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Transcript of Self Nonself 2013
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Immunology: Development of Immunology and Conceptof Self and Non Self (II)
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Blood group antigens
• A variety of glycoproteins found on themembrane of RBC constitute blood
group antigens
• these include:the ABO blood group antigens
the Rhesus antigens
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• The ABO antigens share a commonglycoprotein known as the H-substance.
•Group O has only H-substance
• groups A, B and AB have H-substance joinedto sugars commonly found on bacterial cells – Group A possess N -acetylgalactosamine
– Group B possess D-galactose• Individuals with type AB blood possess both
group A and B type antigens on their surface
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Terminal parts of the blood group antigens found on
(a) group A RBC and (b) group B RBC. These sugars
are also common in bacterial cell walls.
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• individuals without the respective sugars ontheir RBC will have made antibodies andmemory cells early in life.
• individuals with the respective sugars on theirRBC would have undergone the process oftolerance
– therefore do not respond to these sugars.
• That is why individuals with O antigens candonate to any other group since all other groupsare tolerant to the H-substance (universaldonor).
• However these O individuals can only receiveRBC with O antigen since they willspontaneously produce antibodies to eithersugar on the other blood groups.
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• Similarly group A and B cannot donate to eachother due to the existence of spontaneous
antibodies to the different sugars
joined to theH-substance.
• If a mismatch occurs following transfusion,IgM pentamers will effectively cause
agglutination of the donors RBC. – This causes blockage and inflammation throughout
the vascular system leading to death of a patientusually due to kidney failure.
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Rhesus antigens • Rhesus antigens (Rh+ and Rh-), also called the
D-antigen, are not encountered early in life
• are independent of the ABO antigens
• Therefore, an individual does not produce
spontaneous antibodies.• no damage can occur if the first transfusion is
mismatched
• However, on the second transfusion IgG
isotypes are produced and will causedcomplement-mediated lysis.
• Haemolytic disease of the newborn?
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• Is a disease of neonates in which the
mother had previously carried a childwith an opposing Rhesus antigen.
• In the first pregnancy there is no
problem. but during birth of baby, the
placenta tears away from the uterine
wall, some foetal RBC leak into the
mothers bloodstream she makes
antibodies against the antigen.
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• In the second pregnancy (if the foetus also has
an opposing Rhesus antigen) the mother willrespond in a classical anamnestic fashion.
• This will cause massive lysis of foetal RBCresulting in severe anaemia with jaundice due
to accumulation of bilirubin (pre-hepatic jaundice).
• This condition was often fatal in the past butnow is controlled by injecting first opposing
rhesus group child bearing women with anti-rhesus antibodies to destroy the rhesusantigens before the mother can respond.
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Concept of Self and Non Self
• The ability to distinguish self from non selfdepends on the class I MHC proteins or antigensfound on the surface of most nucleated cells
• The immune system does not respond to “self”
antigen
• MHC antigens are already present in the earlystages of embryonic development
• Any thymocytes * encounters and binds with
these antigens, they will destroy→only thymocytes that do not respond to the body’s ownmolecules are retained
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Failure of self/non self recognition
• Autoimmune diseases
• Body produces an inappropriate immuneresponse against its own tissues
• Antibodies attack its own cells
•
T cells attack normal cells because some partof their structure resembles a part of infecting
microorganism
• Rheumatoid arthritis, SLE (systemic lupus
erythematosus), MS (multiple sclerosis), SCID(severe combined immunodeficiency)
• The treatment:
immunosuppression,medication which
decrease immune response
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Rheumatoid
arthritis
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SLE
(systemic lupuserythematosus)
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The Major Histocompatibility Complex
• Transplant between species always failed
• Transplant between animals of the same
species almost always failed
•BUT transplants within one animal almostnever failed
The Major Compatibility Complex
(MHC)
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Organ/Graft Transplant
• Organs or tissues carry antigens in their cells
• Recipient body recognises this as “foreign” or non self→antibodies are produced to counter antigen
• Transplanted organ/graft is attacked and destroyed
primarily by T cell→”rejected” by the body
• Tissue compatibility test→ tissues from donors mustmatch the host’s tissues
• If all MHC antigens are matched,95% chance of
transplant success→ very difficult
• Immunosuppression technique to reduce foreign tissuerejection : azatioprine and clyclosporine
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Different kinds of transplantation:
a) Autograft : one part of body to anotheron the same person, is there any
rejection?
b) Isograft : between two geneticallyidentical persons, rejection?
c) Allograft: from one individual to a
genetically different individual of thesame species
d) Xenograft : between two different
species
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Autograft
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Inflammation
• A local accumulation of fluid, plasma proteins
and white blood cells that is initiated byphysical injury, infection, or a local immuneresponse
• directs the elements of the immune systeminto damaged tissues by increasing the blood
supply to the infected area and increasingcapillary permeability,• these allow larger molecules to pass through
the endothelial layer than would normally doso.
•
types of damage that induce inflammationinclude tissue necrosis, bone fracture, andinjuries due to cuts, burns, infections andallergies
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Signs of inflammation
• swelling, accumulation of fluid (oedema)
• redness (rubor)
•
heat (calor)• pain (dolor)
• loss of function
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Immunopathology
Four ways the immune system can harm the host
rather than protect it:
1. Autoimmunity - mistaken recognition of self
tissues
2. Hypersensitivity - an overly vigorous immuneresponse to an antigen that is not particularly
harmful
3. Immunodeficiency - an ineffective immune
response caused by a defect in one or more immune
components
4. Graft vs. host disease - a condition in which
lymphocytes in grafted tissue attack their
immunocompromised host
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Hypersensitivity
•
Hypersensitivity or allergy denotes acondition in which an immune responseresults in exaggerated or inappropriatereactions that are harmful to the host
•
reactions occur after 2nd contact with aspecific allergen
• need 1st contact to allergen to inducesensitization
• type I, II and III hypersensitivity areantibody mediated and type IV is cell-mediated
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• Failure to control physiologic immuneresponses against foreign antigens or to
maintain self-tolerance can lead todiseases
• The term hypersensitivity arises from
the clinical definition of immunity as“sensitivity” – this is based on the observation that an
individual who is immune to an antigen
responds to, or is “sensitive to” exposure tothat antigen
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• Properly regulated immune responses
and amplification of immune responses
by inflammation are beneficial to the
host (generation of protective immunity)
• However, over-amplification of immune
responses resulting in hypersensitivitywill result in tissue damage due to an
exaggerated/ inappropriate adaptive
immune response
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There are many hypersensitivity
diseases, however the basic pathological
mechanisms can be categorized into 4
types:
1) Immediate hypersensitivity (IH)
2) Antibody-mediated hypersensitivity
3) Immune complex-mediated
hypersensitivity
4) T cell-mediated hypersensitivity (delayed
hypersensitivity)
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Immunodeficiencies
• Primary immunodeficiencies are inherited disorders ofone or more components of the immune system.
• Secondary immunodeficiencies result from extrinsiccauses such as irradiation, malnutrition, drugs orinfections.
• The components of the immune system that areaffected by immunodeficiencies include B and Tlymphocytes, phagocytic cells, and complementcomponents.
• Most immunodeficiency diseases lead to repeated orchronic infections.
• Patients with defects in immunoglobulins (B cells),complement proteins or phagocytes are verysusceptible to recurrent pyogenic infections; these arecaused by encapsulated bacteria that give rise to pusformation
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Acquired Immune Deficiency Syndrome
(AIDS)
• Caused by the Human Immunodeficiency Virus (HIV), a type of retrovirus
• This virus is normally difficult to transmit
since its target cells are mainly lymphocytes
• HIV cripples the human immune system by
weakening and destroying some portions of
the T lymphocytes
• Retrovirus : RNA virus that uses its RNA as atemplate to synthesise DNA using enzyme
reverse transcriptase
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•
HIV can only survive in body fluids such assemen and blood
• HIV is transmitted by –sexual contact,
infected blood entering bloodstream, from
mother to baby
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Mechanism of HIV infection
• Once inside the body, the virus binds to CD4
molecules primarily expressed on T helper cell
• RNA is reverse-transcribed to form DNA,
intergrated into a host chromosome
• DNA→ proteins to form HIV virions→ damageor kill T cell
• Over a long period of time, HIV slowly spreads
thru the immune system→ reduce T cell→
immune system less effective→ death
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Why does AIDS difficult to treat?
• The virus genome is integrated into
the host cell genome, becoming part
of the cell itself• The very cells that initiate immune
response themselves are destroyed
• Vaccine? difficult
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