Primary Immunodeficiency Part I Flashcards
2 pathways that pluripotent haematopoietic Stem cells in bone marrow differentiate through into immune cells
myeloid or lymphoid pathways
2 things immune cells use to migrate from blood circulation into the tissues, which regulate the inflammatory response
cell adhesion molecules, chemotactic factors and complement proteins
what do phagocytic cells do to pathogens when they enter tissues
engulf them by phagocytosis and destroy them with lots of different microbicidal agents
What cells deal with intracellular infections as phagocytes, complement, and antibodies cannot access pathogens once inside the cell
Natural Killer cells
how do natural killer cells differ to T cells
they do not need to be activated by specific antigens
what immunity provides back-up to the innate response
adaptive immunity
how is adaptive immunity different to innate immunity
It’s developed over time in response to exposure to specific pathogens. Unlike innate immunity, adaptive immunity can recognize and remember specific pathogens, for a more targeted and effective response upon re-exposure.
cytotoxic T cells
type of T cell in the adaptive immune response. They have the ability to kill infected or abnormal cells directly.
They are activated when they recognize antigens. Then they release toxic substances that can destroy the target cell.
What can cytotoxic t cells secrete that helps to coordinate the immune response and stimulate other cells to take action
cytokines
what is immunodeficiency disease
group of disorders that impair the function of the immune system, making it less able to fight off infections and diseases
what infections are those who are affected with severe immunodeficiency at risk of
Opportunistic infections which are caused by microorganisms that healthy individuals can easily get rid of, but that cause disease and even death in those with significantly impaired immune function.
many people with what virus develop opportunistic infections
HIV
what are Primary immunodeficiencies (permanent)
Inherited conditions that affect the development or function of the immune system - caused by a genetic defect producing defective protein or glycoprotein.
how rare are primary immunodeficiencies
1 in 10,000
what sex is 1y immunodeficiency more common in and why
More common in males as several 1y immunodeficiencies are x-linked. Males only have one x chromosome
main immunodeficiency syndrome that are caused by mutations of genes located on the x chromosome
x linked agammaglobulinemia
adaptive immunity
immunity to infection caused by an adaptive immune response (response of antigen-specific lymphocytes to antigen, the development of immunological memory)
innate immunity
innate resistance mechanisms that are encountered first by a pathogen, before adaptive immunity is induced (anatomical barriers, antimicrobial peptides, complement system and macrophages and neutrophils carrying non-specific pathogen-recognition receptors)
how many functional groups of primary immunodeficiencies are there
8 (over 350 immunodeficiencies)
what makes immunodeficiencies more severe
how early image defects happen in hematopoietic cell development as they affect everything downstream
IgA deficiency
low levels of or no IgA in your blood - sinopulmonary (lung) and gastrointestinal infections as plays role in immune function of mucous membranes
most common inherited form of immunolglobulin deficiency in populations of european origin - 1 in 700
Reticular dysgenesis
the most severe form of severe combined immunodeficiency (SCID). Rare genetic disorder of the bone marrow resulting in complete absence of granulocytes and decreased number of abnormal lymphocytes
XLA (X-Linked Agammaglobulinemia)
Inherited immune disorder caused by an inability to produce B cells or the immunoglobulins (antibodies) that the B cells make. (due to a defect in the gene encoding the tyrosine kinase BTK)
1 in 200,000
what is IFN-γ and whats it secreted by
is the main cytokine that activates macrophages
secreted by NK cells (innate immunity) and TH1 CD4+* and cytotoxic CD8+* cells (*adaptive immunity)
what happens when IFN-γ binds to IFN-γ Receptor
it causes increased phagocytosis and bacterial killing by activating JAK1 and JAK2 pathways
What mutations cause IFN-γ receptor deficiency
recessive mutations of IFN-γ R1 genes - no R1 polypeptides on the cell surface, so cannot respond to IFN-γ
what do Dominant mutations of IFN-γ R1 cause so they are unable to bind and activate JAK1 signalling
truncated cytoplasmic tails
what form of IFN-γ receptor deficiency is more severe
Dominant mutation as 25% of receptors are normal, so blood monocytes still respond to IFN-γ (only need one mutant allele for a dominant condition)
What reoccurs in patients with antibody deficiency until given antibiotics
pyogenic infections
what are pyogenic bacterial infections
e.g
Infections caused by bacteria that can lead to the formation of pus
e.g. pneumonia, impetigp
why do Encapsulated pyogenic bacteria need to be bound by specific antibody and complement first before being ingested and killed by phagocytes
as they are not recognized by phagocytic receptors of macrophages and neutrophils,
what was the 1st immunodeficiency identified
XLA
what gene, when mutant, causes the B-cells to be arrested at the pre-B-cell stage in XLA
Bruton’s tyrosine kinase (Btk)
why are boys with XLA initially protected by passive immunity during their first few months life
due to transfer of maternal IgG antibodies via placenta
what pyogenic bacteria do
Individuals with XLA have lots of infections
staphylococcus aureus
why are viral infections still easily dealt with in people with XLA
as cell-mediated immunity is normal
2 XLA treatments
Antibiotics
Intravenous Ig administration (passive immunity) against all common pathogens every 3-4 weeks to maintain adequate concentrations of circulating Ig to prevent tissue damage caused by recurrent infections (problematic in lungs)
what causes the rare genetic disorder X-linked hyper IgM syndrome (XHIM)
mutations in the CD40L gene,
why is XHIM more common in males
as mutations in the CD40L gene are located on the X chromosome and males only have one X chromosome.
what does CD40L mutation cause in XHIM, leading to an increased susceptibility to pyogenic infections
no memory cells
no B cell activation, so inability of B cells to produce immunoglobulin class switching, leading to a selective deficiency of IgG, IgA, and IgE,
what immunoglobulin antibody is abnormally high in XHIM
IgM
how can Ig deficiencies be detected
Measure the antibody level to see whether they are below the normal level - blood test
screen serum for natural antibodies
Attempt to induce active immunity but NOT using live vaccines - use diphtheria, tetanusus, pertussis
Enumerate B cells by immunophenotyping - CD19, CD20 , and CD22 are the 3 main B cell markers
