Immunodeficiency

Question 1

What are the 2 ways you can acquire and immune deficiency

Answer 1

1. Congenital - primary (genetic)
2. Acquired - Secondary (disease or therapy)

Question 2

What is the most common cause of secondary immunodeficiency worldwide

Answer 2

Malnutrition

Question 3

What are the 4 classifications of primary immunodeficiencies

Answer 3

1. T cells
2. B cells
3. T and B cells
4. Phagocytes
5. Complement

Question 4

What percentage of males affected by primary immunodeficiency

Answer 4

70&

Question 5

What % of PI affect B cells

Answer 5

50%

Question 6

What % of PI affect T cells only

Answer 6

10%

Question 7

What are the 3 basis of PID

Answer 7

Mutation
Polymorphisms
Polygenic disorder - most common

Question 8

What are common consequences of PID

Answer 8

Opportunistic infection

Question 9

A patient with PID affected by an opportunistic virus is likely due to what defect

Answer 9

T cell

Question 10

A patient with PID affected by an opportunistic bacteria is likely due to what defect

Answer 10

B cells, phagocytes and or complement

Question 11

What is SCID

Answer 11

Severe combined immunodeficiency

Question 12

Most common mutation resulting in SCID

Answer 12

IL2RG (interleukin receptor) - 19% of cases

Question 13

What is functioning in SCID

Answer 13

Complement and phagocytosis

Question 14

What are treatment and maintence of SCID

Answer 14

Maintenance:-Bactrim, Azithroprine -IgRT
Treatment: - Replacement therapy (e.g. ADA injections) - BMT - Gene Therapy (only if you know the gene)

Question 15

How does do George syndrome develop

Answer 15

Microdeletion of 22q

Question 16

Why do people with do George’s syndrome get hypo-calcaemic seizures?

Answer 16

no parathyroid gland

Question 17

What genetic defect creates ataxia-telangiectasia

Answer 17

Autosomal recessive, chromosome 11

Question 18

What is treatment of ataxia-telangiectasia

Answer 18

No cure, slow neurodegeneration (antioxidants)

Question 19

What mutation results in wisdom-Aldrich disease

Answer 19

WASP gene of Xp11 - X linked recessive

Question 20

What is a treatment of Wiscott-Aldrich disease

Answer 20

Bone marrow transplant can cure

Question 21

What is Brutons X linked Agammagloulinemia

Answer 21

Absence or deficiency of a Bruton’s tyrosine kinase: maturation arrest
of pre-B cells

Question 22

What is the treatment of Brutons

Answer 22

immunotherapy - IgRT

Question 23

CVID is the most common ID. What percentage of genes have been identified

Answer 23

Only 10%

Question 24

How does it cause deficiency

Answer 24

Low IL-2, IFN-g, CD40L (defective CD4 function )

Question 25

Treatment for CVID?

Answer 25

immunoglobulin replacement therapy IgRT to keep IgG >400

Question 26

What is the clinical presentation of selective IgA deficiency

Answer 26

Most are clinically normal but with very low IgA

Question 27

What is treatment for IgA deficiency

Answer 27

Just treat problems do not give immunotherapy

Question 28

Examples of PID affecting phagocytes and complement

Answer 28

Complement deficiencies Paroxysmal nocturnal hemoglobinuria (PNH) Hereditary angioedema Chronic granulomatous disease (CGD) * Myeloperoxidase deficiency Glucose-6-phosphate dehydrogenase deficiency Leukocyte adhesion deficiency Chediak-Higashi syndrome Autoinflammatory disorders

Question 29

How does cheddar-Higashi syndrome cause pathology

Answer 29

The lysosomes fail to fuse with the phagosome Neutropenia + diminished chemotaxis + Decreased (slower) neutrophils, NK cell and CTL functions. * The platelets are abnormal (easy bruising). Pyogenic infections. * Oculocutaneous albinism, photophobia, enterocolitis and peripheral neuropathy. * 85% of children with CHS develop fatal lymphoma-like condition. giant lysosomes

Question 30

What is the treatment for cheddar-Higgs hi syndrome

Answer 30

Bone marrow therapy/transplant

Question 31

How many types of LAD is there? Leukocyte adhesion deficiency

Answer 31

3 LADI- lack of CD18 β-2 – lack CR3 & unable to respond to C3b opsonin LADII – defective GDP-fucose transporter & inability to fucosylate sialyl LewisX structures LADIII - mutation of integrin-activating molecule kindlin 3

Question 32

What infectious disease is associated with Leukocyte adhesion deficiency LAD

Answer 32

Widespread pyogenic bacterial infections

Question 33

What mutation produces PNH paroxysmal nocturnal haemoglobinuria

Answer 33

PIG - A gene results in inability to synthesise glycosyl phosphatidylinositol (GPI) anchors

Question 34

What does PNH impact on

Answer 34

RBC Lack of GPI-anchored complement control proteins CD55 and CD59 on erythrocytes Erythrocytes susceptible to complement- mediated lysis

Question 35

What does a Neisseria infection suggest?

Answer 35

complement defect

Question 36

What does candida infection suggest

Answer 36

Phagocyte or T cell deficiency (mainly phagocyte)

Question 37

What does pneumonitis, TB, HHV8, EBV, CMV suggest

Answer 37

T cell deficency

Question 38

What are medical history warning signs for PID

Answer 38

> 8 ear infections / year > 2 serious sinusitis / year > 2 pneumonias / year > 2 deep-seated infections, or infections in unusual areas Recurrent deep skin/organ abscesses Need for IV ABx to clear infection Infections with unusual /opportunistic organisms Family Hx of PID

Question 39

What physical signs would you see suggesting PID

Answer 39

Poor growth, FTT Absent lymph nodes or tonsils Skin lesions: telangiectasias, petechiae, lupus-like rash Ataxia, ocular lesions Oral thrush after 1 year of age Oral ulcers

Question 40

When is IgRT most beneficial

Answer 40

Primary immune defects with no B cells, with hypogammaglobulinemia and impaired specific antibody production

Question 41

What is the mechanics of action of immunoglobulin replacement therapy (IgRT)

Answer 41

IC formation Antinflammatiory DC Complement activation Phagocytosis T cell activation

Question 42

What diseases use bone marrow transplantation as treatment

Answer 42

Hyper-IgE syndrome produce the best outcome SCID Wiscott-Aldrich Chediak-Higashi Kostmann Disease

Question 43

How many PID are there

Answer 43

Approx. 300

Question 44

Give some examples of secondary immunodeficiency causes

Answer 44

Environment and stress HIV and infection Malnutrition Immunosuppressive drugs Surgery and trauma Age (premature and very old)

Question 45

Give examples of infections which can cause immunodeficency

Answer 45

HIV, CMV, EBV, toxoplasma

Question 46

How does HIV cause defficiency

Answer 46

Reduces T cells (specifically CD4 T cells)

Question 47

What cells are affected by HIV

Answer 47

CD4 T cells, macrophages, monocytes

Question 48

What is the treatment for HIV

Answer 48

HAART

Question 49

By the age of 70-80 what happens to the thymus

Answer 49

It is unable to generate any more T cells - immunocompromised