Powell: Immunodeficiency Diseases Flashcards
The first primary immunodeficiency disease to be described was what and by whom?
WHAT: Agammaglobulinemia
WHO: Bruton
In _____, Bruton noted the absence of ________ in a boy w/ history of pneumonias and bac. infections.
1952
immunoglobulins
Burton (the 1st physician to provide specific immunotherapy for agammagloculinemia; X linked disorder) administered _______ ______ of _____.
intramuscular injections
IgG
Passive Immunity
given the cell product (not the cell; B cell/Tcell)
Why did it take until 1952 to describe an immunodeficiency?
- didn’t know what immunity was until 1918 Spanish Flu
- HIV: 1980
Primary or congenital immunodeficiencies:
-are ____ _____ that results in an increased susceptibility to infection
genetic defects
Primary or congenital immunodeficiencies:
-frequently manifested in ____/_____
infancy and childhood
Primary or congenital immunodeficiencies:
-such diseases affect about 1 in ___ ppl in US
500
Secondary or acquired immunodeficiencies:
- develop as a _____ of:
- -_______
- -disseminated _______
- -treatment w/ _______ _______
- -_______ of cells or immune system
consequences malnutrion cancer immunosuppressive drugs infection (HIV)
_______ of the immune system is ______ for defense against ________ organisms and their toxic ______.
-Immune System is important for our survival.
integrity
essential
infectious
products
_______ are conserved across widely diverse species.
Any loss of function mutation affecting a TLR has neg. consequences for survival.
Toll-Like Receptors
Primary Immunodeficiencies:
- ______ determined
- disorders may affect _/__ components of the immune system
- -including T,B lymphocytes, NK cells, phagocytic/complement proteins
genetically
1 or more
Primary Immunodeficiencies:
-may result from defects in _______ maturation or _______/______ in effector mechanism of innate and adaptive immunity
leukocyte
activation
or defects
Primary Immunodeficiencies:
- innate defects= _______/______ ect.
- adaptive defects= ______
cytokines/neutrofils
genes
The principal consequences of an immuno-deficiency is an ______ ______ to ________
increased susceptibility to infection
The nature of the infection in a particular patient depends largely on the ________ of the immune system that is ______
component
defective
The types of _______ infections can predict the type of _________
recurring
immunodeficiency
Deficient _____ immunity usually results in increased susceptibility to infection by _____ _____
humoral
pyogenic bacteria
(B cells/antibody infection)
X-linked Agammaglobulinemia (XLA):
-all antibody isotypes are very ___= not even IgM or IgD
low
X-linked Agammaglobulinemia (XLA):
-circulating __ cells are usually absent
B
X-linked Agammaglobulinemia (XLA):
-____ cells are present in reduced numbers in the ____ _____
Pre-B
bone marrow
X-linked Agammaglobulinemia (XLA):
-______ are usually very small and ___ ____ are rarely palpable due to absence of germinal centers (contain B cells)
tonsils
lymph nodes
X-linked Agammaglobulinemia (XLA):
-____ architectures is normal, as are ___ cell-dependent areas of spleen and lymph nodes
thymus
T cell-dependent
X-linked Agammaglobulinemia (XLA):
-boys remain well during first __ to __ months of life by virtue of maternally transmitted ___ antibodies—repeatedly acquire infections w/ extracellular pyogenic organisms
6-9 months
IgG
X-linked Agammaglobulinemia (XLA):
-defects are associated w/ loss of function of ____ ____ _____ that is important for ___ ___ cell expansion and maturation into Ig-expressing __ ___
Bruton Tyrosine Kinase
Pre-B
B cells
X-linked immunodeficiency w/ Hyper-IgM:
- very low serum Ig__, Ig__, and Ig__
- elevated concentrations of ________ ig__
IgG
IgA
IgE
polyclonal IgM
X-linked immunodeficiency w/ Hyper-IgM:
- like boys with XLA, patients may become symptomatic during the ___ and ___ year of life w/ recurrent _____ _____
- otitis media, sinusitis, pneumonia, tonsillitis
first and second
pyogenic infections
X-linked immunodeficiency w/ Hyper-IgM:
-in contrast to pt with XLA, pts have____ ____ (circulating B cells but only make IgM)
lymphoid hyperplasia
X-linked immunodeficiency w/ Hyper-IgM:
-defects in this disease is associated w/ a loss of function of _____ ligand (aka CD 154) that is expressed on ____ ___ ____
CD40
helper T cells
X-linked immunodeficiency w/ Hyper-IgM:
-loss of _____ prevents __ ____ from co-stimulating _____ ______ __ ______.
CD40
T cell
antigen specific B cells
X-linked immunodeficiency w/ Hyper-IgM:
-___ ____ are not signaled by the ___ ___ to go through isotype switching and only produce ____
B cells
T cell
IgM
Treatment for Immunodeficiencies:
-it is ______
–_____ ______ and ____ _____ _____ (IgG therapy)
by Bruton pioneered this therapy
routine
prophylactic antibiotics
gamma-globulin therapy
Deficient ________ immunity usually results in increased susceptibility to ____ and other ______ pathogens.
cell-mediated
viruses
intracellular
Cell-Mediated Deficiencies:
- ___ treatments for defects associated with deficient T cell responses
- -rare for pts w/ absolute defects in T cell function survive beyond infancy/childhood
few
DiGeorge’s Syndrome:
-a _______ related disease associated with tissue morphogenesis– the _____ does not develop
developmentally
thymus
DiGeorge’s Syndrome:
- _____ ____ results from defects in morphogenesis of the ___ and ____ pharyngeal pouches during early embryogenesis
- -other structures forming at the same age are frequently affected: anomalies of great vessels, esophageal atresia, bifid uvuala, upper limb malformations, congenital heart disease, short philtrum of upper lip, hypertelorism, antimongoloid slant to eye, mandibular hypoplasia, low set notched ears
thymic hypoplasia
3rd and 4th
DiGeorge’s Syndrome:
-percentage of T cells is variably _______
–there is a relative increase in percent of ___ ___
=B cell function is impaired only to the extend of needing helper T cells
decreased
B cells
DiGeorge’s Syndrome:
- most infants die from infections, cardiovascular defects or seizures within the _____/_____ of life= if survive infancy are mentally retarded
- —similar with ___ ___ syndrome
first few months/2nd yr
fetal alcohol
(not just immune problems=other anomalies)
X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs):
-severe combined immunodeficiency is a ____, fatal syndrome characterized by profound deficiencies of __ ___ and __ ___ function
rare
T cell
B cell
X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs):
-__-linked is the most common form= ~42% of cases
X
X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs):
-affected infants present w/in ___ ___ months of life= frequent episodes of diarrhea, pneumonia, otitis, sepsis, cutaneous infections
first few
X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs):
- growth appears ____ initially
- extreme ____ usually after infections and diarrhea begins
normal
wasting
X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs):
- persistent infections w/ _____ ____
- -candida albicans, pneumocystis, carinii, varicella, measles, parainfluenzae, cytomegalovirus, EBV
opportunistic organisms
X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs):
- infants lack the ability to reject _____ ____ and are therefore at risk for ________
- -can result from maternal __ ___ that cross into the fetal circulation while the SCID infant is in utero
foreign tissue
GVHD
T cells
X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs):
-_____ pts have few or no ___ ____ and ____ ____
XSCID
T cells
NK cells (susceptible to any infection)
X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs):
- XSCID pts usually have elevated % of __ ___
- -however these __ ___ do not produce immunoglobulin normally, even after ___ ___ reconstitution by ____ ____ ______
B cells
Bcells
T cell
bone marrow transplatation
Treatment of Immunodeficiencies:
- to minimized and control _____
- to replace the defected or absent components of the immune system by ____ ____ and/or _____
adoptive transfer
transplantation
Treatment of Immunodeficiencies:
-____ ____ w/ pooled ___ ___ is enormously valuable for agammaglobulinemic patients and have been life saving for many
passive immunization gamma globulin (IgG)
Treatment of Immunodeficiencies:
-___ ____ ____ is currently the treatment of choice for various immunodeficiency diseases and has been successful in treatment of ___ and other similar diseases
bone marrow transplants
SCID
Viruses:
- must infect the ____ cell
- -HIV can get into a cell via ____ ____
host
chemokine receptor
Progression of HIV disease:
- primary infection of cells in ____, ____
- infection established in ____ ___ (lymph node)
- acute HIV syndrome= spread of infection throughout body (_____)
- immune response- partial control of viral replication
- clinical latency= establishment of chronic infection–virus trapped in lymphoid tissues by follicular dentric cells; low level virus production–>increaed viral replication—->AIDS (destruction of lymphoid tissue; depletion of CD4+ T cells)
blood, mucosa
lymphoid tissues
viremia
