Immunodeficiency Disorder

Euclides Munoz Perez Florida National University Fall 2020

 

Introduction

 

For us to be able to understand immunodeficiency both defense system and normal immune system must be understood properly, this is because there are normally three lines of defense system which include external barrier, innate immunity, and adaptive immunity. The external barrier which helps the immune system are usually mechanical and physical i.e. epithelial lining of GI tract and skin. The immunodeficiency disorder is usually categorized as primary immunodeficiency disorder and secondary disorder

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There are three defense line against antigens they include:

Innate immunity, external barrier and adaptive immunity

 

 

Immunodeficiency disorder can be categorized as either primary or secondary

 

 

Exact incidence is not known but it is estimated to be 1:10000

 

 

 

Immunodeficiency definition

Immunodeficiency is a state in which the immune system’s ability to fight infectious disease is either compromised or is completely absent.

It results to recurrent infections, Autoimmune disease, Allergic disorder or Oncology

It is associated with mortality and morbidity in a child

 

 

Immunodeficiency is the process where there is a failure of the defense mechanism system of one body part which normally results to recurrent infections of variable degrees, this makes it to be associated with the mortality and morbidity in a particular child. From a study conducted in the US we able to find out thst there are usually over two hundred PIDD which mostly affect over five hundred thousand people in the US. Immunological disorder is normally a condition that is caused by a dysfunctional immune system.

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Types of Immunity

 

 

Innate, Inborn, Non-specific:

 

 

External defense (First Line)

 

 

Internal defense (Second Line): Phagocytes (Macrophages, neutrophils and monocytes), Inflammatory reaction, fever, Interferons, complement system, NK

 

 

Acquired/Adaptive, specific:

 

 

Active Immunity: T Cells, B Cells, antigen presenting Cells

 

 

Passive Immunity: Antibodies artificially produced, injected

 

 

 

B cells

Centre of the adaptive humoral immune system and are responsible for mediating the production of antigen-specific immunoglobulin (Ig) directed against invasive pathogens (typically known as antibodies)

 

T cells

 

T cells originate from haematopoietic stem cells which are produced in the bone marrow. Some of these multipotent cells will becomes progenitor cells that leave the bone marrow and travel to the thymus via the blood.

In the thymus these cells mature:

Cytotoxic T Cells (CD8 T Cells)

T-Helper Cells (Th) (CD4 T Cells)

Memory T Cells

 

 

Phagocytic cells

Neutrophils

Inflammatory Monocytes

Macrophages

Immature Myeloid DCs

Dendritic cells

 

 

Complement system

The complement system, also known as complement cascade, is a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen’s cell membrane.

Complement was discovered many years ago as a heat-labile component of normal plasma that augments the opsonization

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Immunoglobulins

Glycoprotein produced by plasma cells

Functions:

Antigen binding

Effector Functions:

Fixation of complement – This results in lysis of cells and release of biologically active molecules

Binding to various cell types – Phagocytic cells, lymphocytes, platelets, mast cells, and basophils have receptors that bind immunoglobulins

binding can activate the cells to perform some function. Some immunoglobulins also bind to receptors on placental trophoblasts, which results in transfer of the immunoglobulin across the placenta. As a result, the transferred maternal antibodies provide immunity to the fetus and newborn

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IgG

Placental transfer – IgG is the only class of Ig that crosses the placenta.

1. Increases in:

a) Infections of all types b) Hyperimmunization c) Malnutrition (severe) d) Disease associated with hypersensitivity granulomas, dermatologic disorders, and IgG myeloma

2. Decreases in:

a) Lymphoid aplasia b) Selective IgG, IgA deficiency c) Bence Jones proteinemia

 

 

IgM

IgM is the first Ig to be made by the fetus and the first Ig to be made by a virgin B cells when it is stimulated by antigen.

1. Increases in:

a) Trypanosomiasis b) Malaria d) Infectious mononucleosis Note: In the newborn, a level of IgM above 20 ng./dl is an indication of in utero stimulation of the immune system and stimulation by the rubella virus, the cytomegalovirus, syphilis, or toxoplasmosis.

2. Decreases in:

a) Lymphoproliferative disorders (certain cases) b) Lymphoid aplasia

 

IgA

IgA is the major class of Ig in secretions – tears, saliva, colostrum, mucus

 

1. Increases in:

a) Wiskott-Aldrich syndrome b) IgA myeloma

2. Decreases in:

a) Immunologic deficiency states (e.g.congenital and acquired agammaglobulinemia) c) Malabsorption syndromes d) Lymphoid aplasia e) IgG myeloma f) Acute lymphoblastic leukemia

 

 

 

IgE

Involved in allergic reactions – As a consequence of its binding to basophils an mast cells,

 

1. Increases in:

a) Atopic skin diseases such as eczema b) Hay fever c) Asthma d) Anaphylactic shock

2. Decreases in:

a) Congenital agammaglobulinemia b) Hypogammaglobulinemia due to faulty metabolism or synthesis of immunoglobulins

 

 Primary Immunodeficiency

Usually congenital, resulting from genetic defects in some components of the immune system

Types of primary immunodeficiency

B- cell (humoral) defects: 50%

T- cell (cellular immunity) defects (includes combined T & B cell defects): 30%

Phagocytic system defects: 15-20%

Complement defects: 1-2%

 

 

 

Secondary (Acquired)

As a result of other diseases or conditions such as:

Drugs

Infections

Malnutrition

 

Primary immunodeficiency diseases are not usually screened for at any time during life

Most affected do not have abnormal physical features

Extensive use of antibiotics may mask the classic presentation

 

Why diagnosis is difficult

 

 

 

Clinical features which may indicate immune deficiency – Early detection

Three ore more episodes of otitis media in 6 months or 4 in a year.

Persistent purulent ear discharge.

Two or more serious sinus infection in a year.

Two or more episodes of pneumonia in a year.

Failure to thrive.

Recurrent deep skin or organ abscesses.

Persistent or recurrent candidiasis.

Two or more deep tissue or sterile site infections: pneumonia, meningitis, osteomyelitis, deep abscesses.

A family history of primary immunodeficiency.

Early detection of this condition normally comes when an infant is around 4-6 months and his maternal starts to wane, this further leads to pyogenic infection if proper care is not conducted early enough. Incidence of otitis media will increase as a result of this condition therefore having a very negative impact to the infant in question. This further led to the presence of sinusitis and pneumonia

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Features

Predominant T Cell

Early onset 2-6 months ( Gram positive and Negative Bacteria, Mycobacteria, CMV, EBV, Fungi-candida) – Lungs and GI tract

Predominant B Cell

Onset after 5-7 months of age (Pheumococci, staph, strepto, enteroviruses, giardia.- sinopulmonary and GI infections

Phagocytic defect

Early onset ( staph, pseudomonas, candida, nocardia. skin abscess, LN suppuration, oral cavity infections

Complement defect

Onset at any age (Pneumococci and neiserria) – Meningitis, arthritis, sepsis

The following are some of the common diseases found secondary disorder, they include things like Leukemia, HIV, Lymphoma and renal failure. Most of this diseases can be prevented before they occur and this will be a proper way of making sure the defense mechanism is proper in performing any task found in the body of an individual.

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Selected pediatric primary immunodeficiency and clinical presentation

Immunodeficiency

Severe combined immunodeficiency SCID

Wiskott Aldrich Syndrome

Hyper-IgE syndrome

DiGeorge Syndrome

Common variable immunodeficiency

Selective Ig A

 

Clinical presentation

In infancy, failure to thrive, pneumonia, diarrhea, unusual infections

Thrombocytopenia, bloody stools draining ears, atopic eczema, recurrent infections, EBV (Burkit Lymphoma)

Staphylococcal abscess, osteopenia, unusual infections, recurrent pneumonias, recurrent otitis and sinusitis.

Partial Thymic hypoplasia,

Enlarged tonsils, splenomegaly, alopecia areata, Thrombocytopenia

Infections of respiratory, GI and genitourinary tracts.

 

Clinical Presentation

Clinical Presentation

Clinical Presentation

 

 

 

When to do screening labs ?

Infections with unusual organisms (e.g. Aspergillus)

Infections of unusual severity (e.g. varicella complicated by pneumonia)

Infections occurring at unusual sites (e.g. liver abscess)

Clinical manifestations of a specific immune disorder (e.g., DiGeorge anomaly)

Family history of immunodeficiency

Recurrent infections

Initial laboratory evaluation

Complete blood count including a differential white blood cell count with platelet determination. The total leukocyte count and the absolute numbers of lymphocytes, neutrophils, and eosinophils.

Lymphopenia is defined as a lymphocytic count of less than 3000 cells/mm3 in infants

A peripheral blood smear can be very informative.

It is important to include electrolytes, glucose, urine analysis, renal, and liver function tests.

HIV testing is indicated in every patient with suspected T cell defect. Testing is either done by determining the antibody titers or by PCR.

To exclude anatomical factors, a chest x-ray

 

 

 

Diagnostic

Antibody Defect

Quantitative- Immunoglobulin Levels

Functional – Antibody Titer to immunizations

T cell

Quantitative- CBC, Abs lymphocyte count

Functional- Skin test for antigens ( Mumps, candida, etc.)

Chest x-ray

Phagocyte

Quantitative- CBC, Abs neutrophil count

Functional – NBT test

Complement

Quantitative – C3, C4

Functional – CH50

 

 

 

Treatment Immunoglobulin replacement

Treatment of severe antibody disorders

IVIG 400 – 600 mg/kg/m IV drip

Frozen plasma 10 ml/kg/ month

 

 

 

 

Treatment for cellular deficiency

Bone marrow transplantation

Replacement therapy

Enzyme replacement

Gene therapy

Thymic hormones

Cytokines

Fetal thymus transplantation

 

Treatment for phagocytic disorders

 

Interferon gamma: Chronic Granulomatous Disorder

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Interferon gamma for CGD

 

 

Granulocyte transfusion

 

 

 

 

 

Education

Due to unusual nature of infection children with immunodeficiency infection require constant consultation to avoid unnecessary risks

 

To be properly educated on how to manage the health care of children with immunodeficiency disorder, parents as well as their children are usually required to be part of the pediatric health homes. There they will be able to get support and guidance from the pediatricians, since they advocate for their health. It is necessary to constantly seek consultations about immunodeficiency infection due to its unusual nature of infection, so as to avoid unnecessary risks

 

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CONCLUSION

Recurrent or persistent infection is a major manifestation of primary immunodeficiency. While most children with recurrent infection have a normal immunity, it is important to be vigilant in this population for unusually frequent or severe infections. The early involvement of a clinical immunologist in cases of suspected immunodeficiency is crucial since early investigation and treatment of a child with an underlying primary immunodeficiency can prevent significant end-organ damage and improve survival and long-term outlook

Geha RS, Notarangelo LD, Casanova JL, et al. Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. J Allergy Clin Immunol.

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