Self Nonself 2013

8/13/2019 Self Nonself 2013

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Immunology: Development of Immunology and Conceptof Self and Non Self (II)

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

• 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

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.

• 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.

• 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.

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?

• 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.

• 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.

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

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

Rheumatoid

arthritis

(systemic lupuserythematosus)

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

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

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

Autograft

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

Signs of inflammation

• swelling, accumulation of fluid (oedema)

• redness (rubor)

heat (calor)• pain (dolor)

• loss of function

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

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

• 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

• 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

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)

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

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

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

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

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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