Powell: Immunodeficiency Diseases

Question 1

The first primary immunodeficiency disease to be described was what and by whom?

Answer 1

WHAT: Agammaglobulinemia
WHO: Bruton

Question 2

In _____, Bruton noted the absence of ________ in a boy w/ history of pneumonias and bac. infections.

Answer 2

1952

immunoglobulins

Question 3

Burton (the 1st physician to provide specific immunotherapy for agammagloculinemia; X linked disorder) administered _______ ______ of _____.

Answer 3

intramuscular injections

IgG

Question 4

Passive Immunity

Answer 4

given the cell product (not the cell; B cell/Tcell)

Question 5

Why did it take until 1952 to describe an immunodeficiency?

Answer 5

• didn’t know what immunity was until 1918 Spanish Flu

- HIV: 1980

Question 6

Primary or congenital immunodeficiencies:

-are ____ _____ that results in an increased susceptibility to infection

Answer 6

genetic defects

Question 7

Primary or congenital immunodeficiencies:

-frequently manifested in ____/_____

Answer 7

infancy and childhood

Question 8

Primary or congenital immunodeficiencies:

-such diseases affect about 1 in ___ ppl in US

Answer 8

500

Question 9

Secondary or acquired immunodeficiencies:

• develop as a _____ of:
• -_______
• -disseminated _______
• -treatment w/ _______ _______
• -_______ of cells or immune system

Answer 9

consequences
malnutrion
cancer
immunosuppressive drugs
infection (HIV)

Question 10

_______ of the immune system is ______ for defense against ________ organisms and their toxic ______.
-Immune System is important for our survival.

Answer 10

integrity
essential
infectious
products

Question 11

_______ are conserved across widely diverse species.

Any loss of function mutation affecting a TLR has neg. consequences for survival.

Answer 11

Toll-Like Receptors

Question 12

Primary Immunodeficiencies:

• ______ determined
• disorders may affect _/__ components of the immune system
• -including T,B lymphocytes, NK cells, phagocytic/complement proteins

Answer 12

genetically

1 or more

Question 13

Primary Immunodeficiencies:

-may result from defects in _______ maturation or _______/______ in effector mechanism of innate and adaptive immunity

Answer 13

leukocyte
activation
or defects

Question 14

Primary Immunodeficiencies:

• innate defects= _______/______ ect.
• adaptive defects= ______

Answer 14

cytokines/neutrofils

genes

Question 15

The principal consequences of an immuno-deficiency is an ______ ______ to ________

Answer 15

increased susceptibility to infection

Question 16

The nature of the infection in a particular patient depends largely on the ________ of the immune system that is ______

Answer 16

component

defective

Question 17

The types of _______ infections can predict the type of _________

Answer 17

recurring

immunodeficiency

Question 18

Deficient _____ immunity usually results in increased susceptibility to infection by _____ _____

Answer 18

humoral
pyogenic bacteria
(B cells/antibody infection)

Question 19

X-linked Agammaglobulinemia (XLA):

-all antibody isotypes are very ___= not even IgM or IgD

Answer 19

low

Question 20

X-linked Agammaglobulinemia (XLA):

-circulating __ cells are usually absent

Answer 20

B

Question 21

X-linked Agammaglobulinemia (XLA):

-____ cells are present in reduced numbers in the ____ _____

Answer 21

Pre-B

bone marrow

Question 22

X-linked Agammaglobulinemia (XLA):

-______ are usually very small and ___ ____ are rarely palpable due to absence of germinal centers (contain B cells)

Answer 22

tonsils

lymph nodes

Question 23

X-linked Agammaglobulinemia (XLA):

-____ architectures is normal, as are ___ cell-dependent areas of spleen and lymph nodes

Answer 23

thymus

T cell-dependent

Question 24

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

Answer 24

6-9 months

IgG

Question 25

X-linked Agammaglobulinemia (XLA): -defects are associated w/ loss of function of ____ ____ _____ that is important for ___ ___ cell expansion and maturation into Ig-expressing __ ___

Answer 25

Bruton Tyrosine Kinase Pre-B B cells

Question 26

X-linked immunodeficiency w/ Hyper-IgM: - very low serum Ig__, Ig__, and Ig__ - elevated concentrations of ________ ig__

Answer 26

IgG IgA IgE polyclonal IgM

Question 27

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

Answer 27

first and second | pyogenic infections

Question 28

X-linked immunodeficiency w/ Hyper-IgM: | -in contrast to pt with XLA, pts have____ ____ (circulating B cells but only make IgM)

Answer 28

lymphoid hyperplasia

Question 29

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 ____ ___ ____

Answer 29

CD40 | helper T cells

Question 30

X-linked immunodeficiency w/ Hyper-IgM: | -loss of _____ prevents __ ____ from co-stimulating _____ ______ __ ______.

Answer 30

CD40 T cell antigen specific B cells

Question 31

X-linked immunodeficiency w/ Hyper-IgM: | -___ ____ are not signaled by the ___ ___ to go through isotype switching and only produce ____

Answer 31

B cells T cell IgM

Question 32

Treatment for Immunodeficiencies: -it is ______ --_____ ______ and ____ _____ _____ (IgG therapy) by Bruton pioneered this therapy

Answer 32

routine prophylactic antibiotics gamma-globulin therapy

Question 33

Deficient ________ immunity usually results in increased susceptibility to ____ and other ______ pathogens.

Answer 33

cell-mediated viruses intracellular

Question 34

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

Answer 34

few

Question 35

DiGeorge's Syndrome: | -a _______ related disease associated with tissue morphogenesis-- the _____ does not develop

Answer 35

developmentally | thymus

Question 36

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

Answer 36

thymic hypoplasia | 3rd and 4th

Question 37

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

Answer 37

decreased | B cells

Question 38

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

Answer 38

first few months/2nd yr fetal alcohol (not just immune problems=other anomalies)

Question 39

X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs): -severe combined immunodeficiency is a ____, fatal syndrome characterized by profound deficiencies of __ ___ and __ ___ function

Answer 39

rare T cell B cell

Question 40

X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs): -__-linked is the most common form= ~42% of cases

Answer 40

X

Question 41

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

Answer 41

first few

Question 42

X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs): - growth appears ____ initially - extreme ____ usually after infections and diarrhea begins

Answer 42

normal | wasting

Question 43

X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs): - persistent infections w/ _____ ____ - -candida albicans, pneumocystis, carinii, varicella, measles, parainfluenzae, cytomegalovirus, EBV

Answer 43

opportunistic organisms

Question 44

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

Answer 44

foreign tissue GVHD T cells

Question 45

X-linked Recessive Severe Combined Immunodeficiency Disease (SCIDs): -_____ pts have few or no ___ ____ and ____ ____

Answer 45

XSCID T cells NK cells (susceptible to any infection)

Question 46

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 ____ ____ ______

Answer 46

B cells Bcells T cell bone marrow transplatation

Question 47

Treatment of Immunodeficiencies: - 1. to minimized and control _____ - 2. to replace the defected or absent components of the immune system by ____ ____ and/or _____

Answer 47

adoptive transfer | transplantation

Question 48

Treatment of Immunodeficiencies: | -____ ____ w/ pooled ___ ___ is enormously valuable for agammaglobulinemic patients and have been life saving for many

Answer 48

``` passive immunization gamma globulin (IgG) ```

Question 49

Treatment of Immunodeficiencies: -___ ____ ____ is currently the treatment of choice for various immunodeficiency diseases and has been successful in treatment of ___ and other similar diseases

Answer 49

bone marrow transplants | SCID

Question 50

Viruses: - must infect the ____ cell - -HIV can get into a cell via ____ ____

Answer 50

host | chemokine receptor

Question 51

Progression of HIV disease: 1. primary infection of cells in ____, ____ 2. infection established in ____ ___ (lymph node) 3. acute HIV syndrome= spread of infection throughout body (_____) 4. immune response- partial control of viral replication 5. 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)

Answer 51

blood, mucosa lymphoid tissues viremia