detailed description about Immunodeficiency disorders and its symptoms, diagnosis and treatments

1. S. SHANMUGAPRIYA
Biomedical sciences,
Sri Ramachandra University,
Porur, Chennai-m116, India

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 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

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 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.

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 affect
life span.

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, and
surgery to prevent severe heart failure or death .

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 [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.

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 problems.

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 live
longer often develop cirrhosis or lymphoma.

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.
 Children may grow slowly.

30.  Diagnosis
 Blood tests- measures the activity of phagocytes in response to
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 syndrome
 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. Immunosuppressant
 Immunosuppressant are used to prevent rejection of a
transplanted 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 a
critical 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 B
cells and antibody production