Immunodeficiencies Flashcards
What are the 2 types of immunodeficiencies
Primary which are congenital and then there are Secondary which are acquired like AIDS
What are the reasons for acquired immunodeficiencies
- Disease like AIDS
- Nutritional
- Medical treatment
What is the first type of primary ID
- Defects in lymphocyte maturation
What is an example where lymphocytes cant mature
An example is SCID, Severe Combined Immunodeficiency.
- This disease is associated with blocks in lymphocyte maturation.
- Half of all clinical cases of SCIDs are X linked where males are severly effected.
- Mutation in gamma chain, required for a range of ILs signaling
- No T cells and NK cells
Why are there no T cells in SCIDs
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.
Why are there no NK cells in SCID
NK cells require IL15 for their activation and proliferation. The common gamma chain is part of the receptor so no signaling is achieved
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
What are other genetic reasons for SCID
Autosomal versions of SCID.
- They are caused by ADA and PNP mutations (Adenosine Deaminase and Purine Nucleoside Phosphorylase).
- Mutations in JAK3, same ILs affected as X linked SCID
- 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
What is immunodeficiency generally linked to
Autoimmunity
What is another disease associated with lack of maturation of WBCs
X-linked agammagloblulinemia
- Loss of B cells
- Loss of serum Igs
- Mutations in BTK, X linked
- Autoimmunity
What is another disease associated with lack of WBCs maturations
DeGeorge Syndrome. Part of the chromosome 22 is deleted. This leads to
- Heart defects
- Cleft Palate
- Abnormal development
- Incomplete development of thymus leading to low T cell numbers
What are some of the other defects associated with ID
Defects in lymphocyte development and activation
What is the disease associated with it
X linked Hyper IgM Syndrome
- Mutations in CD40L
- 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.
- 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
What is another disease she talked about that is associated with B cell inactivation
Autosomal Hyper IgM Syndrome
- Mutations in Activation Induced Deaminase (AID)
- No antibody switching
- No somatic hypermutation
What are some of the other diseases that are more common
Selective Ig’s deficiency, IgA deficiency is more common but there are no adverse symptoms associated with it
What is the function of IL-4
Induced B cells to make IgA
What are a group of disorders that are associated with ID
They are called Common Variable Immunodeficiency (CVID).
- Reduced serum levels of IgG, IgM and IgA
- Poor antibody responses to infections
- Recurrent infections, autoimmunty and lymphomas
- Mutliple causes, several genes have been identified
Name the disease associated with faulty T cells activation
- Bare Lymphocyte Syndrome
- 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
Describe Th1 and Th17 deficiencies and their concequences
Th1 deficiencies
- Caused by lack of IL12, IL12 R or INF gamma R
- Causes atypical mycobacterium infections
Th17 deficiencies
- Caused by lack of IL17 or IL17 R
- Fungal and staph aureus infections
Wiskot-Alderich Syndrome (WAS)
- Mutations in Wiskott Alderich Syndrome Protein (WASP)
- X linked
- This protein is only expressed in leukocytes and megakaryocytes
- Protein critical for cytoskeleton rearrangement
- T cell function and platelet function is faulty
- The fault is in the T cell mobility and in their cytotoxic ability
ATM
Ataxsia-Telangiectasia
- Mutations in the ATM, it is a DNA repair enzyme and a VDJ recombinase
- Ataxia - gait abnormalities
- Telaniectasia - vascular malformations
- Clinical sign of this disease is low lymphocyte numbers
Are there any primary IDs associated with innate immunity
Yes
- Chronic Granulamtous Disease
- 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
What are some of the other diseases associated with innate immunity
Complement protein deficiencies
- In C1, C2 and C4.
- Associated with bacterial infections
- Associated with autoimmunity - cant clear the immune complex
- Factor I or H - associated with C3 consumption and bacterial infections
Chediak-Higashi Syndrome
- Defects in lysosomal vesicle formaton and traficking
- Neurtophils and macrophages cant carryout phagocytosis
- Imparied granule release from NK cells and CTLs
- Associated with severe bacterial infections
