Immunology

Question 1

What are SPUR features?

Answer 1

Serious infections
Persistent infections
Unusual infections
Recurrent infections
(Clinical features suggestive of immunodeficiency)

Question 2

Commonest form of severe combined immunodeficiency

Answer 2

X-linked SCID

Question 3

Underlying immuno-pathophysiology of X-linked SCID

Answer 3

IL-2 receptor mutation; inability to produce T cells and NK cells

Question 4

Clinical presentation of X-linked SCID (4)

Answer 4

Unwell by 3 months old
Persistent diarrhoea
Failure to thrive
Infections of all types

Question 5

Organised collection of activated macrophages and lymphocytes

Answer 5

Granuloma

Question 6

Key mediators in granuloma formation (3)

Answer 6

IL-12 released by macrophages
gIFN produced by T-cells
TNF

Question 7

Granulomatous conditions (3)

Answer 7

Sarcoidosis
Tuberculosis
Silicosis and other dust diseases

Question 8

Manifestations of antibody dysfunction (2)

Answer 8

Recurrent bacterial infections

Antibody-mediated immune diseases

Question 9

Examples of antibody deficiencies (2)

Answer 9

Common variable immune deficiency (CVID)

Selective IgA deficiency

Question 10

What is Bruton’s agammaglobulinaemia?

Answer 10

An X-linked primary deficiency of antibody production where patients have no B cells

Question 11

Causes of secondary hypogammaglobulinaemia (2)

Answer 11

Protein loss e.g. nephrotic syndrome

Lymphoproliferative disease e.g. myeloma

Question 12

Type I hypersensitivity

Answer 12

IgE-mediated e.g. anaphylaxis

Question 13

Type II hypersensitivity

Answer 13

Antibody-mediated direct cell-killing, e.g. autoimmune haemolytic anaemia

Question 14

Type III hypersensitivity

Answer 14

Immune complex-mediated e.g. SLE

Question 15

Type IV hypersensitivity

Answer 15

Delayed type, T-cell mediated e.g. graft versus host disease

Question 16

How can antibody lead to direct cell killing? (3)

Answer 16

Activation of complement via the classical pathway leading to:

a) opsonization (optimises phagocytosis)
b) formation of the membrane attack complex, causing lysis
c) recruitment of other immune cells

Question 17

What activates the alternative complement pathway?

Answer 17

LPS on microbial surfaces

Question 18

What does complement deficiency predispose to?

Answer 18

Bacterial infection especially meningitis

Question 19

What types of cell do NK cells target? (2)

Answer 19

Cells which lack MHC molecules on surface; especially viruses and cancer cells

Question 20

What are Toll-like receptors? (2)

Answer 20

Receptors on phagocytes providing innate recognition of pathogens; activation leads to release of pro-inflammatory cytokines

Question 21

What are adalimumab and etanercept? What is their mechanism of action?

Answer 21

TNF-inhibitors used in chronic inflammatory conditions such as rheumatoid arthritis and Crohns disease. Inhibit TNF, thus preventing release of pro-inflammatory cytokines

Question 22

What is the main risk/side effect of adalimumab?

Answer 22

Reactivation of tuberculosis

Question 23

Mechanism of hyperacute graft rejection

Answer 23

Type II hypersensitivity- pre-formed antibody and complement activation

Question 24

Timescale and mechanism of acute graft rejection

Answer 24

5-30 days; Type IV hypersensitivity (T cells)

Question 25

What is the drug target of cyclosporin?

Answer 25

Calcineurin. Inhibition helps prevent lymphocyte activation

Question 26

What is the first antibody to be produced in the immune response?

Answer 26

IgM

Question 27

Vaccination stimulates the production of…

Answer 27

Memory T cells

Question 28

Main types of vaccine

Answer 28

Inactivated vaccines

Live attenuated vaccines

Question 29

Disadvantages of inactivated vaccines (2)

Answer 29

Require multiple/booster injections

Require adjuvants to boost immunogenecity

Question 30

Constituents of the 5-in-1 vaccine

Answer 30

Diphtheria
Tetanus
Pertussis
Polio
HiB

Question 31

What type of vaccine is the 5-in-1? When is this given?

Answer 31

Inactivated vaccines. 8, 12 and 16 weeks
(at 3 years and 4 months, given again minus HiB)
(at 14 years given again minus HiB and pertussis)

Question 32

Advantages of live attenuated vaccines (3)

Answer 32

Elicits antibody and T cell responses
Gives strong response
Usually only one dose required

Question 33

Example of a live attenuated vaccine given at one year

Answer 33

MMR

Question 34

How does the lectin pathway of complement work?

Answer 34

Proteins such as MBL coat sugars on the surface of bacteria, thus activating the complement cascade and helping the bacteria be eliminated

Question 35

Why is the “5-in-1” vaccine given at 3 months, 4 months and 3 years?

Answer 35

In order to boost immunity- 5-in-1 vaccine are inactivated and hence have poor immunogenecity

Question 36

How do live attenuated vaccines work?

Answer 36

pathogen is made virulent, but is still live and replicating, and hence is a good immunogen

Question 37

Which antibody is mostly generated during secondary exposure to a pathogen?

Answer 37

IgG

there is also smaller levels of IgM

Question 38

How does IgA selective deficiency usually present?

Answer 38

Most are asymptomatic and will not be detected

Question 39

The main risks of TNF inhbitors is are…

Answer 39

Granulomatous infections, fungal infections

Question 40

Anti-TNFs represent a form of…

Answer 40

Passive immunisation

Question 41

How does imiquimod work?

Answer 41

Activates TLR-8 in macrophages/dendritic cells, leading to activation of these cells. In skin cancer (BCC) it increases infiltration of immune cells into the skin, where they can detect abnormal cancer cells