Immunodeficiency is a state in which the immune system is compromised or absent, making a person susceptible to infections. There are two main types: primary (congenital or inherited) and secondary (acquired). Common variable immunodeficiency is a primary immunodeficiency diagnosed in adults where B cells do not mature properly to produce antibodies. It is treated with immunoglobulin replacement therapy and antibiotics for infections. X-linked agammaglobulinemia is a rare hereditary primary immunodeficiency where boys do not produce B cells or antibodies. It requires lifelong immunoglobulin therapy and antibiotic treatment.

1. S.
SHANMUGAPRIYA
Biomedical
sciences,
Sri Ramachandra
University, Porur, Chennai-

2. What is
immunodeficiency?
Immunodeficiency is a state in which the ability of
immune system is compromised or entirely absent
to fight against infectious diseases and cancer.
Two types of immunodeficiency disorders:
1.primary or congenital or inherited
2.secondary or acquired
Immunodeficiency can be specific or non-specific
1.specific = abnormalities of B & T cells
2. non-specific= abnormalities of non
specific components

3. What is primary
immunodeficiency
disorder?
To date, over 150 different primary immunodeficiency
have been identified.
All are relatively rare
usually present at birth and are usually hereditary.
evident during infancy or childhood. However, some
disorders (such as common variable
immunodeficiency) are not recognized until
adulthood.

4. TYPES OF PRIMARY
IMMUNODEFICIENCY

6. common variable
immunodeficiency
In which number of B cells is usually normal, but the cells do not
mature and thus cannot produce immunoglobulin. In some people
with this disorder, T cells (lymphocytes) also malfunction.
It is usually diagnosed between the ages of 20 and 40 .
The genetic mutations that cause this disorder can be inherited,
but more often, they occur spontaneously.
Symptoms
Recurring sinus and lung infections, particularly pneumonia, are
common. People may develop a chronic cough, cough up blood, or
have difficulty breathing.
Diarrhea may occur. The spleen may enlarge.
Up to 25% of people develop autoimmune disorders.
Mostly people have a normal life span

7. Diagnosis
Blood tests are done to measure immunoglobulin levels and
to determine how well the body produces immunoglobulin
in response to vaccines.
Treatment
Immune globulin (antibodies obtained from the blood of
people with a normal immune system) is given throughout
life to provide the missing immunoglobulin. It is given as IV
(once a month) or subcutaneously (once a week or once a
month).
Antibiotics are promptly given to treat infections.
Autoimmune disorders are treated as needed with drugs
that suppress or modify the immune system's activity
(such
as rituximab, etanercept, infliximab, or corticosteroids).

8. SELECTIVE IMMUNOGLOBULIN
DEFICIENCY
It results in a low level of one type (class) of
antibody
(immunoglobulin) but levels of other IG’s are normal.
most commonly affected class is IgA deficiency.
is usually inherited.
SELECTIVE IGA DEFICIENCY
is a low level of immunoglobulin A (IgA).
caused by a mutation in a specific gene or
by adrug[phenytoin or sulfasalazine] .
Familial history will increases the risk by about 50 times
Symptoms
Mostly no symptoms are observed, but some have
chronic lung infections, sinusitis, and other disorders.
Susceptible to pyogenic infection

9. Life span is usually unaffected.
Patients tend to develop immune complex disease
Diagnosis
• Blood tests to measure immunoglobulin levels
Treatment
• Antibiotics to treat or sometimes to prevent infections
Usually, no treatment is needed. If the disease results
from prolonged drug taking is resolved if the drug is
stopped.

10. Transient
hypogammaglobuline
mia of infancy
At birth, the immune system is not fully developed. Most of the IG are
transferred via the placenta from mother. In normal infants IG
synthesis begins at 3 months.
production of normal amounts of immunoglobulins in infants
is delayed in this disease. Mainly delay in in IgG synthesis .
As a result, immunoglobulin levels become low starting at age 3
to 6 months and return to normal at about age 12 to 36 months.
It rarely leads to serious infections, sinus, lung, or digestive
tract infections, candidiasis (a fungal infection), and
meningitis.
This condition is more common among premature infants because
they
receive fewer immunoglobulins from the mother.
Blood tests are done to measure levels of immunoglobulins.

11. X-linked
agammaglobulinemia
It is a hereditary
due to a mutation in a gene on the X (sex)
chromosome.
The disorder cause no B cells (lymphocytes) and very
low levels of or no antibodies (immunoglobulins).
X-linked disorders usually affects boys.
Symptoms
risk of developing infections in the joints (infectious
arthritis), irreversible widening due to chronic
inflammation of the airways (bronchiectasis), and
certain cancers.

12. Diagnosis
Blood tests are done to measure
immunoglobulin levels and the number of B
cells.
Genetic testing may be done to confirm the diagnosis
of X-linked agammaglobulinemia.
Treatment
Missing immune globulin is injected [ IV
or Subcutaneously] throughout life.
Antibiotics are promptly given to treat bacterial
infections and may be given continuously.

13. chronic mucocutaneous
candidiasis
Its a hereditary.
It is persistent or recurring infection with Candida
(a fungus) due to malfunction of T cells
(lymphocytes).
Because T cells malfunction, the body is less able to
fight fungal infections ( candidiasis), a yeast. It is due
to a mutation in specific genes.
Symptoms
cause infections in mouth, scalp, skin, and nails.
Membranes lining the mouth, eyelids, digestive
tract, and vagina ( vaginal yeast infection) may
also be infected.
Usually, this disorder is chronic, but it does not

14. Diagnosis
Examining a sample from the infected area under a
microscope and identifying the yeast can confirm
that a Candida infection is the cause.
Treatment
an antifungal drug[fluconazole] applied to the skin

15. Digeorge
syndrome
It is a congenital .
Thymus gland is absent or underdeveloped at birth.[problem with
T- cell maturation]
Usually, it is due to a chromosomal abnormality, but it is not inherited.
Reason for disorder is not known.
Boys and girls are equally affected.
Symptoms:
Congenital heart disorder
underdeveloped or no parathyroid glands (which help regulate
calcium levels in the blood). As a result, calcium levels are low,
leading to muscle spasms (tetany) within 48 hours after birth.
Face: unusual facial features, with low-set ears, and wide-set eyes,
cleft palate.
Thymus gland: missing or underdeveloped leads to low number
of T cells, limiting their ability to fight many infections.

16. Diagnosis
Blood tests are done for the following reasons:
To determine the total number of blood cells and the number of T and B
cells
To evaluate how well T cells and the parathyroid gland are functioning
To determine how well the body produces immunoglobulins in response to
vaccines
A chest x-ray may be taken to check the size of the thymus gland.
Because DiGeorge syndrome often affects the heart, ECG is usually
done.
Chromosomal tests may be done to look for abnormalities.
Treatment
For children who have some T cells, the immune system may function
adequately without treatment. Calcium and vitamin D supplements are
given by mouth to prevent muscle spasms.
For children who have no T cells, the disorder is fatal unless
transplantation
of thymus tissue is done. stem cell transplantation may be done.
Sometimes the heart disease is worse than the immunodeficiency,

17. X-linked lymphoproliferative
syndrome
It is inherited as an X-linked recessive disorder.
the disorder is due to a mutation in one or more genes on the X
(sex) chromosome.
occur only in boys.
results from an abnormality in T cells and natural killer cells and
results in an abnormal response to Epstein-Barr virus infection.
Symptoms:
Usually, people with X-linked lymphoproliferative syndrome have no
symptoms until Epstein-Barr virus (EBV) infection develops. The
liver malfunctions, lymphoma, aplastic anemia, another
immunodeficiency disorder, and an enlarged spleen.
About 75% of people die by age 10, and all die by age 40 unless
stem
cell transplantation is done.

18. Diagnosis
flow cytometry testing(analysis of proteins on the
surface of white blood cells), to check for
abnormalities in immune cells.
Prenatal genetic screening is recommended, if
any family history is found.
Treatment
Stem cell transplantation can cure X-linked
lymphoproliferative syndrome if it is done before
EBV infection or other disorders become too
severe.
Rituximab (a drug that modifies the immune
system's activity) can help prevent severe EBV
infection before transplantation is done.

19. Ataxia-
telangiectasia
is a hereditary disorder [autosomalrecessive disorder]
The defects arise from a breakage in chromosome 14 at
the site of TCR and Ig heavy chain genes
Leads to malfunction of B and T cells. Often,
levels of immunoglobulins—IgA and IgE—are also
low.
IgA is considerably reduced (in 70% of the cases).
characterized by incoordination (abnormalities in
the cerebellum result in loss of coordination),
dilated capillaries, and an immunodeficiency
Symptoms
Intellectual disability may develop and progress.
Between the ages of 1 and 6 capillaries in the skin and
eyes
become dilated and visible.

20. The endocrine system may be affected, resulting in
small testes (in boys), infertility, and diabetes.
Sinus and lung infections
The risk of cancer, especially leukemia, lymphoma,
brain
tumors, and stomach cancer, is increased.
Ataxia-telangiectasia usually progresses to
paralysis, dementia, and death, typically by age
30.
Diagnosis
Blood tests to measure the levels of IgA and genetic
tests
can help confirm the diagnosis.
Treatment
To help prevent infections, doctors give people
antibiotics and immune globulin, which provides the
missing immunoglobulins.
However, these drugs do not relieve the other

21. Hyper-IgM
syndrome
is characterized by normal or high levels of
immunoglobulin M (IgM) and decreased levels or
absence of other immunoglobulins. Production of large
amount of IgM >200mg/dl of polyclonal IgM
As a result, people are susceptible to pyogenic infection
.
It may be inherited in one of the following ways: 1)As an
X- linked disorder [ mostly] 2)As an autosomal
recessive disorder
X-linked hyper-IgM syndrome
In this, B cells produce only IgM, not other types of
immunoglobulin. Levels of IgM may be normal or
high. Usually affect only boys.
Infants with this form often develop pneumonia,
frequent sinus and lung infections during the first 2
years of life.
Many children die before puberty, and those who

22. Autosomal recessive hyper-IgM syndrome
Generally, symptoms are similar to those of the
X- linked form.
In some of them, the lymph nodes, spleen, and
tonsils are enlarged, and autoimmune disorders
may develop.
Diagnosis
Blood tests-measure levels of immunoglobulins.
Prenatal genetic testing can be done to same
family history.
Treatment
Treatment by iv gamma globulin
trimethoprim/sulfamethoxazole (an antibiotic) are
given to prevent Pneumocystis jirovecii infection.

23. Hyperimmunoglobulinemia
E syndrome
is a hereditary
Levels of immunoglobulin E (IgE) are very high.
It may be inherited in one of two ways:1)As an
autosomal (not sex-linked) dominant disorder 2)As an
autosomal recessive disorder
Symptoms:
In most infants abscesses form in the skin, joints, lungs,
or other organs. The abscesses are usually caused by
infections with staphylococcal bacteria, and they recur
frequently.
Rashes are seen.
Bones are weak, resulting in many fractures. Facial
features
may be coarse. Loss of baby teeth is delayed.
Life span depends on the severity of the lung infections.

24. Diagnosis
Blood tests to measure IgE levels
Genetic tests can be done to check for the
abnormal genes.
Treatment
Antibiotics, usually trimethoprim/sulfamethoxazole,
are given continuously to prevent staphylococcal
infections.
The rash is treated with moisturizing
creams, antihistamines.
Certain drugs that modify the immune system, such
as interferon gamma, are sometimes helpful.

25. Severe combined
immunodeficiency
It is a serious, potentially fatal immunodeficiency disorder. It is
congenital and can be caused by mutations in many different
genes. All forms are hereditary.
The most common form results from a mutation in a gene on the
X (sex) chromosome (called an X-linked disorder) and occurs
almost exclusively in boys.
The x-linked SCID is due to a defect in gamma-chain of IL-2
also shared by IL-4, -7, -11 and 15, all involved in lymphocyte
proliferation and/or differentiation.
This cause low levels of antibodies (immunoglobulins) and low
or no T cells (lymphocytes).
There are no T cells and because B cells cannot produce
antibodies without the help of T cells, immunoglobulin levels are
low.
Also, natural killer cells do not function normally.
The autosomal SCIDs arise primarily from defects in adenosine
deaminase (ADA) or purine nucleoside phosphorylase (PNP)
genes which results is accumulation of dATP or dGTP,
respectively, and cause toxicity to lymphoid stem cells

26. Symptoms
Most develop pneumonia, persistent viral infections, thrush.
All infants with this disorder have a severely underdeveloped thymus gland.
If not treated, these children usually die before age 1 year.
Diagnosis
Blood tests are done to measure the number and functioning of B and T cells.
Some experts recommend screening all newborns for T-cell receptor excision
circle
(TREC) test.
use genetic tests to identify the specific mutation causing the disorder and thus
help determine how severe the disorder is.
Treatment
People with this disorder are kept in a protected environment to prevent exposure
to
possible infections (called reverse isolation).
Treatment with antibiotics and immune globulin helps prevent infections but
does not cure the disorder.
The only effective treatment is transplantation of stem cells (for example, from
an unaffected sibling with the same tissue type). If transplantation is done by
age 3 months, 96% of infants survive.
Gene therapy may be effective, depending on which form of severe
combined immunodeficiency is present.

27. Wiskott-Aldrich
syndrome
is a hereditary
characterized by abnormal antibody (immunoglobulin) production,
T- cell malfunction, a low platelet count, and eczema( patches of
skin got inflammed).
It results from a mutation in a gene on the X (sex) chromosome (X-
linked disorder), which codes for a protein needed by T and B cells
to function. Thus, these cells malfunction.
It usually affects only boys.
Platelets are small and malformed. The spleen removes and
destroys
them, causing the platelet count to be low.
Symptoms
Because the number of platelets is low, bleeding problems,
usually bloody diarrhea, may be the first symptom.
Susceptibility to viral and bacterial infections, particularly of the RTI
is increased. The risk of developing cancers (such as lymphoma
and leukemia) and autoimmune disorders (such as hemolytic
anemia, inflammatory bowel disease, and vasculitis) is increased.
Life expectancy is shortened.

28. Diagnosis
Blood test is done to determine the no. of WBC and
the percentages of the different types of white blood
cells
The number of platelets
Levels of immunoglobulins
The quantity and type of antibodies produced in response
to vaccines or antigen
Genetic testing may be done to identify the mutation and
confirm the diagnosis
Treatment
Stem cell transplantation is necessary to preserve life. Without
it, most die by age 15.
Antibiotics are given continuously to prevent infections,
and immune globulin is given to provide the missing
antibodies.
An antiviral drug (acyclovir) is given to prevent viral infections,
and platelet transfusions are given to relieve bleeding
problems.

29. Chronic granulomatous
disease
It is inherited as an X-linked recessive disorder, in
which phagocytes malfunction.
occur only in boys.
Sometimes this disease is also inherited as an
autosomal recessive disorder.
Normally, phagocytes (neutrophils, eosinophils,
monocytes, and macrophages) ingest and kill
microorganisms. In chronic granulomatous disease,
phagocytes can ingest but cannot produce the
substances (such as hydrogen peroxide and superoxide)
that kill certain bacteria and fungi.
Symptoms
Chronic infections occur in the skin, lungs, lymph
nodes, mouth, nose, urinary tract, and intestines.
Abscesses can develop around the anus and in the
lungs and liver.

30. Diagnosis
Blood tests- measures the activity of phagocytes in
responseto microorganisms.
genetic tests- to check for the specific mutations that cause this
disorder.
Treatment
Antibiotics, usually trimethoprim/sulfamethoxazole, are given
regularly and indefinitely to prevent infection. Antifungal drugs (such
as itraconazole) are usually also given regularly to help prevent
fungal
infections.
Interferon gamma (a drug that modifies the immune system), injected
3 times a week, can reduce the number and severity of infections.
Transfusions of granulocytes can be lifesaving. Granulocytes are a
type of white blood cell that includes some phagocytes.
Stem cell transplantation has cured some people with
chronic granulomatous disease.

31. Chédiak-Higashi
syndrom
e
is a very rare hereditary disorder
usually inherited as an autosomal recessive disorder.
People are more susceptible to infections because phagocytes
do not function normally.
Symptoms
little or none of the pigment melanin is formed (albinism)
The disorder may also cause vision problems. For
example, acuity, photosensitivity, Nystagmus
also have infections in the respiratory tract, skin,
and membranes lining the mouth.
In about 80% of people, causing fever, jaundice, an enlarged
liver and spleen, swollen lymph glands, and a tendency to
bleed and bruise easily. The disorder can also affect the
nervous system.
Respiratory burst is normal.
Once these symptoms develop, the syndrome is usually
fatal within 30 months.

32. Diagnosis
Genetic testing
Blood test
Treatment
antibiotics to help prevent infections and interferon
gamma to help the immune system function better.
Corticosteroids and removal of the spleen
(splenectomy) sometimes temporarily relieve
symptoms.
However, unless stem cell transplantation is done,
most people die of infections by the time they are 7
years old. About 60% of children are alive 5 years
after transplantation.

33. Leukocyte adhesion
deficiency
white blood cells (leukocytes) do not function normally.
It is inherited as an autosomal recessive disorder.
white blood cells are lacking a protein on their surface. As a
result, white blood cells are less able to travel to sites of
infection and to kill and ingest bacteria and other foreign
invaders.
Symptoms
In severely affected infants, infections develop in soft
tissues, such as the gums, skin, and muscles. No pus
forms in infected areas. Infections become increasingly
difficult to control.
Wounds do not heal well.
Often, the umbilical cord is slow to fall off, taking 3 weeks or
more after birth.[ Normally, it falls off in 1 or 2 weeks after birth]
Most children with severe disease die by age 5

34. Diagnosis
Blood tests - A complete blood count and of
proteins on the surface of white blood cells (called
flow cytometry), are used to diagnose leukocyte
adhesion deficiency.
Treatment
Antibiotics given continuously, to prevent infections.
Transfusions of granulocytes (a type of white
blood cells) can also help.
However, stem cell transplantation is the only
effective treatment. It may provide a cure.
Gene therapy for this disorder is being studied.

35. Cyclic
neutropenia
It is marked by low numbers of circulating neutrophil
.
The neutropenia lasts about a week during which
the patients are susceptible to infection.
The defect appears to be due to poor regulation
of neutrophil production.

36. Disorders of complement
system
 There are genetic deficiencies of various
components of complement system, which lead to
increased infections.
 The most serious among these is the C3 deficiency
which may arise from low C3 synthesis or deficiency
in factor I or factor H.

37. Secondary
disorder
Secondary immunodeficiency disorders happen when
an outside source like a toxic chemical or infection
attacks your body.
The following can cause a secondary immunodeficiency
disorder: severe burns, chemotherapy, radiation, chronic
disorders such as diabetes[diabetes = white blood cells
do not function well when the blood sugar level is high ]
or cancer, Drugs, malnutrition.
Examples of secondary immunodeficiency disorders
include: AIDS, cancers of the immune system, like
leukemia immune-complex diseases, like viral hepatitis
multiple myeloma

38. Nutrition and
age
Undernutrition: When undernutrition causes weight
to decrease to less than 80% of recommended
weight, the immune system is often impaired. A
decrease to less than 70% usually results in severe
impairment
As people age, the immune system becomes less
effective in several ways For example, as people
age, they produce fewer T cells.[ which help the
body recognize and fight foreign or abnormal
cells]

39. SOME DRUG THAT CAN CAUSE
IMMUNODEFICIENCY

41. Immunosuppressan
t Immunosuppressant are used to prevent rejection of
atransplanted organ or tissue and also to the an
autoimmune disorder patient.
Corticosteroids: a type of immunosuppressant,
are used to suppress inflammation due to various
disorders.
Cause changes in circulating leukocytes
Depletion of CD4 cells
Monocytopenia
Decreased in circulating eosinophils and basophils
Inhibition of T cell activation and B cell maturation
Inhibit cytokine synthesis

42. CYCOLOSPORIN:
Have severe effects on T cell signaling and functions
It binds to immunophilins which are believed to have
acritical role in signal transduction
Also inhibit IL 2 dependent signal transduction
Chemotherapy and radiation therapy can also
suppress the immune system, sometimes leading to
immunodeficiency disorders.

43. How To Identify The Type
Of Immunodeficiency
Disorder
Younger than 6 months: Usually an abnormality
in T cells
Age 6 to 12 months: Possibly a problem with
both B cells and T cells or with B cells
Older than 12 months: Usually an abnormality in
Bcells and antibody production