IMMUNODEFICIENCY DISORDERS • Phagocytes- problems with the movement or killing
activity of these cells
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 cells
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.
TYPES OF PRIMARY IMMUNODEFICIENCY
• Humoral Immunity- problems with B cells
(lymphocytes) and their production of antibodies
 Common variable immunodeficiency
 Deficiency of a specific antibody (selective
immunoglobulin deficiency), such as IgA
deficiency
 Transient hypogammaglobulinemia of infancy
 X-linked agammaglobulinemia
• Cellular Immunity- problems with T cells (lymphocytes)
 Chronic mucocutaneous candidiasis
 DiGeorge syndrome
 X-linked lymphoproliferative syndrome
• Combined humoral and cellular immunity- problems
with B and T cells
 Ataxia-telangiectasia
 Hyperimmunoglobulinemia E syndrome
 Severe combined immunodeficiency
 Wiskott-Aldrich syndrome
 Chronic granulomatous disease
 Chediak-Higashi syndrome (rare)
 Cyclic neutropenia
 Leukocyte adhesion defects
• Complement proteins: Deficiency of complement
proteins
 Complement component 1 (C1) inhibitor
deficiency (hereditary angioedema)
 C3 deficiency
 C4 deficiency
 C5, C6, C7, C8, and/or C9 deficiency
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
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).
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 a
drug[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
 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.
TRANSIENT HYPOGAMMAGLOBULINEMIA 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.
- This disorder may last for months to a few years
but usually resolves without treatment.
• 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.
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.
CHRONIC MUCOCUTANEOUS CANDIDIASIS
- It’s 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
affect life span.
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
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.
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, and surgery to prevent
severe heart failure or death.
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.
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.
ATAXIA-TELANGIECTASIA
- is a hereditary disorder [autosomal recessive
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.
- 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
problems.
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 live longer often develop cirrhosis or
lymphoma.
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.
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
- 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
Diagnosis
- Blood tests to measure IgE levels
 - Genetic tests can be done to check for the Diagnosis
abnormal genes.
- Blood tests are done to measure the number and
Treatment functioning of B and T cells.
- Some experts recommend screening all
- Antibiotics, usually trimethoprim/
newborns for T-cell receptor excision circle
sulfamethoxazole, are given continuously to
(TREC) test.
prevent staphylococcal infections.
- Use genetic tests to identify the specific
- The rash is treated with moisturizing creams,
mutation causing the disorder and thus help
antihistamines.
determine how severe the disorder is.
- Certain drugs that modify the immune system,
such as interferon gamma, are sometimes Treatment
helpful.
- People with this disorder are kept in a protected
SEVERE COMBINED IMMUNODEFICIENCY environment to prevent exposure to possible
infections (called reverse isolation).
- It is a serious, potentially fatal immunodeficiency
- Treatment with antibiotics and immune globulin
disorder. It is congenital and can be caused by
helps prevent infections but does not cure the
mutations in many different genes. All forms are
disorder.
hereditary.
- The only effective treatment is transplantation
- The most common form results from a mutation
of stem cells (for example, from an unaffected
in a gene on the X (sex) chromosome (called an
sibling with the same tissue type). If
X-linked disorder) and occurs almost exclusively
transplantation is done by age 3 months, 96% of
in boys.
infants survive.
- The x-linked SCID is due to a defect in gamma-
- Gene therapy may be effective, depending on
chain of IL-2 also shared by IL-4, -7, -11 and 15,
which form of severe combined
all involved in lymphocyte proliferation and/or
immunodeficiency is present.
differentiation.
- This cause low levels of antibodies WISKOTT-ALDRICH SYNDROME
(immunoglobulins) and low or no T cells
- is a hereditary
(lymphocytes).
- Characterized by abnormal antibody
- There are no T cells and because B cells cannot
(immunoglobulin) production, T-cell
produce antibodies without the help of T cells,
malfunction, a low platelet count, and eczema (
immunoglobulin levels are low.
patches of skin got inflamed).
- Also, natural killer cells do not function
- It results from a mutation in a gene on the X (sex)
normally.
chromosome (X- linked disorder), which codes
- The autosomal SCIDs arise primarily from defects
for a protein needed by T and B cells to function.
in adenosine deaminase (ADA) or purine
Thus, these cells malfunction.
nucleoside phosphorylase (PNP) genes which
- It usually affects only boys.
results is accumulation of dATP or dGTP,
- Platelets are small and malformed. The spleen
respectively, and cause toxicity to lymphoid
removes and destroys
stem cells
- them, causing the platelet count to be low.
Symptoms
Symptoms
- Most develop pneumonia, persistent viral
- Because the number of platelets is low, bleeding
infections, thrush.
problems, usually bloody diarrhea, may be the
- All infants with this disorder have a severely
first symptom.
underdeveloped thymus gland.
- Susceptibility to viral and bacterial infections,
- If not treated, these children usually die before
particularly of the RTI is increased. The risk of
age 1 year.
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.
Diagnosis
Diagnosis
- Blood tests- measures the activity of phagocytes
in response to microorganisms.
- Genetic tests- to check for the specific mutations
that cause this disorder.

- Blood test is done to determine the no. of WBC Treatment

and the percentages of the different types of
- Antibiotics, usually trimethoprim/
white blood cells
sulfamethoxazole, are given regularly and
- The number of platelets
indefinitely to prevent infection. Antifungal
- Levels of immunoglobulins
drugs (such
- The quantity and type of antibodies produced in
- As itraconazole) are usually also given regularly
response to vaccines or antigen
to help prevent fungal infections.
- Genetic testing may be done to identify the
- Interferon gamma (a drug that modifies the
mutation and confirm the diagnosis
immune system), injected 3 times a week, can
Treatment reduce the number and severity of infections.
- Transfusions of granulocytes can be lifesaving.
- Stem cell transplantation is necessary to
Granulocytes are a type of white blood cell that
preserve life. Without it, most die by age 15.
includes some phagocytes.
- Antibiotics are given continuously to prevent
- Stem cell transplantation has cured some
infections, and immune globulin is given to
people with chronic granulomatous disease.
provide the missing antibodies.
- An antiviral drug (acyclovir) is given to prevent CHÉDIAK-HIGASHI SYNDROME
viral infections, and platelet transfusions are
- Is a very rare hereditary disorder
given to relieve bleeding problems.
- Usually inherited as an autosomal recessive
CHRONIC GRANULOMATOUS DISEASE disorder.
- People are more susceptible to infections
- It is inherited as an X-linked recessive disorder,
because phagocytes do not function normally.
in which phagocytes malfunction.
- Occur only in boys. Symptoms
- Sometimes this disease is also inherited as
- Little or none of the pigment melanin is formed
an autosomal recessive disorder.
(albinism)
- Normally, phagocytes (neutrophils, eosinophils,
- The disorder may also cause vision problems. For
monocytes, and macrophages) ingest and kill
example, acuity, photosensitivity, Nystagmus
microorganisms. In chronic granulomatous
- Also, have infections in the respiratory tract,
disease, phagocytes can ingest but cannot
skin, and membranes lining the mouth.
produce the substances (such as hydrogen
- In about 80% of people, causing fever, jaundice,
peroxide and superoxide) that kill certain
an enlarged liver and spleen, swollen lymph
bacteria and fungi.
glands, and a tendency to bleed and bruise
Symptoms easily. The disorder can also affect the nervous
system.
- Chronic infections occur in the skin, lungs, lymph
- Respiratory burst is normal.
nodes, mouth, nose, urinary tract, and
- Once these symptoms develop, the syndrome is
intestines. Abscesses can develop around the
usually fatal within 30 months.
anus and in the lungs and liver.
- Children may grow slowly. Diagnosis

- Genetic testing and 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.
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
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.
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.
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.
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
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]
SOME DRUG THAT CAN CAUSE IMMUNODEFICIENCY
• ANTICONVULSANTS- used to treat seizure
 Lamotrigine
 Phenytoin
 Valproate
• IMMUNOSUPPRESSANTS- drugs that suppress the - Also inhibit IL 2 dependent signal transduction
immune system - Chemotherapy and radiation therapy can also
suppress the immune system, sometimes
 Azathioprine
leading to immunodeficiency disorders.
 Cyclosporine
 Myeophenolate mofetil HOW TO IDENTIFY THE TYPE OF IMMUNODEFICIENCY
 Sirolmus DISORDER
 Tacrolimus
- Younger than 6 months: Usually an abnormality
• CORTICOSTEROIDS in T cells
- Age 6 to 12 months: Possibly a problem with
 Methylprednisone
both B cells and T cells or with B cells
 Prednisone
- Older than 12 months: Usually an abnormality in
• CHEMOTHERAPY DRUGS B cells and antibody production

 Alemtuzumab
 Busulfan
 Cyclophosphamide

• OTHER DRUGS SUCH AS ANTIBODIES THAT TARGET

AND SUPPRESS SPECIFIC PARTS OF THE IMMUNE
SYSTEM

 Adalimumab
 Etanercept
 Infliximab
 Muromonab (OKT3)
 Rituximab
 Tocilizumab

IMMUNOSUPPRESSANT

- Immunosuppressant are used to prevent

rejection of a transplanted organ or tissue and to
the 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

• CYCOLOSPORIN

- Have severe effects on T cell signaling and

functions
- It binds to immunophilins which are believed to
have a critical role in signal transduction