Immunodeficiency

Question 1

What is the role of pattern recognition receptors (PRRs) in the immune system?

Answer 1

PRRs are structures found on cells of the innate immune system (eg. dendritic cells, macrophages etc.) they tell you what kind of pathogen you are dealing with and thus enable the innate immune system to instruct the adaptive immune system as to what is the most appropriate type of response through production of different chemokines etc.
(PRRs wouldnt be able to tell you the exact species of pathogen but they could tell you if it was a gram-negative bacteria, a fungus, a virus etc)

Question 2

What are the 5 major components of the innate immune system?

Answer 2

1) Pattern recognition receptors
2) Antimicrobial peptides
3) Cells
4) Complement components
5) Cytokines

Question 3

What is the function of B lymphocytes?

Answer 3

Develop potential to secret antibodies

Question 4

What is the function of CD4+ cells?

Answer 4

(Helper T cells) secrete growth factors (cytokines) which control immune response: help B and T lymphocytes - instruct proper maturation of B cells aswell as cytotoxic T cells

Question 5

In what 4 ways can binding of antibodies to antigens inactivate those antigens?

Answer 5

1) Neutralization (blocks viral binding sites/coats bacteria)
2) Agglutination of microbes (stick in a big lump)
3) Precipitation of dissolved antigens
The above 3 processes enhance phagocytosis by macrophages
4) Activation of complement system
The above leads to cell lysis

Question 6

How do cytotoxic T cells kill infected cells?

Answer 6

Cytotoxic T cell binds to the Ag presented on the surface of the infected cell
Releases perforin molecule which makes holes in the infected cells membrane and an enzyme promoting apoptosis is released by the cytotoxic T cell which can now enter the infected cell and destroy it

Question 7

What is meant by immunodeficiency?

Answer 7

Clinical situations where the immune system is not effective enough to protect the body against infection

Question 8

Does immune deficiency only present in children?

Answer 8

No it can occur at any age but its important to remember that children and the elderly are much more sensitive to infection

Question 9

What is the difference between primary and secondary immunodeficiency?

Answer 9

Primary - caused by genetic defects in individual components of the immune system
Secondary - immunodeficiencies secondary to the effects of external factors

Question 10

What is often a guide to the underlying cause of immunodeficiency in patients, and what confirms it?

Answer 10

Type of infection is often a guide to the underlying cause of the immunodeficiency, laboratory tests confirm the cause

Question 11

Are immunodeficiencies always permanent?

Answer 11

No secondary immunodeficiencies can be transient or long lasting

Question 12

Give 8 external factors which can cause secondary immunodeficiency?

Answer 12

1) Stress
2) Surgery/burns
3) Malnutrition
4) Cancer - especially lymphoproliferative disease
5) Immunosuppressive effect of drugs inc. cancer therapy
6) Irradiation
7) AIDS
8) Other infections eg. measles or TB

Question 13

How common are primary immunodeficiencies?

Answer 13

Very rare

Question 14

When are primary immunodeficiencies typically diagnosed?

Answer 14

In early childhood (note they can present later on in life)

Question 15

Why is family history important to consider when considering a diagnosis of primary immunodeficiency?

Answer 15

Caused by genetic defects

Question 16

What investigations would you carry out when considering a diagnosis of primary immunodeficiency in a person presenting with recurrent or unusual infections? 4

Answer 16

1) Immunoglobulin levels - indicates B cell function
2) Lymphocyte levels
3) Neutrophil levels
4) May test CRP if current infection to see if actually mounting an inflammatory response

Question 17

What role does IRAK have in immune response?

Answer 17

Formed as part of the intracellular signalling pathway of toll like receptors (a type of PRR) when they encounter a pathogen - forms NF-kbeta which is a transcriptional factor which leads to the release of inflammatory cytokines/chemokines which leads to inflammatory and adaptive immune response

Question 18

Why would an IRAK deficiency cause immunodeficiency?.

Answer 18

Because IRAK is a key component in the pathway to release of inflammatory cytokines/chemokines from the cells of the innate immune system which plays a role in the development of an adaptive and inflammatory response

Question 19

Which test could be carried out to determine neutrophil function?

Answer 19

Nitroblue tetrazolium test (NBT)

Question 20

What is the mechanism of phagocytosis?

Answer 20

1) NADPH releases H+
2) H+ transported into the phagosome via a specific proton channel
3) This lowers the pH within the phagosome which tiggers the proteolytic enzymes within the phagosome which can destroy the material within it

Question 21

What is the defect in chronic granulomatous disease?

Answer 21

An inherited disorder of phagocytic cells resulting in an inability to phagocytose pathogenic material

Question 22

What kind of mutation is chronic granulomatous disease normally caused by?

Answer 22

X-linked mutation

Question 23

Would patients with chronic granulomatous disease have a reduced number of neutrophils?

Answer 23

No, they would have a normal number of neutrophils but they would be stuffed full of pathogenic material that they wouldnt be able to destroy

Question 24

Why does chronic inflammation tend to occur in chronic granulomatous disease (CGD)?

Answer 24

As neutrophils are malfunctioning the rest of the immune system components has a frustrated response which leads to inflammation

Question 25

What are the 6 complications of chronic granulomatous disease (CGD)?

Answer 25

1) Osteomyelitis
2) Pneumonia
3) Swollen lymph nodes
4) Gingivitis
5) Non-malignant granulomas
6) Inflammatory bowel disease

Question 26

How would you test terminal complement function?

Answer 26

1) Take sheep RBC’s, incubate with patient serum - human RBCs have structures on the surface which inhibit our own complement system, sheep RBCs dont have this
2) If complement is functioning properly all the sheep RBCs should undergo haemolysis

Question 27

What are the key steps in the common terminal complement activation pathway?

Answer 27

1) Activation of C3 convertase which cleaves C5
2) Cleaving of C5 to C5b allows the rest of the complement (C6-C9) to set on the surface of the bacteria and create pores which leads to the lysis of susceptible microorganisms

Question 28

X-linked agammaglobulinaemia (XLA) is an immunodeficiency with defects in what?

Answer 28

B cells

Question 29

What kind of infection do immunodeficiencies with defects in B cells lead to?

Answer 29

Recurrent bacterial infection with pyogenic organisms

Question 30

Why are defects in B cells usually diagnosed only around 1-2 years?

Answer 30

Maternal IgG protects until this point

Question 31

How are B cell defects treated?

Answer 31

Treat with Abx and IV IgG from a pool of donors for life

Question 32

Name 6 primary B cell deficiencies?

Answer 32

1) Common variable immunodeficiency
2) x-linked agammaglobulinaemia
3) Autosomal recessive Hyper IgM syndrome
4) IgA deficiency
5) IgG subclass deficiency
6) Transient Hypogammaglobulinaemia of infancy

Question 33

Why are primary immunodeficiencies caused by autosomal recessive or x-linked mutations?

Answer 33

Immunodeficiencies are due to a loss in function, need both mutated alleles to aquire that loss of function, so must be recessive or x-linked

Question 34

Why would a severe extensive candida infection indicate an immunodeficiency?

Answer 34

Because candida doesn’t normally cause this kind of infection in healthy people

Question 35

What may be the presentation of chicken pox in a immunodeficient baby compared to a health baby?

Answer 35

Get fulminant (severe and sudden onset) disease rather than mild disease
Get haemorrhagic lesions as opposed to the typical vesicles of chicken pox

Question 36

Severe combined immunodeficiency syndromes (SCID) refers to defects in what 2 kinds of cells?

Answer 36

1) B lymphocytes

2) T lymphocytes

Question 37

What are the symptoms of SCID?

Answer 37

Recurrent infection with opportunistic infections: bacteria, viruses, fungi (candida) and protozoa (pneumocystis)

Question 38

What are the 2 treatments for SCID?

Answer 38

1) Bone marrow transplant is curative

2) Gene therapy

Question 39

Name 4 primary T cell deficiencies?

Answer 39

1) Adenosine deaminase deficiency
2) Purine nucleoside phosphorylase deficiency
3) MHC class II deficiency
4) Wiskott-Aldrich syndrome

Question 40

Defects in PRRs normally present with what 2 infections?

Answer 40

1) Pneumococcus

2) HSV

Question 41

Defects in macrophages and neutrophils usually present with what 2 infections?

Answer 41

1) Staphylococcus

2) Aspergillus

Question 42

Defects in complement often present with what infection?

Answer 42

1) Meningococcus

Question 43

Defects in cytokines normally present with what kind of infection?

Answer 43

Mycobacterium

Question 44

Defects in B cells normally present with what kind of infection?

Answer 44

Recurrent sino-pulmonary infections