The Immune System
The ability of an organism to resist disease.
What makes up the human immune system?
1) The lymphatic system
Thymus gland (site of T-cell maturation)
Peyer patches/ GALT/ MALT (specialised lymphoid tissue containing immune cells located in the lining of the small intestines).
2) Bone marrow (site of B-cell maturation)
3) White Blood Cells (WBC) - 2nd line of defence
Lymphocytes (T-cells and B-cells)
Phagocytes (neutrophils, monocytes/ macrophages)
Basophils (mast cells)
4) 1st line of defence:
Body fluids (tears, saliva, stomach acid, vagina mucous)
Psycho – Neuro – Immunity (PNI)
Includes the interplay of the following 3 aspects and its influence on immunity:
State of mind
When a person is depressed, their immune cell responses are slower and the number of circulating immune cells (in the blood) are lower.
The immune system has two forms of defence against invading pathogens:
(bacteria, viruses, fungi and parasites)
1) Non-specific immunity (innate immunity):
1st line of defence:
Body fluids (tears, saliva, stomach acid, vagina mucous)
Cilia (tiny hairs found in the lungs and nasal passages which traps and expels pathogens)
2nd line of defence:
Phagocytes - specialised non-specific immune cells: travel in the blood and “eat” pathogens by a process known as phagocytosis.
2) Specific immunity (humoral immunity):
3rd line of defence:
Specific cellular immunity
Self vs non-self recognition:
An antigen is a type of protein, located on the surface of all cells. Their function is to “label” cells.
Self-antigens are determined genetically and are unique to every individual (no two people will have the same antigens except identical twins). Antigens tag your cells and help your immune system to recognised your cells as “human” and unique to your DNA, which prevents the immune system from attacking your own cells - as in the pathology; autoimmunity.
Non-self-antigens are antigens which are NOT recognised by your own immune system and are therefore considered foreign invaders (pathogens, allergens, drugs). When your immune cells come into contact with a non-self-antigen, they will produce antibodies which will activate a full immune attack against the foreign cells. This process takes place when any pathogen (bacteria, virus or parasite) enters the body. Another situation where this may happen is when the body (immune system) rejects an organ transplant, since the cells of the organ will contain foreign antigens from another person whose DNA differs from yours.
Self-tolerance is the ability of the immune system to differential between self-antigens and non-self-antigens. This is a learnt process which takes place during the maturation of immune cells, prior to being fully developed and released into the blood stream to perform their specific function as immune cells.
Immune cells gain self-tolerance during cellular maturation in the thymus gland (T-cells) and bone marrow (B-cells)
Interestingly, the RBC (red blood cell), is the only cell in the human body which does not contain self-antigens but instead carry their own type of antigen, these specialised antigens are known as “blood types” and each of us carry one of the 4 types of blood antigens; A, B, AB or O.
Antibodies are a type of protein produced by B-cells (type of immune cell) in response to foreign antigens (found on the cells surface of invading pathogens). There are 5 main types of antibodies; IgG, IgM, IgA, IgD, IgE.
Specific Cellular immunity:
There are many different types of immune cells which are responsible for defending and protecting the body against invading pathogens, these include:
When a B-cell comes into contact with a foreign antigen, they become “triggered” and start to divide into:
Plasma cells - which produce antibodies
B memory cells - which retains a memory of the foreign antigen as non-self this is known as immunological memory (this process allows the body to build an “immunity” against foreign antigens).
When a T-cell comes into contact with a foreign antigen, they become “triggered” and start to divide into:
Cytotoxic T-cells - directly attack and kill cells with foreign antigens
T-helper cells - stimulates the immune response by activating other immune cells
T-suppressor cells - supresses the immune response by inhibiting other immune cells. (problems with T-suppressor cells may lead to autoimmunity, which is when the immune system starts to attack its own body cells – self-antigens).
Natural killer (NK) cells:
NK cells play a major role in destroying virally infected cells by releasing cytotoxic factors which causes programmed cell death (apoptosis).
2) Phagocytes: these cells “eat” pathogens!
Mast cells – release histamine which creates an inflammatory response: heat (fever), redness, pain, swelling. “acute inflammation” creates a hostile environment for pathogens and promotes innate healing.
Involved in fighting parasitic infections and is involved in allergic responses.
What causes our body temperature to rise?
The hypothalamus is an endocrine gland located in the brain which controls our body temperature, a normal body temperature range is set at between 36.5°C and 37.5 °C. This is the optimal temperature at which our human body functions which is closely related to enzymatic function (enzymes are made of protein, which will begin to denature (deform) at higher temperatures - without enzymes our body will lose its ability to function).
Since pathogens thrive in lower temperatures - the hypothalamus intentionally increases our body temperature to create a hostile environment for invading pathogens, which reduces their chances of survival within us. Therefore, an abnormally high body temperature is common during an active infection. Furthermore, an increase in body temperature makes the immune system more effective at fighting against the invasion of pathogens however, a prolonged high fever needs to be monitored to prevent the potential loss of enzymatic function = organ failure.
The phenomenon of “immunological memory” is at the basis of vaccinations.
A vaccine contains = attenuated (weakened or dead) portions of microbes. These microbes are immunogenic and NOT pathogenic, which means that they active an immune response but they do not actually cause the illness. By activating white blood cells (T-cell and B-cells), the body (immune system) is able to store a memory of the foreign antigen, which is artificially injected into our bloodstream via vaccinations. The success of vaccinations is due to this initial sensitisation of the immune system, so that when the body is exposed to these same foreign antigens for the second time, the immune system immediately recognises them (due to stored memory from vaccines) and is therefore, more effective at mounting an attack and overcoming the pathogenic invasion.
How do pathogens invade the human body?
Break in the skin
Caused by a pathogen (bacteria, virus, fungi or parasite)
Acute infection (days – weeks)
Chronic infection (months – years)
Prodromal period = incubation period:
Infected person will be asymptomatic (will present with no symptoms), during this period the pathogen is already invading the body and is looking for favourable conditions within its human host to multiply. Infections are readily spread from person to person during the incubation period, as people do not know that they are infected.
After the incubation period, once the pathogen successfully begins to multiply within the body (host), the infected person will start to express strong symptoms.
Some people are more susceptible to contracting infections than others, factors which put people at a higher risk include:
Age (babies/ young children and the elderly) - due to immature/ compromised immunity.
Being bed bound – toxic fluid fails to drain in a prone position.
Unlike other pathogens, viruses are acellular, which means they are not cells nor do they contain normal cellular components.
A virus is made up of strands of nucleic acid (genetic material), either DNA or RNA, which is surrounded by a protective coat called a capsid which is made up of protein.
Sometimes the capsid is surrounded by an additional spikey glycoprotein coat called the envelope.
Unlike other pathogens, viruses are only alive and able to replicate inside the cells of other living things. The cell in which it replicates is called the host cell. Viruses use their spikey outer surface to latch onto and penetrate host cells.
Once the virus is inside the host cell it uses the host cell’s machinery (cellular components) to replicate its own genetic material (RNA/ DNA). Once the virus successfully replicates itself, viral particles leave the host by either budding or bursting out of the cell (lysis).
Once a new viral particle is formed within a host cell, it pushes itself up against the hosts cellular membrane, the membrane responds by creating an “envelop” around the new virus, this is known as the viral envelope. The new virus is then released from the host cell in a process called “budding”. Overtime, this process uses up the entire membrane of the host cell (to create viral envelopes), which leads to host cell death.
The virus particles burst out of the host cell into the extracellular space resulting in the death of the host cell. Once the virus has escaped from the host cell it is ready to enter a new cell and replicate.
How does the human immune system fight against viruses?
When a virus infects a person (host), it invades the cells of its host in order to survive and replicate. Once inside the host cells, the immune system cannot “see” the virus and therefore does not know that the host cells are infected. To overcome this, infected cells employ a system that allows them to show immune cells that they are infected with a virus and should therefore, be destroyed. They use MHC proteins (major histocompatibility complex) which includes fragments of proteins made by the virus. These MHC proteins are displayed on the surface of infected cells.
There are two types of immune cells which recognised and destroy any infected cells which display MHC proteins on their cell surface, they are called cytotoxic cells and include:
Natural Killer cells
Mechanism of action
Cytotoxic cells (cytotoxic T-cells and NK cells) release cytotoxic factors when they come into contact with an infected host cell, this triggering of cytotoxic factors is due to the presence of MHC proteins on the surface of infected cells. There are two types of cytotoxic factors that these cells use to penetrate and destroy infected host cells which include; perforin (type of protein) and granzymes (specialised enzymes). Once inside the target cell, they initiate a process known as programmed cell death or apoptosis, causing the infected host cell to die (self-suicide).
Another cytotoxic factor is granulysin, which directly attacks the outer cellular membrane of infected host cells, destroying it by a process known as lysis.
As soon as a cytotoxic cell comes into contacted with an infected host cell, it produces and releases inflammatory cytokines (interferon-g and tumour necrosis factor-a) these cytokines alert and active cytotoxic T-cells to kill infected host cells, speeding up the fight against the replicating virus!
Infected host cells, produce and release interferons (type of protein), which directly interferes with the ability of a virus to replicate within an infected cell. Interferons are also “signalling molecules” which means that they have the ability to warn nearby host cells that there is a virus present – this signal causes nearby cells to increase the amount of MHC proteins upon their surfaces, so that cytotoxic T-cells can better identify and destroy the infected host cells.
Viruses can also be destroyed by antibodies before they get the chance to infect a host cell. Antibodies recognise invading pathogens and bind (stick) to them. This binding serves many purposes in the destruction of viruses:
1) Antibodies neutralise the virus, meaning that it is no longer capable of infecting the host cell.
2) Agglutination is the process whereby many antibodies work together, to “stick” virus particles together. Agglutinated viruses (multiple viruses bound together) are easier for cytotoxic cells to kill than single viral particles.
3) Antibodies can activate the immune cells; “phagocytes” (neutrophils, monocytes/ macrophages). These immune cells “eat” viruses that are bound to antibodies, this process is known as phagocytosis.
4) Antibodies can also activate the complement system, which promotes phagocytosis – the “eating” of viruses by immune cells. The complement system can also damage the viral envelope (outer spikey layer of viruses), impacting their ability to enter host cells.
Coronaviruses (CoV) are a large family of viruses
Some are mild and can the common cold
Others are more severe and cause diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV).
Coronaviruses are zoonotic, meaning they are transmitted between animals and people.
Investigations found that SARS-CoV was transmitted from civet cats to humans and MERS-CoV from dromedary camels to humans. Several known coronaviruses are circulating in animals that have not yet infected humans.
Coronaviruses are named after their appearance: Under the microscope, the viruses look like they are covered with pointed structures that surround them like a corona, or crown.
A newly identified type has caused a recent outbreak of respiratory illness, which is called COVID-19.
COVID-19 first appeared in Wuhan, a city in China, in December 2019.
The incubation period for COVID-19 is 14 days, this means that infected people can be asymptomatic (without symptoms) for up to 14 days from the initial exposure to the virus. Although during this time (incubation period) they can still spread and infect others with the virus.
There is no COVID-19 vaccine nor any current anti-viral treatment (antibiotics only work against bacterial infections NOT viral infections).