Immunodeficiency

Question 1

Immunodeficiency

Answer 1

Situation where the capacity of the immune system to mount a response against diseases is impaired or absent
Can be:
Primary x secondary
Affect the innate and/or adaptive immunity

Address each individually because no overarching mechanism

Question 2

Primary immunodeficiency

Answer 2

Inherited (hereditary)
Young animals
Associated with high mortality (or short life)
Genetic defect

One kind can effect all lymphoid precursors and then there will be immunodeficiency for both T and B cells.
Or can have effect on just one or other
Or can affect the innate immunity like neutrophils

Question 3

Secondary immunodeficiency

Answer 3

Acquired (need exposure)
Older animals (Not old!)
Previously normal immune system
Drugs, infection, chronic disease, age

Question 4

Chediak-Higashi Syndrome

Answer 4

Affects lots of animals
Hereford, Japanese black, and Brangus cattle, Aleutian mink, Persian cats, white tigers, beige (bg/bg) mice, Orca whales, and humans.
What they will have in common is abnormally large secretory lysosomes in neutrophils, monocytes, eosinophils, and pigment cells in the skin.

Mutation on the lyst gene (recessive)- regulatin of lysosomal membrane fusion.

• granules may fuse and rupture- tissue damage because contain lysosomal enzymes then explode
• leukocytes have reduced chemotactic activity and exhibit reduced intracellular cytotoxicity. Effectiveness of neutrophils compromised
• weaker membrane and will be larger

Clinical presentation:

• Loss of skin color and dilution of hair pigmentation
• eye abnormalities (cataracts and photophobia)
• Increased susceptibility to infections (upper respiratory tract) and tumors because neutrophils don’t work properly.

Question 5

Leukocyte adhesion deficiency

Answer 5

Leukocytes have lots of proteins like selectin etc
Cytokines released to epithelium,
and that will express P and E selectin
Selectin intereacts with sialyl lewis protein on leukocyte
This induces rolling
Chemokines released and recognized by neutrophils
B integrins change to high affinity state
Intigrins bind to integrin ligand
Migrate through epithelium and to inflammation.

Neutrophils are trapped in blood and so cannot get to soi
Neutrophils cannot respond to chemoattractants, trap complement-coated bacteria or bind to endothelial cells.
Animals die early in life as a result of recurrent severe bacterial infections
Animals have a marked leukocytosis, primarily a neutrophilia and eosinoohilia.

Question 6

LAD I

Answer 6

Defect on CD18 synthesis. Means stable adhesion wont occur
Irish setters
Holstein calves

Question 7

LAD II

Answer 7

Defect on sialyl lewis X
Rolling wont happen properly
and then no stable adhesion

Question 8

LAD III

Answer 8

Defective chemokine signaling
Triggers change to high affinity state (aka wont happen)
so then no stable adhesion
GSD

Question 9

Canine cyclical neutropenia

Answer 9

Grey collie disease- not very common but all look similar
Autosomal recessive disease of border collies
Loss of neutrophils every 11 to 12 days for about 3 days (mechanism unclear)
Severe enteric disease, respiratory infections, mouth infections (gingivitis), bone disease (arthralgia) and lymphadenitis
Rarely live beyond 3 years because 3 days is enough time to be exposed/infected with something.

Question 10

Canine C3 deficiency

Answer 10

Increased susceptibility to infections
Less c3 than they should have
NEED C3- so without it wont activate complememnt

Question 11

Porcine Factor H deficiency

Answer 11

Healthy at birth and for a few weeks
Stop growing, become anemic, and die of renal failure
Attacking self cells.

Question 12

Severe combined immunodeficiency disease (equine)

Answer 12

Most important congenital equine immunodeficiency

• 2-3% of arabian foals
• fail to produce functional T or B cells. Without T you sont have an adaptive immune response and no memory.
• have very few circulating lymphocytes
• born healthy- not really healthy but seems like it is
• Ab in colostrum offer protection in the first 2 months
• Death at 4-6 months of age

Question 13

Severe combined immunodeficiency disease (diagnosis)

Answer 13

3 factors should coexist:
Few circulating lymphocytes-below 1000 cells/ml
Lack of IgM in serum before suckling (normal 160 ug/lm)
Hypoplasia of primary and secondary lymphatic organs

Question 14

Severe combined immunodeficiency disease Mechanism

Answer 14

Defect in an enzyme responsible for DNA recombination
-DNA dependent protein kinase (DNA-PKcs)
-DNA-PK is to rejoin broken DNA strands
-important for VDH recombination and DNA repair
No recombination of variable regions of TCR and BCR (this is how we get different Ag for Abs- variation)
Lymphocytes cannot recognize antigens
Fail to pass positive selection (T and B cells that fails to interact with MHC. So will be eliminated and animal wont have many lymphocytes)

Question 15

Severe combined immunodeficiency disease (dogs)

Answer 15

Jack russell terriers
Leads to lymphopenia, agammaglobulinemia, aplasia of the thymus and lymphoid tissue
Defect located in gene coding DNA-PKsc
1.1% frequency of carrier status

Question 16

X-linked SCID

Answer 16

Basset hounds and corgis
Inherited disorder of the immune system that occurs almost exclusively in males
Frequent infections
Reduced number of lymphocytes
-decreaseing CD4+ and CD8+. The new CD4:CD8 ratio is 15:1 (normal is 1.7 : 1 in healthy puppies)
-B cells numbers may be normal- T cells seem more affected
-normal IgM levl but reduced or lack of IgG and IgA (because normal B cell numbers)( lack of Iga and g because no isotype switching because of lack of IL-4 produced by T cells)
Mutation in the gene encoding y chain of the IL-2 receptor (IL-2R)
-also affect receptors for IL-4, IL-7, IL-9, and IL-15 (yc common y chain)
-IL-2 defective- IL-2 stimulates proliferation of T cells- so T cells wont respond to stimulus for proliferation.

Question 17

Agammaglobulinemia

Answer 17

Lack of production of immunoglobulin- can be general (B cells as a whole) or selective (subclass)
Primary agammaglobulinemia in horses- rare
Common variable immunodeficiency in horses (B cells-more non-selective type of immunodeficiency)
IgG2 selective deficiency- Red Danish cattle (1-2% have no IgG2) (doesnt seems to be a big issue, prob because there are other Ig molecules there that can cover for it)
IgA deficiency in german shepherds, shar-pei- predisposed to GI and respiratory infections
IgM in Doberman pinschers
IgG in King charles spaniels

Question 18

Secondary immunodeficiencies

Answer 18

So many and so varied
More common than primary immunodeficiencies
Medical immunosuppression (chemotherapy, immunosuppressive therapy)
Malnutrition (worry about infection, cortisol overproduction)
Chronic diseases
Stress (cortisones immune depressive effect)
High-intensity exercise
Age
Specific infections

Deficient vit A= reduced NK activity; reduced T cell proliferation (Th2 decreased; th17 increased); Reduced IgA production

Deficient vit D= macrophages, DCs, B cells, T cells.

Question 19

Virus-induced Immunosuppression

Answer 19

Viruses that cause damage to lymphatic tissue
Feline immunodeficiency virus (FIV)
Feline leukemia virus (FeLV)
Feline Panleukopenia virus
Canine distemper virus
BVDV
Porcine circovirus

Viruses that cause lymphoid neoplasia
Mareks Disease virus
Feline Leukemia virus
Mouse leukemia virus