exam 4: autoimmune diseases & immunodeficiency

Question 1

risk factors for autoimmune diseases

Answer 1

middle-older age
female gender
genetics
altered Th1/Th2 balance
exposure to cryptic epitopes on self-antigens

Question 2

what are autoimmune diseases? what type of hypersensitivity reactions can occur?

Answer 2

immune reaction to self

type II, III, IV hypersensitivity

Question 3

how does failure in tolerance lead to autoimmune disease

Answer 3

1. failure of central tolerance (uncommon)
2. failure of peripheral tolerance for example self-reactive T cells are not deleted by Fas, rendered anergic by lack of co-stimulation or suppressed by Tregs and cryptic epitopes are exposed

Question 4

what is an example of a localized autoimmune disease

Answer 4

localized = one tissue/organ
examples:
Autoimmune Polyarthritis
Discoid lupus erythematosus

Question 5

in what animals is autoimmune polyarthritis common? what are the mechanisms? clinical signs?

Answer 5

dogs, cats, humans
mechanism: idiopathic, molecular mimicry (distemper or FeLV), rheumatoid factor or hypersensitivity II,III,IV
clinical signs: fever, lethargy, anorexia, joint swelling, lameness, painful gait

Question 6

what is an example of a generalized autoimmune disease

Answer 6

generalized = multiple tissues/organs
example: Systemic lupus erythematosus

Question 7

what are the risks for developing systemic lupus erythematosus

Answer 7

genetic predisposition
infectious agents
UV damage
environmental exposure
2-4yr old

Question 8

Systemic lupus erythematosus is common in what animals?

Answer 8

dogs, cats, horses, humans

Question 9

how do you diagnose systemic lupus erythematosus

Answer 9

2+ more lesions consistent with autoimmune disease
detection of ANAs
LE test

Question 10

what causes systemic lupus erythematosus?

Answer 10

anti-nuclear antibodies (ANA)
anti-membrane phospholipid antibodies (RBC, platelets, WBC)
Ag:Ab complex deposition
self-reactive T/B cells

Question 11

what lesions develop as a result of systemic lupus erythematosus?

Answer 11

polyarthritis, glomerulonephritis, anemia, leukopenia, dermatitis, polymyositis, fever

Question 12

Complement (C3) Deficiency
- innate or adaptive immunodeficiency
- cellular or non-cellular?
- description
- common in?

Answer 12

innate
non-cellular
failure to bind/ingest pathogens (e.g. unable to clear EC bacteria, bacterial infections/renal dx, persistent wounds, leukocytosis, hyperglobulinemia, non-regenerative anemia)
Brittney spaniels

Question 13

Clad-Canine or Bovine Leukocyte Adhesion Deficiency
- innate or adaptive immunodeficiency
- cellular or non-cellular?
- description
- common in?

Answer 13

innate
cellular
a defect in CD28 that results in the failure of neutrophils to migrate out of vasculature & bind/ingest pathogens in inflamed/infected tissues
CLAD in red Irish setters & BLAD in holsteins

Question 14

Chronic Granulomatous Disease
- innate or adaptive immunodeficiency
- cellular or non-cellular?
- description
- common in?

Answer 14

innate
cellular
failure of neutrophils to kill ingested pathogens via phagocytosis due to impaired function; granulomas form in tissues
Irish setters

Question 15

cyclic neutropenia
description
common in?

Answer 15

increased susceptibility to bacterial infections
gray collies & collie mixes

Question 16

Shwachman-Diamond Syndrome
description?

Answer 16

gene mutation causes decreased neutrophils

Question 17

Myeloperoxidase Deficiency
- innate or adaptive immunodeficiency
- cellular or non-cellular?
- description

Answer 17

innate
cellular
failure of neutrophils to kill ingested pathogens via phagocytosis due to impaired function

Question 18

Chediak-Higashi syndrome
- innate or adaptive immunodeficiency
- cellular or non-cellular?
- description
- common in?

Answer 18

innate
cellular
failure of neutrophils to kill ingested pathogens due to neutrophil granules not forming correctly = function deficits
cats, mink, cattle, orca

Question 19

what are two types of antibody deficiencies?

Answer 19

1. B cell dysfunction
2. congenital hypogammaglobulinemia

Question 20

B cell dysfunction
IgA deficiency common in?
IgG deficiency common in?

Answer 20

IgA = shar pei, german shepards

IgG = weimaraner, cavalier king charles spaniel

Question 21

congenital hypogammaglobulinemia
IgG deficiency common in?
IgM deficiency common in?
IgA deficiency common in?

Answer 21

IgG = cattle

IgM = horses

IgA = beagles, shar pei, german shepards

Question 22

what is an example of a B cell deficiency? description and common in?

Answer 22

Common Variable Immunodeficiency (CVID)
decreased # of B cells & absence of antibodies –> fever, bacterial infections, no vaccine response, lack lymphoid follicles
common in horses

Question 23

how are antibody or B cell deficiencies diagnosed?

Answer 23

radioactive immunoassay for Ab
flow cytometry to detect B cells
histopathology of lymph nodes

Question 24

what is an example of a T cell deficiency? description and common in?

Answer 24

thymic aplasia
recurrent bacterial/viral infections & concurrent pituitary dysfunction
common in cattle, dogs, cats

Question 25

what is severe combined immunodeficiency disorder (SCID)? common in?

Answer 25

defective DNA protein-kinase activity = TCR. & BCR do not undergo gene rearrangement = no functional T or B cells
Arabian horses & basset hounds/toy poodles/rottweilers

Question 26

what are examples of secondary immunodeficiencies

Answer 26

immunosenescence (age-related decline)
chronic disease
stress
malnutrition
drug therapy (prednisone, chemotherapy)