Primary Immunodeficiency Part II Flashcards
Defects in which complement protein result in lots of pyogenic infections and why
C3 because it acts as an opsonin*-enhancing removal of bacteria by phagocytosis (when functioning)
what do deficiences in complement 1-4 cause
immune complex disease - an accumulation of immune complexes in the circulated deposition of the complexes in tissue, damaging it, and activating phagoyctes which causes inflammation, and more damage.
what is the main way of removing pathogens
Phagocytosis by macrophages and neutrophils
Chediak-Higashi disease
rare autosomal recessive genetic disorder caused by mutations in the CHS gene
Neutrophils, monocytes and lymphocytes contain giant lysosomal granules, resulting in phagocytes which are defective in chemotaxis, phagocytosis,& microbicidal activity and NK cell lack cytotoxic activity.
what problems does Chediak-Higashi disease cause
increased susceptibility to infections
lysosomal defects affect the melanocytes causing albinism and platelets causing bleeding disorders.
Leukocyte adhesion deficiency
Rare inherited disorder from a mutation in one of several genes that play a role in leukocyte adhesion (white blood cells attach to and move through blood vessel walls to reach the site of infection)
Lack of CD18 β-subunit of β2 integrins-LFA-1
White blood cells can’t properly attach to blood vessel walls (can’t bind endothelial tissue cells), so they can’t leave the bloodstream and reach the site of an infection.
what does LAD cause for people
more susceptibility to bacterial and fungal infections, particularly of the skin, mouth, and respiratory tract.
delayed wound healing, as white blood cells can’t properly migrate to the site of an injury.
main treatment for LAD and why
Bone marrow transplation as it restores neutrophil function
what is the genetic disorder chronic granulomatous disease (CGD) caused by
mutations in 1 of 4 proteins forming NADPH oxidase which produces hydrogen peroxide (fights infections)
what chromosome do 70% of CGD patients have mutations on
X chromosome ( x linked)
what is CGD characterised by that occurs in phagocytic cells following activation.
Defective respiratory burst, the increased oxidative metabolism
what do the recurrent infections in CGD lead to (Staphylococcus aureus, some gram –ve, some fungi (Aspergillus fumigatus and Candida albicans))
granuloma (cells clumped) which can obstruct gastrointestinal and urogenital systems
One of the reasons for the limited range of recurrent infections in cgd
because many bacteria generate hydrogen peroxide through their own metabolic processes, helping to destroy themselves
2 ways to diagnose CGD
Stimulation of superoxide production
Nitroblue Tetrazolium Test
Nitroblue Tetrazolium Test to diagnose CGD
a blood test that measures the ability of the immune system to convert the colorless nitroblue tetrazolium (NBT) to a deep blue.
If an individual has CGD, the white cells in their blood will not turn blue when exposed to the NBT.
Main treatments for CGD
Prophylactic antibiotics and antifungals taken daily
Interferon γ to stimulate the production of superoxide (less infections)
Bone marrow transplantation but high risk of mortality, the other methods are better
why do defects in t cells often have a greater impact on the immune system than those that affect the b cells or innate responses
Because t cells have an important role in directing the immune response so defects will often affect both humoral and cell-mediated responses.
why can autoimmunity be main symptom in immunodeficiency
as the B and T cell responses to self-antigens are not adequately regulated.
whats the most famous immunodeficiency
Severe Combined Immunodeficiency (SCID)
What is crucial for SCID and bone marrow transplants, to allow for early detection and treatment
Newborn screening
what does newborn SCID screening involve
a blood test that is done shortly after birth which can detect several different types of SCID.
SCID
rare genetic disorder giving people an impaired immune system that makes them susceptible to life-threatening infections
What cell development is usually totally failed in SCID resulting in defective cell-mediated and humoral immunity
total failure of T cell development
how can SCID be treated while child is still in womb
By stem cell transplantation in utero to establish a functional immune system before the fetus is exposed to infections.
This is done by transplanting stem cells from a donor into the developing fetus’s bloodstream while still in the womb
current most effective treatment for SCID
bone marrow transplantation (Haemopoietic stem cells transplant)
a treatment option for a type of SCID caused by a deficiency of ADA enzyme (ADA-SCID) - for those not suitable for BMT/ gene therapy
Enzyme replacement therapy (ERT) with injections of adenosine deaminase (ADA)
in SCID what can lead to recurrent viral, bacterial, fungal, and protozoan infections (pneumonia, meningitis)
Lymphopenia (low levels of lymphocytes)
What pose risk for people with SCID, which usually prevent infections in general people
Live attenuated vaccines e.g. (MMR) vaccine
4 most common mutated genes leading to SCID
IL2RG gene
ADA gene
RAG1 or RAG2 genes
JAK3 gene
if b cells are affected in SCID what treatments are given every 3-4 weeks
intravenous immunoglobulins
what are patients with no T-cells or poor T-cell function vulnerable to (4)
Opportunistic infection
Poor humoral immunity
Allergies
Lymphoid malignancies
Autoimmune diseases (inefficient negative selection in thymus, failure to generate T regulatory cells)
for t cell deficieny diagnosis what are skin tests negative or weak for
tuberculosis, Candida, and mumps
why is Phytohemagglutinin (PHA) commonly used in primary t cell deficiency diagnosis
because PHA activates T-lymphocytes by binding to the T-cell receptor and activating t cells so response to PHA stimulation would be reduced or absent due to the impaired function of T cells.
DiGeorge (Velocardiofacial) syndrome
Developmental disorder affecting thymus (failure of the thymus to develop properly from the third and fourth pharyngeal pouches). and therefore development and maturation of T cells
3 other features of DiGeorge (Velocardiofacial) syndrome
Lack parathyroid (hypothyroidism)
Severe heart abnormalities
Immunodeficiency
moderate learning difficulties
Fish-like mouth
3 things a lack of the thymus leads to
No T cells
Sparsely populated lymphoid tissue (thymus-dependent areas)
Poorly developed lymphoid follicles
No cell-mediated immunity
Subnormal antibody response (as no T cells)
how can DiGeorge (Velocardiofacial) syndrome be diagnosed
karyotype analysis - chromosomes examination test
FISH - genetic test to detect small deletions or duplications of DNA sequences using a fluorescent probe that binds to a specific region of DNA and emits light when exposed to a specific wavelength.
what gene deletion causes DiGeorge (Velocardiofacial) syndrom
TBX1 gene deletion
