IMMUNODEFICIENCY

DISEASES (IDD)
Definition: A disease that is the result of loss of
function (or defective function) of a component of
the immune system. It can be due to the absence
of that component.
Types:
1o - inherent, congenital (Intrinsic defect
in a cell)
2o - acquired (Extrinsic factors e.g.
radiation, drugs)
Clues:
Recurrence of serious infections starting early after
birth caused by:
i. Encapsulated bacteria, e.g. streptococci,
staphylococci, H. influenzae
due to defect in C, phagocytes, Ab

ii. Viruses, fungi or intracellular bacteria

due to defect in CMI

PRIMARY IDD

Defects associated with components of

innate or adaptive immunity

I. B cells .VI

II. T cells.VIII

III. Macrophages .X

IV. Complement.XII
 I. B cell deficiency

 The most common ID diseases

 Wide range of defects: complete absence

of B cells, AFC or only absence of Ab

 Patients suffer from mainly encapsulated

bacterial infections (not fungal or viral
since CMI is normal)
Types:

• X-linked agammaglobulinemia

(Bruton’s agammaglobulinemia)
 Common in male infants
 Immune defect: absence of mature B cells in
lymphoid tissue and blood, no tonsils, small
lymph nodes, low or no serum Ig

 Intact CMI
• Specific abnormality: blockage in maturation of

pre-B cells to B cells in BM

• Infants protected up to 6 months, then manifest

recurrent bacterial

infections

• Treatment: life-long periodic gamma-globulin

injections
 2. Common variable hypo-gamma-
globulinemia
 Affect both sexes, adults (late onset, 15-35 yrs),
familial incidence but no definite genetic basis
 Immune defect: low serum Ig, low plasma cell
level, Abnormal function of B cells but normal
no. of B cells in blood
 Specific abnormality: defective differentiation of
B cells into plasma cells
 Acquired [e.g. viral infection (EBV)]
 Treatment: periodic gamma-globulin injections
 II. T cell deficiency

 defects in CMI lead to defects in HMI

 Defects in CMI lead to opportunistic
infections (viruses, fungi, parasites,
intracellular bact.), live vaccines (e.g.
measls)
 Several Types:
 MHC class II deficiency .1

 Immune defect: No CD4+ mature T cells,

no functional APC leads to reduced
activation of B cells & Tc cell, no Ab

 Specific abnormality: genetic defect in

class II expression on MQ, B cells

 Death by 5 yrs due to bacterial & viral

infections
 2. Severe Combined Immunodeficiency
(SCID)

 Immune defect: low count of T & B cells

 Specific abnormality: defect in lymphoid

stem cell differentiation or defect in
developmental pathways in thymus &
bone marrow
 Most severe form, associated with
recurrent fatal infections early in life,
prolonged diarrhea (Rota virus), pneumonia
(pneumocystis),

Bacterial GIT infections, infection/death after

immunization with attenuated live vaccines e.g.
BCG

Treatment: bone marrow transplantation (or die

within 2 yrs), (gene therapy)
 DETECTION

B cell defects
 Measurement of level of serum Ig
 Enumeration of peripheral B cells

T cell defects
 Enumeration of peripheral T cells and T
cell subpopulations
 T cell proliferation tests
 III- Complement deficiency

Defect in:

C1- C9 components can result in defective

opsonisation of bacteria, recurrent infections
by Neisseria spp., immune complex diseases
(e.g. SLE-like)
 IV- Defects in phagocytes

Defects associated with myeloid cells

(monocyte/MQ lineage, neutrophils)
 Leukocyte adhesion deficiency .1
 Immune defect: Adherence defect in
leukocyte

 Specific abnormality: Defective Adhesion

molecules Consequences:

 Failure of inflammatory cells to migrate

 Defective Phagocytosis of opsonised
bacteria
 Defective T cell help in B cell activation
 Defective CTL killing
Lazy leukocyte syndrome .2

Immune defect: defective

neutrophil chemotaxis
3. Chronic granulomatous disease (CGD)

Immune defect: defective killing of intracellular

bacteria by phagocytes

Specific abnormality: Phagocytes fail to produce

Oxygen intermediates (O2-, H2O2)
Associated with recurrent bacterial & fungal

infections, disseminated granulomas, children

die of septicemia by 7 years of age

Treatment: Antibiotics

Bone marrow transplantation

 SECONDARY IDD

Due to extrinsic, environmental factors:

1 . Therapeutic drugs (post-transplant

immuno-suppression, cancer chemotherapy)

2. Protein malnutrition, aging

3. Chronic conditions (e.g. diabetes)

4. Burns leads to severe loss of Ig via

damaged skin

5. Infections (e.g. HIV)

(Acquired Immunodeficiency Disease (AIDS

 Causative agent: HIV

 Target cells: CD4+ T cells, monocytes,

macrophages, dendritic cells, etc.

 Importance of gp120
Disease is in several stages:

1. Asymptomatic for years (latency)

2. AIDS with fever, wt loss, major

opportunistic infections when no. of CD4+ cells
is low, malignancies
 Cellular defects in HIV infection
cells Abnormality Main effects
Lo cell
proliferation
Low CD4+ count
T cells Lo cytokine
Defective function release
Lo Tc activity
Lo Ag
presentation
Reduced IL-1 & TNF Lo MHC-II
APC expression
production
Lo Chemotaxis
Lo Killing
B cells Polyclonal activation Hi Ig production
NK
Defective killing
cells
 Diagnosis: detection of viral Ag, anti-viral Ab

 Prognosis: CD4/CD8 ratio, skin tests (DTH),

Lymphocyte transformation test

 Treatment:
1. Treatment of microbial infections
2. Anti-viral drugs
3. Immunorestoration: BM transplantation, Ig
injections, cytokines