I’ve spent the last week or so learning about the immune system, something I find absolutely fascinating.
I thought I’d compile all the information to make a concise word document covering:
- Barrier defence
- Innate immunity
- Adaptive immunity
- Cell-mediated defence
- Humoural defence
- Autoimmune disorders
Here is a link to it as a word document: The Immune System
Sorry for the poor quality images, I have to convert my textboxes to JPEG files via paint… please let me know if there is a better way to do that!
Before a pathogen can even enter the body, it has to get past many external defences. This strategy aims to prevent pathogens from entering the body in the first place.
Skin – The biggest defence is the skin, which acts as a physical barrier – physically blocking entry. The skin is made of tough, keratinized dead cells which make penetration hard. Fatty secretions from the sebaceous glands also help to disrupt microbial membranes.
Saliva – Bacteria in the mouth can be flushed out and down to the stomach by saliva – which also contains antimicrobial agents like lysozyme and lactoferrin.
Mucous – The airways (pharynx, trachea etc) are lined with a thick, sticky mucous (secreted by goblet cells) which traps pathogens. The airways also have a lining of ciliated epithelium and the tiny hair-like cilia waft the mucous up to the back of the throat where it can be swallowed.
Urine – Urine helps flush out any pathogens in the genitourinary tract.
Stomach Acid – Finally, the stomach plays a big part. Parietal cells in the stomach lining produce hydrochloric acid which helps to kill many (but not all) of the microbes in digested food, saliva and swallowed mucous.
When you cut yourself, it breaches the physical barrier provided by the skin – meaning that pathogens have a way into the body. When the pathogen (e.g. bacteria) first enters the body, it remains unnoticed as it uses up the body’s resources in order to reproduce. Once a certain population is reached, the pathogens change their behaviour and start damaging the body by changing the environment around them.
However, the first thing your body does is try to stop you from losing too much blood through your damaged blood vessels. This is called Haemostasis. The blood vessels that have been damaged constrict to slow the flow of blood (so that you don’t lose too much) and the damaged epithelial tissue of the vessel wall now has collagen fibres exposed so that as blood flows over it, platelets react with the collagen and become sticky and glue-like. Fibrinogen from the blood is converted by thrombin (a clotting enzyme) into fibrin, which forms a mesh to trap platelets and red blood cells and reinforce the platelets that have already clotted. The strands of fibrin then pull the sides of the wall together so that the vessel can be repaired.
The inflammatory response acts as a message to the rest of the body to prepare for defence.
When the skin is broken, the skin cells (especially Mast cells) release chemicals, such as histamine, that act as messengers to the rest of the immune system.
The first thing histamine does is cause vasodilation. The blood vessels around the damaged area dilate and stretch. This means that more blood can flow to that area, so the site of the wound becomes red (increased blood flow) and heated (blood is warm). As the vessels stretch, they get thinner and small gaps emerge between cells. This makes the vessels permeable to fluids, so plasma and cell fluid start to accumulate in the tissue space. This is what causes swelling. As the tissue swells, it presses on nerves, thus causing pain.
Therefore, the signs of inflammation are:
This is actually a good sign that the body is preparing to repair itself.
As plasma flows through the permeable vessels, it brings proteins like fibrinogen and platelets. Just like with the blood vessel, this helps to form a clot and scab which can block the hole letting pathogens inside the body. The leaked fluid is then picked up by the lymphatic system and it is returned to the blood after filtration.
However, the important part of inflammation is that the histamine attracts lots of local phagocytes. When the skin is broken, it al The increased permeability of your blood vessels helps this by making it easier for the leukocytes to access the inflammation site.
Innate Immune System
The innate system is non-specific – it treats all foreign bodies equally and will respond to any threat in the same way, regardless of whether it has been encountered before. This makes it a very quick response, but most infections don’t get beyond this stage.
Neutrophils are the first to arrive, and they squeeze through the capillaries through a process called diapedesis before entering the tissue (this is possible due to their ability to signal the blood vessels to open up gaps between cells for them. They destroy the pathogens by phagocytosis, but they are very short-lived – they die as soon as they have destroyed the pathogen they targeted. The dead neutrophils then collect as pus. They are also the most abundant leukocyte, making up about 60% of all leukocytes in the body.
Macrophages (big eaters) don’t move around as much or as quickly as the neutrophils. They remain in organs in case of infection so they may be the first to respond. They act almost as bodyguards. These cells have much longer life spans and can eat up to 100 pathogens before dying. Macrophages can be free and able to move around tissues looking for pathogens, or fixed and attached to fibres in specific organs where they lie in wait for any passing pathogens. Quite a lot of macrophages are “resident” in a certain tissue and stick to this area (unlike the neutrophils which move around and flock to where they are needed).
Macrophages also help clear up dead cells and debris as well as anything with foreign antigens.
The final type of phagocyte is a Natural Killer Cell. These are still part of the innate system, and they are cytotoxic cells – this means they destroy human cells as well as pathogens. Body cells have surface receptors called the Major Histocompatibility Complex (or MHC), and these receptors provide information about the cell. Natural Killer Cells monitor these receptors, as an infected cell will avoid displaying (or stop producing) them to evade detection. Natural Killer Cells are activated when they detect reduced numbers of MHC receptors on a cell’s surface, and the NKC will then bind to the infected cell (be it a host to a virus, or a malignant cancer cell) and secrete cell membrane dissolving enzymes into it to enable its destruction.
If this is not enough to defeat the pathogen, then the adaptive/specific immune system is activated.
This response is started off by antigen-presenting cells, which include dendritic cells and also macrophages (which display the antigens of pathogens they have ingested). The cells line all surfaces that come in contact with the environment. After exposure to a pathogen, the dendritic cell is activated. It engulfs the pathogen then displays short peptide chains from the pathogen it has just consumed on its MHC II receptors. It then migrates to the lymph nodes. Here, it presents the antigens to T and B lymphocytes – depending on the required response.
Macrophages are also capable of antigen presenting.
APCs present the microbial antigen first to a helper T-Cell – this has to be a specific type of T-Cell that can recognise it. Information about the pathogens location and properties are communicated through chemicals called interleukins (signalling molecules produced by leukocytes) – specifically interleukin 1. The helper T Cells then travel around the body releasing other interleukins to alert the rest of the immune system and activate other cells. They also serve as confirmation during the initiation of lymphocyte – without which the lymphocyte will remain dormant. They help to organise and coordinate the whole response.
It is important to have Helper T Cells acting like messengers as there are only a few lymphocytes of each specificity (lymphocytes specialise to only recognise one type of antigen). Rapid circulation helps to increase the chance of them encountering pathogens, but they still need Helper T Cells to confirm the threat and initiate replication (this is done via lymphokines).
The KT Cells then migrate to the site of the infection via the blood and lymphatic vessels. They are directed by tissue recognition and the information they have on location as well as by the effects of inflammation and cell damage (e.g. increased tissue permeability).
This response targets pathogens that infect cells.
If the pathogen is a virus or parasite (or even some bacteria) then it is likely that cells will be infected. This is dealt with by Killer T Cells. Once a KTC has encountered a corresponding antigen, it will wait for confirming signals from an HT cell before becoming activated. It then undergoes clonal expansion – a process whereby the matching cell divides into many clones that can then specialise themselves. Effector cells exit the lymph nodes and locate the pathogen that the original KT cell was imprinted with (all clones will have the location/pathogen information presented to the initial KTC by the HT cell).
Memory cells are also formed, and these stay in the lymph nodes in order to quickly recognise the pathogen and provide a rapid response if it ever infects the body again.The KT cells created all have a receptor for the specific antigen representing the pathogen. They then monitor body cells in the infected tissue for this antigen (which will be presented by an infected cell’s MHC receptor). When the KTC recognises the antigen, this means the cell is infected, and the KTC will then proceed to destroy it by releasing granzymes (cytotoxic molecules). These penetrate and pierce the cell membrane to induce cell death – this is known as apoptosis. The important part of this process is that it degrades the contents of the cell (thus killing the cell and the pathogens inside) without releasing the infecting components to limit their spread.
Humoural (or antibody mediated)
Cells are not always infected by pathogens. The humoral response, therefore, targets extracellular pathogens – ones that are in infecting tissue fluids or the blood. These are often bacteria.
The lymphatic system filters the body’s fluids, so if they are infected, the responsible pathogen will eventually be conveyed to the lymph nodes (or to the spleen via the blood). Most of the clones will differentiate into effector (or plasma) B cells. These then locate the infection and produce antibodies that match the parent cells specificity. The antibodies bind tightly to the antigens on the invading pathogen’s surface and disable/immobilise it – making it easier to destroy. They also flag the pathogen as a threat and attract other immune cells (phagocytes), as well as activating the complement system, so that the pathogen can be destroyed.
Antibodies cannot kill the pathogen themselves.
As with the cell-mediated system, some B Cells differentiate into memory cells. Again, this means that in the case of a future infection, the pathogen will be quickly recognised and large amounts of the right antibody will be produced quickly.
For a person with hypersensitivity, when the body is first exposed to an allergen (such as pollen), the white blood cells respond by producing antibodies. These antibodies then bind to mast cells, which means that if the allergen enters the body again, they will bind to the antigens on the mast cells and activate them. The mast cells have stores of chemicals in coarse granules within the cytoplasm. If an allergen links two or more antibodies on the mast cells surface together, then degranulation will be triggered, and the granules will release chemicals like histamine and interleukins.
This process also occurs if a mast cell is damaged by a pathogen – which is what triggers inflammation during an actual infection.
Histamine then binds to the receptors on nearby cells and causes an allergic response:
Vasodilatation – blood vessels dilate allowing leading to increased blood flow (to help white blood cells travel to the site quickly) and increased blood vessel permeability (which in turn causes fluid to collect in the area causing swelling or hives).
Nasal Symptoms – dilated vessels contribute to congestion (blocked nose) and histamine also causes goblet cells to hyper-secrete mucus (a runny nose).
Neurotransmitter – histamine can act as a neurotransmitter, and when they bind to receptors on nociceptors (pain sensing neurones), they produce an itching sensation.
Tear Production – increases tear production to cause watery eyes.
Smooth Muscle Contraction – this is responsible for breathing difficulties and shortness of breath as the airways tighten.
Antihistamines are antagonistic drugs used to control allergic reactions. The antihistamine binds to the receptor and prevents histamine from affecting the cells (because it has to compete with the antihistamine that is already bound).
Autoimmune Disorders (self-sensitivity)
Autoimmune disorders occur when the immune cells are unable to recognise the body’s antigens as “self-antigens”. Instead, they are seen as foreign, and therefore a threat. This leads to the immune system attacking healthy cells.
T cells will attack body cells and B cells will produce autoantibodies (antibodies that bind and to and damage self-antigens). This causes organ damage and inflammation.
It is also thought that the disorder is triggered by a viral or bacterial infection – it is thought that during the infection, B Cells mutate to respond to the infection and these mutations can result in B Cells attacking healthy cells.For unknown reasons, autoimmune disorders affect women more than men, with 2/3 sufferers being female.