Lecture 39 Diseases Flashcards
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- phagocyte defect -> can’t make any ROS to kill pathogen -> granuloma formation
- primary immunodeficiency because of genetic origin
- recurrent infections with intracellular fungi/bacteria
- tx with infection management and hematopoietic stem cell transplant
CGD – Chronic Granulomatous Disease
- genetic origin
- integrin protein mutation -> doesn’t roll and stick to place of infections -> non-efficient chemotaxis
Leukocyte Adhesion Deficiencies
- genetic origin
- mutation in protein LYST which helps trafficking of lysosomes -> no phagolysosomes -> no destruction of pathogen
- reduced resistance to infection
- albinism, nerve defects, or bleeding disorders
- CTL and NK cells also can be affected
- tx with infection management and hematopoietic stem cell transplant (broken melanocytes can’t be fixed with hematopoietic transplant because they didn’t come from that generation)
Chediak-Higashi Syndrome
- deficiencies of C1q, C2 or C4 can lead to systemic lupus erythematosus (autoimmune)
- no C3 -> no opsonization (Strep, Neisseria, other encapsulated bacteria)
- no terminal complement components -> no MAC-attack (Neisseria infections)
- no control factors like C1 esterase inhibitor -> recurrent angioedema
Complement System Deficiencies
- mainly impaired T-cell development with possible B-cell maturation defect
- defect T-cells could lead to defective humoral immunity -> no activation of B-cells for antibody production
- no antibodies -> no neutralization -> life-threatening infections like bacteremia (bacteria all up in blood)
- susceptible to systemic infection, CMV can be reactivated = fatal pneumonia
- GI infections with rotavirus or CMV, giardia or cryptosporidium
- live attenuated vaccines can cause infections in SCID patients
Severe Combined Immunodeficiencies (SCID)
(defective cytokine receptor on T-cells-no growth)
- common gamma chain for cytokine receptors is broke (can’t understand IL-2, 4, 7, 9, or 15)
- no maturation of T or NK cells -> reduced numbers
- B-cells are fine -> don’t need the receptors
X-linked SCID
- most common of autosomal recessive SCID
- no degradation of dATP by developing lymphocytes -> needed for maturation
- tx with hematopoietic stem cell transplant
adenosine deaminase deficiency
- defective conversion of inosine to hypoxanthine and guanosine to guanine
- accumulation of crap then bad for lymphocytes -> mainly T-cells
purine nucleoside phosphorylase deficiency
adenosine deaminase deficiency
purine nucleoside phosphorylase deficiency
SCID by defects in nucleotide metabolism
-adenylate kinase (AK2) gene mutation -> discombobulated intracellular energy transport -> no development of hematopoietic cells
reticular dysgenesis
SCID by other defects in metabolism
reticular dysgenesis
- RAG1 or RAG2 deficiency -> no recombination -> reduced Ig serum, reduced T/B cells
- double-stranded break repair and checkpoint -> same
SCID by defects in VDJ Recombination
-adenylate kinase (AK2) gene mutation -> discombobulated intracellular energy transport -> no development of hematopoietic cells
reticular dysgenesis
- X-linked -> decrease Ig serum and reduced B-cells
- mutations on Bruton tyrosine kinase (Btk) -> needed for B-cell maturation past pre-B cell stage
- no antibodies in blood
- most common congenital immunodeficiencies, dx in boys at 6 months when maternal antibodies are waning
- recurrent infections
- tx with IV gamma globulins
Agammaglobulinemia (Bruton)
- decreased T-cells because of thymic hypoplasia
- thymic hypoplasia due to embryonic defect -> 3rd/4th pharyngeal pouches -> “CATCH-22 -> (cardiac issues, abnormal facies, thymic aplasia, cleft palate, hypocalcemia and chromosome 22q11)”
- highly variable immunodeficiency depending on degree of thymic hypoplasia
- T-cells usually improve with age
- tx with thymic or bone marrow transplant
DiGeorge Syndrome
- defective cytoplasmic protein WASP -> expressed in bone marrow-derived cells
- no actin polymerization -> defective T-cells and APC interactions -> no activation, no mobility
- tx with hematopoietic stem cell transplant
Wiskott-Aldrich Syndrome
- hypomorphic mutations of VDJ genes (RAG) -> reduced function of T-cells
- low ratio of Tregs vs effector T-cells
- no receptor editing in B-cells
- erythroderma, lymphadenopathy, and eosinophilia
Omenn’s Syndrome
- aka Job’s syndrome (idk why) -> autosomal dominant-mutations in STAT3 -> defective T17 responses
- autosomal recessive -> DOCK8
Hyper-IgE Syndromes (HIES)
- IgG3 -> common in adults; IgG2/IgA -> common in children
- recurrent bacterial infections
Selective Ig Isotype Deficiencies
- heterogeneous disorders -> reduced Ig serum, reduced antibody response to infections or vaccines
- most common immunodeficiency seen in adolescents and young adults, lots of genes contributed
- highly variable -> decreased IgM or IgA and poor response to vaccines
- present mature B-lymphocytes but none or few memory B-cells
Common Variable Immunodeficiency (CVID)
Hyper-IgM Syndromes
X-linked
autosomal recessive
- CD40L mutation -> no activation of B-cell, macs, or DC by T-helpers
- no somatic mutation, class switching, or germinal center formation, broken CMI because no activation of effector cells
X-linked Hyper-IgM Syndrome
- CD40 mutation -> same effects as above
- antibody defect -> broken somatic mutation or isotype switching, thus only IgM
- mutation in activation-induced deaminase (AID)
autosomal recessive Hyper-IgM Syndromes
- neurological impairment, ataxia
- mutation on protein kinase called ATM (ataxia-telangiectasia mutated, wtf?) -> genome instability syndrome because checkpoints in cell cycle is now out of whack -> can affect B/T cells
- IgA/IgG2 deficiency -> common with class-switch recombination defect
- thymic hypoplasia, resp infections
Ataxia-telangiectasia
