16. Primary Immunodeficiency

Question 1

What antibodies protect babies in the first few months of life?

Answer 1

IgG

Question 2

What are the classifications of immunodeficiency?

Answer 2

Primary (congenital)

Secondary (acquired)

Question 3

What causes primary immune deficiency?

Answer 3

Part of the immunity is missing of does not work properly

Mainly chased by mutation do can also be caused by autoimmunity

Question 4

Where may the abnormality responsible for primary immunodeficiency be?

Answer 4

Components of the innante immune system
Stages of lymphocyte development
Response of mature lymphocytes to antigenic stimulation

Question 5

What disorder affect the innate immune system?

Answer 5

Chronic granulomatous disease
Leukocyte adhesion type 1,2 and 3
NK cell deficiencies
Toll like receptor defects
Mendelian susceptibility to mycobacterium

Question 6

What diseases affect the B cells (defects in antibodies)

Answer 6

Agammagkobulinemias

Hypogammaglobukinemias- selective IgA/Ig2 deficiency, ICF syndrome, common variable immunodeficiency,

Hyper IgM syndromes

Defective T cell signaling- proximal TCR signalling defects, hyper IgE syndromes

Familial hemophagocytic lymphohistiocytoses

Question 7

What are the features of B cell deficiency?

Answer 7

Succeptibility to pyogenic bacteria, pneumonia, meningitis, enteric bacteria, viruses and some parasites

Reduced serum IgG

Normal DTH reactions to common antigens

Absent or reduced germinal follicles and germinal centres

Question 8

What are the features of T cell deficiency?

Answer 8

Pneumocystis jiroveci, many viruses, atypical mycobacteria, fungi

Serum Ig levels normal or reduced

DTH reduced

Question 9

What should you suspect with neisseria infection?

Answer 9

Complement defects

Question 10

What should you suspect with invasive candida infections?

Answer 10

TH17 defect

Question 11

What happens if you are deficient to IgG and IgA?

Answer 11

Recurrent respiratory infections with pneumococcus or haemophilus spp

Question 12

Infections with staph, gram -ve and fungi are associated with what?

Answer 12

Reduced phagocytes

Question 13

What happens if latent herpes is reactivated or shingles?

Answer 13

T cell deficiency

Question 14

What does kaposi sarcoma, burski sarcoma and EBV suggest?

Answer 14

T cell deficiency

Question 15

What is a mutation

Answer 15

Permenant alterations the a part of the DNA. This can lead to an abnormal protein or complete loss of the protein. Can lead to severe disease

Question 16

What is a polymorphism?

Answer 16

Not necessary pathological. One of two base pairs are normal but typically doesn’t cause problems. However can cause some mild disease

Question 17

What is a polygenic disorder?

Answer 17

More than one gene is involved in the disease. Pretty common, if they affect immune system they affect antibodies

Question 18

What is SCID?

Answer 18

Severe combined immunodeficiency

Severe effect on B cells and T cells. Severity varies depending on how quickly they are treated after birth. Treatment is stem cell transplant. Will die in first few months unless treatment is given

Question 19

What are the different types of SCID?

Answer 19

Defective thymic development.

Defects in nucleoside pathways

Defects in cytokine signalling

Question 20

What are the most common change in the immune gene due to polymorphism?

Answer 20

HLA gene that codes for MHC. This leads to defective antigen presentation.

Question 21

What is the most common polygenic disorder?

Answer 21

Common variable immunodeficiency (CVID) IgA deficiency and specific antibody deficiency. Patients have low levels of IgG, levels of IgA and IgM, B and T cells are variable

causes recurrent respiratory tract infection

Question 22

What primary immunodeficiency are caused by autoimmunity?

Answer 22

Autoimmune polyendocrinpoathy candidiasis ectodermal dysplasia
(APECED)
Frequenlty encounter severe recurrent candida infections
produce autoantibodies against interleukin 17

Question 23

How do you diagnose primary immune deficiencies?

Answer 23

Recurrent infections, unusual infections, infections that are hard to treat, always have diarrhoea, rashes without cause,

Low lymphocytes count (<1x10^9/L) (measured by flow cytometry)

Question 24

How can you lose antibodies?

Answer 24

Kindney disease, gut disease

Question 25

How do you treat primary immunodeficiency?

Answer 25

Prophylaxis with antibiotics
Immunoglobulin replacement therapy
Antibodies against a wide range of latnlfems
Ig pooled fro, thousands of normal donors
If replacement can be given IV or sub cut
Plasma screened for HIV and hep B and C antibodies

Question 26

How do you treat SCID?

Answer 26

Avoid live vaccines
Prophylaxis against opportunistic infections such as pneumocystis jiroveci

Stem cell transplantation can be applied and are the most successful if done a few weeks after birth. If that doesn’t work you can use gene therapy

Question 27

How do you treat primary immunodeficiency with gene therapy?

Answer 27

Using recombiant technology to correct the genetic defect in the patients own stem cells which can reconstitute the immune system.
Used in patients with SCID for whom no suitable stem cell donor was available

Question 28

What criteria must be met before gene therapy is successful?

Answer 28

Genetic mutation for each patient must be identified and evidence showed that correcting mutation will improve condition
The transfected gene must confer a proliferation or survival advantage
Gene therapy must not cause malignancy