Immunology & 
Blood Groups

Topic Notes

Additional Support Materials

i.e. animations, quizzes, pictures,  worksheets

 
Immunology

Immunology Tutorial & Problems 
(The Biology Project, University of Arizona)

Immune System Tutorial 
(The Life Wire)

Humoral Immune Response Tutorial
(The Life Wire)

Cellular Immune System

Helper T cells

B and T cells picture

Antibodies Picture
(Access Excellence)

The Immune System 
(NIAID NetNews)

 
Blood Groups

 

Blood Types Tutorial
(The Biology Project, University of Arizona)

Blood Typing Tutorial & Game 
(Nobel e. Museum)

  
The Rhesus Factor

    

 

 


Immunology

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An infectious disease is caused by pathogens, where they are said to be parasitic.  Pathogens are organisms that live on or in their host, and gain nutrients from that host.  There are two types of pathogens:

Many pathogens do not harm us because we have physical, chemical and cellular defences that prevent them from entering the body.  If they do enter, then our immune system can prevent them from spreading though the body.  The immune system is involved in the recognition and rejection of foreign cells and tissues. 

 All of the cells in your body contain membrane proteins.  In module 1 you would have studied membrane proteins such as channel proteins, carrier proteins and protein pumps that transport material in and out of cells.  Other membrane proteins can combine with carbohydrate and lipid molecules to function as a sort of ‘name tag’ that identifies your cells as belonging to your body.  Most of the white blood cells of your immune system recognise a foreign cell or virus as something that does not belong in your body, because that foreign cell or virus does not have the correct ‘name tag’.   When white blood cells of the immune system identify the foreign cell or virus, white blood cells respond by attacking the invader.  Any protein/carbohydrate/lipid name tag that can trigger a response by the immune system is called an antigen. 

   

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White blood cells are important in the body’s natural defenses against pathogens.  The following table identifies the major WBCs function and the type of immune response:

White Blood Cell Type Function Immune System Category
Monocytes Exit blood vessels and turn into macrophages. Engulf invaders and debris by phagocytosis Non-specific
Neutrophils Stay in blood vessels and engulf invaders and debris by phagocytosis Mainly non-specific but can be specific when directed by antibody targeting.
Basophils Release histamines and participate in the inflammatory and allergic reactions Non-specific
Eosinophils  Chemically attack parasitic invaders similar to natural killer cells Non-specific
Lymphocytes Form T-cells and B-cells Specific except for Natural killer cells

The immune system has two main components the non-specific and specific immune response

Non-specific immune response [back to top] [back to top]

 

Summary of the Non-Specific Immune Response:

Component Functions
Skin and mucous membranes – mechanical factors
Intact skin Forms a physical barrier to the entrance of microbes.
Mucous membranes Inhibit the entrance of many microbes, but not as effective as intact skin.
Mucus Traps microbes in respiratory and digestive tracts.
Hairs Filter microbes and dust in nose.
Cilia Together with mucus, trap and remove microbes and dust from upper respiratory tract.
Tear ducts Tears dilute and wash away irritating substances and microbes.
Saliva Washes microbes from surfaces of teeth and mucous membranes of mouth.

Epiglottis

Prevents microbes and dust from entering trachea.
Urine Washes microbes from urethra.
Skin and mucous membranes – chemical factors
Gastric juice Destroys bacteria and most toxins in stomach.
Acid pH of skin Discourages growth of many microbes.
Unsaturated fatty acids Antibacterial substance in sebum.
Lysozyme Antimicrobial substance in perspiration, tears, saliva, nasal secretions, and tissue fluids.
Antimicrobial substances
Interferon (IFN) Protects uninfected host cells from viral infection.
Complement Causes lysis of microbes. Promotes phagocytosis, contributes to inflammation attracts white blood cells to site of infection
Other responses
Phagocytosis Ingestion and destruction of foreign particles by microphages and macrophages.
Inflammation Confines and destroys microbes and repairs tissues.
Fever Inhibits microbial growth and speeds up body reactions that aid repair.

Specific immune response
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Specific immune response occurs when a particular antigen passes the body’s passive defenses.  It involves cells and proteins within the blood and lymph that attach, disarm, destroy and remove foreign bodies.   The specific system gives a highly effective, long lasting immunity against anything the body recognise as foreign.  It responds to specific microorganisms and enhances the activity of the non-specific system.

 The central feature of the specific immune system is the ability to distinguish between self and non-self.  Every cell has complex molecules (proteins and glycoproteins) on its surface membrane which act as recognition devices and have specific shapes.  These molecules are called antigens or immunoglobins.  The immune system is usually tolerant to the body’s own antigens (self antigens) and does not attack against them.  However, breakdown of the recognition system can lead to autoimmune disease such as AIDS and rheumatoid arthritis, which result in self-destruction of body parts.

When a foreign organism (bacteria, viruses or even another person’s cells) enters the body, the foreign antigens on the invading cells activate an immune response.  The foreign antigens are called non-self antigens.  The immune system produces antibodies and specialised cells that attempt to destroy foreign cells and particles that have entered the body.  There are two types of responses: Humoral(antibody) response (involving B cells) and cell mediated immunity (involving T cells).

Humoral (antibody-mediated) Response - B-cells  [back to top]

The humoral immune response is initiated by an activation phase.  This is where macrophages (white blood cells) engulf and digest microbes (including their antigens) through a process of called phagocytosis. 

Some of the digested antigens are then displayed on the surfaces of the macrophages (called epitopes).  This display provides other cells of the immune system with an opportunity to recognise the invader and become activated.  This is called antigen presentation.

The effector phase involves specific lymphocytes (white blood cells) that mature in the bone marrow.  These are called B lymphocytes (B-cells).  B-cells can produce a specific antibody in response to a particular antigen.  An antibody is a type of globular protein that reacts with a specific antigen. 

 

Antibodies are y-shaped molecules composed of heavy chains and light chains, which are kept together by S-S bonds.  The ends of the Y arms are the binding sites for an antigen.

 When a B cell meets an antigen it will divide through mitosis and after several generations will differentiate into plasma cells.  All plasma cells are formed from one type of B cell and will secrete the same antibody.  Plasma B-cells can synthesise and secrete up to 2000 antibody molecules per second!   The antibodies produced circulate in the blood and lymph or secrete antibodies onto the surfaces of mucous membranes, such as those found lining the lungs.

Different antibodies work in different ways:

  When confronted with an antigen for the first time, B cells produce memory cells as well as plasma cells; this is called the primary response.  The primary response is usually slow, taking days or even weeks to recruit enough plasma cells to bring an infection under control.  However, when a second invasion occurs, the response is quicker.  Memory cells are involved in the secondary response and stick to and destroy antigens

 


 

Cell Mediated Response - T Cells   [back to top]

The cell-mediated response involves cells that are specific to the antigens on the invading pathogens.  The cells involved are lymphocytes, called T cells, which mature in the thymus.  In the thymus the T cells develop surface receptors called T-cell receptors where they become ‘programmed’ for the antigen of their specific enemy.  Many different kinds of T cells are produced which recognise, attach and destroy infected, mutant or ‘foreign’ cells.  After encountering a specific foreign antigen, T cells reproduce rapidly, however they do not produce antibodies like B cells. 

Macrophages that have ingested foreign material carry some of the foreign antigen on their surface.  The macrophages then carry the foreign cells to the T helper (Th) and T killer (Tk) cells in the lymph nodes, spleen and blood.

Another type of T-cells is the T-suppressor cells, Ts – These play an important role in regulating that action of the lymphocytes, where they can help prevent the immune system overreacting to a stimulus.

Location of Immune SystemWhen the B and T cells develop in the bone marrow and thymus (respectively), they enter the blood stream, then leave it, and move around the body in the lymphatic system.

The immune system contains a number of lymphoid tissues and organs, such as the spleen, tonsils, and lymphnodes; these are connected to a network of vessels (similar to that of the blood).

The lymphatic vessels contain lymph, which drains from nearby tissues.  Memory B and T cells circulate in the lymph, ready to react with their antigen.  Antigens that enter the body are carried by the macrophages to a lymphatic organ, where there is a high concentration of white blood cells, such as Th and Tc cells. 

If you have an infection, you may have noticed that your glands (lymph nodes) may be swollen and sore, indicating that you have an infection of some kind

Summary of the immune response involving B and T cells

Immunity  [back to top]

Types of immunity:

Natural passive immunity - Antibodies made in one individual are passed into another individual of the same species. This only affords temporary protection, for, as the antibodies do their job, or are broken down by the body's natural processes, their number diminishes and protection is slowly lost. For example, antibodies from a mother can cross the placenta and enter her foetus. In this way they provide protection for the baby until its own immune system is fully functional. Passive immunity may also be conferred by colostrum (the mother’s first milk), from which antibodies are absorbed from the intestines of the baby.

Acquired passive immunityHere, antibodies which have been made in one individual are extracted and then injected into the blood of another individual which may, or may not, be of the same species. For example, specific antibodies used for combating tetanus and hepatitis B are cultured in horses and later injected into Man. They act to prevent tetanus and hepatitis respectively. This type of immunity is again short-lived – a matter of weeks only.

Natural active immunity - The body manufactures its own antibodies when exposed to an infectious agent. Since memory cells produced on exposure to the first infection are able to stimulate the production of massive quantities of antibody, when exposed to the same antigen again.  This type of immunity is most effective and generally persists for a long time - sometimes even for life.

When a bacterial infection occurs and an antigen is presented for the first time, time is taken for the B and T cells to proliferate.  Once the B cells have differentiated into plasma cells, specific antibodies can be secreted.  This primary response lasts several days or weeks and then the concentration of antibody decreases as the plasma cells stops secreting them.  Once the infection is eradicated, plasma cells die, but B memory cells are left in the body.

If another infection of the same pathogen occurs, then the same antigen is reintroduced.  There is a more rapid response, called the secondary response.  This is much faster because there are many more memory B-cells that can produce many plasma cells and the appropriate antibody.    These destroy the pathogen before it has the chance to cause any symptoms to occur.

Memory cells are the basis for immunological memory – they last for many years, often a lifetime.  It is possible for suffer repeated infections from a single pathogen because pathogens occur in different form, each having minor changes in the shape of the antigen, due to a possible mutation, and therefore requiring a primary response.

Acquired active immunity - This is achieved by injecting small amounts of antigen - the vaccine - into the body of an individual. The whole process is called vaccination or immunisation. The small dose of antigen is usually safe because the pathogen is either killed or attenuated (= crippled). This ensures that the individual does not contract the disease itself, but is stimulated to manufacture antibodies against the antigen. Often a second, booster, injection is given and this stimulates a much quicker production of antibody which is long lasting and which protects the individual from the disease for a considerable time. Several types of vaccine are currently in use.

 

Vaccinations (additional info for your own interest)   [back to top]

Currently vaccines come in three forms:Child being vaccinated

Are vaccines safe to use?

It is never possible to prove that any medical treatment is totally safe for all people under every set of conditions. The safety of medical procedures and agents always carry a degree of risk, just as driving your car to work always carries a degree of risk.

This is a decision that each individual must make for themselves and their children, but it should be an informed decision and not one made from scary tales told over the back fence or from the tabloids. Modern vaccines are about as safe as anything in this dangerous world. Everyone who drives or is driven on the highways is in far more danger of harm than they are being vaccinated.

The UK is one of the safest countries in the world when it comes to communicable diseases, but we probably are not the safest. Diseases are always present and they do not recognise borders. We are so intimately connected with the rest of the world today that diseases can appear from anywhere. The strawberries or lettuce you just purchased at the supermarket yesterday may have come from a country with far less sanitation than we practice, or the person you sit by on the bus may be a recent immigrant or traveller coming from another country that is carrying a disease the UK is "free" of. In these cases your only real protection is vaccination. Think about it!

   

    

Blood Groups
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 Blood typing is a way to categorise different types of antigens found on the surface of red blood cells.  The antigens on the surface of red blood cells have a special nametag: agglutinogens.  The ABO blood group describes just one set of agglutinogens (antigens), which are genetically determined carbohydrate molecules carried on the surface membranes of the red blood cells (there are over 100 different ways to type blood).  Your blood type is a description of what kind of agglutinogens are present on the surface of your own red blood cells.

Blood Typing: ABO groups   [back to top]

According to the ABO blood groups, there are two different types of agglutinogens (antigens): type A agglutinogens and type B agglutinogens.  These agglutinogens may or may not be present on the surface of your red blood cells in four different combinations.

If you are:

The white blood cells of your immune system recognise agglutinogens (antigens) of your own blood type as belonging inside your body, and therefore do not attack your own blood cells.  However, what would happen is a physician accidentally transfuses type B blood into a person with blood type A?

In this case, the immune system of a person with type A blood would respond by attacking the ‘foreign’ type B blood cells. The immune response would involve the production of antibodies.  There are a number of ways the antibodies can attack an invader, but the most common is for antibodies to chain invading cells or viruses together in large clumps.  These clumps are then easily attacked and destroyed by phagocytic white blood cells. 

In the case of the mismatched blood transfusion above, antibodies in the type A person would attack and clump together the foreign type B blood cells.  This reaction, where foreign cells are chained together by antibodies and form clumps, is called agglutination.  Antibodies that attack foreign red blood cells also have a special name called agglutinins.

A person’s blood type will determine what types of agglutinins (antibodies) are present in the body.   The B-lymphocytes of the immune system will not produce agglutinins (antibodies) that attack the agglutinogens (antigens) found on your own red blood cells.

Blood type

Agglutinogens (antigens)

Agglutinins (antibody)

A A Anti-B
B B Anti-A
AB AB none
O O Anti-A and Anti-B
  

(Source: http://gslc.genetics.utah.edu/units/basics/blood/types.cfm)

When two types of blood are mixed during a transfusion, the antibody given by the donor can be ignored because the plasma containing the antibody is rapidly diluted by the recipient’s blood and has little effect on the recipient’s red blood cells.

Blood Group Antigens on RBC Antibodies (serum) Can donate blood to Can receive blood from
A A Anti-B A and AB A and O
B B Anti-A B and AB B and O
AB A and B None AB All groups
O None Anti-A and Anti-B All groups O

 

Blood Group % of population in the UK
O 46
A 42
B 9
AB 3

   

The Rhesus Factor   [back to top] 

What is the Rhesus Factor?

The second major blood grouping system is the Rhesus (Rh) system.  Like the ABO blood types, the Rh factor is an inherited blood protein, or antigen, on red blood cells.  People who have it are "Rh positive"; those who don't are " Rh negative". The Rh factor is connected to the ABO blood type e.g. an individuals blood type may be AB+, which means that they type AB blood and are Rh positive.  

The four major ABO blood types or groups (A, B, AB and O) are each further divided into Rh positive or Rh negative types, putting individuals into one of each blood groups.  The eight blood groups, and their approximate percentage of the population, are as follows:

Rh Positive Rh Negative
0+    37% 0- 6%
A+ 34% A- 6%
B+ 10% B- 2%
AB+ 4% AB- 1%
85% positive

15% negative

It is particularly important for expectant mothers to know their blood type and Rh factor.  Occasionally a baby will inherit  an Rh positive blood type from its father while the mother has Rh negative blood type.  This means that the baby's life could be in danger if the mothers Rh negative blood attacks the baby's Rh positive blood.  

 

History behind the rhesus factor  [back to top]

In 1940 Landsteiner and Wiener used blood from a monkey (Macacus rhesus) to immunise rabbits and guinea pigs in order to define new antibody specificities.  One of the antibodies they produced appeared to have the same specificity as a human antibody found in several woman who had stillborn foetuses.  Consequently, the antibodies were named anti-Rh for rhesus.  The antibodies were directed against a molecule called the rhesus (Rh) antigen, about 85% of individuals possess the antigen and are called Rh positive.  The remaining 15% who did not carry it were called Rh negative.  Natural antibodies against the Rh antigens do not occur.  Rhesus antigens are very hydrophobic cell surface proteins - probably transporter proteins.  

Inheriting Rhesus blood group system         
The Rhesus blood group system involves the Rhesus D gene locus. There are 2 common alleles - D and d. If an individual has the allele D, they synthesise an antigen (known as Rhesus D) on the surface of their red cells, and are Rhesus positive (Rh+).  If they are homozygous for the alternative allele (dd) they do not synthesise the D antigen, and are Rhesus negative (Rh-).  Unlike the ABO antibodies, the antibody that recognises the D antigen (known as anti-D) is not naturally occurring. It only arises as a result of the immunisation of a Rhesus negative person with the D-antigen, via Rhesus positive blood – usually during childbirth, but possible following blood transfusion.  Different ethnic groups have different patterns of Rhesus antigens; Rhesus negative is only at all common in Caucasian (white) people.

 

Genotype
Which 2 alleles are present in the cell?

What Rhesus antigen is present on the surface of the red cell?

Phenotype
(Rh blood group)

DD

D

Rhesus positive

Dd

D

Rhesus positive

dd

none

Rhesus negative

Note: The ABO blood group system and the Rhesus blood group system are just 2 of the 60 or more different inherited blood group systems that have been discovered in humans. Fortunately they are the only two that normally need to be taken into consideration when selecting blood for the purposes of transfusion.  
    

Rhesus Incompatibility    [back to top]
What is Rhesus incompatibility?

Rhesus incompatibility occurs when the blood group of a pregnant woman is incompatible with the blood group of her baby.   Since the blood of the foetus and mother are kept separate by the placenta, only the antibodies of the mother can cross over into her foetus and attack it – see below.  

Why is rhesus incompatibility a problem?

In certain circumstances, this incompatibility can lead to the blood disorder ‘Haemolytic Disease of the Newborn’ or HDN. [Haemolysis is the term used to describe the destruction in the body of red blood cells].  In the past, HDN was a common cause of stillbirth, but is now extremely rare, primarily due to the use of the anti-D injection given to Rh negative mothers to prevent their sensitisation.  

What is the cause of Rh incompatibility?

During childbirth some of the baby’s Rh-positive blood can escape into the blood stream of the mother. Rh incompatibility only arises when a woman’s blood is Rh- and her baby’s blood is Rh+ (thus the baby’s father’s blood must also be Rh-positive).

There are usually no problems during a woman’s first pregnancy with a baby whose blood is Rh+. However, when the baby’s blood enters the mother’s blood stream the mother will begin to produce antibodies against the baby’s Rh+ blood.  These antibodies "sensitise" the woman to Rh+ blood. If she has another pregnancy with an Rh+ baby these antibodies will pass through the placenta and may harm the baby.   A woman whose blood is Rh- can also be sensitised if she is mistakenly given a transfusion of Rh+ blood, but with today’s blood screening procedures, this is unlikely.  

 

How often does Rh incompatibility occur?

Among white skinned people, about 15% are Rh-, and in about 9% of pregnancies the mother’s blood is Rh- and the baby’s Rh+. Rh incompatibility is less common in black and oriental families than in white families because of a comparative rarity of the Rh-negative blood group in these races.  

What is the treatment?

An injection of anti-D antibody is given to Rh+ women immediately after the birth of the baby (the parents are too preoccupied with the new arrival to notice!).  The injection contains antibodies to Rh factor, which destroy any of the baby’s blood cells that may have entered the woman’s bloodstream before they have a chance to sensitise her.  This injection prevents Rh sensitisation in 99% of cases.

Anti-D antibody is also given to Rh-negative women after any miscarriage or abortion, since that might result in exposure of the mother to the foetal blood cells.

If a woman has Rh- blood, she is tested for the presence of Rh antibodies during pregnancy and if antibodies are present, extra treatment may be necessary, since there may be a risk to the baby if the mother’s immune system treats the foetal blood cells as "foreign" and rejects them.

 

What are the symptoms of haemolysis?

In mild cases, the newborn baby becomes jaundiced during the first 24 hours of life (due to excess bilirubin in the blood) and slightly anaemic. In more severe cases, the level of bilirubin in the blood may increase to a dangerous level, causing a risk of brain damage.   The most severely affected babies have marked anaemia while still in the uterus, become very swollen, and are often stillborn.

 

What is the treatment?

If the condition is mild, no treatment is required. In other cases, the aim is to deliver the baby before anaemia becomes severe, which usually means an induced birth at between 35 and 39 weeks gestation.   If the baby is severely affected before he or she is mature enough to be delivered safely, foetal blood transfusions may be necessary, i.e. Rh-negative blood is injected into the foetus.   After the baby is born, blood tests assess jaundice and anaemia. Phototherapy (light treatment that converts bilirubin in the skin into a water-soluble form that is easily excreted) and plenty of fluids, help reduce the jaundice. If the bilirubin level becomes dangerous, exchange transfusions may be performed.

 

What is the long-term outlook?

HND is far less common since the introduction and use of anti-D antibody in the early 1970s. Nowadays, because this is available to the Rh-negative woman within hours of childbirth, any Rh- positive blood cells from the foetus are destroyed before they have had time to sensitise the mother’s immune system.   Improved general obstetric and paediatric care has also resulted in a reduction in the severity of the cases that still occur.
  

Mother’s Blood   Foetus’s blood   Risk?  
Positive   Positive   O  
Positive   Negative   O  
Negative   Positive   O  
Negative   Positive  

First child O
All other children P  

It is, of course, not possible for a Rh+ woman to make antibodies against her RH- foetus - for the foetus' blood has no antigens for her immune system to respond to!

  


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Last updated 26/03/2005