A21.2 Immunity

What is a pathogen's?

A disease causing microorganism. Some microorganisms can be harmless and may be useful, however if they are pathogenic they can cause disease or sometimes even death. So we need to find a way to prevent these from entering our body.

What is specific and non-specific immunity?

Specific immunity- A mechanism tailored for a specific pathogen e.g. lymphocytes. This is a slow process however provides long term immunity.

Non-specific immunity- A mechanism that is not specific for a particular pathogen e.g. phagocytosis.

What are the natural barriers of the body and how do they work?

Stomach-contains HCl to kill any microorganisms

Saliva/sweat/tears-contain an enzyme called lysozyme which digest bacterial cell walls

Skin-tough outer layer which pathogens cannot penetrate through unless there is a cut

Respiratory tract- contains mucus to trap bacteria and particles and the cilia to push mucus away from lungs

What is the inflammatory response and phagocytosis?

If the natural barriers do not work, we move onto to phagocytosis. This is done by white blood cells called phagocytes and is non-specific but can be rapid. Inflammatory response- the local non-specific response to tissue damage. When a bacteria enters the cell, the capillaries become leaky as they have become permeable meaning blood can leave the cell and enter the surrounding tissue causing swelling. The inflamed parts are full of dead pathogens, cell debris and phagocytes. Blood flow increases into the infected cell causing the area to turn red. There will be lots of macrophages and phagocytes present here. Then phagocytosis begins. The phagocyte moves towards the pathogen as it is attracted to the chemical it produces. The phagocyte invaginates and engulfs the pathogen. Then a vesicle is formed around the pathogen called a phagosome, from which lysosomes are attracted to. The lysosomes contain a hydrolytic enzyme which hydrolyses the pathogen. The soluble digested products are absorbed into the cytoplasm of the phagocyte.

How does lymphocytes cause a specific immune response?

Lymphocytes are an example of a specific immune response. The lymphocytes respond to foreign cells i.e. cells that the body does not recognise (non-self cells). These foreign cells are known as antigens. Each pathogen has its own antigen. The lymphocytes can tell if the antigen is non-self or self cells due to the lymphocyte having a receptor on its cell membrane which is complementary and specific in shape to the antigen. Antigens are usually made of proteins, polysaccharides, glycoproteins or glycolipids.

How do you know which cells are self and non-self cells?

In the foetus the lymphocytes will collide with self cells. The antigens on the self cells that are complementary and specific to a lymphocyte will bind and be switched off. So when you are born, you only contain lymphocytes specific to non self cells. They are many lymphocytes and only a few antigens that is why the process is so slow.

B-lymphocytes?

They are formed in the stem cells in the bone marrow and mature in the bone marrow. They are involved in antibody-mediated immunity and produces antibodies in response to antigens found in body fluids from bacterial or viral infections.

T-lymphocytes?

They are formed in the stem cells in the bone marrow and mature in the thymus gland. They are involved in cell-mediated immunity and produces antibodies in response to antigens found in body cells due to viral infections.

What is antibody-mediated immunity?

Invading microorganisms in body fluids have specific antigens. The B-lymphocyte contains a receptor which is specific and complementary to this antigen, which it then attaches to sensitising/activating the B-lymphocyte. The lymphocyte then divides rapidly by mitosis (cloning) to produce plasma and memory cells. The plasma cells produce antibodies which are specific and complementary to the antigens, which it attaches to leading to their destruction e.g. agglutination. The memory cells remain in circulation for a long period of time, sensitising rapidly if met with the same antigen again. It divides to produce more plasma and memory cells.

What is cell-mediated immunity?

The body cells infected by a virus contains antigens which the receptors on the T-lymphocytes are complementary to, meaning they can attach sensitising/activating the T-lymphocyte. The lymphocytes will divide rapidly by mitosis (cloning) to produce memory T-cells, suppressor T-cells, killer T-cells and helper T-cells. Memory T-cells remain in circulation to provide long term immunity. Suppressor T-cells switch off immune response and prevent autoimmune response. The killer T-cells kill any infected cells by enzyme action. They release toxic substances to help e.g. hydrochloric acid, nitric acid and perforin (creates holes in the cell membrane causing lysis). The helper T-cells attach opsonins to mark for phagocytosis, release cytokines to stimulate B-lymphocytes to divide into plasma and memory cells and secrete interferon to prevent virus replication.

Antibodies and antigens?

Antigen- a substance that stimulates the production of antibodies.

Antibodies- a globular protein that is specific and complementary to a particular antigen which it can react to leading to its destruction.

Passive immunity?

Passive immunity involves receiving antibodies from someone else. It can be natural passive immunity where antibodies from the mother are passed to the child during pregnancy through the placenta or during mothers first milk (colostrum). There can also be artificial passive immunity where a serum is given to the individual containing ready made antibodies for that pathogen. The serum contains antibodies from someone else who is recovering from the illness. This is rapid but not long term.

How do we obtain antibodies now?

Through monoclonal antibody production. We inject a particular antigen into a mouse and extract the sensitised/activated and cloned B-lymphocytes from the mouse and combine them with cancer cells to produce long term lymphocytes. Then placed in a fermenter for a period if time to create antibodies. This is good as it can be produced in large quantiles and a single type of antibody can be produced.

Active immunity?

Active immunity is the production of your own antibodies. There is natural active immunity, where the individual has already had the disease and so the secondary response is triggered. However this secondary response is so effective and rapid, the individual may not even know they had the disease. Then artificial active immunity is where the individual is given vaccination which contains attenuated or killed pathogens. This triggers the primary response, however doesn’t do much damage as it’s weakened or killed pathogens. However it provides memory cells allowing a rapid and beneficial secondary response. Vaccines usually leave the individual immune. Some vaccines require a booster vaccine.

What are social and economic benefits of vaccines?

Social- less people are sick, length of lives are extended, healthy children tend to do better at school.

Economic-carers don’t have to take time off work to care for the sick, less people of sick from work so productivity increases, less treatment costs.

What is herd immunity?

The idea that if majority of people are vaccinated those who are not are less likely to get sick. As there are less people who can catch the illness so the less people they will encounter with who has the disease.

Why does transplanted tissue produce an immune response?

An immune response is triggered by non-self cells. When organs or tissues are transplanted from someone else they will have different antigens to whom it is being transplanted to, therefore causing transplant rejection. Transplant rejection works by the antigen being recognised as a non-self cells, therefore the receptor binds to the specific antigen, sensitising the T-lymphocyte causing it to divide and clone by mitosis producing killer T-cells. These killer T-cells kill the transplanted tissue. Transplanted organs can be used as a last resort to save someone’s life, so we need to reduce the rate of transplant rejection. A transplant or skin graft will only not contain non-self antigens if transferred from the same person or an identical twin.

What ways can we reduce transplant rejection?

Tissue typing- This means matching the donor and the recipient, so there isn’t much difference in their antigens.

Immunosuppression techniques- using drugs to inhibit DNA replication of T-lymphocytes, slowing down the cloning and preventing transplant rejection

X-rays- inhibit production of T-lymphocyte by irradiation of bone marrow and lymph tissue. This is used as a back up option to immunosuppression as it can cause some harmful side effects.

What does immunosuppression cause (both drugs and x-rays)?

Immunosuppression will ruin the recipients immune system causing them to be more susceptible to infection. There are several methods to ensure after a transplant an infection does not occur. Antiviral drugs, anti-bacterial mouth wash or monoclonal antibodies instead of T-lymphocytes.

How do blood transfusions work?

Red blood cells also have antigens on their cell surface membrane, so when blood transfusions happen, we need to ensure it is compatible. As an antigen A cannot come into contact with an antibody a as it would cause agglutination (clumping together) of the red blood cell carrying antigen A. Agglutination is dangerous as it can cause blockage of capillaries leading to organ failure or even death. Blood group ABO is polymorphism due to the several distinct categories to form. Donor=antigen, recipient=antibody

Blood group A= antigen A and antibody b.

Blood group B= antigen B and antibody a

Blood group AB= antigen A and B and no antibody a or b

Blood group O= no antigen A or B and antibody a and b

Universal donor=O as it has neither A or B antigen

Universal recipient=AB as it has neither a or b antibody

What is the Rhesus system?

This is the presence or absence of an antigen D which is present on some red blood cells. Individuals who are Rh+ do not contain anti-D antibodies, those who are Rh- do not either unless during a blood transfusion there blood is contaminated with Rh+ or during pregnancy. During the first pregnancy and the child is Rh+ some of the foetal red blood cells leak into the mother Rh- circulation, this is known as a non-self cell and so antibodies are formed to destroy this, however these are made after the baby is born causing it no harm. During the second pregnancy if the same thing happens and some of the Rh+ foetal blood cells leak into mother circulation, the secondary response is rapid and will destroy these antigens D causing agglutination while the baby is still not born yet therefore causing haemolytic disease of the newborn. However this can be resolved by giving the mother after the baby is born antibody b injection. This will stimulate the antibodies to destroy the antigen D while also not creating any memory cells for next time.

Antibiotic resistant bacteria?

Antibiotics are used to kill bacterial infections. They usually work by inhibiting the enzyme involved in cells wall formation so the bacterial will be killed as the cell wall bursts, or due to inhibiting a metabolic process like protein synthesis, e.g erythromycin destroys ribosomes in prokaryotic cells. Most bacteria are now becoming resistant to the bacteria as when one bacteria becomes resistant it can reproduce rapidly by binary fission. The advantages of antibiotics are less treatments costs, productivity increases, less people sick.

What does disease spreads depend on?

How easily it it spreads, if there’s a vaccine, percentage uptake of vaccine, how likely someone will fall ill and if bacterial is it antibiotic resistant.

Epidemics and pandemics?

Epidemics- a small region of area with a larger number of people than normal affected.

Pandemic- multiple countries with thousands of people affected.

Viruses?

Viruses are now the main cause of pandemics and epidemics as they have a small genome that are prone to mutation. They are retroviruses which contain RNA, these are much less stable and they aren’t effected by antibiotics.

What are animals as reservoirs?

Animal species that carry disease causing pathogens and pass them onto to humans are known as reservoirs. They don’t receive any harm from the viruses as they are meant to transfer viruses to humans taking part in inter-species transfer. The main example of animal reservoir is bats. They are good examples of reservoirs as they are mammals and similar physiology to humans, they are very sociable animals and that’s how disease spreads more rapidly between bats. They also fly large ranges and are potentially in contact with many humans. The main way nowadays that inter-species transfer happens is by man entering bat habitats due to urbanisation and clearing of woodlands for hosing or agriculture.

What is ELISA?

ELISA has been a way of indicating infection earlier providing an earlier response and solution to pathogens. Using this we can detect pathogens and the cytokines used as biomarkers released during cell mediated immunity from the T-helper cells causing B-lymphocytes to clone to plasma and memory cells providing more immunity. ELISA (Enzyme linked immunosorbent assay) is a technique which involves antibodies, antigens, enzymes and other molecules. Using this method several pathogens can be tested for at the same time. So we add body fluids to wells on the plate, then we add particular antibodies for the disease we are testing for, the antibody has a enzyme attached and if an antibody-antigen complex forms then the enzyme will cause a odour change indicating the presence of the pathogen. This can be used to test for things like pregnancy, pathogens, cancer cells, cardiac disease.

How do pregnancy tests work referencing to ELISA?

As an egg is implanted in the uterine wall, a hormone hCG is released during pregnancy. So we can test for this hormone, on our plate we add the antibodies for the hCG hormone, add a sample of the individuals urine as that’s where the hormone is released. If an antibody-antigen complex forms this causes the enzyme attached to the antibody to cause a colour change, showing the individual they are pregnant

How do we test for viral antigens?

We use the ELISA plate to add the viral antigens on the plate then add a blood serum of the patient as if the patient has had or has the viral infection antibodies will indicate that. So if an antibody-antigen complex forms and then enzyme attached to the antibody will cause a colour change indicating the viral infection.