Primary Immunodeficiency Part II

Question 1

Defects in which complement protein result in lots of pyogenic infections and why

Answer 1

C3 because it acts as an opsonin*-enhancing removal of bacteria by phagocytosis (when functioning)

Question 2

what do deficiences in complement 1-4 cause

Answer 2

immune complex disease - an accumulation of immune complexes in the circulated deposition of the complexes in tissue, damaging it, and activating phagoyctes which causes inflammation, and more damage.

Question 3

what is the main way of removing pathogens

Answer 3

Phagocytosis by macrophages and neutrophils

Question 4

Chediak-Higashi disease

Answer 4

rare autosomal recessive genetic disorder caused by mutations in the CHS gene

Neutrophils, monocytes and lymphocytes contain giant lysosomal granules, resulting in phagocytes which are defective in chemotaxis, phagocytosis,& microbicidal activity and NK cell lack cytotoxic activity.

Question 5

what problems does Chediak-Higashi disease cause

Answer 5

increased susceptibility to infections
lysosomal defects affect the melanocytes causing albinism and platelets causing bleeding disorders.

Question 6

Leukocyte adhesion deficiency

Answer 6

Rare inherited disorder from a mutation in one of several genes that play a role in leukocyte adhesion (white blood cells attach to and move through blood vessel walls to reach the site of infection)

Lack of CD18 β-subunit of β2 integrins-LFA-1

White blood cells can’t properly attach to blood vessel walls (can’t bind endothelial tissue cells), so they can’t leave the bloodstream and reach the site of an infection.

Question 7

what does LAD cause for people

Answer 7

more susceptibility to bacterial and fungal infections, particularly of the skin, mouth, and respiratory tract.

delayed wound healing, as white blood cells can’t properly migrate to the site of an injury.

Question 8

main treatment for LAD and why

Answer 8

Bone marrow transplation as it restores neutrophil function

Question 9

what is the genetic disorder chronic granulomatous disease (CGD) caused by

Answer 9

mutations in 1 of 4 proteins forming NADPH oxidase which produces hydrogen peroxide (fights infections)

Question 10

what chromosome do 70% of CGD patients have mutations on

Answer 10

X chromosome ( x linked)

Question 11

what is CGD characterised by that occurs in phagocytic cells following activation.

Answer 11

Defective respiratory burst, the increased oxidative metabolism

Question 12

what do the recurrent infections in CGD lead to (Staphylococcus aureus, some gram –ve, some fungi (Aspergillus fumigatus and Candida albicans))

Answer 12

granuloma (cells clumped) which can obstruct gastrointestinal and urogenital systems

Question 13

One of the reasons for the limited range of recurrent infections in cgd

Answer 13

because many bacteria generate hydrogen peroxide through their own metabolic processes, helping to destroy themselves

Question 14

2 ways to diagnose CGD

Answer 14

Stimulation of superoxide production
Nitroblue Tetrazolium Test

Question 15

Nitroblue Tetrazolium Test to diagnose CGD

Answer 15

a blood test that measures the ability of the immune system to convert the colorless nitroblue tetrazolium (NBT) to a deep blue.
If an individual has CGD, the white cells in their blood will not turn blue when exposed to the NBT.

Question 16

Main treatments for CGD

Answer 16

Prophylactic antibiotics and antifungals taken daily

Interferon γ to stimulate the production of superoxide (less infections)

Bone marrow transplantation but high risk of mortality, the other methods are better

Question 17

why do defects in t cells often have a greater impact on the immune system than those that affect the b cells or innate responses

Answer 17

Because t cells have an important role in directing the immune response so defects will often affect both humoral and cell-mediated responses.

Question 18

why can autoimmunity be main symptom in immunodeficiency

Answer 18

as the B and T cell responses to self-antigens are not adequately regulated.

Question 19

whats the most famous immunodeficiency

Answer 19

Severe Combined Immunodeficiency (SCID)

Question 20

What is crucial for SCID and bone marrow transplants, to allow for early detection and treatment

Answer 20

Newborn screening

Question 21

what does newborn SCID screening involve

Answer 21

a blood test that is done shortly after birth which can detect several different types of SCID.

Question 22

SCID

Answer 22

rare genetic disorder giving people an impaired immune system that makes them susceptible to life-threatening infections

Question 23

What cell development is usually totally failed in SCID resulting in defective cell-mediated and humoral immunity

Answer 23

total failure of T cell development

Question 24

how can SCID be treated while child is still in womb

Answer 24

By stem cell transplantation in utero to establish a functional immune system before the fetus is exposed to infections.

This is done by transplanting stem cells from a donor into the developing fetus’s bloodstream while still in the womb

Question 25

current most effective treatment for SCID

Answer 25

bone marrow transplantation (Haemopoietic stem cells transplant)

Question 26

a treatment option for a type of SCID caused by a deficiency of ADA enzyme (ADA-SCID) - for those not suitable for BMT/ gene therapy

Answer 26

Enzyme replacement therapy (ERT) with injections of adenosine deaminase (ADA)

Question 27

in SCID what can lead to recurrent viral, bacterial, fungal, and protozoan infections (pneumonia, meningitis)

Answer 27

Lymphopenia (low levels of lymphocytes)

Question 28

What pose risk for people with SCID, which usually prevent infections in general people

Answer 28

Live attenuated vaccines e.g. (MMR) vaccine

Question 29

4 most common mutated genes leading to SCID

Answer 29

IL2RG gene
ADA gene
RAG1 or RAG2 genes
JAK3 gene

Question 30

if b cells are affected in SCID what treatments are given every 3-4 weeks

Answer 30

intravenous immunoglobulins

Question 31

what are patients with no T-cells or poor T-cell function vulnerable to (4)

Answer 31

Opportunistic infection
Poor humoral immunity
Allergies
Lymphoid malignancies
Autoimmune diseases (inefficient negative selection in thymus, failure to generate T regulatory cells)

Question 32

for t cell deficieny diagnosis what are skin tests negative or weak for

Answer 32

tuberculosis, Candida, and mumps

Question 33

why is Phytohemagglutinin (PHA) commonly used in primary t cell deficiency diagnosis

Answer 33

because PHA activates T-lymphocytes by binding to the T-cell receptor and activating t cells so response to PHA stimulation would be reduced or absent due to the impaired function of T cells.

Question 34

DiGeorge (Velocardiofacial) syndrome

Answer 34

Developmental disorder affecting thymus (failure of the thymus to develop properly from the third and fourth pharyngeal pouches). and therefore development and maturation of T cells

Question 35

3 other features of DiGeorge (Velocardiofacial) syndrome

Answer 35

Lack parathyroid (hypothyroidism)
Severe heart abnormalities
Immunodeficiency
moderate learning difficulties
Fish-like mouth

Question 36

3 things a lack of the thymus leads to

Answer 36

No T cells
Sparsely populated lymphoid tissue (thymus-dependent areas)
Poorly developed lymphoid follicles
No cell-mediated immunity
Subnormal antibody response (as no T cells)

Question 37

how can DiGeorge (Velocardiofacial) syndrome be diagnosed

Answer 37

karyotype analysis - chromosomes examination test

FISH - genetic test to detect small deletions or duplications of DNA sequences using a fluorescent probe that binds to a specific region of DNA and emits light when exposed to a specific wavelength.

Question 38

what gene deletion causes DiGeorge (Velocardiofacial) syndrom

Answer 38

TBX1 gene deletion