Final Immunodeficiencies Flashcards
What are the two types of immunodeficiencies?
-primary and secondary
What is primary immunodeficiency?
-inherited conditions resulting in a defect in leukocyte development or function
What consequences for the patient does primary immunodeficiency cause?
- renders the patient susceptible to cancer and infection
- this susceptibility varies greatly depending on the defect
How many general classes of primary immunodeficiencies are recognized?
8 general classes consisting of over 120 specific conditions
List all the deficiencies that are included under primary
- combined B and T-cell
- mostly B cell
- mostly T cell
- myeloid
- complement
How are primary immunodeficiencies classified?
According to the developmental stage of the cells involved
What are the consequences of primary combined B and T cell immunodeficiency? (6)
- SCID
- severe and recurring infections early in life
- frequent viral or fungal infections
- lymphophenia
- fatal if untreated
- bone marrow transplant
What is lymphophenia
Low circulating lymphocytes
What is ADA deficiency?
Mutation in adenosine deaminase
What does ADA deficiency cause?
-causes combined B and T-cell immunodeficiency
How does ADA deficiency cause immunodeficiency? (4)
- 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
What is autosomal SCID caused by?
- mutation in DNA repair or RAG 1 or 2
- failure to successfully rearrange V(D)J genes
What does autosomal SCID cause?
-causes combined B and T-cell immunodeficiency
What causes X-linked SCID?
Mutation in IL-R common gamma chain
What does X-linked SCID cause?
-combined B and T-cell immunodeficiency
What does the mutation caused by X-linked SCID result in
A defect in cytokine signalling
What causes X-linked Hyper-IgM Syndrome?
Mutation in CD40L
What does X-linked Hyper-IgM Syndrome cause?
B cell immunodeficiency
How does X-linked Hyper-IgM Syndrome cause immunodeficiency? (3)
- 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
What does Autosomal Hyper-IgM Syndrome cause?
B cell immunodeficiency
What causes autosomal Hyper-IgM Syndrome
Mutation in AID
What is the difference between X-linked Hyper-IgM Syndrome and autosomal Hyper-IgM Syndrome?
First one primarily affects men and second affects both men and woman
What causes Bare-Lymphocyte Syndrome?
Lack of MHC2 expression
What does Bare-Lymphocyte Syndrome cause?
T cell immunodeficiency
How does Bare-Lymphocyte Syndrome work? (6)
- 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
What causes TAP-deficiency syndrome?
Lack of MHC1 expression
What does TAP-deficiency syndrome cause?
T cell immunodeficiency
What causes DiGeorge Syndrome?
No thymus
What does DiGeorge Syndrome cause?
T cell immunodeficiency
What is a phagocyte immunodeficiency? (4)
- 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
What tests for chronic granulomatous disease?
-NBT and DHR test
What is the NBT test?
- nitroblue-tetrazolium test
- substrate that turns blue in the presence of ROS
- more blue=more ROS
What are secondary immunodeficiencies?
-acquired conditions resulting in a defect in leukocyte development or function
How do secondary immunodeficiencies come about
Various medical treatments or infections, can be transient (drug induced) or permanent
What are the mechanisms of HIV? (3)
- occur at mucosal surfaces
- virions are picked up by DC and transported to the draining lymph node
- virus transfers to CD4+ helper cells
What drug was introduced and helped HIV?
AZT
What was the second drug introduced for HIV?
- HAART highly active anti-retroviral therapy
- 2 anti retrovirals + protease inhibitor
- increases life expectancy
