Final Immunodeficiencies

Question 1

What are the two types of immunodeficiencies?

Answer 1

-primary and secondary

Question 2

What is primary immunodeficiency?

Answer 2

-inherited conditions resulting in a defect in leukocyte development or function

Question 3

What consequences for the patient does primary immunodeficiency cause?

Answer 3

• renders the patient susceptible to cancer and infection

- this susceptibility varies greatly depending on the defect

Question 4

How many general classes of primary immunodeficiencies are recognized?

Answer 4

8 general classes consisting of over 120 specific conditions

Question 5

List all the deficiencies that are included under primary

Answer 5

• combined B and T-cell
• mostly B cell
• mostly T cell
• myeloid
• complement

Question 6

How are primary immunodeficiencies classified?

Answer 6

According to the developmental stage of the cells involved

Question 7

What are the consequences of primary combined B and T cell immunodeficiency? (6)

Answer 7

• SCID
• severe and recurring infections early in life
• frequent viral or fungal infections
• lymphophenia
• fatal if untreated
• bone marrow transplant

Question 8

What is lymphophenia

Answer 8

Low circulating lymphocytes

Question 9

What is ADA deficiency?

Answer 9

Mutation in adenosine deaminase

Question 10

What does ADA deficiency cause?

Answer 10

-causes combined B and T-cell immunodeficiency

Question 11

How does ADA deficiency cause immunodeficiency? (4)

Answer 11

• ADA normally breaks down adenosine
• if deficient there will be a build up of adenosine and S-adenylhomocyteseine
• this inhibits ribonucleotide reductase
• inhibiting DNA replication and high levels of S are cytotoxic

Question 12

What is autosomal SCID caused by?

Answer 12

• mutation in DNA repair or RAG 1 or 2

- failure to successfully rearrange V(D)J genes

Question 13

What does autosomal SCID cause?

Answer 13

-causes combined B and T-cell immunodeficiency

Question 14

What causes X-linked SCID?

Answer 14

Mutation in IL-R common gamma chain

Question 15

What does X-linked SCID cause?

Answer 15

-combined B and T-cell immunodeficiency

Question 16

What does the mutation caused by X-linked SCID result in

Answer 16

A defect in cytokine signalling

Question 17

What causes X-linked Hyper-IgM Syndrome?

Answer 17

Mutation in CD40L

Question 18

What does X-linked Hyper-IgM Syndrome cause?

Answer 18

B cell immunodeficiency

Question 19

How does X-linked Hyper-IgM Syndrome cause immunodeficiency? (3)

Answer 19

• low levels of blood IgG, IgA and IgE and elevated IgM
• lack of CD40L leads to a lack of costimulation of B cells which leads to reduced B cell activation in response to T-dependent antigens
• failure to produce germinal centres, no class-switching, reduced hypermutation and few memory cells

Question 20

What does Autosomal Hyper-IgM Syndrome cause?

Answer 20

B cell immunodeficiency

Question 21

What causes autosomal Hyper-IgM Syndrome

Answer 21

Mutation in AID

Question 22

What is the difference between X-linked Hyper-IgM Syndrome and autosomal Hyper-IgM Syndrome?

Answer 22

First one primarily affects men and second affects both men and woman

Question 23

What causes Bare-Lymphocyte Syndrome?

Answer 23

Lack of MHC2 expression

Question 24

What does Bare-Lymphocyte Syndrome cause?

Answer 24

T cell immunodeficiency

Question 25

How does Bare-Lymphocyte Syndrome work? (6)

Answer 25

- APC do not express MHC2 - peptide is not presented to helper cells - failure of positive selection in the thymus-no CD4+ T cells - lack of T cell help for B cells - generalized immune deficiency and susceptible to infections - bone marrow transplant with replaced APC's

Question 26

What causes TAP-deficiency syndrome?

Answer 26

Lack of MHC1 expression

Question 27

What does TAP-deficiency syndrome cause?

Answer 27

T cell immunodeficiency

Question 28

What causes DiGeorge Syndrome?

Answer 28

No thymus

Question 29

What does DiGeorge Syndrome cause?

Answer 29

T cell immunodeficiency

Question 30

What is a phagocyte immunodeficiency? (4)

Answer 30

- chronic granulomatous disease - can't generate ROS thus no hydrogen peroxide - can't kill microorganisms leading to formation of granulomas - susceptible to bacterial and fungal infections

Question 31

What tests for chronic granulomatous disease?

Answer 31

-NBT and DHR test

Question 32

What is the NBT test?

Answer 32

- nitroblue-tetrazolium test - substrate that turns blue in the presence of ROS - more blue=more ROS

Question 33

What are secondary immunodeficiencies?

Answer 33

-acquired conditions resulting in a defect in leukocyte development or function

Question 34

How do secondary immunodeficiencies come about

Answer 34

Various medical treatments or infections, can be transient (drug induced) or permanent

Question 35

What are the mechanisms of HIV? (3)

Answer 35

- occur at mucosal surfaces - virions are picked up by DC and transported to the draining lymph node - virus transfers to CD4+ helper cells

Question 36

What drug was introduced and helped HIV?

Answer 36

AZT

Question 37

What was the second drug introduced for HIV?

Answer 37

- HAART highly active anti-retroviral therapy - 2 anti retrovirals + protease inhibitor - increases life expectancy