Exam 3 Lecture 18: Immunodeficiency Flashcards
What are the two major types of immunodeficiencies and how are they different?
Inherited/primary
inherited genetic diseases
cause disease in newborns and very young
diagnosed from a history of recurrent infections
Acquired/secondary
consequence of other diseases (viral, stress, poor nutrition, old age)
What are the two types of inherited IFNɣ receptor immunodeficiency?
Homozygous recessive
affected individuals completely lack IFNɣR1 and never responds to IFNɣ signaling, severe form of disease that appears early in children
Heterozygous dominant
mutant truncated IFNɣR1 chain that cannot signal. Individual with one mutant allele will still be able to respond to IFNɣ but response will not be as strong, mild form of the disease
Causes of leukocyte adhesion deficiency in cattle (BLAD)
Defect in tight binding, CD18 loss of function (defective LFA-1)
Single amino acid mutation
Causes of leukocyte adhesion deficiency in dogs (CLAD)
CLAD-I tight binding defect, CD18 loss of function
seen in Irish red setters
CLAD-II integrin activation defect
seen in german shepherds
Causes of leukocyte adhesion deficiency in humans (LAD)
Type I
tight binding defect, CD18 loss of function
Type II
rolling adhesion defect
Type II
integrin activation defect
Symptoms of LAD (in all species)
deficiency in phagocyte recruitment to sites of infection
recurrent bacterial infection
delayed wound healing
frequent fevers and weight loss
early fatality if untreated
What is Severe Combined Immunodeficiency (SCID) in horses?
Have no B or T cells, suffer from recurrent infections after the first few weeks/ 2 months of life
Die by 4-6 months from infection
Defect in ability to rejoin ends of DNA during V-D-J
rearrangement due to a mutation in DNA-dependent protein kinase
Autosomal recessive
What is Severe Combined Immunodeficiency (SCID) in humans?
IL-2Rgamma (common gamma chain or CD132), a component of cytokine receptors hat are necessary for T and B cell development, located on the X-
chromosome
Adenosine deaminase (ADA), a mutation leads to accumulation of toxic nucleotide metabolites
that block T and B cell development
Human Immunodeficiency Virus (HIV)
Causes Acquired Immunodeficiency Syndrome (AIDS)
38 million people currently living with HIV
>750,000 people die every year
Transmitted through bodily fluids
RNA retrovirus: infects CD4+ T cells, macrophages, DCs
Reverse transcriptase to generate cDNA and then integrate into host genome
High mutation rate that commonly leads to “viral escape” from drugs
CD4+ T cell depletion leads to risk for opportunistic infection (tuberculosis, herpesvirus- Kaposi’s sarcoma)
What is antiretroviral therapy and why do multiple drugs need to be used simultaneously?
Combination of medicines that reduce viral load by targeting: viral entry, reverse transcription, integration, protein cleavage (protease inhibitors)
Need to use multiple drugs because virus mutates very quickly
What protein in HIV do broadly neutralizing antibodies target?
The spike protein
What cells do Feline Immunodeficiency virus (FIV) targets and how does this cause
immunodeficiency?
Lymphocytes: CD4, CD8 T-cells, B cells, macrophages, non immune cells
What are non-viral causes of secondary immunodeficiencies?
obesity
undernutrition
vitamin and trace element deficiencies
aging and immune senescence
chronic disorders: diabetes, chronic kidney disease
cancer
stress
excessive exercise
