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The immune system

Immunity against invading pathogens is a crucial part of maintaining health. The body has adaptations which prevent invasion by pathogens, as well as processes in place to deal with those that manage to penetrate the body's primary defenses. The skin and mucous membranes (e.g. mouth) are examples of such defenses. Sweat contains lysozyme which is an enzyme that breaks down bacterial walls. Stomach acid also destroys microorganisms that are ingested.

If pathogens do invade the body, the subsequent immune response is split between:

1. Non-specific
2. Specific

The non-specific immune response is inflammation and phagocytosis. The specific immune response involves the formation of memory following an infection, in order to better fight and prevent recurrent infections by the same agent that is highly specifically identified.

Neutrophils are the most abundant white blood cell that identifies foreign agents in the body and digests them by phagocytosis.




Opsonins are part of opsonisation, and are antigens that mark invading particles for phagocytosis. The plasma membrane of a phagocyte envelops the invading agent, forming a phagosome vesicle. This fuses with a lysosome that contains the digestive enzymes that will break down the invading agent.

Macrophages are present in tissue and have a similar phagocytic function, but additionally present fragments of the invading agent as antigens to the type of lymphocyte (T cell) that requires this information to identify the invader and mount a specific response against it.

All these cells are able to produce small proteins called cytokines that act in cell signalling to bridge the cell-mediated and humoral responses and regulate the action of all the different cells available.

Different cells have different molecules presented on their surface to the immune system. These are often protein-based and enable the identification of:

-pathogens
-cells from other organisms of the same species
-abnormal body cells
-toxins

The specific immune response is split into humoral immunity and cell-mediated immunity. Humoral is to do with the blood and antibodies. Distinguishing between an antigen and an antibody is very important.

Antigen = protein or carbohydrate foreign (not normally present) to a host's organism
Antibody = protein made as a response to detecting an antigen which binds to the antigen and prevents the pathogen from harming the host.



Alongside the previously mentioned opsonisation, antibodies also serve to agglutinate pathogens upon binding. Agglutination is the clumping together of particles to form a larger mass that attracts phagocytes.


Humoral response

Antibodies are made by B cells or T cells which come from stem cells from bone marrowB cells release antibodies, while T cells secrete antibodies which stay on the surface of the cell. Helper T cells stimulate cytotoxic T cells, B cells and phagocytes.

B cell --> O - -   -   - - -
T cell --> O-

where "-" is an antibody. Apologies for the horrendous visual representation.

So when a bacterium invades, B cells would release antibodies with a shape complementary to that of the bacterium's antigen. This antibody would then bind to the antigen. T cells on the other hand would secrete the antibodies on their surface, then personally greet the bacterium and bind to it via the antibody. You could say the B cell is shooting the bacterium, while the T cell is strangling it. But for goodness' sake, don't write that in the exam.

When a pathogen invades the body and a B cell releases the appropriate antibody to manage the infection, it's not just the one B cell. They come in their thousands, they are clones of a B cell with a specific antibody, and they are called plasma cells. Plasma cells release a high amount of antibodies, but they are short-lived. Other cells called B memory cells may survive for much longer, up to several years. Memory cells such as memory T cells are involved in the secondary immune response which happens if a high enough amount of antigens are present. The memory cells replicate into a large number of plasma cells which then release enough antibodies.

T regulatory cells (suppressor T cells) eventually deactivate the immune response by both B and T cells.

When a pathogen invades the body and a B cell releases the appropriate antibody to manage the infection, it's not just the one B cell. They come in their thousands, they are clones of a B cell with a specific antibody, and they are called plasma cells. This response is called clonal selection and expansion

Plasma cells release a high amount of antibodies, but they are short-lived. Other cells called memory cells may survive for much longer, up to several years. Memory cells are involved in the secondary immune response which happens if a high enough amount of antigens are present. The memory cells replicate into a large number of plasma cells which then release enough antibodies.


Common flu

OK, so if we have all these fancy cells doing our work for us, how come the cold virus gets us again and again and again? Surely our memory cells could identify the cold virus, replicate and defeat it?

Memory cells are specific to certain antigens. The flu virus has many different variations of antigens which change constantly, so by the time we've acquired some resistance to this year's antigen, a new one will have emerged.


Cell-mediated response

The response not dependent on antibodies involves all the aforementioned phagocytosis-inducing cells like macrophages and neutrophils, as well as cytotoxic T-lymphocytes and the cytokine response to invaders.

White cells (the most common ones are neutrophils) engulf any foreign particles such as dust or bacteria, then digest them and dispose off of the remains. It's badass, trust me. I've got proof:


The enzymes used to break invaders down are lysosomes which fuse with the vesicle which contains the bacteria. All this action happens within the white cell. At the end, the undigested leftovers are disposed off of by exocytosis (kind of like a burp).

T killer cells (a.k.a. cytotoxic) recognise their target and release toxic chemicals to kill them.




The blue cell in the centre is a tumour cell, while the surrounding cells are killer T cells about to release their toxic cargo found in the vesicles stained red. Bye-bye, tumour cell.


Hay fever

Hay fever is an example of immune response hypersensitivity. Is is a cold-like condition (minus fever) caused by exposure to "hay", more specifically the pollen of plants. Therefore it comes on seasonally.

Exposure to pollen results in the mounting of an immune response to its antigens, and the production of histamine by mast cells (white blood cells). Histamine regulates inflammation and causes the symptoms of watery eyes, runny nose, sneezing and swelling.

Early exposure to animals and multiple siblings is associated with a decreased risk of developing hay fever (allergic rhinitis). Other conditions of the immune system are associated with allergic rhinitis, such as allergic conjunctivitis, asthma and atopic dermatitis.

Other allergies are also rooted in the hypersensitive response of the immune system.

Our natural immunity does not cover certain pathogens such as the flu virus. Vaccination attempts to induce artificial immunity which is an add-on to our natural immunity, by adding an artificially triggered response specific to a new pathogen that we did not have innately.

Active immunity refers to immunity acquired as a result of an illness. This is also the type of immunity induced via vaccination, as the body is responding in the same way when it encounters the pathogenic antigen and responds appropriately.




Passive immunity is the type of immunity acquired directly via the relevant antibodies rather than by developing them afresh following disease or other ways of contacting antigens. An example is the immunity passed to a foetus via the placenta during gestation.


Antibody and antigen tests for TB and HIV

Antibody testing is done to check if blood contains specific antibodies of the TB bacterium or HIV. A positive result indicates the patient has mounted an immune response against the pathogen and is therefore infected.

Antigen testing looks for antigens of the pathogen present in blood. Monoclonal antibodies are used to detect these antigens.


Monoclonal antibodies

These are antibodies which can be cloned from a single cell to make a high amount of them. They can bind to pretty much any substance, and are used in pregnancy tests as well as cancer treatment.The process involves taking a cell which produces antibodies such as a lymphocyte, and crossing it with a tumour cell. Tumour cells divide uncontrollably, so the end hybrid cell will produce many antibodies via its many clones.

The high specificity of the antigen-antibody bond makes use of antibodies as a lab technique high on the list. Antibodies are used with proteins as a labelling method to detect presence of the target moiety (in biochemical reactions, testing or disease detection), or with whole tissue samples to detect presence of specific organelles for visualisation under a microscope.


Immunoassays

Assays are carried out in multi-well plates to detect the presence of a specific antigen, against which an antibody is added. If the antibody binds to the antigen, it causes a shift in a reporter enzyme added or linked to it, resulting in a colour change quantifiable by a spectrophotometer.

Antigens are any identifiable, specific parts of a molecule, and can be found on proteins, tissue samples, patient samples, pathogens, etc. Antibodies recognise antigens specific to them. The antigen-antibody relationship is at the heart of an organism's self-identification and identification of invading species.




The enzyme-linked immunosorbent assay (ELISA) is a common immunoassay used to detect antigens in samples. It relies on adding the samples to a multi-well plate made of polystyrene, that can immobilise the antigen-containing molecules. The specific antibody is then added and allowed to bind, if it is to bind. After washing away the unbound molecules, the reporter enzyme is added to produce the colour change. Voila!

There are other versions of ELISA where the "capture" antibody is immobilised to the plate well instead of the sample, and the sample is added on top. The key principles of antigen-antibody binding, and antibody-indicator binding/activating are the same.

The antibody for the antigen is the primary antibody, while the "second antibody" binding the primary antibody (if applicable) is the secondary antibody. The latter can be the one with the indicator attached that produces a colour change.

TB and HIV antigens or antibodies can be used in ELISA to test diluted blood samples.

The Mantoux test for TB uses the antigen tuberculin which is administered intradermally and left for a couple of days to allow for an immune response to build up. It tests for presence of antibodies in the blood.




The diameter of the skin test site that has raised (induration) e.g. 5 - 15 mm across, is used alongside the known risk factors of the individual to interpret the test result. Risk factors include exposure to someone with TB, travel to or from a high TB risk area, HIV infection and being immunocompromised. Presence of risk factors requires a lower induration value to give a positive result i.e. the patient has TB. Absence of risk factors requires a higher induration value to give a positive result.

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