2. TREY
research
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. Brutonโs Syndrome and X-
linked Hyper-IgM ID
2
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 bodyโs immune system. 3
4. TREY
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PID Continued
4
โข Autosomal recessive traits(
SCID)
โข Autosomal dominant traits
โข x-linked recessive traits(Bruton'
s syndrome)
โข Some occur sporadically and
do not appear to be due to
single gene defects (CVID).
โข Are categorized based on part
of immune system disrupted
namely: complement system,
B/T-lymphocyte system.
โข 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.
โข Are caused by genetic or
developmental defects in the
immune system.
โข Some are inherited as:
5. TREY
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PID Categories
5
โข T-lymphocyte system
โข T cell/Cellular immunity def.
โข DiGeorge Syndrome
โข Ataxia-telangiectasia
โข Wiskott-Aldrich Syndrome
โข Phagocytic system
โข Defects in myeloid Lineage
โข Complement system
โข Disorders of complement
system
โข ID associated with aging
IMMUNE COMPARTMENTS
โข B-lymphocyte system
โข B cell deficiencies
โข SCID
โข Transient
hypogammaglobulinemia
in infancy
โข CVID
โข Brutonโs syndrome
โข X-linked Hyper-IgM ID
โข Selectively IgA deficiency
6. TREY
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SCID[Severe Combined Immunodeficiency]
6
โข Caused by deficiencies in gene
encoding CD3 chains, CD45 &
adenosine deaminase
โข Adenosine deaminase [ADA] is
essential for metabolic
functions of T cells.
โข Mutations in gene coding ADA
leads to accumulation of toxic
metabolic by-products within
lymphocytes => cell death.
โข Low T, B, NK-lymphocyte count
โข Conglomerate of the absence
of T & B cell immunity.
โข Distinguished by absence/low
numbers of T & B lymphocytes,
lack/defective T cell receptor
โข 50%: x-linked; 50%autosomal
Types
โข Autosomal recessive SCID
โข Affects both boys & girls
โข Defect of common precursors
of T and B cells
7. TREY
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SCID continuedโฆ
7
they are not functional
In General:
โข Ig are low in SCID
โข Treated with bone marrow
transplant
โข X-linked SCID
โข Affects only males
โข T-, B+, NK- phenotype
โข 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
โข Reduced no. of peripheral
blood T & NK cells; B-
lymphocyte no.s are high but
8. TREY
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Transient hypogammaglobulinemia in infancy
8
Common Variable
Immunodeficiency
โข Chronic & potentially life-
threatening condition affecting
adults and older children.
โข 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.
โข Ig replacement therapy
โข Affects infants between 6 and
18 months of age.
โข Characterized by low levels of
IgG in the blood, which can
persist for several months,
eventually normalizing without
treatment.
โข Benign condition that does not
cause significant immune
dysfunction or recurrent
infections.
โข Resolves on its own
9. TREY
research
Brutonโs Syndrome & X-linked Hyper-IgM ID
9
bacterial infections, low IgG
levels, short life-span.
X-linked hyper-IgM ID
โข Inherited genetic x-linked
recessive trait affecting males
โข Females are carriers of allele
โข Results from B-cell isotype
switching inability: inability to
switch from IgM to other
classes. This is due to defects
in CD4 T cells.
โข x-linked recessive inheritance
in males.
โข Most severe
hypogammaglobulinemia with
low B-cell and Ig count.
โข Mutation occurs at Bruton's
tyrosine kinase gene leading to
a block in B cell development &
reduced Ig production.
โข Characterized by: Absence of
B cells in blood, and Lack of Ig.
โข Clinical manifest: recurrent
10. TREY
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X-linked Hyper-IgM & Selectively IgA Deficiency
10
Selectively IgA Def.
โข Low levels of IgA
[normal=7mg/dL].
โข 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.
โข Clinical manifest:
โข Low IgA and IgG
concentrations
โข Susceptible to pyogenic
[local inflammation]
infections
โข Lung infections;
pneumonia and bronchitis
โข Ear infections; otitis
โข Pink eye; conjunctivitis
โข Sinus infections; sinusitis
โข Chronic diarrhea
11. TREY
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DIGEORGE SYNDROME
11
idism, congentinal heart disease,
low set notched ears, fish-mouth
โข Immunological features: absent
thymus => decreased cellular
immunity:
โข Depression of T cell
numbers
โข Absence of T cell response
โข Poor humoral response
โข Clinical manifest: recurrent viral,
fungal, protozoan and bacterial
infections.
โข Non-hereditary ID caused by
chromosome 22 deletion
[mostly caused by
environmental factors and
rarely inherited]
โข Results in abnormal fetus
development in 6th to 10th week
โข 6th โ 10th wk of gestatn
โข Development of parathyroid,
thymus, aortic arch, ears,
and lips
โข Associated with hypoparathyro-
12. TREY
research
DIGEORGE SYNDROME & Ataxia-telangiectasia
12
Ataxia-telangiectasia
โข 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.
โข Signs & Symptoms
โข Respiratory difficulties
โข Frequent infections
โข Underdeveloped chin, low
set ears, wide set eyes
โข Cleft palate
โข Delayed growth
โข Poor muscle tone
โข Seizures & hypothyroidism
โข Delayed speech
โข Autoimmune disease
13. TREY
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Ataxia-telangiectasia & Wiskott Aldrich Synd.
13
control respiratory
complications), chemotherapy
for cancer.
WISKOTT ALDRICH
โข Aka Eczema
Thrombocytopenia ID
Syndrome
โข X-linked ID; more prevalent in
males than females.
โข Caused by gene mutation of
Wiskott Aldrich Syndrome
โข Characterized by:
โข Difficulty in movโt coordinatn
โข Enlarged facial blood
vessels
โข Clinical Manifest:
โข Increased susceptibility to
chronic lung disease
โข High malignancy incidence:
Lymphoma
โข Managemnt: Avoid sunlight
exposure (prevent blood
vessels dilation), IgG inject (
14. TREY
research
Wiskott Aldrich Syndrome
14
Defects in Myeloid
Lineage
โข Part of non-specific/phagocytic
system.
โข Defects in phagocytic & NK
cells of the complement
system.
โข Example of defects include:
โข Congenital Agranulomatosis
โข Autosomal recessive
inherited disorder.
protein (WASp) that is necessary
in forming T -cells.
โข Signs & symptoms:
โข Eczema: red patches on
skin
โข Thrombocytopenia:
excessive bleeding
โข Recurrent infections:
inadequate help by helper
T-cells to B-cells.
โข Autoimmunity due to
impaired T regulatory cells.
15. TREY
research
Defects in Myeloid Lineage
15
โข Lymphadenopathy,
hepatosplenomegaly &
chronic draining lymph
nodes.
โข Leukocyte have poor intra-
cellular killing & low
respiratory burst
โข Chediak-Higashi syndrome
โข Reduced intracellular killing
& chemotactic movโt ;
inability of phagosomes 2
fuse with lysosomeโฆ
โข Due to defects in myeloid
progenitor cell differentiatn
in2 neutrophils.
โข Characterized by
neutropenia, recurrent inf.
โข Cyclic neutropenia
โข Defects due 2 poor
regulation of neutrophil
product
โข Neutropenia
โข CGD [Chronic granulomatous
disease]
16. TREY
research
Disorders of Complement System
16
โข Susceptibility to pyogenic
bacteria: lack of sufficient bact.
Opsonization.
โข Susceptibility to gram โve
bacteria: inability to attack
outer membrane of gram โve
bacteria
ID Associated with Aging:
Type 2 Diabetes; Alzheimerโs;
Atherosclerosis; Inflammatory
bowel disease; Rheumatoid
Arthritis.
โข SLE [Systemic Lupus
Erythematosus]: high immune
complexes precipitatn in
tissues; inflammation
โข Meningococcal meningitis:
lack of bacteria opsonization
โข Hereditary angioedema:
overproductn of C2b
โข Severe bacterial infect: lack
of bacteria opsonizatn &
inability 2 use MAP
[membrane attack pathway]
17. TREY
research
SIDs[Secondary Immunodeficiency]
17
โข Are acquired immunodeficiencies as a result of exposure to:
โข disease agents
โข Drugs
โข Environmental Factors
โข Immunosuppression
โข Aging
โข Some examples include chronic infections, iatrogenic [due to
diagnostic and therapeutic procedures] infections, and drug
regimens.
18. TREY
research
SIDs continuedโฆ
18
function decrease in proportn 2
level of protein deficiency
โข Drug regimens: chemotherapy
Other conditions associated
with SID: Sickle cell anemia,
Diabetes, Burns, Protein calorie
malnutritn, Alcoholic cirrhosis,
Rheumatoid arthritis, Renal
malnutrition.
SIDs
โข Loss of immune function due
to: disease agents, drugs,
environmental factors,
immunosuppressive therapy
or aging
Causes of SIDs:
โข Chronic infections
โข Iatrogenic: long-term admin of
drugs
โข Malnutrition: T-cell number &
19. TREY
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Management & Treatment outcomes of IDs
19
communities to generate herd
immunity
โข Most SIDs resolved by treating
the primary condition.
โข Routine preventive use of
antibiotics and antifungal
drugs.
โข Bone marrow transplant
before 3 months [SCID
patients]
โข B cell disorders are managed
with immunoglobulin
replacement therapy
โข Avoid live vaccines for SCID
patients
โข Enough vaccine coverage in
20. TREY
research
Conclusion - Perspectives
โข โID isnโt a weakness, itโs just another obstacle that we learn to
overcomeโ
โข โID isnโt a curse, itโs a challenge to be faced with courage &
strengthโ
โข โThe human body is a remarkable machine, but even jeeps
need maintenance and repair. ID is a reminder of this factโ
โข โID is not a death sentence, itโs an opportunity to learn how
to live and thrive with a compromised immune systemโ
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21. TREY
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References
โข Dr. Nyamweya. (n. d). Immunology. Pdf
โข 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
โข 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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