Immunodeficieny Flashcards
Describe the 2 types of immunodeficiencies.
1) primary/congenital = genetic defects -> increased susceptibility to infection
2) secondary/acquired = develop as a consequence of malnutrition, cancer, immunosuppressive drugs, infections of cells of IS
Describe humoral VS cell mediated immunodeficiency.
- Deficient humoral immunity = infection by encapsulated pus forming bacteria & viruses
- Defects in cell mediated immunity = infection by virus/intracellular microbes or reactivating of latent infections
Describe combined & opportunistic infections.
-combined deficiencies = all classes of microbes
-opportunistic infections = susceptible to cancer
Describe primary (congenital) immunodeficiencies via autosomal recessive inheritance.
*monogenic disease caused by germ line mutations in genes that reg the development/function of IS
Autosomal recessive inheritance
>consanguineous families (mutation inherited from both parents)
>offspring of non consanguineous = one defective allele of gene inherited from one parent & a diff defective mutation in same gene inherited from other parent
Describe primary (congenital) immunodeficiencies via autosomal dominant inheritance.
Autosomal dominant inheritance
-repeated infections
-diagnosis via serum Ig levels, cytometry of immune cells, assessment of neutrophil function in vitro
-primary T cell immunodeficiencies = diagnosed by reduced # of peripheral blood T cells, low prolif resp of blood lymphocytes to polyclonal T cell activators
-immunodeficiency result from defects in lymphocyte development/activation or defects in effector mechanism of innate/adaptive immunity
Describe the defects found in innate immunity.
- Defects in NK cells & phagocytes = Chediak-Higashi syndrome
- Pelger-Huet Anomaly
- Canine Leucocyte Adhesion Deficiency (LAD)/(CLAD)
- Bovine leucocyte adhesion deficiency (BLAD)
- Canine cyclical neutropenia (grey collie syndrome)
Describe Chediak-Higashi syndrome.
-innate immunity
-defects in NK & phagocytes
-inherited disease of cattle, mink, cats, humans
-rare autosomal recessive disorder
-recurrent infections by pyogenic bacteria etc
-caused by mutations in gene encoding lysosomal trafficking regulator (LYST)
-neutrophils, monocytes, lymphocytes = lg lysosomes & rupture -> tissue damage
-cytotoxic T cell & NK cells cant excrete granules
-animals susceptible to respiratory infections & tumors
Describe Peiger-Huet anomaly.
-innate immunity
-inherited disorder
-failure of granulocyte nuclei to segment into lobes = appear immature
-humans, cats, horses
-minimal effect of health of animal
Describe Leucocyte Adhesion Deficiency (LAD).
-innate immunity
-neutrophils = diapedesis -> adhere to vascular endothelium (mediated by neutrophil integrins)
-3 types
1. LAD I
-loss of function mutation on gene encoding B2 integrity (CD18)
2. LAD II
-defect in fucose metabolism = deficiency of carbohydrate structure & impaired neutrophil rolling
3. LAD III
-defects in activation of B integrins
Describe canine leucocyte adhesion deficiency. (CLAD)
-CLAD is LAD I due to defect in integrin Mac 1 (CD18) irish setters
>neutrophils cant respond to chemoattractant, trap complement coated bacteria, or bind to endothelial cells = infections (despite high neutrophil #)
-die early due to recurrent bacterial infections etc
-leucocytosis = defect in adhesion dependent activity
-cant ingest C3b opsonized particles & poor migration to chemotatic stim
Describe bovine leucocyte adhesion deficiency (BLAD).
-innate immunity
-LAD I in calves = autosomal recessive disease -> recurrent bacterial infections etc
-calves die early, survivors grow slow
-large # of intravascular neutrophils but few extravascular
-T cells express CD18 = poor delayed hypersensitivity
-neutrophils have less resp to chemotatic stim & cant attach to vascular endothelial cells/emigrate from blood vessels
Describe canine cyclical neutropenia (grey collie syndrome).
-innate immunity
-autosomal recessive disease of border collies
-diluted skin pigmentation, eye lesions, fluctuation in leucocyte #
-hair & nose is grey
-loss of neutrophils followed by normal/elevated count
-severe enteric & respiratory (dont live past 3y)
-puppies are weak, grow poorly, fail to heal wounds, increased mortality
Describe adaptive inherited defects in the immune system.
- Immunodeficiencies of horses
>immunoglobulin deficiencies
>SCID
>common variable immunodeficiency
>foal immunodeficiency syndrome - Immunodeficiencies of cattle
>severe combined immunodeficiency (SCID)
>selective IgG2 deficiency
>hereditary parakeratosis - Immunodeficiencies of pigs
>porcine SCID - Immunodeficiencies of dogs
>combined immunodeficiencies
>immunoglobulin deficiencies
>T cell deficiencies
Describe immunodeficiencies of horses.
-adaptive
-cell & antibody mediated resp defective = genetic lesion prior to thymic & burial cell processing -> stem cell lesion
-defect in thymic development = failure of cell mediated IR (normal Ab)
-lesion in B cell = impaired antibody resp
Describe severe combined immunodeficiency (SCID).
-adaptive immunity
-horse
-foals fail to make functional T or B cells & few circ lymphocytes
-suckle success = get maternal Ig
-born healthy = sicken by 2mo & death by 4
-bronchopneumonia = equine adenovirus
Describe immunoglobulin deficiencies.
-adaptive immunity
-horse
-primary agammaglobilinemia rare in foals = no B cells & low serum Ig
-lymphoid tissue = no primary follicles, germinal center, plasma cells
-foals = recurrent bacterial infection but live up to 18mo
-develop septicemia or recurrent respiratory tract infections
-most foals = Arabian (genetic)
Describe common variable immunodeficiency.
-adaptive
-horses
-late B cell lymphopenia due to impaired B cell production in bone marrow
-specific genes have less expression
-primary immunodeficiency but occur in animals over 3yrs
-recurrent infections dont resp to treatment = bacterial meningitis
-serum = trace levels of IgG, IgM, low IgA & normal T cell, undetectable B cells
-necropsy = no B cells in lymphoid organs, blood, bone marrow
Describe foal immunodeficiency syndrome.
-adaptive
-horse
-B cell immunodeficiency, anemia, hematocrit
-lack germinal centers & plasma cells
-B cells number drop & serum Ig levels = maternal Ab catabolization
-respiratory disease - opportunistic - adenovirus + diarrhea
-foals die 1-3mo
-autosomal recessive disease = mutate in gene coding
Describe severe combined immunodeficiency.
-adaptive
-cattle
-calf normal when born, suckle normal until 6 weeks -> pneumonia/diarrhea
-lymphopenic & hypogammaglobulinemic (undetectable IgM & IgA, low IgG)
-animal die within week w systemic candidiasis = syndrome is similar to equine SCID
Describe selective IgG2 deficiency & hereditary parakeratosis.
-adaptive
-cattle
-born health -> few weeks = exanthema, hair loss, parakeratosis
Describe porcine SCID.
-adaptive
-pig
-inbred Yorkshire pigs = normal while suckling but eventually overcome by opportunistic infections
-reduced growth, skin lesions, respiratory distress (death within 60d)
-thymus not visible, LN small, B & T lack in bloodstream but normal NK & neutrophils = no antibody resp to viral infections
-2 spontaneous mutation in Artemis gene
Describe combined immunodeficiencies in dogs.
-adaptive
-jack russel terrier = SCID phenotype
>lymphopenia, agamaglobulinemia, thymic & lymphoid aplasia
-autosomal recessive - point mutation -> stop codon
-X linked SCID in basset hound & corgi = stunted growth, susceptible to infection & absence of LN
-born normal - 6-8wk develop pyoderma, otitis, pneumonia, enteritis, sepsis = 4 mo
*X linked breeding of carrier female to normal male = half males in litter affected & all females (phenotypically normal)
Describe immunoglobulin deficiencies in dogs.
-adaptive
-selective IgM deficiency (Doberman) = high IgA, low IgG & IgM
-selective immunodeficiencies of IgA (germ shep, sharpei)
-King Charles w pneumonia = reduced IgG
Describe T cell deficiencies in dogs.
-adaptive
-family of inbred Weimaraner = immunodeficiency & dwarfism
-normal at birth -> 6-7wk wasting syndrome = emaciation & lethargy
-thymus = atrophied & lack cortex, normal Ig levels, Th cell activity normal
-disease bc deficiency of GH bc lesion in hypothalamus = thymus requires GH to function
