Transplantation Immunology Flashcards
One of the MOST POLYMORPHIC
gene system known
Human
Leukocyte
Antigen
in human leukocyte antigen, Associated protein is coded in the
______ in the
major histocompatibility complex
short arm of chromosome 6
Can occur in special case in which
immunocompetent tissue is
transplanted into an
immunocompromised host (Bone
Marrow, Thymus, Fresh Whole Blood)
Graft vs
Host
Disease (GvHD)
T cells from the transplant recognize
the host MHC molecules as non
-self
and attack the host
gvhd
Preformed antibodies and complement
that reacts with donor
Hyperacute
“White graft”
Reactivation of sensitized T cells
Pre-sensitized T cells; due to low level of
antibody present in the body in
pretransplant period
Accelerated
Primary activation of T cells
Development of allogenic reaction to
donor Ag
Acute
Causes are unclear , antibodies, immune
complex, slow cellular reaction, recurrence
of disease; side effects of
immunosuppressive drugs
Chronic
HLA Typing in
Laboratory
- DNA sequencing (Polymerase Chain
Reaction) - Serological assay
- Mixed lymphocyte culture / Mixed
lymphocyte reaction (MLC/MLR) - Crossmatching
– Amplification and specific probes to
detect different alleles
– Highly specific / sensitive
– Method of choice
DNA SEQUENCING (POLYMERASE CHAIN
REACTION)
– Cells from the donor and recipient are
reacted with a battery of antibodies,
each one of which is specific for a
different class I and II protein
– Complement is then added, and any
cell bearing an MHC protein
homologous to the known antibody
will lyse
– Satisfactory in most cases
SEROLOGICAL ASSAY
“Stimulator” lymphocytes from a potential donor are first killed
by radiation and then mixed with live “responder” lymphocyte
from the recipient
- MLC/MLR
Result: the greater the amount of DNA synthesis in the
responder cells, the more foreign are the Class I and II MHC
proteins of the donor cell
– The fetus is an allograft that is not rejected
– Trophoblast layer of the placenta does not allow maternal T cells
to enter the fetus
CROSSMATCHING
KINDS OF IMMUNOSUPRESSIVE AGENTS
*Corticosteroids
*Antimetabolic Agents
*Calcineurin Inhibitors
*Monoclonal antibodies
*Polyclonal antibodies
To suppress antigraft immune response in solid-organ and stem cell
transplantation
Increase susceptibility to infection, malignancies , and other
associated toxic side effects
IMMUNOSUPPRESSIVE AGENTS
can cause uninhibited cell division if their
expression is altered or if they are mutated
into oncogenes
- PROTO-ONCOGENES
- TUMOUR SUPPRESSOR GENES
- PROTO-ONCOGENES
are characterized by slow growth restricted
anatomic location and do not cause deatH
BENIGN NEOPLASM
MALIGNANT NEOPLASM OF
– is often referred as cancer or tumor.
They are
characterized by:
a. Anaplasia in which cells lose their differentiating features
b. Invasion of the body
c. Metastatic spread which can result in death
Often named by adding the suffix –oma (lipoma) to the cell
type but there are exceptions such as lymphomas,
melanomas, hepatoma
BENIGN TUMOR
Benign tumors arising from glands are called _____ and
those from epithelial surfaces are termed ________
Benign tumors arising from glands are called adenomas and
those from epithelial surfaces are termed polyps or
papillomas
CHARACTERISTICS OF BENIGN TUMOR
Usually are encapsulated
Grow slowly
Usually are nonspreading
Have minimal mitotic activity
Resemble the parent tissue
MALGNANT TUMOR those arising
from glandular epithelium are
called
adenocarcinoma
Referred to as carcinoma or
cance
MALIGNANT
TUMOR
CHARACTERISTIC
OF MALIGNANT
TUMOR
Increase in the number of cells that accumulate
Involves invasion of tissue
Dissemination by lymphatic spread or by seeding within a body cavity
Metastasis
Characteristic nuclear cellular features
Receptors for intergrin molecules
is when the malignant cells travel through
the body, causing new foci of malignancy
until body function is so disrupted that death
occurs
METASTASIS
Most widely used cancer staging
system
TNM
System
The T refers to the size and extent of the
main tumor. The main tumor is usually called
the primary tumor.
* The N refers to the the number of nearby
lymph nodes that have cancer.
* The M refers to whether the cancer has
metastasized. This means that the cancer has
spread from the primary tumor to other parts
of the body.
Primary Tumor (T)
Primary Tumor (T)
* TX: Main tumor cannot be measured.
- T0: Main tumor cannot be found.
- T1, T2, T3, T4: Refers to the size and/or extent of the main
tumor. The higher the number after the T, the larger the
tumor or the more it has grown into nearby tissues. T’s may
be further divided to provide more detail, such as T3a and
T3b
Regional Lymph Nodes (N)
- NX: Cancer in nearby lymph nodes cannot be measured.
- N0: There is no cancer in nearby lymph nodes.
- N1, N2, N3: Refers to the number and location of lymph nodes that contain cancer. The higher the number after the N, the more lymph nodes that contain cancer.
Distant Metastasis (M)
- MX: Metastasis cannot be measured.
- M0: Cancer has not spread to other parts of the body.
- M1: Cancer has spread to other parts of the body.
n the course of malignant
transformation of a cell, new
antigens or tumor associated
antigens develop at the cell
surface and the host recognize
malignant cells as “non self”
Tumor
Associated
Antigens
(TAA)
The quantity of TAA increases
proportionally with tumor growth
and decreases with effective
threrapeutic response
TUMOR SASSOCIATED ANTIGEN- ABSAHIN ANG HABA POTA
Oncofetal
Antigens
AFP AND CEA
synthesized by fetal liver cells. Most
but not all hepatomas secrete
large amounts of AFP. Its presence
in serum is not diagnostic of
hepatoma but is merely suggestive
AFP OR ALPHA FETO PROTEIN
– glycoprotein found in
glycocalyx of cells derived from
endoderm and present in gastro
intestinal carcinomas especially
cancer of colon
CARCINOEMBRYONIC ANTIGEN
(CEA)
These viral “finger prints”
form a major part of the
evidence that links viruses
with human malignancy.
Virus –
Induced
TAA
have
found in the cells of patients with
Burkitt’s Lymphoma and
Nasopharyngeal carcinom
EPSTEIN –BARR VIRUS (EBV)
Virus –
Induced
TAA
AND WHERE THEY CNA BE FOUND
- HEPATITIS B found in Primary Liver
Cancer - HUMAN PAPILLOMA VIRUSES 16
AND 18 in Cervical Cacinoma - HUMAN T-CELL LEUKEMIA VIRUS
found in Adult T-Cell leukemia
Antigens that can induce a protective immune response in the
host if they occur in the membrane of the malignant cell
Tumor Specific
Transplantation Antigens
(TSTA)
Immunosurveillance READ
EFFECTOR MECHANISM AGAINST CANCER
- Monocyte / macrophage release lytic enzymes and
phagocytose necrotic material - Antibody against tumour antigens
- Induction of tumour-specific CTL and TIL
- Initiation of NK / CTL cytotoxic responses
- Release of cytokines / chemokines (TNFα, IFNs etc) and
antiangiogenic factors
Immunoediting- The Great Escape!
*Strong evidence that IR controls and
eradicates nascent cancer cells
*“Immunoediting” eventually produces low
antigenicity tumour cells
*Pressure from immune system coupled
with genomic instability selects for escape
Three Es of Immunoediting
Elimination Equilibrium Escape
– can detect expressed antigens using labeled antibodies,
Immunohistochemistry
Many cancers are associated with particular karyotypes.
However, as more precise knowledge of the exact gene
defects present in various cancers is gained, testing for the
aberrant genes is becoming more prevalent.
- Cytogenetic Studies
Polymerase chain reaction (PCR) and its variants increase the inherent
level of DNA or RNA, allowing the detection of small populations of
cancer cells (including circulating cells in metastasis) and the detection
of mutations, deletions, and gene rearrangements/translocations
Nucleic Amplification Technique
Nucleic acid probes capable of binding to sequences of interest are
tagged with fluorophors and applied to cells. Cells containing the
sequence of interest can be visualized with fluorescent microscopes.
Similar techniques using nonfluorescent labels such as enzymes and
silver stains are also becoming available
Flourescent In Situ Hybridization
The goal of active immunotherapy is to have the patient
develop an immune response that will help eliminate the
tumor
ACTIVE IMMUNOTHERAPY
- Passive transfer of allogeneic cellular immunity from one
person to another to fight cancer has many barriers: - Possible recipient rejection of foreign cells
- Graft-versus-host disease (GVHD)
- Fragility of live cells, although research models are being
studied
- PASSIVE IMMUNOTHERAPY
