Lecture 33 (Immunodeficiency & Immunosuppression)

-disease in which immune function is partially or totally absent
-primary immunodeficiency

a) immunodeficiency
b) immunosuppression

a) immunodeficiency

-inhibition of the immune system by an extraneous fact
-secondary immunodeficiency

a) immunodeficiency
b) immunosuppression

b) immunosuppression

inherited

a) primary immunodeficiency
b) secondary immunodeficiency

a) primary immunodeficiency

primary immunodeficiencies are classified according to what?

the branch of immune system involved

what are some findings that may point to immuno-deficient state

-unexplained neonatal illness affecting more than one animal in a litter
-illness due to commensal or low pathogenic organism
-recurrent illness
-disease from MLV

what is this disorder?

-autosomal recessive disorder

-dysplastic or immotile cilia due to abnormalities in microtubule organization

-breeds: OES, Dachshunds, Bull Terrier, Springer Spaniel, Doberman

-signs include: poor weight gain, coughing, nasal discharge, bronchopneumonia

ciliary dyskinesia

what is this disorder?

-accompanied by dilution of skin/hair pigment
-cyclic fluctuation in WBC numbers
-disease is due primarily to decreased numbers & function in neutrophils
-recurrent infections

Cyclic hematopoiesis of grey collies

what is this disorder?

-autosomal recessive disease
-incomplete albinism, prolonged bleeding, recurrent infections
-enlarged granules within granulocytes
-species: Persians, foxes, minks, cattle, whales, humans
-diagnosed w/ signs and blood smears

Chediak Highashi Syndrome

Chediak Highashi Syndrome is due to a mutation in ________ gene

CHS1

what disease is this?

-autosomal dominant disorder w/ incomplete penetrance
-described in dogs (foxhounds, Australian shepherds)
-incomplete segmentation of granulocyte nuclei
-impaired ability to extravasate
-dogs are usually asymptomatic

Pelger Huet Anomaly

what disease is this?

-AKA canine leukocyte adhesion deficiency
-autosomal recessive trait described in Irish Setters and Holsteins
-neutrophils have defective respiratory burst
-severe infections: skin, gingiva, etc.

canine granulo-cytopathy syndrome

what disease is this?

-mutation in integral - neutrophils cannot emigrate from blood vessels
-also unable to phagocytose bacteria coated with C3b
-recurrent, severe infections

leukocyte adhesion deficiency

immunodeficiency of Weimaraners

-congenital
-recurrent fevers, diarrhea, pneumonia, pyoderma, osteomyelits
-low levels of IgG, IgA, IgM
-defective neutrophil function

what disease is this?

-Arabian horses
-autosomal recessive
-in 2-3% of all foals
-defect in DNA-dependent protein kinase: cannot "paste" DNA strands after cutting
-no functional V region of B and T cell receptors; thus no functional T or B cells

Severe Combined Immunodeficiency

what is SCIDS?

Severe combined immunodeficiency
-defect in DNA-dependent protein kinase: cannot "paste" DNA strands after cutting

what disease is this?

-x-linked (males only)
-normal B cell level but decrease immunoglobulin
-decreased CD8's
-thymus is small
-mutation in IL-2 receptor

canine SCID

dogs with SCID often die from what vaccine?

distemper MLV

what disease is this?

-no B cells, antibody
-x-linked disorder
-mutation in Bruton tyrosine kinase
-impairs B-cell signaling
-seen in male foals

Agammaglobulinemia

what disease is this?

-breed: Arabian and quarter horses

-low IgM in adults associated with infection, stress, lymphoma

IgM deficiency

what disease is this?

-delayed immunoglobulin synthesis
-lymphocyte numbers are normal
-typically self-limiting
-gotta distinguish this from SCID

transient Hypo-gammaglobulinemia

what disease is this?

-breed: Black pied Danish and Friesan (cattle)
-autosomal recessive
-cannot absorb zinc
-T cell function is impaired
-decreased CMI
-skin abnormalities

Trait A46

Zinc is needed for which hormone?

Thymic hormone

which is inherited?

a) primary immunodeficiency
b) secondary immunodeficiency

a) primary immunodeficiency

what are the 3 classes of primary immunodeficiency?

a) Defects in Mechanical Barriers
b) Defects in Non-Specific Immunologic Defenses
c) Defects in Specific Immunologic Defenses

what should you be thinking when you see the following issues:

-several litter mates affected with unexplained disease
-commensal/low pathogenic organisms causing disease
-recurrent illness
-disease after a MLV

primary immunodeficiency

Ciliary Dyskinesia is seen primarily in:

a) Dachshund, Doberman, Bichon Fries, etc.
b) Grey collies
c) Persians, foxes, cattle, etc.

a) Dachshund, Doberman, Bichon Fries, etc.

Cyclic hematopoiesis is seen in:

a) Dachshund, Doberman, Bichon Fries, etc.
b) Grey collies
c) Persians, foxes, cattle, etc.

b) Grey collies

Chediak Highashi is seen in:

a) Dachshund, Doberman, Bichon Fries, etc.
b) Grey collies
c) Persians, foxes, cattle, etc.

c) Persians, foxes, cattle, etc.

signs: poor weight gain, coughing, nasal discharge, bronchopneumonia

a) Ciliary dyskinesia

b) Cyclic Hematopoiesis

c) Chediak Highashi Syndrome

a) Ciliary dyskinesia

signs: diluted pigments, decreased neutrophil presence, decreased neutrophil function, recurrent infections, changing WBC counts

a) Ciliary dyskinesia

b) Cyclic Hematopoiesis

c) Chediak Highashi Syndrome

b) Cyclic Hematopoiesis

signs: incomplete albinism, recurrent infection, enlarged granules/granulocytes, prolonged bleeding times, photophobia

a) Ciliary dyskinesia

b) Cyclic Hematopoiesis

c) Chediak Highashi Syndrome

c) Chediak Highashi Syndrome

in addition to classical signs, what test can we do to support the diagnosis of Chediak Highashi Syndrome?

blood smear: look for giant lysosomes containing big granules

which of the following is an example of a specific, primary immunodeficiency:

a) Ciliary dyskinesia
b) Cyclic Hematopoiesis
c) Chediak Highashi Syndrome
d) SCID

d) SCID

in which do we see no functional B or T cells and rudimentary lymph nodes without follicles?

a) SCID
b) SLE

a) SCID

which disease is only in males:

a) Equine SCID
b) Canine SCID

b) Canine SCID

what is the difference in mechanism between Equine SCID and Canine SCID?

Equine: DNA-dependent protein kinase defect; cannot reattach strands during recombination; no functional V regions on B and T cells

Canine: defect in the IL-2 receptor

which is importantly decreased in canine SCID?

a) CD4+ TH
b) CD4+ Treg
c) CD8+ CTLs

c) CD8+ CTLs

which is induced?

a) primary immunodeficiency
b) secondary immunodeficiency

b) secondary immunodeficiency

Parvovirus leading to pancytopenia is an example of:

a) primary immunodeficiency
b) secondary immunodeficiency

b) secondary immunodeficiency

what is the most common source of immunodeficiency?

failure of passive immunity transfer

what is the major source of passive immunity?

maternal antibody transfer