Lecture 30: Immunodeficiencies Flashcards
2 types of immunodeficiencies
Primary - genetic
Secondary - acquired
characteristics of primary immunodeficiency
- develop in VERY young animals (<6mo) when maternal protection wanes
- typically involve genetic mutations
- rare conditions
Characteristics of secondary immunodeficiency
- tend to occur in adult animals
- can be transient or permanent deficiencies
which type of immunodeficiency is more common
secondary
what can primary immunodeficiency result from
defects in lymphocyte maturation, lymphocyte activation/function, defects in innate immunity
patients with innate immune deficiencies are especially susceptible to infections from…
encapsulated bacteria
deficits of innate immunity typically occur during what processes of cell defense
phagocytosis, intracellular killing, or proteins of the complement system
severe recurrent bacterial infections are typically observed in _____ complement deficiency
C3
most severe of the complement deficiencies
C3
- skin and respiratory most common
Factor H (CFH) Deficiency causes
increased inflammation (Glomerulonephritis)
- common in yorkshire pigs
- increases C3&C5 convertase activtiy
Chediak-Higashi Syndrome
- **defect in gene LYST (CHS1) **which regulates intracellular protein trafficking of lysosomes and secretory granules
- -mutation interferes w/ synthesis and function of granules
Chediak-Higashi Syndrome is characterized by
- albinism
- photophobia
- peripheral neuropathy
- bleeding disorder
- increased infections
Pelger-Huet Anomaly (PHA)
- mutation in LBR=lamin B receptor
- failure of granulocyte to segment into lobes (nuclear hyposegmentation)
Trapped Neutrophil Syndrome
- mutation in VPS13B
- Border Collies
- mutation results in failure of bone marrow to release neutrophils, results in severe neutropenia
Characteristics of Trapped Neutrophil Syndrome
- abnormally long head and legs
- failure to thrive
- weakness
- joint pain
- swelling
* recurrent bacterial infections
Leukocyte Adhesion Deficiencies
- Deficiency of CD18= integrin B2 chains, results in impaired extravasation of WBCs
- results in high WBC counts and reccurent bacterial infection
Cyclic neutropenia (gray collie syndrome)
mutation in AP3B1 encoding neutrophil elastase, results in decreased enzyme activity
patients with B cell deficiencies are more susceptible to…
- some bacteria
- parasites
- viruses in which immunity is primarily antibody mediaated
F
Foal Immunodeficiency syndrome is a ____ cell deficiency
B
Foal Immunodeficiency syndrome
- mutation of the sodium/myo-inositol cotransporter gene, SLC5A3
- mainly affects Fell and Dales ponies
- SLC5A3 plays a role in regulation cellular responses to osmotic stress
Characteristics of Foal Immunodeficiency syndrome
abnormally low RBCs and B cell levels
as levels drop, foals become progressively more anemic and susceptible to recurrent infections
X-linked Agammaglobulinemia (XLA)
- mutation in gene encoding Bruton’s tyrosine kinase (Btk)
- results in inability of pre-B cells to synthesize and express complete RBC, results in apoptosis of pre-B cells
characteristics of XLA
- lack of B cells, lack of Igs in serum, no follicles or germinal centers in lymphoid tissues
- recurrent bacterial infections (commonly resp and GI)
A common Ig deficiecny is selective ____ deficiency
IgA
What is selective IgA deficiency
inability of B cells to differentiate into IgA-secreting plasma cells
leads to recurrent infections on mucosal surfaces, higher allergy rates
Shar pei and German shepherds
T-cell Deficiencies cause patients to be more susceptible to..
- viruses
- intracellular microorganisms
- many opportunistic pathogens
Patients w/ Tcell deficiencies are usually also deficient in _______ and _______ immune responses
cell-mediated immunity and humoral immune responses
Thymic Aplasia
mutation in gene FOXN1 invovled in the regulation of Tcell maturation
Thymic Aplasia is characterized by…
reduced Tcell production
increased susceptibility to opportunistic infections
congenital hypotrichosis (no hair growth)
is deficiency in B or T cells more severe
T cells
bc regulators of immune system and help assist activation of B cells
what is SCID
Severe combined immunodeficiencies
severe deficit in the quantity and or functions of BOTH B and T lymphocytes
signs of disease occurs after maternal production wanes
SCID patients are highly susceptible to…
- life threatening viral, bacterial and fungal infections early in life
Mutation in DNA-Dependent Protein Kinase (DNA-PK)
autosomal recessive
DNA-PK is involved in VDJ recombination process in both B and T cells
enzyme involved in ligating the DNA breaks, resulting in a lack of both B and T cell maturation
T/F: a mutation in DNA-PK that prevents VDJ recombination is preventing B and T cells from synthesizing their specific antigen receptors
T
DNA-PK characteristics
- severe lymphopenia
- lacks of all serum Igs, hypoplasia of lymphatic tissues
- severe infections beginning around 6-8 weeks
Mutation in the common y subunit of cytokine receptors
common y subunit is a component of several cytokine receptors
lack of this renders cytokine receptors non-functional
cytokines are important in lymphocyte maturation & function
Characteristics in common y subunit mutation
poorly developed thymus
lack of T cells
lack of serum IgG/IgA
severe infections beginning around 6-8 weeks
most common causes of secondary immunodeficiences
- malnutrition & overnutrition
- medical immunosuppression
- infections
- chronic disease
- stress
- immunosenescence
severe malnutrition increases susceptibility to infection due to …..
impairement of T cell function
impairment of T cell function caused by malnutrition is related to levels of…?
leptin = adipokine related to body fat mass
less body fat = less leptin
patients with decreased leptin levels have an increased susceptibility to infection due to …
- decreased T cell numbers and function
- increase in immunosuppressive cytokines (IL-10)
obese tissue is rich in what type of macrophages
Classically activated M1
large quantities of leptin stimulates the production of _____ cytokines
pro inflammatory
