Immunology Flashcards
when do primary immune deficiencies (PIDs) clinically manifest? why?
first years of life (≥ 5-6 months) because maternal IgG stops at this time
-immune deficiencies are not detected in the newborn
what immune deficiency presents with recurrent infections with encapsulated bacteria?
B cell deficiency
humoral immune deficiency (B cell deficiencies) results from what?
impaired antibody production
- often severe upper and lower resp tract infections with encapsulated bacteria (e.g., strep pneumoniae, haemophilus influenzae)
- present with recurrent otitis media, sinusitis, and pneumonia
- uncomplicated viral infections
- chronic infections by intestine pathogens (e.g., giardia, salmonella, etc.)
- autoimmune disorders are common
all of these may present as what type of immune deficiency?
B cell deficiency
pts with suspected antibody deficiency should have measurement of what?
total serum IgG, IgA, and IgM
if a progenitor cell cannot mature into a pro-B cell, there is a deficiency in what?
ADA (adenosine deaminase)
-ADA deficiency inhibits progenitor»_space; pro-B cell
the ability of pro-B cells to mature into pre-B cells is inhibited with mutations in what? (3)
RAG1, RAG2, Artemis mutation
the maturation of a pre-B cell into an immature B cell is inhibited if there are mutations in what? (5)
BTK BLNK Ig-alpha chain mu chain gamma-5 chain
CD19 mutations inhibit what?
CD19 mutations inhibit the conversion of mature/activated B cells into plasma cells or memory cells
TQ
vaccination with live oral polio vaccines is contraindicated in pts with what?
agammaglobulinemias (e.g., BTK)
i.e., don’t give polio vaccine to pts with B cell deficiency
X-linked agammaglobulinemia (XLA) is assoc with a mutation in what enzyme’s gene? what two B lineage cells are involved?
- X-linked agammaglobulinemia (XLA) is assoc with a mutation in BTK (Bruton’s tyrosine kinase)
- pre-B cell cannot become an immature B cell
classical XLA have < 1% positive lymphocytes with what 2 CD markers?
CD19- or CD20-
i.e., no B cells
TQ
-X-linked
-mutations in BTK gene ***
-diagnosed at 5-6 months old
-caused by defect in rearrangement of the Ig heavy chain genes
-early B cell development is stopped at the pre-B cell stage»_space; absent or low # of circulating B cells
-low or totally absent IgG, IgA, and IgM *
[ T+ B– NK+ ] *
X-linked agammaglobulinemia
Bruton disease
the only difference between X-linked and autosomal recessive agammaglobulinemia is what?
the genetic defects AR agammaglobulinemia has mutations in: mu Ig-alpha gamma-5 BLNK
CVID involves the impaired ability to produce what 2 cells?
plasma cells
B memory cells
TQ
-impaired B cell differentiation with defective Ig production
-poor or absent response to immunization ** (never have B memory cells)
-recurrent bacterial infections with encapsulated bacteria *
-low IgG and IgA **
-normal or low IgM **
[ T+ B+(70%) NK+ ] **
common variable immune deficiency (CVID)
TQ
-recurrent respiratory and GI infections **
-low IgA **
-normal IgG and IgM ***
-often remain asymptomatic and undiagnosed
-may cause anaphylactic shock in pts with Abs against IgA (anti-IgA IgE) in blood transfusions
[ T+ B+ NK+ ]
IgA deficiency
TQ -high IgM with low IgG and IgA *** -impaired Ig class switching -low memory B cells -CD40L mutation *** (expressed on CD4+ T helper cells) [ T+ B+ NK+ ]
IFN(gamma) favors:
IL-4 favors:
TGF-ß favors:
hyper IgM syndrome (HIGM)
IFN(gamma) favors IgG subclasses
IL-4 favors IgE
TGF-ß favors IgA
- low IgG and IgA
- low or normal IgM
- intrinsic Ig production is delayed for up to 36 months (normalize between 2 and 4 years of age)
transient hypogammaglobulinemia of infancy
TQ -low IgM -normal IgG -elevated IgA and IgE -selective depletion of circulating mature B cells -decrease # and function of T cells -impaired chemotaxis of phagocytic cells -defective Ab responses to some vaccine antigens * [ T low B low NK+ ] ***
characterized by:
- thrombocytopenia *
- small platelets *
- platelet dysfunction
- eczema *
- susceptible to infections
Wiskott-Aldrich syndrome (WAS)
hypogammaglobulinemia M
what immunodeficiency may present with lymphopenia within hours of birth?
combined T and B cell deficiency
(severe combined immunodeficiency)
cannot use vaccines on these pts
TQ
-MC form of SCID
-X-linked recessive trait (only males)
-gene encodes gamma-chain shared by T cell growth factor receptor (IL-2Rgamma) *
-low IgG, IgA, and IgE *
-no functional B cells, plasma cells, or memory cells
[ T– B+ NK– ] *
- opportunistic fungal infections
- chronic diarrhea
- skin, mouth and throat lesions
common gamma chain deficiency
gamma-c or IL-2Rgamma
TQ -mutations in ADA gene -autosomal recessive -2nd MC form of SCID -low IgM, IgG, and IgA * [ T– B– NK– ] *
-live vaccines may be fatal *
adenosine deaminase deficiency (ADA deficiency)
TQ -SCID caused by mutation in a gene on Chr. 19 that encodes Janus kinase 3 (Jak3) -defect in IL-2 receptor signaling ** -both and girls affected (AR) -low IgG, IgA, and IgE * [ T– B+ NK– ] *
-opportunistic infections (same as gamma-c)
Deficiency of Jak3
TQ
- defective development of the pharyngeal pouch system **
- T cell deficits
- most pts have mild defects, but severe form imitates SCID
- deletion of 22q11
- hypocalcemia ***
- neonatal hypocalcemia may present as tetany and seizures
Dx:
- facial abnormalities
- major outflow tract defect of the heart
- h/o recurrent infections
-susceptible to opportunistic infections
DiGeorge syndrome (DGS)
a child who is wheelchair-bound by age 12 may have what immunodeficiency?
ataxia telangiectasia
TQ
- gene involved encodes protein that detects double-strand breaks in DNA
- ataxia assoc with inability to coordinate muscle activity *
- problems walking by age 10-12 years
- defect in eye capillary seen at 3-6 years of age (telangiectasia)
- low IgA and IgE **
ataxia telangiectasia
TQ
- mutations in genes which control expression of MHC II genes *
- no MHC II expression on professional APCs
- deficiency in CD4+ T cells
- variable hypogammaglobulinemia (mainly IgA and IgG2)
- recurrent infections
bare lymphocyte syndrome
CD4 T cell deficiency
TQ
- mutations in TAP1 molecules to transfer peptides to ER *
- only CD8+ cells are deficient (recurring viral* infections)
- normal CD4+ cells
- normal Ab production
- normal DTH (delayed type hypersensitivity)
CD8+ T cell deficiency
MHC I deficiency
list 5 diseases/syndromes involving defects in phagocytic cells.
- chronic granulomatous dz
- Chediak-Higashi syndrome
- G6PD deficiency
- myeloperoxidase deficiency
- leukocyte adhesion deficiency
TQ
- MC phagocytic primary immunodeficiency
- MC in males
- dx made by testing of neutrophil function and mutation analysis **
- deficiency of NADPH oxidase ***
- results in defective elimination of extracellular pathogens, such as bacteria and fungi; formation of granulomas
- recurrent infection with catalase(+) organisms (e.g., staph)
chronic granulomatous dz (CGD)
TQ
- AR disorder
- partial albinism ***
- no NK activity ***
- abnormal giant granules in neutrophils ***
- granules do not contain cathepsin G or elastase
- defects in chemotaxis and degranulation
- recurrent pyogenic infections
- giant azurophilic cytoplasmic inclusions in blood cells *
Chediak-Higashi syndrome
what enzyme deficiency is assoc with resistance to malaria?
G6PD deficiency
TQ
- X-linked
- mostly asymptomatic
- lack of substrate for NADPH *
- deficiency present with resistance to Plasmodium falciparum malaria ***
- weakened RBC membrane
- assoc with anemia *
- recurrent infections with catalase(+) bacteria and fungi
G6PD deficiency
- mutation and lack of expression of LFA-1 **
- defective migration of neutrophils *
clinical manifestations:
- delayed detachment of umbilical cord *** (USMLE)
- slow wound healing
- severe bact infections
- failure to form pus
-can receive routine vaccinations *
leukocyte adhesion deficiency
- disruption of one of the proteins involved in activation of complement cascade
- MC – classical pathway
- autoimmunity disorders, including lupus-like syndromes
- alternative pathway defects present with Neisseria infection
complement deficiencies
which complement factor deficiency is the “star” and affects both classical and alternative pathways?
C3
factor B and properdin deficiencies affect which complement pathway?
alternative pathway
which Ig classes do NOT cross the placenta? (3)
IgM, IgA, and IgE
which Ig is transported from the mother to the fetus by transcytosis and is detectable in the fetus at 17 weeks?
IgG
maternal-fetus transfer of IgG
IgG of the fetus and newborn are almost solely from the mother. when does maternal IgG disappear and the baby begins its own synthesis of IgG and IgM?
9 months of age
how do we know IgM and IgA of the the neonate are due solely to endogenous synthesis?
because IgM and IgA do not cross the placenta
Th1 immunity may be particularly limited in the neonate and young infant because why?
decreased IL-12 production by DCs
aging impairs the functions of NK cells, neuts/macrophages, and DCs. What some of the outcomes? (5)
- impaired activation of the immune response
- poorer vaccine responses
- higher susceptibility to infectious disease
- higher susceptibility to cancers (failure of immune system to recognize cancer cells)
- greater morbidity and mortality
age-related changes of neutrophils (3)
- decr oxidative burst
- decr bactericidal activity
- decr chemotaxis
age-related changes of macrophages (3)
- decr phagocytic activity
- decr oxidative burst
- decr MHC II expression
age-related changes of NK cells (3)
- INCR # of cells
- decr cytotoxicity
- decr proliferative response to IL-2
in low grade inflammation and mortality, are there more CD4 cells or CD8 cells?
CD8 > CD4
we expect immunosuppression during surgery and trauma. what is released to control inflammation? (3)
IL-10
TGF-B
PGE2
T/F: chronic stress-induced suppression of immune responses may decrease the efficacy of vaccination and wound healing and decrease resistance to infection and cancer.
TRUE
UV light causes immunosuppression by what 2 mechanisms?
- skin lymphocytes undergo apoptosis by DNA damage
- activation of kinases»_space; activation of NF-kB and apoptosis
T/F: steroids, like glucocorticoids, are bad for immune system.
TRUE
T/F: neutrophil function is inhibited by NSAIDs.
TRUE
T/F: NSAIDs decrease the expression of L-selectin.
TRUE
most mutations during HIV replication affect what gene?
env gene, which produces envelope glycoproteins
M-tropic viruses express a gp120 that binds to what?
CCR5 – macrophages
T-tropic viruses express a gp120 that binds to what?
CXCR4 – T cell lines
describe acute phase of HIV infection.
- occurs 1 to 6 weeks after infection – fever, fatigue, myalgia, and headaches
- gut-associated lymphoid tissue is severely depleted with loss of memory CD4+ T cells
- crossing of the BBB
describe chronic phase of HIV infection.
- absence of signs or symptoms
- the loss of CD4+ T cells is corrected by replenishment from progenitors
- HIV evasion from neutralizing Abs **
- continued CNS infiltration
- immune defense overcome by viral escape strategies
- depletion of T cells (<200 cells/mm^3)
- HIV-associated neuro disorders and dementia
- risk of opportunistic infections
AIDS
Describe HIV disease progression phases in terms of M- and T-tropism.
Initial: M-tropism (CCR5–macrophages)
Middle phase: Dual tropism
Later phases: T-tropism (CXCR4–T-cells)
What are the major reservoirs for HIV-1 in tissues of the body?
Macrophages
HIV dx is confirmed by using what 2 lab tests?
Western blot
PCR
