Immunodeficiency Disorder
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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