Immunodeficiency Flashcards
immunocompromised
animals susceptible to infectious agents that often don’t cause disease in most animals
immunodeficiency
condition where immune system has been compromised to the extend that the animal becomes more susceptible to infection than most other members of its species
opportunistic pathogens/opportunists
don’t cause disease in healthy animals
may infect & cause disease in animals with impaired defenses (barrier functions, innate immunity, adaptive immunity)
Evidence for immunodeficiency (primary or secondary)
- chronic or recurring infection
- infections involving multiple body sites
- infection by opportunistic pathogens
- persistent lymphopenia or hypogammaglobulinemia
- failure to respond to vaccine
lymphopenia
significantly lower than 1000 lymphocytes per microL of blood
Classification of Immunodeficiencies
primary
secondary
primary immunodeficiency
inherited or cogenital
secondary immunodeficiency
acquired immunodeficiencies
Components of Immune System affected by immunodeficiencies
Innate immunity & Adaptive Immunity (Humoral immune deficiencies, cell-mediated immune deficiencies, severe combined immunodeficiency)
Humoral Immune Deficiency
B cells and Immunoglobulins
Cell-Mediated Immune Deficiency
T cells
Severe Combined Immunodeficiency
BOTH T and B cells are deficient
Primary Immunodeficiency present
at birth
primary immunodeficiency normally due to
genetic mutations
primary immunodeficiency features
- become apparent as maternal Abs decline
- may occur in siblings (litters)
- may affect a particular breed
- QUITE RARE
Types of Severe Combined Immunodeficiencies
- DNA-Dependent Protein Kinase (DNA-PKcs)
- common gamma-chain issue
DNA-Dependent Protein Kinase (DNA-PKcs)
SCID found in Arabian foals & related breeds (also in jack russell terriers)
-incomplete rearrangement of immunoglobulin & T-cell receptor genes =>no T or B cells
Common gamma-chain SCID
common for IL2, IL4,IL5,IL7,IL9,&IL15.
-critical failure probably b/c of defective signaling for IL7 which is needed for lymphocyte maturation
Selective IgA Deficiency
relatively common in dogs
- a relative not an absolute deficiency
- IgA below normal range but NOT absent
reason why is unknown
Immunosenescence
age-related alteration in immune system & its function
Immunosenescence effects
- fewer circulating CD4 & more CD8
- predominantly memory cells, fewer naive lymphocytes (maybe decreased ability to respond to new Ags)
- elevated IgA levels (serum & mucosal)
Pharmacologic immunodeficiency
results from use of immunosupressive drugs to treat autoimmune disease or chemotherapeutic agents to treat cancer
Infectious immunodeficiencies
caused by certain infectious agents affecting:
- certain classes of lymphocytes
- lymphoctes or WBCs in general
- damage to lymphoid tissues &/or bone marrow
Stress as a secondary immunodeficiency
stress induces it by release of higher levels of glucocorticoids from adrenal cortex.
an immune suppression
Malnutrition
primarily affects T-cell function. particularly protein-calorie malnutrition
Metabolic immunodeficiencies
endocrine disorders impair inflammatory responses & adaptive immune responses
Splenectomy
impairs clearance of blood-borne pathogens by the mononuclear phagocyte system
types of Secondary Immunodeficiencies
Immunosenescence, Pharmacologic, Infectious, Stress, Malnutrition, Metabolic, Splenectomy
Innate Immunodeficiencies
Neutrophils
Complement (rare)
Barrier Functions
Adaptive Immunodeficiencies
B cell, antibodies
T cell
Severe Combined Immunodeficiency (SCID)
Minor & Selective Immunodeficiencies
less dramatic clinical presentation
may not be life-threatening
may influence susceptibility to a LIMITED range of opportunistic pathogens
Assessment of Immune Function
Physical: Palpation, Biopsy
Tests of Humoral Immunity: Total Ig Measurement
Test of Cellular Immune Function
Tests of Humoral Immunity: Total Ig Measurement
Serum Albumin & Globulin levels (Albumin:Globulin ratio)
Serum Electrophoresis
Direct Measurement of Immunoglobulin Concentration
Test of Cellular Immune Function
Total Lymphocyte Counts (from CBC) Lymphocyte Subclass Counts: CD3, CD4, CD8, CD79
Serum Albumin & Globulin levels (A:G ratio)
low A:G due to: low albumin levels or high globulin levels
high A:G likely due to low Ig levels
Serum Electrophoresis
hypergammaglobulinemia: general increase in gamma-globulins due to chronic infectious disease
single spike in gamma-globulins due to: plasma cell tumor or some chronic infectious diseases
Types of Direct Measurement of Ig Concentrations
Radial Immunodiffusion, ELISA,
Radial Immunodiffusion
most accurate but slow direct measurement of [Ig]
ELISA
semi-quantitative direct measure of [Ig].
fast
usually measures IgG
Indirect Measures of testing for Humoral Immunity
sulfate (sulfite) precipitation, others based on species
sulfate precipitation
sulfate ions precipitate globular proteins from serum
Total Lymphocyte Counts (from CBC)
show low (lymphopenia) in some immunodeficient animals & in some infectious diseases
Lymphocyte Subclass Counts
CD3, CD4, CD8, B Cell counts
-not validated as immunodeficiency test
-validated for lymphoma & leukemia typing
only available in few labs (usually cvms)
