Immunology

Question 1

What are the clinical features of immunodeficiency?

SPUR

Answer 1

Serious infections
Persistant infections
Unusual infections
Recurrent infections

Question 2

What is Kostmann Syndrome?

Answer 2

failure of neutrophil maturation so no neutrophils

Question 3

What is the treatment of Kostmann Syndrome?

Answer 3

stem cell transplantation

prophylactic antibiotics and antifungals

Question 4

What is Leukocyte adhesion deficiency?

Answer 4

failure of neutrophil adhesion and trans endothelial migration
i.e. have neutrophils but they cannot bind to the infection

Question 5

What is Leukocyte adhesion caused by?

Answer 5

defect in leukocyte integrins (CD18)

Question 6

What is Chronic Granulomatous disease?

Answer 6

failure to produce free radicals

• excessive inflammation
• persistant accumulation of neutrophils, activated macrophages and lymphocytes
• failure to degrade chemoattractants and antigens

Question 7

What are phagocyte deficiencies?

Answer 7

Chronic granulomatous disease
Leukocyte Adhesion Deficiency
Kostmann Syndrome

Question 8

How do you diagnose chronic granulomatous disease?

Answer 8

nitroblue tetrazolium test

Question 9

What is the treatment of phagocyte deficiencies?

Answer 9

• aggressive management of infection
• surgical draining of abscess
• bone marrow transplant

Question 10

What is SCID?

Answer 10

Severe Combined Immunodeficiency

- unable to produce T cells and B cells so body cannot fight infection

Question 11

What are the clincial presentations of SCID?

Answer 11

present by 3 months of age
failure to thrive
persistant diarrhoea
infections of all types

Question 12

What causes SCID?

Answer 12

Mutation of IL-2 receptor

Question 13

Why does SCID only present after 3 months?

Answer 13

Baby is protected by maternal IgG until then

Question 14

What is DiGeorge Syndrome?

Answer 14

T cell deficiency
- T cells are produce in the thymus however these individuals have an underdeveloped thymus so there is no where for them to mature

Question 15

What are the consequences of DiGeorge Syndrome?

Answer 15

congenital heart defects
cleft palate
failure of thymic development
hypocalcaemia
etc...

Question 16

What is the treatment for DiGeorge Syndrome?

Answer 16

antibiotics

immunoglobin replacement

Question 17

What is a hypersensitivity reaction?

Answer 17

immune response that results in bystander damage to the self

Question 18

Breifly outline Type 1-4 hypersensitivity reactions according to the Gel and Coombs Classification?

Answer 18

Type 1 - immediate hypersensitivity
Type 2 - direct cell killing
Type 3 - immune complex mediated
Type 4 - delayed type hypersensitivity

Question 19

Desribe Type 1 Hypersensitivtiy?

Answer 19

IgE mediated in response to an external antigen
e.g. allergy or asthma
IgE is produced by B lymphocytes with the help of TH2 cells

Question 20

Describe the IgE mediated response to an external antigen?

Answer 20

• IgE - allergen complex binds to mast cells via Fc receptors
• degranulation of mast cells
• release of preformed and newly synthesised inflammatory molecules

Question 21

Describe Type 2 Hypersensitivity?

Answer 21

Direct killing
activation of complement pathway -> cell lysis -> opsonisation -> antibody mediated phagocytosis
e.g. blood transfusion mismatch

Question 22

Describe the classical, alternative and lectin complement pathway?

Answer 22

classical - antigen + antibody + C1 complex
alternative - MBL + mannose pathogen
lectin - spontaneous C3 cleavage

Question 23

What is the treatment for blood transfusion hypersensitivity?

Answer 23

plasmapheresis

Question 24

Describe Type 3 Hypersensitivity?

Answer 24

Immune Complex
In the presence of excess antigen, antibody antigen complexes get stuck in areas (alveoli and bronchi) and activate complement, attracting macrophages and phagocytes.
e.g. Extrinsic Allergic Alveolitis

Question 25

How is Type 3 Hypersensitivity managed?

Answer 25

Avoidance of allergen | Corticosteroids to decrease inflammation

Question 26

Describe Type 4 Hypersensitivity?

Answer 26

Delayed T cell mediated - initial sensitisation to antigen which generates primed effector Th1 cells + memory T cells. Subsequent exposure to antigen = activation of previous T cells and recruitment of macrophages and lymphocytes which release proteolytic enzymes and cause persistent infection e.g. TB/Sarcoidosis/organ rejection

Question 27

What do Th1 cells cause?

Answer 27

normal response to an allergen

Question 28

What do Th2 cells cause?

Answer 28

atopic (hay fever, asthma etc..) response to allergen

Question 29

How is the allergic reaction in asthma brought about?

Answer 29

Allergen is detected by CD4 cells. This activates T helper cells. TH2 cells activated in the allergic pathway, TH2 cells activate B cells. IL4 + IL5 cause B cells to mature to P cells. IgE is released. Mast cells display Fc receptors which Bind IgE. When IgE binds to Fc receptors there is calcium influx degranulation and release of inflammatory mediators (e.g. histamine) = ALLERGIC RESPONSE.

Question 30

What is measured in acute anaphylactic episodes?

Answer 30

Tryptase