What is immunity?
Immunity is the ability of the human body to *tolerate the presence of material indigenous to the body (“self”), and to *eliminate foreign (“nonself”) material.
What is immunodeficiency ?
Immunodeficiency (or immune deficiency) is a state in which the *immune system’s ability to fight infectious disease and cancer is compromised or entirely absent
What are primary immune deficiencies?
Genetic or developmental defects in the immune system which are present at birth but may show up later on in life.
Secondary or acquired immunodeficiency is defined as?
This is defined as the loss of immune function as a result of exposure to disease agents, environmental factors, immunosuppression, or aging.
A person who has an immunodeficiency of any kind is said to be?
immunocompromised
Classification if primary immune disorders?
Based in the component of the immune system that’s deficient, absent or defective
- Humoral immunity
- cellular immunity
- Combined humoral and cellar immunity
- Phagocytic cells
- Complement proteins
Disorders of specific immune system includes? (Defects in T,B or immunoglobulins)
- Reticular dysgenesis
- Severe combined immunodeficiency (SCID)
- Disorders of T cell
- Disorders of B cell
- Disorders if T cell with variable B-cell function
Other names for Reticular Dysgenesis ?
- Also known as AK2 deficiency
- Also known as congenital aleukocytosis
- Also known as De Vaal disease
- Also known as Generalized hematopoietic hypoplasia
- Also known as SCID with leukopenia
What kind of mutation is seen in Reticular dysgenesis ?
- Inherited autosomal recessive disease
- mutations in both copies of AK2 gene
- Patients with RD have a genetic defect that affects the T cells and at least one other type of immune cell.
- Since more than one type of immune cell is affected, this disease is classified as a severe combined immunodeficiency disease (SCID).
- Treated with BMT, often fatal
Mutations in AK2 gene leads to what?
- Absence of AK2 protein then, hematopoietic stem cells will not be able to differentiate or proliferate
- Patients with RD have a genetic defect that affects the T cells and at least one other type of immune cell.
- A weakened immune system leaves patients susceptible to different kinds of infection. Commonly, patients who are diagnosed with RD also have bacterial sepsis and/or pneumonia
Sever combined immunodeficiency (SCID) entails?
- Lymphoid progenitor cells are defective, both the T and B cell lineages are affected and result in the SCID
- Both are characterized by an absence of T cell and B cell immunity and absence (or very low numbers) of circulating T and B lymphocytes
X-linked SCID is as a result of what?
X-linked SCID is due to a defect in IL-2 which is involved in lymphocyte proliferation and/or differentiation
Autosomal SCID is as a result of ?
- Autosomal SCIDs arise primarily from defects in adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP) genes
- Which results is accumulation of dATP or dGTP, respectively, and cause toxicity to lymphoid stem cells
Precautions in patient with SCID
If suspected of SCID, the patient must not receive live vaccine, as it will result in progressing disease
Disorders of T cell affect which type of immunity ?
- T cell disorders affect both cell-mediated and humoral immunity
- making the patient susceptible to viral, protozoal and fungal infections.
- Viral infections such as those by cytomegalovirus and attenuated measles in the vaccine can be fatal in these patients.
DiGeorge’s Syndrome chromosomal abnormality found ?
- It is also known as 22q11.2 Deletion Syndrome
- It is autosomal dominant and is caused by a deletion of a small segment of chromosome 22
The most clearly defined T cell immunodeficiency is ?
DiGeorge’s Syndrome
Embryonic implication of DiGeorges syndrome ?
- Portions of the heart, head and neck, thymus, and parathyroids derive from the third and fourth pharyngeal pouches, and this developmental field is disrupted due to the chromosomal microdeletion.
- During the 6th to 10th week
Clinical manifestations if DGS?
- associated with hypoparathyroidism, congenital heart disease, low set notched ears and fish shaped mouth
Treatment of DGS?
A thymic graft taken from an early fetus (13 - 14 weeks of gestation) can be used for treatment.
•Older grafts may result in GVH reaction
Examples of T Cell deficiency with variable degrees of b cell deficiency ?
Ataxia-telangiectasia
What’s are the features of Ataxia talengiectasia ?
- **Deficiency of T cells*^ associated with a lack of coordination of movement (ataxis) and dilation of small blood vessels of the facial area (telangiectasis).
- T cells are reduced
- B cell and IgM are considered normal or low
- IgG is reduced
- IgA is considerable reduced
Incidence of malignancies increase with patients Ataxia telangiectasia due to ?
Breakage in chromosome 14 and immunoglobulin heavy chain genes
Wiskott - Aldrich syndrome features?
- Associated with normal T cell numbers with reduced functions, that gets progressively worse
- IgM levels are reduced
- IgG levels are normal.
- Both IgA and igE levels are elevated
