Lecture 30: Immunodeficiencies Flashcards
Immunodeficiencies result from the ____
Absence or failure of normal function of immune system
What is the primary consequence of immunodeficiencies
Increased susceptibility to infection
What type of infections by organisms do not commonly cause disease in immunocompetent animals
Recurrent or chronic infections
What is the common infectious consequence of B cell deficiencies
Bacterial infections
What is the common consequence of T cell deficiencies
Viral and intracellular microbial infections
What is the common consequence of innate immune deficiencies
Bacterial and viral infections
What type of immunodeficiency is inheritable and develop in young animals
Primary (genetic)
What type of immunodeficiency is acquired and tend to occur in adult animals
Secondary
Primary immunodeficiencies can result in defects in __maturation, ___ activation or components of ___immunity
Lymphocyte maturation, lymphocyte activation and innate immunity
Innate immune deficiency defects typically occur in what processes
Phagocytosis and intracellular killing or complement
What complement involves C1, C4 and C2 to form C3 convertase
Classical
What pathway involve sMASP, C4, and C2 to form c3 convertase
Mannose binding lectin
What pathway involves C3, CFB, and CFD to form c3 convertase
Alternative
What is the most severe complement innate deficiency
C3 deficiency
What complement deficiency results in severe recurrent bacterial infections usually in skin and respiratory systems
C3 deficiency
What complement deficiency results in increased C3a and C5a convertase activity
Factor H deficiency
Factor H deficiency results in increased ___
Inflammation
What gene is affected in Chediak Higashi Syndrome
LYST (CHS1)
What doe LYST regulate
Intracellular protein trafficking of lysosomes and secretory granules
What does a mutation of LYST result in
Abnormally large granules:
Lysosomes of leukocytes and platelets
Secretory granules of various cells
Melanosomes of melanocytes
What symptoms characterize chediak higashi syndrome
Albinism, photophobia, peripheral neuropathy, bleeding disorders, increased infections
What genetic mutation causes Pelger Huet Anolay
Lamin B receptor (LBR)
What is the result of a mutation in LBR
Failure of granulocyte nuclei to segment into lobes (hypo segmentation)
Granulocytes appear immature, left shift on CBC, may be mistaken for early stage lymphoma
PHA is generally lethal in what type of inheritance
Homozygous
A mutation in what gene causes trapped neutrophil syndrome
VPS13B
What does a mutation in VPS13B cause
Failure of bone marrow to release neutrophils resulting in severe neutropenia
What characterizes trapped neutrophil syndrome
Long head and legs, failure to thrive, weakness, joint pain and swelling, recurrent bacterial infections
Leukocyte adhesion deficiencies is caused by what
Deficiency in Cd18-integrity B2 chain
What is the result of leukocyte adhesion deficiency
Impaired WBC extravasation resulting in high WBC counts
What mutation causes cyclic neutropenia
AP3B1
What does a mutation in AP3B1 result in
Shorter PMN life span, cyclic PMN counts, recurrent bacterial infections, joint pain and bleeding disorders
What is the genetic mutation in foal immunodeficiency syndrome
Sodium/myo inositol co-transporter SLC5A3
What is the result of a mutation in SLC5A3
Low levels of RBC’s and B cells, become progressively anemic and more susceptible to recurrent infections
What is the mutation in XLA
Btk
What does mutation in Btk cause
Inability of Pre-B cells to synthesis and express complete BCR, resulting in B cell apoptosis
What disease is characterized by a lack of B cells and Ig’s in serum and results in recurrent bacterial infections
XLA
IgA deficiency results in what
Inability to differentiate into IgA secreting plasma cells which results in recurrent infections on mucosal surfaces
What Ig deficiency is correlated with higher rates of allergies
IgA
Immunoglobulin deficiencies can cause what problem in foals
Failure of passive transfer
What gene is mutated in thymus aplasia
FOXN1
What is FOXN1 involved in
Regulation of T cell maturation
Thymus aplasia is characterized by what
Reduced T cells production resulting in increased susceptibility to opportunistic infections
What mutation is associated with congenital hypotrichosis (no hair growth)
FOXN1
Severe combined immuno-deficiencies results in deficit in what cells
B and T lymphocytes
Patients with severe combined immuno-deficiencies are highly susceptible to
Life-threatening viral, bacterial, and fungal infections
What is DNA-Pk involved in
VDJ recombination process in both B and T cells
What does a mutation in DNA-pk result in
Failure of B and T cell maturation resulting in severe lymphopenia
What SCID causes patients to lack all serum Ig’s, hypoplasia of lymphatic tissues and severe infections beginning at 6-8 weeks of age
Mutation in DNA-PK
What is the common y subunit a component of
Cytokine receptors
A mutation in y subunit results in
Nonfunctional cytokine receptors which are important for lymphocyte maturation and function
How is y subunit mutation characterized
Poorly developed thymus, lack of T cells, lack of IgG/IgA (IgM okay), failure to thrive and severe infections around 6-8 weeks of age
Malnutrition shows increased susceptibility to infection due to impairment of what cell
T cell function
Effects of malnutrition have thought to been related to levels of what hormone
Leptin
Malnutrition results in decrease ___ cells and release of immunosuppressive cytokines such as __
T cells, IL-10
Over nutrition activates what macrophages and results in what
M1- release of pro-inflammatory cytokines
What drug has numerous immunosuppressive effects
Glucocorticoids
What drug inhibits NFAT and therefore T cell production
Cyclosporine
FIV primarily affects and destroys what cells and results in what
CD4T resulting in decline of cell mediated immunity and increased susceptibility to infection
BLV infects and transforms what cells
B cells
Chronic stress leads to elevation of endogenous ___ which results in what
Glucocorticoids, immunosuppression
Stress induced immune suppression plays a major role in susceptibility to ____ disease
Infectious
Describe the decline in immune function with age
Immunosenescence
