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Immune System summary notes

We use passive and active ways to protect ourselves from attack by foreign invaders (bacteria and
viruses).

Passive (physical barriers)

Behaviour – personal hygiene, cook food, safe water

Skin – upper layer of cells dead, sweat and oils contain anti-microbial chemicals – e.g., antibiotics.

Mucus membranes -mucus coats and immobilises pathogens. Cilia move mucus out of lungs. Mucus
contains lysozyme, which destroys bacterial cell walls.

Saliva- contains anti-bacterial and anti-viral agents.

Active (immune system)

Immune system – innate and adaptive (acquired) immunity

Cells of immune system.

Multipotent stem cells in red bone marrow divide and produce myeloid stem cells and lymphatic
stem cells.

Myeloid stem cells/progenitors form erythrocytes (red blood cells), megakaryoblasts, which produce
thrombocytes (platelets), and mast cells.

Myeloid stem cells/progenitors ALSO form myeloblasts, which give rise to eosinophils, basophils,
neutrophils, and monocytes. The monocytes give rise to macrophages and dendritic cells.

Lymphatic stem cells/lymphoid progenitors form small lymphocytes which give rise to T-lymphocytes
(or T-cells) and B-lymphocytes (or B-cells). B-lymphocytes give rise to plasma cells.

Lymphatic stem cells/lymphoid progenitors also form large lymphocytes called natural killer cells.

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Innate immunity – defences we are born with, responds quickly but in a non-specific way.

1 Cut with dirty knife – pathogens enter body.

2 Damaged tissue and mast cells both release histamine, which alerts the immune system of the
damage.

3 Histamine causes blood capillaries in damaged area to dilate (widen).

4 Pathogens recognised and phagocytosed (engulfed) by macrophages and dendritic cells, which
then secrete cytokines.
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5 Neutrophils and monocytes in blood migrate through capillary walls to get to the damaged tissue.
These cells also engulf the pathogens.

6 Blood clotting occurs in damaged blood vessels. Platelets release clotting factors that help the
blood to clot via formation of fibrin net to trap red blood cells.

7 In this way, pathogens are being removed to allow cells of skin and capillary to divide and repair
damaged areas.

Natural killer cells – from lymphoid lineage – destroy virus-infected cells and cancer cells. They
achieve this by identifying cells that LACK a cell surface receptor called major histocompatibility
complex class I (MHC-I). Natural killer cells bind to cells lacking MHC-I and punch holes in the
membrane.

Complement – made up of blood plasma proteins, which amplify (complement) some immune
responses.

1. Trigger release of histamine from mast cells.

2. Attract phagocytes.
3. On activation, these proteins form a membrane attack complex, which makes holds in the
walls of invading bacteria. This allows water and salts to enter until the bacterial cell bursts.

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Adaptive (acquired) immunity

Slower to respond first time, recognizes specific parts of pathogens.

Responsible for immune system memory.

Involves B-cells and T-cells. (B=bone, T=thymus).

Both B- and T-cells recognise antigens (on pathogens) because they have specific receptors.

Examples of antigens = sugars on cell wall of bacteria, receptors on surface of viruses.

B-cells

- Make antibodies (soluble proteins that are released into the blood, engineered to bind to
one antigen)
- The cells are activated in the lymph nodes and spleen.
- B-cell receptors (BCR) bind to antigens on invading bacteria/virus and respond via antibody-
mediated immunity.
- Each B-cell or group of B-cells have a different BCR.
- Once a B-cell recognises and links to a particular antigen, then it is activated.
- B-cell activation triggers an activated response, which leads to clonal expansion (cell
division), resulting in 100s of B-cells.
- B-cells stimulated to divide via cytokines, secreted from helper T-cells.
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- End up with clonal army of B-cells each with correct receptor, which will recognise the
antigen on the pathogen.
- Most of these B-cells become plasma cells. These turn the receptor protein into antibody,
which is secreted into the blood. This is how antibodies are made. Plasma cells have a short
life span, and they die via programmed cell death (apoptosis).
- Some B-cells become memory cells. These don’t make antibodies but just hang around in
blood. They replicate slowly but have the same BCR so if you are invaded by the same
pathogen again then the memory B-cells rapidly divide to give rise to a clonal army of
plasma cells so you are very quickly ready to attack the antigen again.
- Each invading bacteria or virus might have hundreds of antigens, and you can produce
antibodies to each antigen.
- The antibodies will attach to the antigens on the virus/bacterium. The pathogens are
inactivated because it is like them being coated in mucus. Also, if the antigen is a receptor
that the virus uses to get into cells, then the antibody attached to that antigen prevents the
virus from invading cells.

Antibody structure

Antibodies are Y-shaped made up of heavy and light chains.

Each chain has a constant (C) region and a variable (V) region.

It is the V-regions of the heavy and light chains that form the antigen binding sites.

Antigen recognition occurs due to VDJ recombination in the germline DNA. Unique to immune
system.

Light chains have V and J regions, heavy chains have V, D, and J regions.

During B-cell maturation, double-stranded breaks occur, and they are repaired the number of V, D,
and J sections varies a lot. This changes the variable region of the antibody slightly and because of
this, each B-cell recognises a different antigen.

VDJ recombination occurs BEFORE B-cell activation and clonal expansion, so after clonal expansion,
all the B-cells are genetically the same.

T-cells

T-cells don’t produce antibodies. They attack pathogens directly.

Educated in thymus because they cannot recognise antigen without help.

Antigen presented to T-cell by an antigen-presenting cell (APC). APCs have a major histocompatibility
protein (MHC) on surface.

Examples of APCs – dendritic cells, macrophages and B-cells.

Dendritic cell engulfs pathogen (e.g., virus). It then presents the viral antigen in the groove of an
MHC 1 antigen on its surface. T-cell recognises the viral antigen in this form, it is activated and
undergoes clonal expansion.
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T-cells are similar to B-cells because their recognition of an antigen is due to VDJ recombination.
Also, when T-cells respond to antigen, they are activated and undergo T-cell clonal expansion.

T-cells are different from B-cells because T-cells are only activated if antigen presented via an MHC
protein on another cells. Also, two types of T-cells – helper T-cells and cytotoxic T-cells.

Cytotoxic T-cells

Attack and destroy cells. Fine for pathogens (viruses and bacteria) but not for normal healthy cells.

Elaborate fail-safe system to ensure only activated in presence of pathogens.

This fail-safe occurs because T-cells have co-receptors (e.g., CD 8), which make sure that only
legitimate MHC-I proteins are recognised. Remember virtually every cell has an MHC-I.

The CD 8 on T-cells verify the MHC-I on the APC (dendritic cell) BEFORE the T-cell recognises the
antigen.

Infected cells can have a fragment of the pathogen on its MHC-I.

Infected cells include any cell that has been invaded by a virus or an APC such as a dendritic cell that
phagocytoses pathogens (virus or bacteria).

Therefore, MHC-I activates cytotoxic T-cells.

As well as MHC-I, there is MHC-II.

MHC-II ONLY found on specialised APCs such as dendritic cells.

Cytotoxic T-cells directly kill invading pathogens, infected cells, and cancer cells. These cells recognise
MHC-I, on all cells of the body.

Helper T-cells

MHC-II on APCs activates helper T-cells.

Helper T-cells generate cytokines, which help stimulate cytotoxic T-cells and B-cells to expand. These
cells recognise MHC-II, on APCs.

How do cytotoxic T-cells kill invaders?

Expanded clone of T-cells in blood

Dock on target cell

Vesicles in cytotoxic T-cells fuse with target cell membrane and transfer perforins to the membrane.

Perforins make holes in the target cell membrane. This changes the usual balance of ions and ATP in
the target cell.
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Cytotoxic T-cells ALSO contain enzymes called granzymes, which are proteases that trigger apoptosis
(programmed cell death), in the target cells without harmful substances being released.

Like B-cells, cytotoxic T-cells and helper T-cells undergo clonal expansion and maintain memory cells
in your circulation. This means that if there is recurrence of a viral infection or tumor then there is a
reservoir of cells that can be activated and expanded rapidly to mount a new defence. This is called
immune memory.

Immune memory is the basis of vaccination. Immunization involves priming the system, by injecting
dead viruses or bacteria into our body, to establish a memory in your system of a specific antigen.

In the case of vaccination, then if you do it right, it won’t make the person sick, but it will expose
them to the antigen that is on the pathogen. Both B- and T-cells are activated in this way.

We can see how memory works for immunization by measuring the levels of antibodies in the blood
plasma.

Passive Immunity

In addition to immunization by vaccination, there is also passive immunization.

Temporary – no memory cells.

Received from another person – e.g., during development and child-birth, and in milk during breast
feeding.

Also – anti-venom – ready-made antibodies against snake toxin.

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Lymphatic system

Linked to circulatory system (blood vessels) and immune system.

Lymphatic system

- Returns excess fluid from tissues back to blood stream.

- Absorbs fats from digestive tract and transports them to bloodstream.
- Defends the body against disease.
- T-cells and B-cells (lymphocytes) are cells of the lymphatic system.
- Consists of vessels of varying sizes.

Lymphatic capillaries, small closed-ended vessels with thin walls. These merge into larger vessels.
The larger vessels merge into major ducts in the thorax (body cavity).

Lymphatic system organs

Primary lymphoid organs

Red bone marrow – where B-cells and T-cells are made, and where B-cells mature.

Thymus – where T-cells mature and are educated to recognise ‘self’. T-cells that will recognise the
cells of the body are eliminated via apoptosis.

Secondary lymphoid organs

Where lymphocytes are activated when they encounter foreign molecules. After activation,
lymphocytes go into the blood and track down site of infection.

Spleen

Lymph nodes – trap invaders and expose them to lymphocytes.

Lymphatic capillaries

Dead end vessels with one-way flap-like valves, which let water and proteins into the lymphatic
system.

Water + proteins = lymph.

Lymph carries from lymphatic capillary to lymphatic vessel to lymph node.

If lymphatic vessel breaks, then lymph spills into tissues causing a swelling – edema.

Excess water in tissues can come from the blood capillaries.

Capillaries have constant osmotic pressure but hydrostatic pressure of the blood at the arteriole end
is higher than at the venule end. This higher net pressure at the arteriole end pushes more water out
of the capillary and into the tissues.
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All this water (can by 3 liters) is picked up by the lymphatic system.

Lymph nodes

Located along lymphatic vessels.

Packed full of lymphocytes (B-cells and T-cells). Also contain macrophages.

Lymph (water, proteins + garbage [bacteria and viruses]) passes through lymphatic vessels interacts
with lymphocytes in the lymph nodes.

Lymphocytes scan the garbage and deal with any pathogens.

This is where your immune defence is at its strongest.

Spleen

Consists of outer capsule, and inner red and white pulp.

Red pulp contains macrophages, which ingest old red blood cells

White pulp contains T-cell and B-cells, which are exposed to foreign invaders. These cells then go
into the blood serum and provide acquired immunity.

This organ can be ruptured following trauma. Not absolutely required but without it we are more
susceptible to infections.

Immune system disorders

Allergic reactions

Caused by substances that don’t normally harm the body (e.g., pollen, food, animal hair).

Antigens on these substances are called allergens – i.e., a substance that causes an allergy.

The immune cells that are responsible for the allergic reaction are the mast cells, which release
histamine.

Histamine causes blood capillaries to dilate. They become leaky, causing the fluid to leak out and this
causes edema. This is what happens to your nose if you inhale a pollen grain or some other allergen
– your nasal passages constrict because they are full of fluid…and then your nose runs.

To combat allergies, take an anti-histamine. Histamine levels drop, swelling goes down and runny
nose clears up.

Mast cells react due to antibodies called IgE on their cell surface. The allergen attached to IgE and
this stimulates the production of histamine.
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Incompatible blood types

If you are blood group AB, then you have antigens to A and B, and you don’t have any A or B
antibodies in your blood plasma. Therefore, you can only give blood to other people who are AB, but
you can receive blood from anybody (AB, A, B, O).

If you are blood group A, then you have antigens to A, and anti-B antibodies. Therefore, you can give
blood to people who are A or AB, and you can receive blood from people who are A or O.

If you are blood group B, then you have antigens to B, and anti-A antibodies. Therefore, you can give
blood to people who are B or AB, and you can receive blood from people who are B or O.

If you are blood group O, then you don’t have antigens to A or B, and you have both anti-A and anti-
B antibodies. Therefore, you can give blood to people who are any blood type (A, B, AB or O), but
you can only receive blood from people who are O.

Type A recipient + Type A donor = no red cell clumping. Everything is fine.

Type B recipient + Type A donor = red cell clumping because anti-A antibody (of recipient) binds to A
antigen in donor. This can lead to a stroke.

Tissue rejection

Unlike A and B antigens in blood, cells of heart of kidney have many different antigens on cell
surface. All will be recognised by recipient’s immune system as being foreign. The B-cells and T-cells
attack the new organ and kill it.

Very difficult to find a good matched of organs for transplantation between two different people.

Rejection can be made less severe by supressing the entire immune system. This gives the body time
to educate the thymus, so it recognises the new organ as ‘self’.

Autoimmune disease

Cytotoxic T-cells or antibodies attack a person’s own cells.

Myasthenia gravis – attack of neuromuscular junctions

Multiple sclerosis – attack of myelin sheath that surrounds nerve cells

Lupus – kidney damage

Rheumatoid arthritis – damages joints.