10.1 Immunodeficiency

A condition where the immune system fails to function properly due to defects in either the humoral or cell-mediated immune responses.

Immunodeficiency caused by an inherited genetic defect in components of the immune system.

Immunodeficiency that develops later in life due to external factors like infections, medications, or disease.

The specific cells involved in the immune response might not develop properly due to a genetic glitch.

Defective immune cells can arise during various stages of development, from stem cell to mature cells like lymphocytes.

A genetic disorder caused by a mutation in a gene that regulates lysosomal membrane trafficking.

Large secretory lysosomes in neutrophils, monocytes, eosinophils and melanocytes, leading to the presence of numerous large granules in these cells.

Granules may fuse, rupture and cause tissue damage leading to lesions such as cataracts in the eye.

Leukocytes have reduced chemotactic activity and exhibit reduced intracellular cytotoxicity.

Loss of skin color and dilution of hair pigmentation.

A condition where immune cells are excessively present in the blood, potentially suggesting an overactive immune response.

A condition where immune cells are too low in the blood, potentially suggesting an impaired immune response.

A condition in dogs where neutrophils lack the CD11b/CD18 integrin, preventing them from migrating to inflammation sites. This leads to severe infections, poor wound healing, and increased susceptibility to death.

A genetic defect in Holstein calves where a mutation in the CD18 gene causes neutrophils to be unable to migrate to inflammation sites. This leads to severe infections and death.

A genetic condition in dogs resulting in a cyclic arrest of myeloid progenitor cell maturation in the bone marrow. This causes periodic neutropenia with recurring infections and abnormal blood clotting.

The absence of CD18 protein in neutrophils, caused by a mutation in the gene encoding CD18. This disrupts the function of neutrophils and leads to severe immune deficiencies.

Neutrophils in CLAD fail to respond to chemotactic factors and cannot bind to endothelial cells.

Affected animals often die due to severe infections, characterized by lymphadenopathy, impaired pus formation, and delayed wound healing.

A single missense mutation in the beta chain of CD18 leads to a cysteine-to-serine substitution, disrupting disulfide bonds and altering the protein's structure and function.

The mutation disrupts disulfide bonds within the CD18 molecule, altering its structure and function. This prevents CD11b from being expressed on the cell surface.

A rare, autosomal recessive disorder in Border Collies characterized by cyclic fluctuations in neutrophil count, leading to recurrent infections and impaired inflammatory responses.

A severe, autosomal recessive immunodeficiency disease in horses, characterized by a lack of functional T and B lymphocytes.

The molecular basis of SCID in horses lies in a mutation affecting the DNA-PKcs gene, responsible for DNA recombination.

SCID in horses is diagnosed based on low lymphocyte counts, absence of IgM before suckling, and characteristic histological features.

An autosomal recessive immunodeficiency disease in Jack Russell terriers, resulting in severe deficiencies of T and B lymphocytes.

A rare, X-linked immunodeficiency disorder affecting primarily male Basset hounds and Corgis, causing a complete lack of functional T lymphocytes.

The molecular basis of X-SCID involves mutations in the gene encoding the gamma chain of the IL-2 receptor, essential for T cell development.

X-SCID manifests in puppies around 6-8 weeks of age, leading to frequent infections, severe lymphopenia, and often fatal outcomes.

A condition that affects young animals, making them susceptible to repeated infections. Characterized by lack of response to antibiotics and infections spreading to multiple sites.

A procedure used to determine the specific part of the immune system that is malfunctioning in an animal with a suspected immunodeficiency.

A diagnostic test that involves analyzing blood cells to evaluate the number and types of white blood cells.

A test used to evaluate the ability of the immune system to mount a delayed response to antigens, often using a substance like phytohemagglutinin (PHA).

Immunodeficiencies where the early defense mechanisms, the innate immune system, are impaired.

A type of test that can help identify specific genetic mutations responsible for immune deficiencies in some animals.

A genetic disorder where a gene mutation disrupts lysosomal membrane trafficking, causing large secretory lysosomes to form in neutrophils, monocytes, eosinophils, and melanocytes.

Granules in CHS neutrophils are abnormally large and may fuse together. This can lead to rupture, releasing enzymes that cause tissue damage and cause conditions like cataracts in the eye.

Leukocytes in CHS have reduced chemotactic activity, meaning they are less attracted to signals of infection. They also exhibit reduced intracellular cytotoxicity, making them less effective at killing pathogens.

People with CHS have a reduced ability to fight infections, particularly in the upper respiratory tract due to the reduced function of neutrophils. They are also prone to bleeding problems and may develop eye abnormalities like cataracts and photophobia.

CHS is a rare autosomal recessive disorder characterized by albinism, neutropenia, and giant lysosomal granules in various cell types. It is caused by a mutation in the CHS gene, affecting lysosomal trafficking.

SCID in horses is a serious condition and often leads to death, particularly in young foals. Affected foals typically die within the first 6 months of life.

SCID in dogs is a serious condition that often leads to early death. Affected puppies typically die within the first few months of life due to severe infections.

Genetic defects that can cause primary immunodeficiency occur during different stages of immune cell development, starting from stem cell differentiation to mature lymphocyte formation.

Persistent or recurrent infections, especially in young animals, can be a strong sign of underlying immunodeficiency, suggesting an impaired immune system.

Recurring infections in young animals, especially when antibiotics and standard treatments are ineffective, are suggestive of a weakened immune system.

Atypical infections, caused by organisms that usually don't cause disease in healthy individuals, can be a sign of a weakened immune system.

A full panel of tests is crucial for identifying the specific immune system component responsible for the immunodeficiency.

A bone marrow biopsy is used to evaluate the production and maturation of immune cells, providing insights into the underlying cause of immunodeficiency.

Genetic testing can help identify the specific mutation causing the immunodeficiency, offering insights into the inherited nature of the condition.

The mutation in CHS causes an accumulation of large, abnormal lysosomes called "giant granules" primarily in neutrophils, monocytes, eosinophils, and melanocytes. These granules can fuse and rupture, releasing enzymes that damage tissues.

CHS affects the function of immune cells, especially neutrophils. Leukocytes in CHS have reduced chemotactic activity, meaning they are less attracted to infection sites. They also exhibit reduced intracellular cytotoxicity, making them less effective at killing pathogens.

CHS causes a variety of clinical symptoms, including:

• Loss of skin color and dilution of hair pigmentation (albinism)
• Increased susceptibility to infections, particularly of the upper respiratory tract due to reduced neutrophil activity
• Eye abnormalities such as cataracts and photophobia
• Tendency to bleed abnormally following simple surgery or hematomas at injection sites

Septicemia, a serious blood infection, can occur in neonates with CHS due to the weakened immune system. This is a life-threatening condition requiring immediate medical attention.

A genetic disorder in dogs that results in a lack of the CD11b/CD18 integrin on neutrophils, preventing them from responding to chemotactic factors and migrating to sites of infection. This leads to severe infections, impaired pus formation, and delayed wound healing.

It is a mutation in the β chain of CD18, where cysteine is replaced by serine. This disrupts disulfide bonds within the CD18 molecule, altering its structure and function, preventing CD11b from being expressed on the cell surface.

A genetic defect in Holstein calves that causes a mutation in the gene encoding CD18. This leads to neutrophils being unable to migrate to inflammation sites, resulting in severe infections and premature death.

A genetic condition in dogs that causes a cyclic arrest of myeloid progenitor cell maturation in the bone marrow, resulting in periodic neutropenia. This leads to recurring infections and abnormal blood clotting.

A single missense mutation at position 107 in the β chain of CD18 substitutes cysteine with serine. This disrupts disulfide bonds within the CD18 molecule, altering its structure and function, preventing CD11b from being expressed on the cell surface.