Immunodeficiencies

1. IDs: Immunodeficiencies
Group 7: CLINICAL MEDICINE GROUP

2. TREY
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5. DiGeorge Syndrome
6. Ataxia-telangiectasia
7. Defects in myeloid lineage
8. Disorders of complement
system and IDs-associated
with aging
9. SIDs
10. Management and
treatment outcome of PIDs
and SIDs
11. Wiskott-Aldrich syndrome
and Selectively IgA deficiency
TableofContents
1. Introduction and
Definitions
2. SCID
3. Transient
hypogammaglobinemia in
infancy and CVID
4. Bruton’s Syndrome and X-
linked Hyper-IgM ID
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3. TREY
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INTRO&DEFINITIONS
Immunodeficiency: Absence/failure
of normal function of one/more
elements of the immune system
PID [Primary
Immunodeficiency]
- Inherited inborn/intrinsic
disorders of the immune system
occurring due to missing/
abnormal functioning of a part of
the body’s immune system. 3

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PID Continued
4
• Autosomal recessive traits(
SCID)
• Autosomal dominant traits
• x-linked recessive traits(Bruton'
s syndrome)
• Some occur sporadically and
do not appear to be due to
single gene defects (CVID).
• Are categorized based on part
of immune system disrupted
namely: complement system,
B/T-lymphocyte system.
• Can be due to defects in
specific [target particular
pathogen-types. T&B cells] or
non-specific [equal response to
all pathogens. E.g fever]
immune mechanisms.
• Are caused by genetic or
developmental defects in the
immune system.
• Some are inherited as:

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PID Categories
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• T-lymphocyte system
• T cell/Cellular immunity def.
• DiGeorge Syndrome
• Ataxia-telangiectasia
• Wiskott-Aldrich Syndrome
• Phagocytic system
• Defects in myeloid Lineage
• Complement system
• Disorders of complement
system
• ID associated with aging
IMMUNE COMPARTMENTS
• B-lymphocyte system
• B cell deficiencies
• SCID
• Transient
hypogammaglobulinemia
in infancy
• CVID
• Bruton’s syndrome
• X-linked Hyper-IgM ID
• Selectively IgA deficiency

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SCID[Severe Combined Immunodeficiency]
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• Caused by deficiencies in gene
encoding CD3 chains, CD45 &
adenosine deaminase
• Adenosine deaminase [ADA] is
essential for metabolic
functions of T cells.
• Mutations in gene coding ADA
leads to accumulation of toxic
metabolic by-products within
lymphocytes => cell death.
• Low T, B, NK-lymphocyte count
• Conglomerate of the absence
of T & B cell immunity.
• Distinguished by absence/low
numbers of T & B lymphocytes,
lack/defective T cell receptor
• 50%: x-linked; 50%autosomal
Types
• Autosomal recessive SCID
• Affects both boys & girls
• Defect of common precursors
of T and B cells

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SCID continued…
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they are not functional
In General:
• Ig are low in SCID
• Treated with bone marrow
transplant
• X-linked SCID
• Affects only males
• T-, B+, NK- phenotype
• Due to gene mutation of IL-2
receptor g chain. Mutation on
X chromosome encoding a
component shared by T-cell
growth factor receptor & other
growth factor receptors
• Reduced no. of peripheral
blood T & NK cells; B-
lymphocyte no.s are high but

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Transient hypogammaglobulinemia in infancy
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Common Variable
Immunodeficiency
• Chronic & potentially life-
threatening condition affecting
adults and older children.
• Characterized by low levels of
multiple Ig: IgG, IgA, and IgM;
leads to recurrent bacterial
infections of the respiratory &
digestive tracts, & increased
risk of autoimmune disease.
• Ig replacement therapy
• Affects infants between 6 and
18 months of age.
• Characterized by low levels of
IgG in the blood, which can
persist for several months,
eventually normalizing without
treatment.
• Benign condition that does not
cause significant immune
dysfunction or recurrent
infections.
• Resolves on its own

9. TREY
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Bruton’s Syndrome & X-linked Hyper-IgM ID
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bacterial infections, low IgG
levels, short life-span.
X-linked hyper-IgM ID
• Inherited genetic x-linked
recessive trait affecting males
• Females are carriers of allele
• Results from B-cell isotype
switching inability: inability to
switch from IgM to other
classes. This is due to defects
in CD4 T cells.
• x-linked recessive inheritance
in males.
• Most severe
hypogammaglobulinemia with
low B-cell and Ig count.
• Mutation occurs at Bruton's
tyrosine kinase gene leading to
a block in B cell development &
reduced Ig production.
• Characterized by: Absence of
B cells in blood, and Lack of Ig.
• Clinical manifest: recurrent

10. TREY
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X-linked Hyper-IgM & Selectively IgA Deficiency
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Selectively IgA Def.
• Low levels of IgA
[normal=7mg/dL].
• Signs & symptoms: Recurrent &
persistent Sino pulmonary & GIT
infections [Reason: IgA is found
in mucosal surf. 4 mucus
product thus protects against
infections]; increased allergic
rxtns; anaphylaxis [severe &
rapid allergic rxtn] after IgA
transfusion.
• Clinical manifest:
• Low IgA and IgG
concentrations
• Susceptible to pyogenic
[local inflammation]
infections
• Lung infections;
pneumonia and bronchitis
• Ear infections; otitis
• Pink eye; conjunctivitis
• Sinus infections; sinusitis
• Chronic diarrhea

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DIGEORGE SYNDROME
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idism, congentinal heart disease,
low set notched ears, fish-mouth
• Immunological features: absent
thymus => decreased cellular
immunity:
• Depression of T cell
numbers
• Absence of T cell response
• Poor humoral response
• Clinical manifest: recurrent viral,
fungal, protozoan and bacterial
infections.
• Non-hereditary ID caused by
chromosome 22 deletion
[mostly caused by
environmental factors and
rarely inherited]
• Results in abnormal fetus
development in 6th to 10th week
• 6th – 10th wk of gestatn
• Development of parathyroid,
thymus, aortic arch, ears,
and lips
• Associated with hypoparathyro-

12. TREY
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DIGEORGE SYNDROME & Ataxia-telangiectasia
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Ataxia-telangiectasia
• Caused by mutation of ATM
[Ataxia-telangiectasia
mutated (ATM) gene is an
oncosuppressor, located on
chromosome 11q23, that
encodes a 350-KDa protein
consisting of 3056 amino
acids] (Stucci et al, 2021) gene
& chromosome 14 breakage at
site of T-cells receptors and Ig
heavy chain gene.
• Signs & Symptoms
• Respiratory difficulties
• Frequent infections
• Underdeveloped chin, low
set ears, wide set eyes
• Cleft palate
• Delayed growth
• Poor muscle tone
• Seizures & hypothyroidism
• Delayed speech
• Autoimmune disease

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Ataxia-telangiectasia & Wiskott Aldrich Synd.
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control respiratory
complications), chemotherapy
for cancer.
WISKOTT ALDRICH
• Aka Eczema
Thrombocytopenia ID
Syndrome
• X-linked ID; more prevalent in
males than females.
• Caused by gene mutation of
Wiskott Aldrich Syndrome
• Characterized by:
• Difficulty in mov’t coordinatn
• Enlarged facial blood
vessels
• Clinical Manifest:
• Increased susceptibility to
chronic lung disease
• High malignancy incidence:
Lymphoma
• Managemnt: Avoid sunlight
exposure (prevent blood
vessels dilation), IgG inject (

14. TREY
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Wiskott Aldrich Syndrome
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Defects in Myeloid
Lineage
• Part of non-specific/phagocytic
system.
• Defects in phagocytic & NK
cells of the complement
system.
• Example of defects include:
• Congenital Agranulomatosis
• Autosomal recessive
inherited disorder.
protein (WASp) that is necessary
in forming T -cells.
• Signs & symptoms:
• Eczema: red patches on
skin
• Thrombocytopenia:
excessive bleeding
• Recurrent infections:
inadequate help by helper
T-cells to B-cells.
• Autoimmunity due to
impaired T regulatory cells.

15. TREY
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Defects in Myeloid Lineage
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• Lymphadenopathy,
hepatosplenomegaly &
chronic draining lymph
nodes.
• Leukocyte have poor intra-
cellular killing & low
respiratory burst
• Chediak-Higashi syndrome
• Reduced intracellular killing
& chemotactic mov’t ;
inability of phagosomes 2
fuse with lysosome…
• Due to defects in myeloid
progenitor cell differentiatn
in2 neutrophils.
• Characterized by
neutropenia, recurrent inf.
• Cyclic neutropenia
• Defects due 2 poor
regulation of neutrophil
product
• Neutropenia
• CGD [Chronic granulomatous
disease]

16. TREY
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Disorders of Complement System
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• Susceptibility to pyogenic
bacteria: lack of sufficient bact.
Opsonization.
• Susceptibility to gram –ve
bacteria: inability to attack
outer membrane of gram –ve
bacteria
ID Associated with Aging:
Type 2 Diabetes; Alzheimer’s;
Atherosclerosis; Inflammatory
bowel disease; Rheumatoid
Arthritis.
• SLE [Systemic Lupus
Erythematosus]: high immune
complexes precipitatn in
tissues; inflammation
• Meningococcal meningitis:
lack of bacteria opsonization
• Hereditary angioedema:
overproductn of C2b
• Severe bacterial infect: lack
of bacteria opsonizatn &
inability 2 use MAP
[membrane attack pathway]

17. TREY
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SIDs[Secondary Immunodeficiency]
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• Are acquired immunodeficiencies as a result of exposure to:
• disease agents
• Drugs
• Environmental Factors
• Immunosuppression
• Aging
• Some examples include chronic infections, iatrogenic [due to
diagnostic and therapeutic procedures] infections, and drug
regimens.

18. TREY
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SIDs continued…
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function decrease in proportn 2
level of protein deficiency
• Drug regimens: chemotherapy
Other conditions associated
with SID: Sickle cell anemia,
Diabetes, Burns, Protein calorie
malnutritn, Alcoholic cirrhosis,
Rheumatoid arthritis, Renal
malnutrition.
SIDs
• Loss of immune function due
to: disease agents, drugs,
environmental factors,
immunosuppressive therapy
or aging
Causes of SIDs:
• Chronic infections
• Iatrogenic: long-term admin of
drugs
• Malnutrition: T-cell number &

19. TREY
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Management & Treatment outcomes of IDs
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communities to generate herd
immunity
• Most SIDs resolved by treating
the primary condition.
• Routine preventive use of
antibiotics and antifungal
drugs.
• Bone marrow transplant
before 3 months [SCID
patients]
• B cell disorders are managed
with immunoglobulin
replacement therapy
• Avoid live vaccines for SCID
patients
• Enough vaccine coverage in

20. TREY
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Conclusion - Perspectives
• “ID isn’t a weakness, it’s just another obstacle that we learn to
overcome”
• “ID isn’t a curse, it’s a challenge to be faced with courage &
strength”
• “The human body is a remarkable machine, but even jeeps
need maintenance and repair. ID is a reminder of this fact”
• “ID is not a death sentence, it’s an opportunity to learn how
to live and thrive with a compromised immune system”
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References
• Dr. Nyamweya. (n. d). Immunology. Pdf
• Massaad, M. J., et al. Review article: Secondary Immune
Deficiency and Primary Immune Deficiency Crossovers.
Hematological Malignancies and Autoimmune Diseases.
https://www.frontiersin.org/articles/10.3389/fimmu.2022.9280
62/full
• Stucci, L. S., et al. (2021, May 13). The ATM Gene in Breast
Cancer: Its Relevance in Clinical Practice.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152746/
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