Like any rather complicated machine, and
the immune system consists of quite a
lot of different cells and molecules, and
they have to interact in various ways.
Things can go wrong sometimes in the immune response, and you
can end up with immunodeficiency - a deficient immune response.
Sometimes this is due to external agents, and in
that case we refer to secondary immunodeficiency.
But now we’re going to discuss
So primary immunodeficiency is defective immunity that
is due to either a inherited or an acquired gene defect.
The distribution of cellular primary
immunodeficiency defects is that around about
half of them are caused by defects in B-cells,
and therefore in antibody production.
Around about 20% of primary immunodeficiency
defects are combined T and B-cell defects.
Approximately 20% affect
the phagocytic cells.
And around about 10% affect just the T-cells without
affecting other parts of the immune response.
The consequences of primary immunodeficiency
are that we see opportunistic infections.
These are infections that most of us, most
of the time are not really troubled by.
We will deal with them
But in patients with primary immunodeficiency,
these infectious agents take
opportunity of the fact that there is defective
immune response, to establish disease.
The type of infections
actually reflects the defect.
So a defect in phagocytic cells will result in a different
spectrum of infections, to for
example, a defect in B-lymphocytes.
Immunodeficiency affecting T-cells results
in predominantly intracellular infections.
For example, viruses,
mycobacteria and so forth.
Whereas immunodeficiency affecting phagocytic cells and B-cells
and complement, mainly results in extracellular bacteria.
A little bit of background
about primary immunodeficiency.
Most primary immunodeficiencies are
caused by an inherited gene defect.
Although, as already mentioned, some
are due to spontaneous mutations.
The inheritance may be autosomal recessive,
in other words, both copies need to
be defective, or autosomal dominance where
only one copy needs to be defective.
Others are X-linked and therefore
more common in boys than girls.
The severity will vary depending
on the nature of the mutation.
These diseases tend to
manifest themselves in infancy.
The vast majority of them
are inherited gene defects.
Therefore you tend to pick them
up in the early years of life.
When infants are a few months, or one or two years
old, they’ll keep getting recurrent infections.
They’ll be investigated for this,
and in some of those individuals,
they will be found to have a primary immunodeficiency.
Most primary immunodeficiencies
have a low prevalence.
They’re fairly rare
diseases generally speaking.
However, the study of primary immunodeficiencies has provided
valuable insights into individual
components of the immune response.
So although they’re relatively
uncommon, it’s enabled us to answer
questions about how the immune system functions because we can
identify individuals that have one
particular component of the immune
system that is dysfunctional due
to these inherited gene defects.
As already mentioned, quite a few primary immunodeficiencies
are caused by genes that are present in the X chromosome.
And therefore these diseases
are more common in boys.
And here is a list of some of the
X-linked primary immunodeficiencies.
And as you can see, there
are a number of these.
And we will be discussing some of
these a little later in this lecture.
Examples of primary immunodeficiencies that
affect the innate response include complement
deficiencies, paroxysmal nocturnal hemoglobinuria,
hereditary angioedema, chronic granulomatous
disease, myeloperoxidase deficiency, glucose-6-phosphate
dehydrogenase deficiency, the leukocyte
adhesion deficiency, Chediak-Higashi syndrome,
and a number of autoinflammatory disorders.