IMMUNE SYSTEM

1. THE NORMAL IMMUNE SYSTEM

For an immune response to occur the immune system must first identify
foreign material.
Most foreign material can be identified by the unique antigens (=a
substance that enters the body and starts a process that can cause
disease) which are present on its surface.

The immune system provides protection against foreign threats to the

body.
Several different mechanisms contribute to the overall function of the
immune system.
Broadly these can be divided into two groups: non-specific or innate
immunity and specific or acquired immunity.
In the normal immune system, non-specific and specific immunity work
hand in hand.

White blood cells are largely responsible for the immune response.
The innate response is non selective, while the acquired response is highly
specific and based on memory.
Memory refers to the process that occurs when the immune system
mounts (=organize and begin something) a response to foreign material.
The first response is generally quite slow, and as result of the foreign
bacteria or viruses have the opportunity to cause disease.
After the immune system has encountered a foreign material once, it is
then primed (=prepare somebody for a situation so that they know what
to do) to mount a rapid powerful response should it encounter the foreign
material again.
This is memory.
The fast and powerful response by the immune system frequently
prevents disease occurring, and is the basis of vaccination.

Phagocytic white cells (usually macrophages) engulf (=surround or to

cover something completely) and destroy foreign cells.
 They are responsible for innate immunity.
The white cells involved in innate immunity take antigens from the foreign
material and "present" then to the cells involved in acquired immunity,
thus switching the acquired immune response on.

The lymphocytes are responsible for acquired immunity.

Lymphocyte memory is enhanced by each exposure to the foreign
material.
There are two main lymphocyte types.
The B lymphocytes are responsible for producing antibodies (=a substance
that the body produces in the blood to fight disease) that combine with
antigens the surface of foreign cells making them easier to destroy.
The antibodies present in the blood are also known as immunoglobulins.

There are a variety of T lymphocytes.

T-helper cells are responsible for switching on the immune response.
This occurs when macrophages show them the antigen they have removed
from the foreign material.
The T-helper cells then produce chemicals known as cytokines that
stimulate other T and B lymphocytes.

The following flow chart will help to clarify the process:

Foreign antigen ingested by macrophage
Macrophage presents foreign antigen to T (helper) cell
T (helper) cell produces cytokines
Cytokines stimulate T (cytotoxic) cells and B lymphocytes
T cytotoxic cells destroy cells with the foreign antigen on its surface,
while B lymphocytes produce antibodies which combine with the foreign
antigen and make the cell easier to destroy.

The combination of antigen with antibody is recognised by phagocytes

which engulf (or eat) the foreign material.

Some activated T and B lymphocytes become memory cells, which remain

in the circulation, prepared to mount a large and rapid immune response
should the antigen which they are seeking be found again.
 Virus infected cells, and many tumour cells will express foreign antigens on
their surface.
Thus the immune system is an important defence against viral diseases
and cancer.
The immune response to these cells is achieved almost solely by the T
lymphocytes.

The body will not normally attack cells with self antigens which were
present in the body during early foetal life.
However, sometimes self attack may occur, producing an autoimmune
disease.

The immune system may be suppressed by malnutrition, concurrent

(=existing or happening at the same time) disease, stress and drugs
(particularly immunosuppressive drugs and corticosteroids).

2. AGEING AND THE IMMUNE SYSTEM

The function of the immune system decreases with ageing, although the
changes vary across different cell types.

T cells
With ageing, there is decreased output of nave T cells, which are capable
of responding to new antigens.
The immune system becomes less able to respond to new challenges.

The production of cytokines, which are needed to stimulate the immune

response, decreases with age.
In addition, the cellular response to cytokines is also decreased.
Consequently, the proliferation (=the sudden increase in the number or
amount of something) of T lymphocytes is limited.
It becomes harder to switch the immune response on.

The proportion of memory cells in the T lymphocyte population increases

with ageing.
 However, the memory T cells become less efficient as people age so
effectively the immune system struggles to remember if it has
encountered a pathogen before.
The immune system becomes less able to cope with pathogens it has
encountered before, including encounters due to vaccination.

It appears that the CD8 (cytotoxic) T cells are unaffected by ageing.

The cells are particularly effective against viruses, and it is possible that
the production of vaccines that stimulate these cells will offer good
protection against viral infections in the aged in the future.
The effects of ageing are not uniform.
Some cell types are affected more than others.

B cells
The effect of ageing on the B lymphocytes appears to be less dramatic
than the effect on the T cells.
Some studies have reported a decrease in B lymphocyte activity, whilst
others have found no change.
B cells-the antibody producing cells-are less affected by ageing than T cells.

Few changes in immunoglobulin levels of any significance have been

reported.
The effects of ageing are not uniform.
Some cell types are affected more than others.

How does the general function of the immune system change with ageing?
Are the effects spread uniformly across the different parts of the immune
system?
As we would expect from the module is preceding this one, there is a general
decrease in overall in function as a person ages.
However it is important to emphasise that we are talking about overall function
- activity in some parts of the immune system will be significantly affected,
whereas other parts of the immune system be less affected.

Innate immunity
 Phagocytic cells in aged people are often less effective at killing bacteria
than those in younger people.
The activity of the cells that present the foreign antigens to the
lymphocytes may also be decreased.
There is a decrease in the function of the innate immune system.
This may make it more difficult to activate the acquired immune system.

A decrease in immune function will increase the likelihood of infections and

neoplasms in the aged.
It may also explain the observation that diseases which have been controlled by
the immune system for many years can become reactivated as people age.
Examples include tuberculosis and shingles (=A reactivation of the chickenpox
virus in the body, causing a painful rash).

Decreased immune function may also be responsible for the generally poorer
response to vaccination in the elderly.

3. VACCINATION

Although the previous comments have indicated that the efficacy of vaccination
may be decreased, older people should be vaccinated.
In fact, vaccination is extremely important.

Vaccination works by alerting the immune system to the existence of a foreign

antigen.
In other words it puts the immune system on alert.
The immune system has memory, and mounts a rapid and intense immune
response against foreign antigens it has been previously exposed to.
By introducing a foreign antigen (in a non pathogenic form) into a person,
immune memory can be stimulated without the development of disease.

Vaccination is strongly recommended for the elderly.

The current Australian recommendation is that everyone aged sixty-five years
and over should receive an annual influenza (=flu) vaccination, and should be
vaccinated against pneumococcal disease (=Illnesses range from mild
infections, such as ear infection, to pneumonia and life-threatening infections of
the bloodstream and central nervous system, such as meningitis).

Vaccination never provides perfect protection against disease, even in young

people.
Just because someone has been vaccinated, it doesnt mean they wont get the
disease.
Influenza vaccines are only 30 to 40% effective in people aged 65 and over, and
the effectiveness of tetanus (=a disease in which the muscles become stiff)
vaccination decreases from the age of 40.
Although the normal recommendation is that tetanus booster (=an extra small
amount of a drug that is given to increase the effect of one given earlier, for
example to protect you from a disease for longer) vaccinations be administered
every 10 years, by the age of 60, 16% of people vaccinated within the previous
five years are no longer fully protected against tetanus.
However, if they do develop the disease, its severity and duration may be
decreased.

There are several possible reasons why vaccination becomes less effective with
age.
The first potential reason for failure is that the immune system does not
respond to the vaccine in the appropriate way.
If someone has a suppressed immune system due to disease, malnutrition,
drugs or age related changes, the immune response stimulated by the vaccine
may not be sufficient to protect against the development of disease.
Another possible reason for failure is that the vaccine did not contain the
antigens specific to the disease.
For example, the influenza virus frequently changes its antigenic structure.
This means that a vaccine which was protective in one year may be ineffective
the next.
Another possible reason is genetic some people may respond strongly to a
particular vaccine, whereas others may not.

Vaccination is not perfect, but all older people should be fully vaccinated.
Because of the risk of spreading disease, and the serious consequences of
infection in the aged, all health care workers should be vaccinated, and workers
who are sick should stay at home.

Health professionals working with older people should also ensure that they are
vaccinated.

What is the important practical implication decrease in immune function in

the aged population?
We know that aged people are likely to develop disease.
One of the reasons is the decrease in immune function.
Disease in turn can accelerate the rate at which ageing occurs.
The decrease in immune function also decreases the efficacy of strategies such
as vaccination that are used to prevent disease.
Although vaccination is recommended for the aged population, it must be
recognised that it may not be as effective in an aged person as it would be in a
younger person.

From a practical point of view this means that infection control procedures in
aged care facilities are extremely important.
Staff working in aged care facility should ensure that they are vaccinated and
should not go to work if they are sick.
However, although the efficacy of vaccination may decrease as people age, it
still remains extremely beneficial.
We must aim to get every older person fully vaccinated.

Why the immune system ages

Although of the underlying reasons for ageing of the immune system are the
same as those discussed in the first module, there are some special factors.
Recurrent infections increase the rate at which the immune system ages.
In particular cytomegalovirus, which infects about 50% of adults, appears to
hasten immune ageing.
The immune system is unable to eradicate the virus from the body, and is
therefore constantly stimulated in order to keep it controlled.
Chronic stress also appears to hasten the loss of immune function.

Linking aspects of ageing

In the first module use all that inflammation is believed to be an important

factor contributing to ageing.
Inflammation is part of the immune response - so we can say that the immune
response contributes to ageing.
Inflammation is also important in disease, as it is often the inflammatory
response that produces clinical signs.
The inflammatory response is related to other risk factors as the following
shows.

COPD is just one of the common diseases of ageing that may have
inflammation as an underlying factor.
In particular, commonly identified risk factors for disease may exert their effect
by up regulating (=increase) inflammation.
Most chronic diseases-such as cancer, cardiovascular disease (CVD), Alzheimer
disease, Parkinson disease, arthritis, diabetes and obesity-are becoming leading
causes of disability and death all over the world.
Some of the most common causes of these age-associated chronic diseases are
lack of physical activity, poor nutrition, tobacco use, and excessive alcohol
consumption.
All the risk factors linked to these chronic diseases have been shown to up-
regulate inflammation.

As we have seen previously, changes in various body systems are frequently

interrelated.
A good example is the relationship between immunity and nutrition
demonstrated in the following.

Zinc homeostasis and signalling are critical in immune activation, and an

imbalance in zinc homeostasis is associated with the development of chronic
diseases.
Zinc deficiency causes significant impairment in both adaptive and innate
immune responses, and promotes systemic inflammation.
The elderly are a population particularly susceptible to zinc deficiency.
There are remarkable similarities between the hallmarks (=a feature or quality
that is typical of somebody/something) of zinc deficiency and immunological
dysfunction in aged individuals.

Frailty is a syndrome of general decline that leads to loss of function and

disability.
There is increasing evidence for inflammation to be a major contributor to
frailty.
Conditions such as poor dental hygiene can increase inflammation and the
risk of other diseases.

Although the ageing immune system may be less responsive to vaccination,

the aged should be vaccinated, as should those who work with the aged.
Pneumonia is a common cause of death in the aged which frequently occurs
as a complication of influenza.

These abstracts illustrate the fact that ageing of the immune system results in
two broad deleterious changes decreased immunity to infection and cancer,
but increased inflammation, which may contribute to frailty.

How do changes in other body systems effect immune function in the aged?
The specific function of the immune system is only one aspect of an individual's
overall immunity.
Normal cardiovascular system function is required to circulate immune cells
through the body.
If a person has cardiovascular limitations, then poor blood flow may diminish the
ability of the immune system to cope with infection.
This is particularly important in type II diabetes, where disease damages the
circulation as occurs.

In the previous module you saw that structural changes in the respiratory
system decrease the effectiveness of the laryngeal seal, and the function of the
cilia increase the risk of infection.
The skin is also an important barrier to infection.
In a subsequent module on skin you will see that age-related changes decrease
its ability to act as an effective barrier to infection.

You should return to your concept map, and try to integrate changes in
immune function with some of the more general changes that are observed in
an aged person.
Loss of regulation in the immune system can lead to chronic inflammation that
results in adverse changes in the cardiovascular system, the respiratory system
and muscle.
These changes may contribute to a loss of mobility and the associated
complications that have been discussed in previous modules.

In general, exercise has a beneficial effect on the immune system.

A lack of exercise decreases immune function, and immobility may also increase
stress which has its own independent adverse effects on immune function.
In a subsequent module you will see that an increased risk of infection results in
an increased risk of delirium - a risk factor for falls.