primary immunodeficiency

Question 1

immunodeficiency diseases

Answer 1

Defects in one or more components of the immune system can lead to serious and often fatal disorders
-some associated with increased autoimmunity

Question 2

Primary immunodefiency

Answer 2

genetic, congenital disorders
immune system either missing or abnormal
-mainly caused by mutations
-predisposes to infections and tumours

Question 3

Abnormality in Pri ID

Answer 3

components of innate system
stages of lymphocyte development
responses of mature lymphocytes to antigenic stimulation

Question 4

congenital disorders

Answer 4

chronic granulomatous disease

Leukocyte adhesion defiency type 1 &2

Question 5

antibody deficiencies

Answer 5

agammaglobulinemias
X linked
Autosomal recessive
Hypogammaglobulinemia

Question 6

Defects in T cell activation

Answer 6

proximal TCR signalling defects

wiskott- aldrich syndrome

Question 7

Neisseria

Answer 7

suspect defect in complement

Question 8

B cell defects

Answer 8

Encapsulated

Question 9

Tuberculosis

Answer 9

Th1

Question 10

Candida,
Infections with staphylococci, gram-negative bacteria, and fungi are associated with reduced number or function of phagocytes.

Answer 10

TH17

Question 11

mycobacterium tuberculosis

Answer 11

causes lung infection in immunocompetent people.

Question 12

herpes simplex

Answer 12

Recurrent attacks of cold sores (herpes simplex) or shingles (herpes varicella zoster) may suggest mild immunodeficiency
-associated with stress and sick

Question 13

T cell dysfunction

Answer 13

Herpesvirus-induced tumours, notably Kaposi sarcoma (human herpesvirus 8 [HHV8]), and non-Hodgkin lymphoma (Epstein-Barr virus [EBV

Question 14

causes of pri imm deficiency

Answer 14

mutations
polyporphisms
polygenic disorders

Question 15

mutation

Answer 15

permanent alteration in the DNA sequence that makes up a gene, such that the sequence differs from what is found in most people

Question 16

polymorphisms

Answer 16

different variations of same gene, different allele but still produce functional protein, but still can cause problems

Question 17

polygenic disorders

Answer 17

These are disorders caused by the combined action of more than one gene.
Polygenic disorders of the immune system are relatively common and affect mainly antibodies.

Question 18

severe combined immunodeficiency (group of diseases)

Answer 18

affect both T and B cells
die in the first few months of life unless treatment is given
autoso­mally inherited
Stem cell transplant can cure SCID but it has to be done quickly
screening

Question 19

types of SCID

Answer 19

defective pre TCR checkpoint
Di George syndrome
Fox N1 deficiency
X linked

Question 20

polymorphism

Answer 20

• Human leukocyte antigen (HLA) alleles are polymorphic and affect the outcome of infections.
• HLA alleles that are unable to bind viral peptides have a worse outcome.
• Mannan-binding lectin (MBL) is a collagen-like protein that binds sugars in bacterial cell walls and activates the classic complement pathway. Polymorphisms in MBL and complement affect the risk for infections.

Question 21

polygenic disorders common variable immunodeficiency

Answer 21

requiring treatment and occurs in about 1 in 20,000 young people affecting men and women equally.
low levels of IgG
-recurrent respiratory tract infections.
-pneumococcus orHaemophilusspp. despite normal total IgG.
-autoimmunity common
-consanguinity

Question 22

Monogenic

Answer 22

T and B cells
autosomal recessive SCID
RAG mutations

Question 23

severe combined immunodeficiency clinical presdefective

Answer 23

defective T cells and B cells and therefore develop infections in the first few weeks of life.
Unusual or recurrent infection
Diarrhoea
Unusual rashes
History
Family history of neonatal death
Family history of consanguinity
Lymphocyte count
very low total lymphocyte count (less than 1 × 109/L [106/mL]).
Lymphocyte numbers should be measured by flow cytometry.

Question 24

antibody deficiency

Answer 24

Clinical presentation
Antibody deficiency presents later in life.
Babies are born with maternal immunoglobulin transferred across the placenta.
Some forms of antibody deficiency, such as CVID, do not present until adulthood.
Chronic or recurrent bacterial respiratory infection.
Antibody levels
IgG, IgA, and IgM should be measured.
With low levels of immunoglobulins, causes of secondary immunodeficiency should be excluded.
If total Igs are normal, specific antibodies against Haemophilus spp. and pneumococcus should be measured.
If these tests are all normal, it is important to check no problems are apparent with complement or neutrophil function.

Question 25

treatment of primary

Answer 25

mild-prophylactic antibiotics
more severe- Ig replacement therapy
Antibodies against a wide range of pathogens
Ig pooled
plasma screened for HIV and hepatitis B and C antibodies

Question 26

When definite treatment

Answer 26

when SCID confirmed
until definite
-avoding live vaccines
-Prophylaxis against opportunist infections such asPneumocystis jiroveci

Question 27

T cell deficiency stem cell transplatation

Answer 27

-required in SCID
most successful if it can be done within a few weeks of birth, before the infant has developed any infections.
If this is possible, SCT carries a 90% success rate and is curative.
When SCT is not an option, gene therapy may be attempted.

Question 28

gene therapy

Answer 28

recombinant technology to correct the genetic defect in the patient’s own stem cells, which can then reconstitute the immune system.
used in patients with SCID for whom no suitable stem cell donor was available.

criteria:

1. The genetic mutation for each patient must be identified, and there must be evidence that correcting the mutation will improve his or her condition.
2. The transfected gene must confer a proliferation or survival advantage.
3. Gene therapy must not cause malignancy. (not near oncogenes)