Contents- Introduction to Immunodeficiency | Types | SCID | LAD Immunodeficiency is the inability to produce an adequate immune response because of insufficiency or absence of antibodies, immune cells or both. SCID & LAD are the two immunodeficiencies from primary immunodeficiency.

1. IMMUNODEFICIENCY

2. CONTENTS
INTRODUCTION TO IMMUNODEFICIENCY
Classification of immunodeficiency
• Primary immunodeficiency
• Secondary immunodeficiency
SCID – SEVERE COMBINED IMMUNODEFICIENCY
• Overview
• Types
• Symptoms, diagnosis and treatment
LAD – LEUKOCYTE ADHESION DEFICIENCY
• Overview
• Molecular basis
• Symptoms, diagnosis and treatment

3. INTRODUCTION – IMMUNODEFICIENCY
Immunodeficiency is the inability to produce an adequate immune response because of insufficiency
or absence of antibodies, immune cells or both.
It results from a failure or absence of elements of the immune system, including lymphocytes,
phagocytes and the complement system.
Immunodeficiency can occur in T cells, B cells, complement, and phagocytes.
A functional defect of the immune system is suspected when a patient:
• Has unusual frequency of infections with common or opportunistic microorganisms.
• Has unusually severe infections and is unable to eradicate infections with antibiotics to which the
microorganisms are sensitive.
• Recurrent infections with certain viruses, protozoa, and fungi indicate a T-cell deficiency, whereas
recurrent infections with pyogenic bacteria (such as staphylococci) indicate a B-cell deficiency.

4. CLASSIFICATION OF IMMUNODEFICIENCY
Immunodeficiency disorders can be classified as
(a) primary immunodeficiencies & (b) secondary immunodeficiencies.
Primary immunodeficiency: A condition resulting from a genetic or developmental defect in the immune
system is called a primary immunodeficiency. It may affect either adaptive or innate immune functions.
Most defects that lead to immunodeficiencies affect either myeloid or lymphoid cell lineages. The
lymphoid cell disorders may affect T cells, B cells, or both B and T cells, whereas the myeloid cell disorders
may affect phagocytic function.
Primary immunodeficiency diseases can be classified as:
(a) B-cell immunodeficiencies
(b) T-cell immunodeficiencies
(c) Combined B-cell and T-cell deficiencies
(d) Complement immunodeficiencies
(e) Phagocyte deficiencies.

5. Secondary immunodeficiency: When the immune responses are adversely affected by extrinsic factors,
they produce the state of secondary immunodeficiency and consequent increased risk of infection.
They occur as a consequence of therapeutic measures that depress the immune system.
Most immunodeficient patients have secondary forms of immunodeficiency, caused by either
conditions that affect the immune system or the administration of therapeutic compounds with
immunosuppressive effects.
Secondary immunodeficiencies are more common than primary immunodeficiencies and include AIDS,
chemotherapy by immunosuppressive drugs, psychological depression, burns, radiation, Alzheimer’s
disease, celiac disease, sarcoidosis, malnutrition, aging, neoplasia, diabetes mellitus, and numerous other
conditions.
Secondary immunodeficiencies may be categorized as
(a) B-cell deficiencies
(b) T-cell deficiencies
(c) Complement deficiencies
(d) Phagocytic deficiencies

6. SCID – SEVERE COMBINED IMMUNODEFICIENCY
Severe combined immunodeficiency (SCID) is a primary immunodeficiency disease (PIDD) that
typically present in infancy which results in profound immune deficiency condition resulting in a
weak immune system. It is a group of rare disorders caused by mutations in different genes
involved in the development and function of infection-fighting immune cells.
Severe combined immunodeficiency (SCID) includes many syndromes with severe deficiency of both
humoral and cell-mediated immune responses. All these are inherited diseases with a defect in the
differentiation of early stem cells.
Affected individuals frequently die during the first 2 years of life. Clinically, they may develop a
measles-like rash, show hyperpigmentation, and develop severe recurrent (especially pulmonary)
infections.
These patients have heightened susceptibility to Pneumocystis carinii, C. albicans, and other
pathogens.
Even attenuated microorganisms, such as those used for immunization, e.g., attenuated
poliomyelitis viruses, may induce infection in SCID patients.

7. SCID are of two types: X-linked and autosomal.
X-linked SCID: It is associated with a defect of the gene that codes for a polypeptide chain
common to several interleukin receptors (IL-2, IL-4, IL-7, IL-11, and IL-15).
This chain is involved in signaling of second messages, thus in its absence, T-cell precursors fail
to receive the signals necessary for their proliferation and differentiation.
There is T- and B-cell lymphopenia and decreased production of IL-2.
There is an absence of delayed-type hypersensitivity, cellular immunity, and of normal antibody
synthesis following immunogenic challenge.
Autosomal SCID: This is due to a mutation in the gene encoding a tyrosine kinase called ZAP-
ZAP-70, which plays an important role in signal transduction in T cells.
Other SCID patients show mutations in other genes, such as RAG-1 or RAG-2, that are essential
to produce T-cell antigen receptor and the IgM monomer on the B cell that acts as antigen
carrier.
All these forms of SCID can be corrected with a bone marrow graft from HLA-DR matched
siblings. The graft is usually successful, but there is a great risk for the development of graft-
versus-host disease.

8. Symptoms:
In addition to frequent and often very severe respiratory infections, other symptoms of SCID in
include poor growth, rashes that look like chronic diarrhea and recurrent thrush in the mouth,
all of these symptoms may not be present.
Often, SCID is associated with recurrent viral infections and causes several hospitalizations before it is
discovered.
One unusual infection that can be present with SCID early on is pneumocystis pneumonia. Presence
this infection is a red flag for the need to evaluate the immune system for SCID
Diagnosis:
 Early detection of SCID is extremely important. Treating the disease in the first months of life offers a
very positive success rate in helping to combat SCID.
 As with other PIDD, screening tests can measure blood lymphocytes levels. A diagnosis of SCID can
be made in utero, which is especially helpful if there is a family history of immunodeficiency diseases.

9. LAD – LEUKOCYTE ADHESION DEFICIENCY
► It is a primary immunodeficiency
disorder .
► It is inherited as an autosomal recessive
disorder.
► Inability of neutrophils, monocytes and
lymphocytes to adhere to vascular
endothelial cells , thus extravasation of
these cells into extravascular tissue
space does not occur.
i.e. inability of leukocytes to emigrate
from the circulation to the site of injury.

10. MOLECULAR BASIS
► Molecular basis is found to be due to
defective beta-chain synthesis of CD18, a
membrane adhesion molecule of integrin
family and defect in PSGL-1.
► PSGL-1 : platelet selectin glycoprotein
ligand -1 (selectins are a family of cell
adhesion molecules )
► CD18 : Cluster of differentiation. It plays a
significant role in cellular adhesion and cell
surface signaling .

12. SYMPTOMS
► Begins during infancy and include frequent infections in soft tissues, such as gums ,
skin and muscle.
► In severely infected infants, the infections become worse and affected tissue may die.
► No pus forms in infected areas . Infections become increasingly difficult to control.
► Wounds do not heal.
► Often the umbilical cord is slow to fall off , taking 3 weeks or more after birth .
Normally it falls off on its own a week or two after birth .
► Most children with severe disease die by age 5 unless treated .
► Less severely infected infants have few serious infections , but intellectual and physical
development is often slow .

14. DIAGNOSIS & TREATMENT
DIAGNOSIS:
► Blood test: A complete blood count is done. Also special blood tests including
analysis of proteins on surface of WBC.
► Flow cytometry are used to diagnose leucocyte adhesion deficiency .
► Genetic testing is recommended for siblings .
TREATMENT:
► Stem cell transplantation is the only effective treatment .
► Antibiotics prevent infections
► Granulocyte transfusion (white blood cell )
► For children with one type of disorder , taking fructose may help.
► Gene therapy for this is being studied .

15. REFERENCES:
• https://www.aaaai.org/Conditions-Treatments/Primary-Immunodeficiency-Disease/severe-
combined-immunodeficiency
• https://courses.lumenlearning.com/microbiology/chapter/immunodeficiency/
• https://www.niaid.nih.gov/diseases-conditions/severe-combined-immunodeficiency-scid
• https://www.msdmanuals.com/en-in/home/immune-disorders/immunodeficiency-
disorders/leukocyte-adhesion-deficiency
• https://rarediseases.org/rare-diseases/leukocyte-adhesion-deficiency-syndromes/
• KUBY - Immunology
• Textbook of Microbiology and Immunology by Subhash Chandra Parija