Primary immunodeficiency

Primary immunodeficiency

Primary immune deficiencies are

primary because the immune
system is the primary cause and
most are genetic defects that may be
inherited.

Primary immunodeficiency

The primary immunodeficiency

diseases are a group of disorders
caused by basic defects in immune
function that are intrinsic to, or
inherent in, the cells and proteins of
the immune system. There are more
than 185 primary immunodeficiency
diseases. Some are relatively
common, while others are quite rare.
Some affect a single cell or protein of

Primary immunodeficiency

Although primary immunodeficiency

diseases may differ from one another
in many ways, they share one
important feature. They all result
from a defect in one or more of the
elements or functions of the normal
immune system such as T-cells, Bcells, NK cells, neutrophils,
monocytes, antibodies, cytokines or
the complement system. Most of

Brutons syndrome

X-linked agammaglobulinaemia
Immunological features: absence of B
cells (in blood) and IgG
Pathogenesis: block in the
differentiation and development of
pre-B cells
Genetic features: x-linked recessive
inheritance, males

Severe combined
immunodeficiency

also known as alymphocytosis,

GlanzmannRiniker syndrome, severe
mixed immunodeficiency syndrome,
and thymic alymphoplasia, is a
genetic disorder characterized by the
disturbed development of functional
T cells and B cells caused by
numerous genetic mutations that
result in heterogeneous clinical
presentations. SCID involves

Severe combined
immunodeficiency

Consequently, both "arms" (B cells

and T cells) of the adaptive immune
system are impaired due to a defect
in one of several possible genes.
SCID is the most severe form of
primary immunodeficiencies, and
there are now at least nine different
known genes in which mutations lead
to a form of SCID. It is also known as
the bubble baby disease and bubble

Primary immunodeficiency

Other primary immunodeficiencies,

such as Common Variable Immune
Deficiency (CVID) and Selective IgA
Deficiency are not always inherited in
a clear-cut or predictable fashion. In
these disorders, the cause is
unknown, but it is believed that the
interaction of genetic and
environmental factors may play a
role in their causation.

Common variable
immunodeficiency

is the most commonly diagnosed

primary immunodeficiency. It is
characterized by low antibody levels
and recurrent infections.

Selective immunoglobulin A
(IgA) deficiency (SIgAD)

is a genetic immunodeficiency.
People with this deficiency lack
immunoglobulin A (IgA), a type of
antibody that protects against
infections of the mucous membranes
lining the mouth, airways, and
digestive tract. It is defined as an
undetectable serum IgA level in the
presence of normal serum levels of
IgG and IgM. It is the most common

Primary immunodeficiency

Because the most important function

of the immune system is to protect
against infection, people with
primary immunodeficiency diseases
have an increased susceptibility to
infection. This may include too many
infections, infections that are difficult
to cure, unusually severe infections,
or infections with unusual organisms.
The infections may be located

Primary immunodeficiency

Another function of the immune

system is to discriminate between
the healthy tissue (self) and foreign
material (non-self). Examples of
foreign material can be
microorganisms, pollen or even a
transplanted kidney from another
individual. In some
immunodeficiency diseases, the
immune system is unable to

Primary immunodeficiency

There are also a few types of primary

immunodeficiencies in which the
ability to respond to an infection is
largely intact, but the ability to
regulate that response is abnormal.
Examples of this are autoimmune
lymphoproliferative syndrome (ALPS)
and IPEX (an X-linked syndrome of
immunodeficiency,
polyendocrinopathy and

Autoimmune
lymphoproliferative
also known
as Canale-Smith
syndrome
(ALPS)

syndrome, is a form of
lymphoproliferative disorder (LPDs).
It affects lymphocyte apoptosis. It is
a RASopathy.

It is a rare genetic disorder of

abnormal lymphocyte survival
caused by defective Fas mediated
apoptosis. Normally, after infectious
insult, the immune system down-

IPEX

IPEX (immunodysregulation
polyendocrinopathy enteropathy Xlinked syndrome) is a rare disease
linked to the dysfunction of the
transcription factor FOXP3, widely
considered to be the master
regulator of the regulatory T cell
lineage.

Primary immunodeficiency

Primary immunodeficiency diseases

can occur in individuals of any age.
The original descriptions of these
diseases were in children. However,
as medical experience has grown,
many adolescents and adults have
been diagnosed with primary
immunodeficiency diseases. This is
partly due to the fact that some of
the disorders, such as CVID and

Primary immunodeficiency

Primary immunodeficiency diseases

were initially felt to be very rare.
However, recent research has
indicated that as a group they are
more common than originally
thought. It is estimated that as many
as 1 in every 1,2002,000 people
may have some form of primary
immunodeficiency

Secondary
immunodeficiency

Factors causing Acquired

Immunodeficiency

Secondary, or acquired,
immunodeficiency is by far the most
common immunodeficiency and
contributes a significant proportion
to hospital admissions.
Factors causing secondary
immunodeficiency mainly affect
phagocytic and lymphocyte
functions and include infections
(HIV), malnutrition, tumors, cytotoxic

Factors causing Acquired

Immunodeficiency

Secondary, or acquired,
immunodeficiency is by far the most
common immunodeficiency and
contributes a significant proportion
to hospital admissions.
Factors causing secondary
immunodeficiency mainly affect
phagocytic and lymphocyte
functions and include infections
(HIV), malnutrition, tumors, cytotoxic

Factors causing Acquired

Immunodeficiency

Secondary, or acquired,
immunodeficiency is by far the most
common immunodeficiency and
contributes a significant proportion
to hospital admissions.
Factors causing secondary
immunodeficiency mainly affect
phagocytic and lymphocyte
functions and include infections
(HIV), malnutrition, tumors, cytotoxic

Malnutrition

Worldwide, the major predisposing

factor for secondary
immunodeficiency and, in particular,
proteincalorie malnutrition (PCM).
Lack of certain dietary elements
(e.g., Iron, Zinc) and1 metabolic
derangements (glucocorticoids)

Tumors

Tumors can release factors,

including, IL-10, TGF, VEGF, and
prostaglandins, that are
immunosuppressive.
They can recruit host regulatory cells
such as

Tregs and Myeloid Suppressor Cells

Anti-tumor therapies must not only

focus on tumor killing.

Therapy using Cytotoxic

Drugs and Irradiation

Cytotoxic drugs and irradiation that

especially target dividing cells are widely
used for tumor therapy.
Cytotoxic drugs are also used to suppress
allogeneic graft rejection in patients
receiving kidney or other grafts.
These therapies also kill normal immune
cells, including stem cells, neutrophil
progenitors, and rapidly dividing precursors
for all leukocytes, and thus compromise
immune defense against pathogens.

Immune Senescence:
Consequences of Aging

With aging, memory T cells increase but

become less able to expand.
Fewer new (naive) T cells enter the pool
due to thymic involution, diminishing the
immune repertoire and the quality of T- and
B-cell responses.
B-cell development in the bone marrow
may also decrease
This reduction in immune capability in the
elderly results in a decreased response to
infection and vaccination.

Trauma

Patients suffering trauma (e.g., associated

with burns or major surgery) are less able
to deal with pathogens, perhaps as a result
of the release of factors that dampen
immune responses, e.g. glucocorticoids.
Removal of the spleen, the primary organ
for removing microbes from the circulation
(e.g., after an accident), results in
decreased phagocytosis of microbes and
thus increased susceptibility to blood-borne
infections, especially to infections by