Immunodeficiencies

Question 1

What are the 2 types of immunodeficiencies

Answer 1

Primary which are congenital and then there are Secondary which are acquired like AIDS

Question 2

What are the reasons for acquired immunodeficiencies

Answer 2

1. Disease like AIDS
2. Nutritional
3. Medical treatment

Question 3

What is the first type of primary ID

Answer 3

1. Defects in lymphocyte maturation

Question 4

What is an example where lymphocytes cant mature

Answer 4

An example is SCID, Severe Combined Immunodeficiency.

1. This disease is associated with blocks in lymphocyte maturation.
2. Half of all clinical cases of SCIDs are X linked where males are severly effected.
3. Mutation in gamma chain, required for a range of ILs signaling
4. No T cells and NK cells

Question 5

Why are there no T cells in SCIDs

Answer 5

IL-7 signaling is blocked, IL7 is essential for the survival of T cells in the periphery and for proliferation of T cells at different stages of development in the thymus.

Question 6

Why are there no NK cells in SCID

Answer 6

NK cells require IL15 for their activation and proliferation. The common gamma chain is part of the receptor so no signaling is achieved

Question 7

Answer 7

Has to do something with class switching, didnt really understand this concept. The answer is B. IgG is most abundant antibody found in the serra but in this case most of the antibodies would be IgM

Question 8

What are other genetic reasons for SCID

Answer 8

Autosomal versions of SCID.

1. They are caused by ADA and PNP mutations (Adenosine Deaminase and Purine Nucleoside Phosphorylase).
2. Mutations in JAK3, same ILs affected as X linked SCID
3. Mutations in RAG1 and 2 leading to a complete loss of their function.

If there is some expression of functional RAG1 and 2 then there are some T cells. This condition is called Omen’s Syndrome

Question 9

What is immunodeficiency generally linked to

Answer 9

Autoimmunity

Question 10

What is another disease associated with lack of maturation of WBCs

Answer 10

X-linked agammagloblulinemia

1. Loss of B cells
2. Loss of serum Igs
3. Mutations in BTK, X linked
4. Autoimmunity

Question 11

What is another disease associated with lack of WBCs maturations

Answer 11

DeGeorge Syndrome. Part of the chromosome 22 is deleted. This leads to

1. Heart defects
2. Cleft Palate
3. Abnormal development
4. Incomplete development of thymus leading to low T cell numbers

Question 12

What are some of the other defects associated with ID

Answer 12

Defects in lymphocyte development and activation

Question 13

What is the disease associated with it

Answer 13

X linked Hyper IgM Syndrome

1. Mutations in CD40L
2. So T cells do not express any CD40L, there is nothing to bind to the CD40 on the B cells, no class switching takes place which leads to B cells inactivation to certain antigens.
3. Anytime a B cell gets activated by the other ligands such as MHC 2 or cytokines it makes more IgMs (since there is no class switching) and hence there will be more IgMs

Question 14

What is another disease she talked about that is associated with B cell inactivation

Answer 14

Autosomal Hyper IgM Syndrome

1. Mutations in Activation Induced Deaminase (AID)
2. No antibody switching
3. No somatic hypermutation

Question 15

What are some of the other diseases that are more common

Answer 15

Selective Ig’s deficiency, IgA deficiency is more common but there are no adverse symptoms associated with it

Question 16

What is the function of IL-4

Answer 16

Induced B cells to make IgA

Question 17

What are a group of disorders that are associated with ID

Answer 17

They are called Common Variable Immunodeficiency (CVID).

1. Reduced serum levels of IgG, IgM and IgA
2. Poor antibody responses to infections
3. Recurrent infections, autoimmunty and lymphomas
4. Mutliple causes, several genes have been identified

Question 18

Name the disease associated with faulty T cells activation

Answer 18

1. Bare Lymphocyte Syndrome
2. Selective T cell deficiencies are usually rare and they effect the function of only one type of T cells such as T1, T2 or T16 cells

Question 19

Describe Th1 and Th17 deficiencies and their concequences

Answer 19

Th1 deficiencies

1. Caused by lack of IL12, IL12 R or INF gamma R
2. Causes atypical mycobacterium infections

Th17 deficiencies

1. Caused by lack of IL17 or IL17 R
2. Fungal and staph aureus infections

Question 20

Wiskot-Alderich Syndrome (WAS)

Answer 20

1. Mutations in Wiskott Alderich Syndrome Protein (WASP)
2. X linked
3. This protein is only expressed in leukocytes and megakaryocytes
4. Protein critical for cytoskeleton rearrangement
5. T cell function and platelet function is faulty
6. The fault is in the T cell mobility and in their cytotoxic ability

Question 21

ATM

Answer 21

Ataxsia-Telangiectasia

1. Mutations in the ATM, it is a DNA repair enzyme and a VDJ recombinase
2. Ataxia - gait abnormalities
3. Telaniectasia - vascular malformations
4. Clinical sign of this disease is low lymphocyte numbers

Question 22

Are there any primary IDs associated with innate immunity

Answer 22

Yes

1. Chronic Granulamtous Disease
2. LAD, Lymphocyte Adhesion Deficiency: LAD 1 is when there is absence of CD18 (which is part of LFA1, it is made of C11a and CD18) and LAD2 or 3 is when there are defects in selectin ligand expression

Question 23

What are some of the other diseases associated with innate immunity

Answer 23

Complement protein deficiencies

1. In C1, C2 and C4.
2. Associated with bacterial infections
3. Associated with autoimmunity - cant clear the immune complex
4. Factor I or H - associated with C3 consumption and bacterial infections

Question 24

Chediak-Higashi Syndrome

Answer 24

1. Defects in lysosomal vesicle formaton and traficking
2. Neurtophils and macrophages cant carryout phagocytosis
3. Imparied granule release from NK cells and CTLs
4. Associated with severe bacterial infections

Question 25

What are some of the reasons for secondary immune deficiencies

Answer 25

1. HIV 2. Cancer treatments involving chemotherapy and irradiation 3. Immunosuppressive drugs that are used in graft rejections and inflammatory disease 4. Lack of protein in diet