafted cells are
established in the host. Because donor lymphoid cells can
still cause GVHD, anti-rejection drugs may be necessary.
An
amazing
consequence
of
bone
marrow
transplantation is that a recipient’s blood type may
change to the blood type of the donor.
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