Immunodeficiences

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What is immunodeficiency?

A condition where the immune system produces excessive antibodies, leading to autoimmune diseases

A failure in the humoral or cell-mediated limbs of the immune response, often resulting to intrinsic or extrinsic defects (correct)

A condition where the innate immune system functions normally, but the adaptive immune system is overly active

A transient immune response suppression caused solely by environmental factors

If the defect results from a loss of function of antibody and/or lymphocytes, the condition is known as _______________

Secondary immunodeficiency/acquired immuno deficiency

If there are intrinsic defects in T and/or B lymphocytes, the condition is termed as ___________

Primary immunodeficiency/congenital immunodeficiency

What is the primary distinction between primary and secondary immunodeficiencies?

Primary immunodeficiencies are caused by genetic defects, while secondary immunodeficiencies are triggered by external factors. Signup and view all the answers

Which of the following scenarios would most likely be classified as a secondary immunodeficiency?

An older animal with recurrent infections caused by stress and malnutrition Signup and view all the answers

At what stages of immune cell development can genetic defects lead to primary immunodeficiency?

Failure of differentiation of pluripotent stem cells or production of functional neutrophils and macrophages Signup and view all the answers

What are the three other key stages/occurrences that can lead to primary immunodeficiency? (Primary was pluripotent stem cells)

Failure of differentiation of lymphoid/myeloid lineage, and failure of T and B cell development Signup and view all the answers

When should you suspect a patient with primary immunodeficiency?

When you see chronic or recurrent infections in relatively young animals or multiple sites of infection occurring in young animals or litter mates Signup and view all the answers

What is the primary objective in diagnosing primary immunodeficiency?

To localize the immunological defect within the immune system components Signup and view all the answers

Which of the following testing approaches is ideal for examining potential primary immunodeficiencies?

A comprehensive panel targeting both cell-mediated and humoral immunity Signup and view all the answers

What is the “gold standard” procedure to confirm a patient has primary immunodeficiency?

Full necropsy of dead littermates Signup and view all the answers

What is the underlying cause of tissue damage in Chediak-Higashi syndrome?

Mutation in the lyst (CHS1) gene, causing a lysosomal defect to fuse and great large secretory granules Signup and view all the answers

What is the gene that causes Chediak-Higashi syndrome?

A missense mutation in the lyst gene Signup and view all the answers

What species is Chediak-Higashi Syndrome in?

Persian cats, cattle (Hereford, Japanese black cattle), horses, mink, and white tigers Signup and view all the answers

What is the primary defect in Chediak-Higashi syndrome?

Disrupted lysosomal membrane trafficking Signup and view all the answers

What are the possible clinical manifestations of Chediak-Higashi syndrome?

Melanocyte defects and increased risk of infection Signup and view all the answers

Which cells are primarily affected by the fusion and rupture of large lysosomes in Chediak-Higashi syndrome?

Neutrophils, eosinophils, and monocytes Signup and view all the answers

What consequences might result from endothelial defects in Chediak-Higashi syndrome?

Formation of hematomas and hemorrhage Signup and view all the answers

What are the consequences of neutrophil/monocyte/NK/T cell defects in patients with CHS?

Increased risk to infection , higher risk of tumors and septicemia Signup and view all the answers

What is CLAD?

Canine leukocyte adhesion deficiency Signup and view all the answers

Which molecular defect underlies the failure of neutrophil extravasation in LAD?

Mutation causing defective CD18/CD11b (Mac-1), preventing integrity functionality Signup and view all the answers

What causes the incorrect protein formation in Canine Leukocyte adhesion deficiency?

A missense mutation in the Beta chain of CD18 Signup and view all the answers

What structural change occurs in the CD18 molecule due to the mutation?

Disruption of disulfide bonds Signup and view all the answers

Why is the CD11b not expressed on the cell surface in Canine Leukocyte adhesion deficiency?

It requires interaction with the Beta chain of CD18 for expression Signup and view all the answers

What is the primary effect of the mutation in the Beta chain of CD18 on neutrophil function?

Impaired binding of neutrophils to blood vessels Signup and view all the answers

In what species is the defect of Canine Leukocyte Adhesion deficiency found in?

Irish Red or White setters Signup and view all the answers

This disease has similar clinical presentation as CLAD. What is this disease and in what animal(s) is it found in?

It is Bovine Leukocyte Adhesion Deficiency. This is found in Holstein calves Signup and view all the answers

The clinical signs in CLAD present dogs dying between 2-7 months of severe infections , whereas in BLAD calves have recurrent infections despite high number of neutrophils

False Signup and view all the answers

The cause of BLAD is due to the __ mutation in the gene encoding , in which it replaces _ with ___, instead of cysteine with serine in CLAD.

The cause of BLAD is due to the point mutation in the gene encoding CD18, in which it replaces aspartic acid with glycine, instead of cysteine with serine in CLAD Signup and view all the answers

Canine Cyclic Neutropenia is also known as _________

Canine Cyclic Neutropenia is also known as Grey Collie syndrome Signup and view all the answers

What is the primary result of the mutation in the AP3β1 gene in Canine Cyclic Neutropenia?

Compromised trafficking of granular proteins Signup and view all the answers

How frequently do the neutrophil numbers fluctuate in a dog with Canine Cyclic Neutropenia?

Every 11-12 days Signup and view all the answers

What impact does chronic neutropenia have on a dog's immune response?

Compromised inflammatory response Signup and view all the answers

What is the duration of neutrophil drop experienced in Canine Cyclic Neutropenia?

2-4 days Signup and view all the answers

Which of these best describes the histological findings in the bone marrow of a dog with Canine Cyclic Neutropenia?

Cyclic arrest of myeloid progenitor maturation Signup and view all the answers

What are clinical signs of dogs with Grey collie syndrome?

Discoloration of hair and nose, bleeding, and respiratory tract infections. Signup and view all the answers

What does SCID stand for?

Severe Combined Immunodeficiency Disease Signup and view all the answers

What species are prone to SCID?

Arabian horses and Jack Russels Signup and view all the answers

What mutation is most commonly associated with SCID in horses?

Deletion of nucleotides in DNA-PKcs leading to defective DNA repair. Signup and view all the answers

What is the consequence of the lack of recombination of variable regions of TCR and BCR in horses with SCID?

Inability for lymphocytes to effectively recognize antigens. Signup and view all the answers

How does the mutation associated with SCID affect lymphocyte circulation in affected horses?

It results in very low numbers of T and B lymphocytes in circulation. Signup and view all the answers

What specifically is removed from the gene coding region in the case of SCID in horses?

Five nucleotides causing a substantial loss of genetic material. Signup and view all the answers

Which aspect of immune function is primarily impaired due to the mutation in SCID in horses?

The ability to recognize and respond to antigens. Signup and view all the answers

Which combination of factors is needed to confirm SCID in horses?

Few circulating lymphocytes, absence of IgM pre-suckling, marked lymphoid organ hypoplasia Signup and view all the answers

What are the primary immune cells that may still function in horses with SCID?

Natural Killer cells, neutrophils, and monocytes Signup and view all the answers

What is a significant histological finding characteristic of SCID in horses?

Hypoplasia of primary and secondary lymphoid organs Signup and view all the answers

Which of the following characterizes the serum immunoglobulin levels in horses diagnosed with SCID?

Lack of IgM present in serum before suckling Signup and view all the answers

SCID in dogs is an _______ disease of Jack Russel terriers

SCID in dogs is an autosomal recessive disease of Jack Russell terriers Signup and view all the answers

What is the primary genetic defect associated with SCID in dogs?

Mutation in the gene coding for DNA-PKsc Signup and view all the answers

Which of the following conditions primarily results from SCID in Jack Russell terriers?

Lymphopenia, agammaglobulinemia, and aplazia of the thymus and lymphoid tissue Signup and view all the answers

Which of the following best describes the inheritance pattern of SCID in dogs?

Autosomal recessive inheritance Signup and view all the answers

What specific immunological structures are reduced or absent in dogs affected by SCID?

Thymus and lymphoid tissue Signup and view all the answers

What characterizes the immune response of Jack Russell terriers afflicted with SCID?

Absence of adaptive immune response Signup and view all the answers

What key protein is affected in X-SCID due to the mutation in the gene encoding the IL-2 receptor?

γ chain of IL-2 receptor Signup and view all the answers

Which of the following accurately describes the immunological consequence of X-SCID?

Lack of mature T lymphocytes and reduced IgG levels Signup and view all the answers

What is the primary reason for the premature STOP codon generated in the gene encoding the IL-2 receptor in Corgis?

An insertion of a cytosine Signup and view all the answers

Which anatomical finding is indicative of X-SCID upon autopsy?

Thymus weight at 10% of normal Signup and view all the answers

Which statement best describes the production of immunoglobulins in individuals with X-SCID?

Impaired production of IgG and IgA, but normal IgM Signup and view all the answers

X-SCID is a disease of and _

X-SCID is a disease of bassets and corgis Signup and view all the answers

For bassests with X-SCID, what is the molecular basis behind the disease?

The removal of 4 nucleotides causes a STOP codon to be generated. Signup and view all the answers

Which immunoglobulin deficiency is most common in humans?

Selective IgA deficiency Signup and view all the answers

What is a potential genetic cause of selective immunoglobulin deficiencies?

Block in B cell differentiation Signup and view all the answers

Which breed is associated with selective IgG deficiency?

Cavalier King Charles Spaniel Signup and view all the answers

Which of these deficiencies is NOT commonly noted in a specific dog breed?

Selective IgD in Labrador Retrievers Signup and view all the answers

What might occasionally cause selective immunoglobulin isotype deficiencies?

Homozygous deletions of constant region genes Signup and view all the answers

What primarily leads to the insufficient production of Ig in Common Variable Immunodeficiency (CVID)?

Lack of appropriate stimulation of B cells by helper CD4+ T cells for sufficient Ig Signup and view all the answers

In which age group are horses typically observed to develop Common Variable Immunodeficiency (CVID)?

Older horses over 3 years of age Signup and view all the answers

What genetic defect is known to be associated with Common Variable Immunodeficiency (CVID) in humans?

Genetic defect in the co-stimulatory molecule ICOS Signup and view all the answers

What serious health issue can result from Common Variable Immunodeficiency (CVID)?

Recurrent bacterial infections, such as meningitis Signup and view all the answers

What is the role of the co-stimulatory molecule ICOS in lymphocyte stimulation?

It is required for optimal lymphocyte activation and function. Signup and view all the answers

Secondary immunodeficiencies result from damage to a normal functioning immune system due to __________

Infectious agents such as viruses, toxins, stress, malnutrition and old age Signup and view all the answers

What is the other term used to describe “old age”?

Immunosenescence Signup and view all the answers

What is one of the direct consequences of virus-induced damage to lymphatic organs?

Lymphopenia Signup and view all the answers

A reduction in which of the following could indicate viral infection-induced immunosuppression?

Lymphocyte reactivity to mitogens Signup and view all the answers

What are examples of virus that cause damage to lymphatic tissue?

FIV, FeLV, Feline Panleukemia, Canine distemper virus and BVDV Signup and view all the answers

What virus highly stimulates activity of lymphoid tissue, as identified in class?

Porcine reproductive and respiratory syndrome virus (PRRSV) Signup and view all the answers

List the viruses that cause lymphoid neoplasia as discussed in class.

Bovine leukemia virus and feline leukemia virus Signup and view all the answers

Which cells are primarily targeted by Canine distemper virus (CDV) during infection?

T and B lymphocytes, particularly in the tonsils, bronchial lymph nodes, and spleen Signup and view all the answers

What mechanism does canine distemper virus use to destroy infected immune cells?

Binding to CD150 on activated T cells, resulting in viral replication and destruction of the host cell Signup and view all the answers

Which cells are primarily targeted by Feline Leukemia virus (FeLV)?

T lymphocytes, particularly CD4+ cells leading to immunosuppression Signup and view all the answers

What syndrome is commonly associated with feline Leukemia Virus (FeLV) infection?

Wasting syndrome due to recurrent infections in thymic atrophy Signup and view all the answers

How does FeLV contribute to the development of secondary infections?

By reducing CD4+ T cell numbers; depending on the severity of secondary infections there may be atrophy or hyperplasia Signup and view all the answers

Which cells are primarily targeted by Feline immunodeficiency virus (FIV)?

CD4+ T cells, B cells and macrophages, leading to immunosuppression Signup and view all the answers

How does FIV contribute to the development of secondary infections?

By activating CD4+/CD25+ regulatory T cells, and increasing IL-10 production, leading to immunosuppression Signup and view all the answers