IMMUNODEFICIENCY

DISEASES
PROFESSOR SHAHENAZ M.HUSSIEN
 IMMUNODEFICIENCY
IMMUNODEFICIENCY DISORDERS:
DISORDERS:
Aim
Aim of
of the
the lecture:
lecture:

 At
At the
the end
end of
of this
this lecture
lecture the
the student
student will
will be
be able
able
to
to describe
describe the
the clinical
clinical features
features and
and diagnose
diagnose
humoral
humoral andand cellular
cellular immune
immune deficiency,
deficiency, and
and
acquired
acquired immunedeficiency
immunedeficiency Syndrome
Syndrome (AIDS).
(AIDS).
Immune
Immune deficiency
deficiency diseases:
diseases:
Definition:
Definition:

 Deficiencies
Deficiencies ofof host
host defense
defense systems
systems result
result in
in an
an
immunologic
immunologic imbalance
imbalance that
that can
can lead
lead toto aa
susceptibility
susceptibility to to infection,
infection, anan autoimmune
autoimmune
disease,
disease, or
or aa predisposition
predisposition toto malignancies.
malignancies.

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Types of immunodeficiency disorders:
1- Primary: Causes in immune system component:
a. According of component:
i. Complements. ii. Phagocytic. iii. B cells. iv. T Cells.
b. According to the etiology:
i. Congenital (X-linked disease) ii. Acquired (AIDS)
iii. Embryogenesis (Digoerge syndrome). iv. Idiopathic

2- Secondary: Non Immunogenic causes:

a. Prematurity. b. Mal nutrition.
c. Hodgkin`s and others malignancy. d. Injury, Burns, Splenectomy.
e. Drugs.

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 A) B-cell defect:
• Causative agents are most commonly extracellular
organisms, namely pyogenic and enteric bacteria,
because patients are deficient in serum opsonins
(antibodies) necessary for phagocytosis.
• Patients with X-linked (Bruton) agammaglobulinemia
may also have problems with certain enteric viruses
(e.g., polio virus, echo virus, coxsackicvirus).
• Patients with IgA deficiency or common variable
hypogammaglobulinemia are by Giardia lamblia
parasite.
• Sites of infection include the skin, sinuses, meninges,
and the respiratory, urinary, and gastrointestinal
tracts. 4
 B-Cell Deficiency Disorders
Therapy Clinical Features Disorder
Immune serum Recurrent pyogenic infections; 1- X-linked agammaglobu-
globulin; antibiotics infections of lungs, sinuses, middle linemia (Bruton disease)
ear, skin, central nervous system
Antibiotics; immune Recurrent pyogenic infections; 2-Transient hypogamma-
serum globulin frequent in families with other globulinemia of infancy (1st
(selected patients) immunodefi­ciencies 3 years of life)
Antibiotics; immune Recurrent infections of lungs, 3-Selective immuno-
serum globulin (IgG sinuses; gastrointestinal disease; globulin deficiency
subclass defi­ciencies allergy; frequent in families with (IgA, IgM, IgG sub­
only) common variable classes)
immunodeficiencies
Immune serum Infections of lungs, sinuses, middle 4-Immunoglobulin defi­
globulin; antibiotics ear; increased frequency of ciency with increased IgM
autoimmune disease Ectodermal (and IgD)
displasea
Immune serum Infections of lungs, sinuses, middle 5-Common variable
globulin; antibiotics ear; giardiasis; malabsorption; immunodeficiency
autoimmune disease 5
(B) T-cell deficiency disorders, also known as cell-mediated (cellular)
immuno­deficiencies, result from abnormalities in T-cell functions.
Antibody production is also likely to be affected in patients with
severe T-cell abnormalities because T cells are important
immunoregulators of B-cell differentiation and function.
*Recurrent infections --Causative agents are intracellular pathogens
(e.g., herpesviruses, mycobacteria, fungi {Candida}, and protozoa
{Pneumocystis carinii, Toxoplasma}.
--Sites of infection include a variety of sites, both local and systemic.
*Congenital cell-mediated immunodeficiencies represent a complex
spectrum of immunodeficiencies. At one extreme are defects in
lymphoid stem cell differentiation, which result in severe
combined immunodeficiency disorders. At the other extreme are
isolated defects that affect only cell-mediated immunity to one
particular pathogen (e.g., chronic mucocutaneous candidiasis).
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 T-Cell and Combined Deficiency
Therapy Clinical Features Disorder

Bone rn,irrow transplan­tation Recurrent infections; wast­ing; chronic diarrhea; failure *Severe combined immuno
Antibiotics and IVIG to thrive: graft versus host disease, anemia, Alopacia deficiency
* Nezelof syndrome
Bone marrow transplan­ Recurrent infections; dysostosis (adenosine deaminase Defects of the purine sal­
tation; enzyme deficiency); anemia and mental retardation vage pathway
replacement therapy (purinenucleoside phosphory­lase deficiency) -Adenosine deaminase
Rib and Scapula abnormality in ADA deficiency
-Purine nucleoside
phosphorylase deficiency
Thymus graft or thymosin Hypoparathyroidism (hypocalcemia); facial *DiGeorge anomaly (third
therapy) abnormalities; cardio­vascular abnormalities; infections; and fourth pouch/arch
mental defi­ciency (some patients); gastrointestinal tract syndrome)
malformation (some patients).
Topical and systemic Chronic candidal infection of the skin, nails, scalp, and *Chronic mucocutaneous
antifungal agents; transfer mucous mem­branes; autoimmune endocrine disorders candidiasis
factor; thymus transplantation Intestinal malabsorption recurrent infections
Bone marrow transplantation Oculocutaneous telangictasia; progressive cerebellar *Ataxia-telangiectasia
ataxia; bronchiectasis, malignancy; defective
chromosomal repair; raised a-fetoprotein
Bone marrow transplan­tation; Eczema; thrombocytopenia; susceptibility to *Wiskott-Aldrich syndrome
antibiotics; splenectomy infections; malignancy; small, defective platelets

Immune serum globulin Short-limbed dwarfism; lymphopenia *Short-limbed dwarfism

IVIG, Antibotics Caltilage hair hypoplasia
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 C) Phagocyte disorders:
Clinical features: Affected individuals are prone to infections with low-grade
bacteria such as Staphylococcus aureus and gram-negative enteric bacteria.
Phagocyte Disorders in Children

Therapy Clinical Features Inheritance Disorder

Antibiotics; Infections with catalase-positive X-linked 1) Chronic
γ-interferon bacteria and fungi affecting skin, (66%); granu-
lungs, liver; granuloma formation; autosomal re­ lomatous
NBT test is screening test cessive (33%) disease
Antibiotics Fungal infections (candidiasis) in Autosomal 2)Myeloperoxida
deep tissues, especially in presence of Recessive se deficiency
diabetes
Antibiotics Delayed separation of the umbilical Auto­somal 3)Leukocyte
cord; skin infections; otitis media; recessive adhesion
pneumonia; gingivitis; periodontitis deficiency
Antibiotics Recurrent skin infections with Variable 4)Abnormal
staphylococci. enteric bacteria, chemotaxis
Neuropathy, Occulo cultaneous -Hyper IgE
albinism in chediak higashi -chediak-Higashi
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 Complement disorders )D(
1. Deficiency of early complement components (C1, C4,
C2) results in a symptom com­plex resembling collagen
vascular disorders (e.g., systemic lupus erythematosus
(SLE)] and increased susceptibility to pyogenic infections.
2. C3 deficiency results in severe pyogenic infections.
Several patients have also had SLE and
glomerulonephritis.
3. Deficiency of late complement components (C5, C6, C7,
C8) results in systemic Neisseria infections such as
meningococcal sepsis and meningitis, and disseminated
gonococcal infections.
4. Abnormalities of the control proteins of the alternative
pathway (factor H, factor I, properdin) may result in
recurrent infections.
5. Deficiency of complement inhibitors (C1 esterase
inhibitor, carboxypeptidase N) leads to recurrent 9
angioedema.
 Diagnosis of immunodeficiency
disease
1- Clinical Features.
2- laboratory investigation:
1- C.B.C: increase PMNL suspect phagocyte deficiency.
2- Cuture: to know the organism and chose the antibodies.
3- ESR: to follow up.
3- X- rays:
a. Chest pneumonia---------B cells deficiency.
b. Ribs and scapula ---------ADA.
c. Chronic sinusitis --------- Karatagener syndrome.
d. Long bone ---------------- short limbs dwarfism (cartilage
hair hypoplasia)
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5- Suspected cells has specific tests:
a. B-cells:
i. Total lg ii. Selected lg A and lg G
iii. Anti A and Anti B iv. Antibodies for pervious
vaccination
b. T cells:
i. Lymphocyte count.
ii. Delayed hypersensitivity reaction for Tobuclin and Candida
antigerm.
iii. T cells and macrophage function test.
c. Phagocyte:
i. Neutrophil count ii. NBT test for screening.
d. Complement: Total and specific complement count.

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 ACQUIRED IMMUNE DEFICIENCY
SYNDROME (AIDS( Infection
Definition:
It is a disorder associated with a profound deficiency in T-cell
immunity, and, in children, T-cell and B-cell abnormalities.
Etiology and Pathogenesis:
Causative agent and mechanisms of transmission HIV-1, a
retrovirus, is the cause of AIDS.
Transmission
(1) Approximately 85% of childhood HIV infections occur because of
perinatal transmission from an HIV-infected mother to her newborn.
The average risk of perinatal transmission is such that 20%-25% of
babies born to infected mothers will become infected. There is
evidence that a large proportion of perinatal infections occur at
parturition. Breast feeding can also transmit HIV infection to an
infant.
(2) Transmission to recipients of blood, blood products, or organ
transplantation.
(3) Adolescents acquire infection via sexual contact and intravenous
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drug abuse.
IMMUNOLOGIC ABNORMALITIES
1. Progressive depletion of CD4 T cells (helper-
induced T cells)

2. Impaired T-cell immunity (even when CD4 T

cells are present in normal numbers)

3. Impaired mononuclear macrophage function.

Impaired production of specific antibody
despite a polyclonal increase in serum
immunoglobulins that lack antibody
functions
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Clinical Features:
CDC classification of clinical manifestations of HIV infection
a. Category E (perinatally exposed infant) describes HIV-exposed infants in
whom infection has not been confirmed or excluded.
b. Category N (infected infant) describes HIV-infected infants that are not
sympto­matic.
c. Category A (mildly symptomatic infection). Manifestations include
lymphadenopathy, hepatosplenomegaly, parotitis, recurrent upper respiratory
infections.
d. Category B (moderately symptomatic infection). Manifestations include
chronic oral candidiasis, diarrhea, failure to thrive, anemia,
thrombocytopenia, lympho-cytic interstitial pneumonitis, cardiomyopathy.
e. Category C (severely symptomatic infection) includes AIDS-defining
conditions.
(1) Recurrent, serious bacterial infections
(2) Opportunistic infections include P. carinii pneumonia, Mycobacterium
avium-complex, candidia esophagitis, disseminated cryptococcosis,
toxoplasmosis encephalitis, cryptosporidiosis, and disseminated tuberculosis.
(3) Wasting syndrome
(4) CNS affection.
(5) Malignances: lymphoma.
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 Diagnosis of HIV infection
(A) Infants born to HIV-infected mothers (category E)
(1)Serologic testing (ELISA and Western blot). Maternal
antibodies may persist for up to 18 months in exposed
infants; hence, a positive HIV serology in such infants is
not diagnostic until after 18 months.
(2) HIV p24 antigen detection. Not all infected infants
have positive tests; a negative test does not exclude HIV
infection, but a positive test generally makes the
diagnosis.
(3) HIV culture of blood lymphocytes. When available,
this is the most reliable diagnostic test; but a negative
culture does not rule out HIV infection.
(B) In infants and children without known perinatal HIV
exposure, a complex of presenting signs and symptoms
may raise suspicions of HIV infection, or children may
present with AIDS-defining infections. 15
Therapy:
General management includes antiretroviral therapy,
treatment of secondary infections, prophylaxis against P.
carinii pneumonia, and nutritional support.
(A)Antiretroviral therapy. Nucleoside analog drugs
available for pediatric use include zidovudine (AZT, ZDV),
didanosine (ddl), zalcitabine (ddC), and stavudine (d4T).
These drugs may provide short-term benefits, especially if
used in combination.
A newer drug, lamuvidine (3TC), used in combination with
AZT, appears to manifest more sustained antiviral effects
because 3TC selects for viral mutants that remain sensitive
to AZT.
The efficacy of other classes of drugs, such as inhibitors of
HIV protease were also used.

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(B) Prophylaxis for P. carinii pneumonia
• Prophylaxis is recommended for all perinatally exposed
infants from 6 weeks to 12 months of age, or until immune
status has been clarified.
• For infected children 12 months to 6 years of age, prophylaxis
is given if the CD4 T-cell number is less than 500/u.l;
• For children older than 6 years, prophylaxis is given when the
CD4 T-cell number is less than 200/u.l.
• The drug of choice is trimethoprim-sulfamethoxazole
(TMP-SMX), which is given 3 times a week. Dapsone is used
in children who do not tolerate TMP-SMX.

PREVENTION
(A) Decreasing the number of births to HIV-infected women.
(B) Treating HIV-infected mothers during pregnancy and
delivery with ZDV.
(C) No effective vaccine against HIV infection is likely to be
available.
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