Transcript 7. Lecture Assignment

Immunogenetics
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The immune system has two ways of recognizing antigens:
B-cells recognize intact antigens using immunoglobulin (antibody)
as their receptor
T-cells have evolved to recognize antigens originating from within
other cells using their T-cell antigen receptors (TCRs)
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Red blood cells have antigens on their surface known as red-cell antigens
made up mainly of glycoproteins
Each blood group belongs to a different locus
Antibodies against most red blood cell groups are produced only following a
challenge with the appropriate antigen.
Exceptions are: J system in cattle
AB system in cats
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transfusions were inconsistent
with many recipients in that
their body had strong rejection
responses to the transfused
blood
Only later was blood correctly
matched
from
donor
to
recipient due to the discovery
of blood group systems
Blood systems include the ABO
group, Rh factor etc.
Our knowledge of the ABO and
Rhesus blood groups has
resulted
in
safe
blood
transfusion
This has also prevented Rhesus
haemolytic disease of the
newborn
THE ABO BLOOD GROUPS
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ABO blood group phenotypes and genotypes
----------------------------------------------------------------------------------------------Red blood cells
React with antiserum
Phenotype
Genotype
Antibodies
Antigen – A
Antigen – B
----------------------------------------------------------------------------------------------O
OO
anti – A,B
A
AA, AO
anti – B
+
B
BB, BO
anti – A
+
AB
AB
+
+
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The rhesus (Rh) blood group system involves
three sets of closely linked antigens
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D is very strongly antigenic and persons are
either Rh positive (possessing the D antigen)
or Rh negative (lacking the D antigen).
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A proportion of women who are Rh negative
have an increased chance of having a child
who will either die in utero or be born
severely anemic because of haemolysis
unless transfused in utero (i.e.. lysis of red
blood cells)
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an Rh-negative mother carrying an Rh
positive fetus can induce the formation of
Rh antibodies in the mother. In pregnancy
these antibodies can cross the placenta and
enter the fetal circulation. This leads to
haemolysis of the fetal red blood cells if the
fetus is Rh positive
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Therefore Rh-compatible blood must be
always be used in any blood transfusion
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1.
2.
3.
The MHC plays a central role in the
immune system
MHC molecules occur in three
classes:
class I molecules occurring on
virtually all cells and which are
responsible for recruiting
cytotoxic T cells
class II molecules that occur on B
cells and macrophages and are
involved in signaling T helper cells
to recruit further B cells and
macrophages
class III molecules that include a
number of other proteins with a
variety of other immunological
functions.
Name
Function
Expression
MHC
class
I
Encodes heterodimeric peptide-binding
proteins, as well as antigen-processing
molecules such as TAP and Tapasin.
All nucleated cells. MHC class I proteins
contain an α chain & β2-micro-globulin
(not part of the MHC). They present
antigen fragments to cytotoxic T-cells via
the CD8 molecule and also bind inhibitory
receptors on NK cells.
MHC
class
II
Encodes heterodimeric peptide-binding
proteins and proteins that modulate
antigen loading onto MHC class II proteins
in the lysosomal compartment such as
MHC II DM, MHC II DQ, MHC II DR, and
MHC II DP.
On most immune system cells, specifically
on antigen-presenting cells. MHC class II
proteins contain α & β chains and they
present antigen fragments to T-helper
cells by binding to the CD4 receptor on
the T-helper cells.
MHC
class
III
regi
on
Encodes for other immune components,
such as complement components (e.g.,
C2, C4, factor B) and some that encode
cytokines (e.g., TNF-α) and also hsp.
Variable
• The genes encoding class I, II and III molecules are known as the Human
Leukocyte Antigen (HLA) system
•success of transplants depends on the degree of antigenic similarity between the
donor and recipient
•antigenic similarity of donor and recipient has to be assessed by testing them with
suitable antisera
•The HLA system is highly polymorphic, two unrelated individuals are therefore
very unlikely to have identical HLA phenotypes
•A finding which helps to throw light on the pathogenesis of certain diseases is the
demonstration of their association with certain HLA types
• e.g. In the case of narcolepsy (a sleeping sickness) almost all affected individuals
are HLA DR2.
•In general, the mechanisms involved in most HLA disease associations are not well
understood.
 Innate
immunity system - is a roving
military patrol unit that is continuously
observing and circling the body’s system
for any imbalances
 The
adaptive immunity system - is like a
sniper that has specific targets, plans an
attack, and has learned from prior
experience with the targets how to
assassinate them.
 Searches
for antigens continuously by
identifying infectious organisms that have
entered the body
 Works rapidly to destroy the organisms in
the same manner each time the innate
immune system comes across a foreign
organism
 No increase in the amount of time that it
takes to destroy the infectious organism
based upon the frequency of encounters.
 Uses skin and mucous membranes, bloodborn molecular enzymes, lymphocyte
cells, inflammatory properties, and
phagocyte cells on order to scan and
destroy the organisms.
 more
rapid immune response as they
specifically target the area needing attention
 immune response takes place upon exposure to
an antigen that is familiar and this is the
reason why immunizations are given to
children prior to exposure to life threatening
diseases such as polio
 unclear if there has been a determining factor
as to why there is an ability of T-cells to gain
memory in the adaptive immunity process
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the humoral response - B cells secreting antibodies
to neutralize, clump, and stimulate the
destruction of pathogens by recognizing and
binding specific foreign antigens.
Antibodies - Y-shaped polypeptides with constant
and variable regions.
the cellular immune response - helper T cells that
stimulate B cells to produce antibodies and
cytotoxic T cells to secrete cytokines. Some T cells
bind to non-self cells and virus covered cells and
allow them to burst.
 AIDS-
Acquired virus replicates and kills Tcells important for immune function
 FIV in cats- lentivirus causing
immunosuppression
 Transmitted via biting (fights)
 Recurrent absesses, mouth infections etc
 Arabian foals (SCID)
 Abnormal
reaction to allergens
 Histamines and leucotrienes
 Mast cell inhibitors
 Feline rhinotracheitis, skin dermatitis in dogs
(food allergy related)
 Special diets formulated (eg Hill’s
Prescription Diet z/d)
 Immune
system of animal attacks organs
and tissues of that animal
 Antigens, antibodies or immunogenesis
 Retained fetal cells
 Mutations in certain genes may show as
an autoimmune disease
 Hemolytic anaemia, lupus erythematosis,
polyarthritis, immune-mediated
thrombocytopenia where immune system
destroys cells responsible for blood
clotting
Vaccines:
These are disabled pathogens or their parts
that elicit an immune response, protecting
against infection by the active pathogen
Uses immune system component to fight
disease.
Hybridomas are artificial cells that consists of
a B-cell fused with a cancer cell and produce
monoclonal antibodies (Mabs) that can target
specific antigens.
Cytokines boost immune function and destroy
cancer cell.
 Organ
transplant is the moving of an organ
from one body to another or from one part
to the other in the same body, for the
purpose of replacing the recipient’s damaged
organ.
 Problem: Organ Rejection
where the body has an immune response to an
organ which causes failure to the transplant.
Types of Transplants
 Autograft
transplant of tissue to the same person,
e.g. skin graft.
 Allograft
transplant of an organ or tissue between
two non-identical members of the same
species
 Isograft
transplant of organ or tissue between
genetically identical twins.
 Xenograft
transplant from one species to another
 The
success rate of transplants is improved
by the use of immunosuppressor drugs, by
stripping antigens from donor tissue, and by
matching donor to the recipient.
 Examples of immunosuppressor drugs
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Calcineurin inhibitors- Cyclosporin
 It
is an adaptive immune response and is
mediated through both T-cell mediate and
humoral immune (antibodies) mechanism.
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Innate
Anatomical features - function as a barrier to
infection.
Mediated by phagocytes.
2. Acquired
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Elimination of pathogens - late phase of
infection.
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Generation of immunological memory.
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2.
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Mutual evolution of microbe-victim
ecological system.
3 systems of Immunogenesis
Constitutional
Phagocytic
Lymphatic
Pathogenicity of microbes – depends on
genetically-determined molecular
structure of targets in the potential victim.
Evolution of an epidemic process: transformation of a population in the fight against
infectious agent (Rumyantsev, 2002, modified).