Immunology 2

Question 1

what is primary immunodeficiency

Answer 1

congenital, resulting from genetic defects
deficiency causes disease
normally recessive inheritance
rarely dominant
a lot are X linked

Question 2

how can primary immunodeficiency present in young children

Answer 2

allergies
autoimmunity
abnormal lymphocyte proliferation
cancer

Question 3

describe B cell deficiency in primary immunodeficiency

Answer 3

absent or reduced follicles and germinal centres in lymphoid organs
reduced serum Ig levels
leads to pyogenic bacterial infections

Question 5

describe T cell deficiency in primary immunodeficiency

Answer 5

may be reduced T cell zones in lymphoid organs
reduced DTH reactions to common antigens
defective T cell proliferative responses to mitogens in vitro
leads to viral and other intracellular microbial infections
- virus associated malignancies

Question 6

describe innate immune deficiency in primary immunodeficiency

Answer 6

variable, depending on which component of innate immunity is defective
leads to variable; pyogenic bacterial infections

Question 7

what is X-linked SCID

Answer 7

combined immunodeficiency (without syndromic features)
mutations in cytokine receptors
- il2ry chain (il2 receptor leads to stimulation of T cell proliferation)
cant make a working common gamma chain (cant make receptor)
T cells and NK cells fail, B cells normal but no help for efficient antibody repsonses

Question 8

what is ADA-SCID

Answer 8

combined immunodeficiency (without syndromic features)
adenosine deaminase deficiency
depletes T, B and NK cells
basal expression in all cells, enhanced in thymocytes

Question 9

describe therapy for ADA-SCID

Answer 9

bone marrow stem cells from suitable donor
manipulate immune system to make an autonomous bone marrow transplant
complicated, difficult, expensive and dangerous

Question 10

list some examples of combined immunodeficiency (without syndromic features)

Answer 10

X-linked SCID
ADA-SCID
hyper IgM syndrome (CD40L deficiency)

Question 11

describe hyper IgM syndrome

Answer 11

CD40L deficiency
high IgM, low others
molecular defect lies on CD40L molecules (T cells)
limited proliferation of B cells

Question 12

what causes hyper IgM syndrome

Answer 12

fault in class switches - can’t produce IgG
- IgG is more effective than IgM in responding to bacterial infections

Question 13

lit examples of combined immunodeficiency with syndromic features

Answer 13

FOXN1 deficiency
Bruton’s agammaglobulinemia
IgA deficiency

Question 14

describe FOXN1 deficiency

Answer 14

athymic and alopecia
- no hair and thymic epithelium fails to develop - ineffective thymus - no T cells
B cells are normal but no help

Question 15

describe Bruton’s agammaglobulinemia

Answer 15

X-linked, recessive
first describe immunodeficiency
mutation in Bruton’s tyrosine kinase gene
prevents B cell development
pro-B to pre-B stage
few follicles in lymph nodes
results in low serum antibody levels

Question 16

describe IgA deficiency

Answer 16

most common
cytokines needed to mature lymphocyte into mature IgA plasma cell

Question 17

how does IgA deficiency manifest

Answer 17

many asymptomatic
- only notice if diet changes sufficiently to alter gut microbiome)
children with mild deficiency will outgrow

Question 18

what is the impact of a lack of antibodies

Answer 18

recurrent sepsis
bacterial infections often in airways
chronic gastroenteritis
failure to thrive

Question 19

give examples of phagocyte defects

Answer 19

defects of neutrophil function
Mendelian susceptibility to mycobacterial disease (MSMD)

Question 20

describe chronic granulomatous disease

Answer 20

no superoxide burst
multiple granulomas form as a result of a defective elimination of bacteria
when macrophage3 consumes bacteria, cannot kill it
- defects in the NADPH enzymes that generate the superoxide radicals involved in bacterial killing
nodule of persistent immune cells trying to kill bacteria
- eventually compromises gaseous exchange/ lung function

Question 21

describe familial Mediterranean fever

Answer 21

inflammasome converts pro-il to il1 -> drive inflammation
in FMF, inflammasome regulators are mutated
inflammasome activated, increase il1 produced

Question 22

describe therapy for FMF

Answer 22

identify the trigger and avoid that circumstance
inflammation can respond to anti il1 antibody
targets specific immune molecule
supresses symptoms