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

Blood group antigens

A variety of glycoproteins found on the membrane of RBC constitute blood group antigens these include:
the ABO blood group antigens the Rhesus antigens

 The ABO antigens share a common glycoprotein known as the H-substance. Group O has only H-substance groups A, B and AB have H-substance joined to sugars commonly found on bacterial cells Individuals with type AB blood possess both group A and B type antigens on their surface
Group A possess N-acetylgalactosamine Group B possess D-galactose

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 on their RBC will have made antibodies and memory cells early in life. individuals with the respective sugars on their RBC would have undergone the process of tolerance therefore do not respond to these sugars. That is why individuals with O antigens can donate to any other group since all other groups are tolerant to the H-substance (universal donor). However these O individuals can only receive RBC with O antigen since they will spontaneously produce antibodies to either sugar on the other blood groups.

 Similarly group A and B cannot donate to each other due to the existence of spontaneous antibodies to the different sugars joined to the H-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 patient usually due to kidney failure.

 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 caused complement-mediated lysis. Haemolytic disease of the newborn?

Rhesus antigens

 Is a disease of neonates in which the mother had previously carried a child with 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 will respond in a classical anamnestic fashion. This will cause massive lysis of foetal RBC resulting in severe anaemia with jaundice due to accumulation of bilirubin (pre-hepatic jaundice). This condition was often fatal in the past but now is controlled by injecting first opposing rhesus group child bearing women with antirhesus antibodies to destroy the rhesus antigens before the mother can respond.

Concept of Self and Non Self

The ability to distinguish self from non self depends on the class I MHC proteins or antigens found on the surface of most nucleated cells The immune system does not respond to self antigen MHC antigens are already present in the early stages of embryonic development Any thymocytes * encounters and binds with these antigens, they will destroyonly thymocytes that do not respond to the bodys own molecules are retained

Failure of self/non self recognition

Autoimmune diseases Body produces an inappropriate immune response against its own tissues Antibodies attack its own cells T cells attack normal cells because some part of 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

SLE (systemic lupus erythematosus)

The Major Histocompatibility Complex

Transplant between species always failed Transplant between animals of the same species almost always failed BUT transplants within one animal almost never failed

The Major Compatibility Complex (MHC)

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 cellrejected by the body Tissue compatibility test tissues from donors must match the hosts tissues If all MHC antigens are matched,95% chance of transplant success very difficult Immunosuppression technique to reduce foreign tissue rejection : azatioprine and clyclosporine

Different kinds of transplantation:

a) Autograft : one part of body to another on the same person, is there any rejection? b) Isograft : between two genetically identical persons, rejection? c) Allograft: from one individual to a genetically different individual of the same species d) Xenograft : between two different species

Autograft

 A local accumulation of fluid, plasma proteins and white blood cells that is initiated by physical injury, infection, or a local immune response directs the elements of the immune system into damaged tissues by increasing the blood supply to the infected area and increasing capillary permeability, these allow larger molecules to pass through the endothelial layer than would normally do so. types of damage that induce inflammation include tissue necrosis, bone fracture, and injuries due to cuts, burns, infections and allergies

Inflammation

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 immune response 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 a condition in which an immune response results in exaggerated or inappropriate reactions that are harmful to the host reactions occur after 2nd contact with a specific allergen need 1st contact to allergen to induce sensitization type I, II and III hypersensitivity are antibody mediated and type IV is cellmediated

 Failure to control physiologic immune responses against foreign antigens or to maintain self-tolerance can lead to diseases 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 to that 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 hypersensitivity will result in tissue damage due to an exaggerated/ inappropriate adaptive immune response

1) 2) 3) 4)

There are many hypersensitivity diseases, however the basic pathological mechanisms can be categorized into 4 types: Immediate hypersensitivity (IH) Antibody-mediated hypersensitivity Immune complex-mediated hypersensitivity T cell-mediated hypersensitivity (delayed hypersensitivity)

Immunodeficiencies
Primary immunodeficiencies are inherited disorders of one or more components of the immune system. Secondary immunodeficiencies result from extrinsic causes such as irradiation, malnutrition, drugs or infections. The components of the immune system that are affected by immunodeficiencies include B and T lymphocytes, phagocytic cells, and complement components. Most immunodeficiency diseases lead to repeated or chronic infections. Patients with defects in immunoglobulins (B cells), complement proteins or phagocytes are very susceptible to recurrent pyogenic infections; these are caused by encapsulated bacteria that give rise to pus formation

 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 a template to synthesise DNA using enzyme reverse transcriptase

Acquired Immune Deficiency Syndrome (AIDS)

 HIV can only survive in body fluids such as semen 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 damage or 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