Immunodeficency

Question 1

Immunodeficiency Def

Answer 1

Failure/absence immune system functional elements (lymphocytes, phagocytes and complement). 2 types: primary and secondary

Question 2

Primary Immunodeficiencies Outline

Answer 2

Gene defects for immune system components. Some are only diagnosed in adulthood due to: compensating immune systems (redundancy) and deficiency related to deterioration. 3 subsections

Question 3

Secondary Immunodeficiencies Outline

Answer 3

External factors (malnutrition, medication, malignancy)/medical conditions damage immune components. Often reversible (remove Cause)

Question 4

3 Primary Immunodeficiency Subsections

Answer 4

Disorder specific immunity (B, T, combined immunodeficency), Compliment deficiency (membrane attack complex), Phagocytosis disorder (macrophages and neutrophils)

Question 5

Causes of Primary Immunodeficiency

Answer 5

Genetic: autosomal, x-linked, recessive. Can be either single or multigene defects (eg CVID or selective IgA)

Question 6

Common Variable Immunodeficiency (CVID) Outline

Answer 6

B cell deficiency: mature B cells are present but can’t differentiate into antibody producing plasma cells. No memory B cells present. Indicated by recurrent bacterial infection

Question 7

(Bruton) agammaglobulinemia

Answer 7

Defective bruton tyrosine kinase (BTK), due to x-linked gene. Low B cell levels and low antibody (of all classes) levels

Question 8

Selective IgA Deficiency

Answer 8

Increased susceptibility to respiratory and GI infections (most people are asymptomatic)

Question 9

DiGeorge Syndrome Outline

Answer 9

Thymic hypoplasia (underdevelopment/absence) resulting in reduce T cell number. Common features cardiac abnormalities (both effected by mutated Q22 gene) and hypocalcemia

Question 10

Chronic Granulomatous Disease Outline

Answer 10

Phagocyte defects due to NADPH oxidase (ROS generating enzyme) mutations. Results in impaired bacterial killing. Indication: recu9rrent bacterial/fungal infections

Question 11

CVID Supportive (non-curative treatments

Answer 11

IV immunoglobin infusions or subcutaneous immunoglobulin injection + prophylactic antibiotic

Question 12

Agammaglobulinemia Supportive Treatment

Answer 12

IV immunoglobulin infusion or subcutaneous immunoglobulin injection + prophylactic antibiotic

Question 13

Selective IgA Deficiency Supportive Treatment

Answer 13

N/A. Only administer antibiotics when infection occurs

Question 14

DiGeorge Supportive Treatment

Answer 14

Allogenic (donor) thymus transplant (>70% sucessful uptake)

Question 15

X-linked severe combined immunodeficiency Supportive Treatment

Answer 15

IV immunoglobulin infusion

Question 16

ADA SCID Supportive Treatment

Answer 16

ADA-PEG enzyme replacement therapy (peg increases ADA suration in circulation)

Question 17

Ataxia Telangiectasa Immunodeficiency

Answer 17

Ataxia telangiectasia mutated (ATM) protein gene mutation. Impedes DNA reapir. Progressive IgA, IgE and T cell deficiency

Question 18

Ataxia Telangiectasa Supportive Treatment

Answer 18

IV Immunoglobulin infusion

Question 19

Chronic Granulomatous Disease Supportive Treatment

Answer 19

Lifelong antibiotic + antifungal prophylaxis and INF gamma (macrophage boost)

Question 20

Complement Deficiency Outline

Answer 20

Defect in opinisation, phagocytosis, pathogen lysis and Ag-Ab complex clearing. 4 types: C1q esterase inhibitor, C1/C2/C4, C3 and MAC (C5-C8)

Question 21

C1q esterase inhibitor Deficency Outline

Answer 21

Uncontrolled complement cascade action

Question 22

C2/C1/C4 Deficiency Outline

Answer 22

Inability to remove Ag-Ab complexes. C2 is associated with SLE

Question 23

C3 Deficiency Outline

Answer 23

Complete breakdown in compliment cascade. Indicated by repeated infections by pyogenic bacteria

Question 24

MAC Deficiency Outline

Answer 24

Inability to pierce pathogen membranes. Infection risk

Question 25

C1q inhibitor deficiency supportive treatment

Answer 25

Infusion of C1 inhibitor during acute attacks

Question 26

C1-C4 Inhibitor deficiency supportive treatment

Answer 26

Prophylactic antibody therapy

Question 27

MAC Complex Deficency supportive treatment

Answer 27

H influenzae and nerissa meningitis vaccination

Question 28

Curative Treatment For ADA SCID

Answer 28

Hematopoietic Stem Cell Therapy. 2 types; allogeic (haploid identical donor) and autologous (gene therapy)

Question 29

Chronic Granulomatus Disease Curative Treatment

Answer 29

Autologous haemopoitetic stem cell therapy (gene therapy) to fix mutations for NADPH oxidase gene

Question 30

Autologous HSCT Steps

Answer 30

Haemopoietic stem cells made from patient's bone marrow. Enriched with CD34+ in GMP lab, provides long-term bone marrow reconstitution. Lenti-viral vector designed with ADA. Patient undergoes chemo reductive therapy (to make space for stem cells). HSCT are reinfused intravenously, on enzyme replacement therapy for 30 days after reinfusion

Question 31

Secondary Immunodeficiency Causes

Answer 31

Immunosuppressive therapy, chronic microbial infection (eg HIV), malignancy, neurological, autoimmune disorders, cancer, malnutrition, Biochemical homeostasis disruption, trauma/environmental exposure

Question 32

Drug Induced Immunosupression

Answer 32

Neutropenia, thrombocytopenia and lymphocytes. Increased susceptibility to infection

Question 33

How Corticosteroids (eg Prednisone) Effect Secondary Immunodeficiencies

Answer 33

Lymphopenia (T cell in particular) and impaired macrophage/neutrophil function. Non-cytotoxic

Question 34

How Calcineurin Inhibitors (eg cyclosporine) Effect Secondary Immunodeficiencies

Answer 34

Suppress T cell activation, inhibits Calcineurin-NFAT pathway. Non-cytotoxic

Question 35

Methotrexate Effect of Secondary Immunodeficiencies

Answer 35

Prevents proliferation of rapidly dividing (immune) cells. Results in lymphopenia and impaired immune response. Cytotoxic

Question 36

Azathioprine Effect of Secondary Immunodeficiencies

Answer 36

Inhibits DNA/RNA synthesis, reduced immune cell production. Can lead to lymphopenia. Cytotoxic

Question 37

TNF Inhibitors Effect on Secondary Immunodeficiencies

Answer 37

Blocks TNF action, increasing infection risk

Question 38

IL6 Inhibitor effect on Secondary Immunodeficencies

Answer 38

Suppress inflammation response also inhibits immune function

Question 39

Rituximab Inhibitors Effect on Secondary Immunodeficiencies

Answer 39

B cell depletion, higher risk of chronic encapsulated microorganism infection

Question 40

Small Molecule Drugs Inhibitors (eg toficitinab) Effect on Secondary Immunodeficiencies

Answer 40

JAK inhibitors interfere with signaling pathways

Question 41

How to minimise infection risk with immunosuppression

Answer 41

Update vaccinations and screen for TB & Hep B prior to admin. Patient education and proper management

Question 42

Antibody Deficiencies Treatment

Answer 42

Prophylactic antibiotics and immunoglobulin replacement therapy

Question 43

Neutropenia Treatment

Answer 43

Remove causal factor. Both antibiotic and antifungal prophylaxis. Injectable G-CSF for bone marrow treatment

Question 44

T cell Deficiency Treatment

Answer 44

Donor lymphocyte infusion. Antivirals/Antifungals/Antibiotics as appropriate