immunodeficiencies Flashcards
what is relative production of neutrophils to erythrocytes
neutrophils made 3x more than erythrocytes in blood marrow
which immune cells are made where
T cells are only immune cells not made in the bone marrow
the rest are made in the bone marrow
what are the different immune cell progenitors, what do they lead to
lymphoid progenitors lead to NK cells, T cells and B cells
myeloid progenitors lead to dendritic cells, macrophages, monocytes, neutrophils
adaptive family is cells from lymphoid progenitors - NK cells
innate family is the rest
describe rate of IgG,M and A production
IgG production does not occur till birth but at a slow rate, normal adult rate of IgG production does not occur till 12
IgM is produced from 7 months before birth by foetus
IgA is produced about 2 months before birth
while foetus is in womb maternal IgG is transferred passively, these last in the child till about 7 years old
between 3 months-4 years old there are relatively low levels of IgG
what are primary immunodeficiency disorders
they are rare inherited conditions
susceptible to infection, associated with autoimmunity, inflammation and increased risk of cancer
300 genes known associated with this
these disease are related to mainly either the adaptive system (T and B cells) or neutrophils
people with T cell defects do make antibodies but they are usually abnormal
what is Di George syndrome
a primary immunodeficiency, thymus does not develop so no T cells are made
what do different types of primary immunodeficiencies lead to
neutrophil disorders can lead to lots of abscesses (like boils)
T cell disorders can lead to lots of viral and fungal infections
fungal infections due to lack of Th17
neutrophils and B cells are important for bacterial clearance
macrophages and T cells are important for responding to mycobacteria
how is immune function measured
T cells:
full blood count can be used to measure cell numbers
T cell function : blood is taken and either PHA or antibodies are added and measure to see how much the cells have multiplied
B cells:
vaccine is given and antibody levels are measured before and afterwards
other tests used in diagnosis of immune deficiency are genetic tests and western blot tests for specific proteins of diseases
describe the neutrophil lifecycle
neutrophil produced in bone marrow, then released to blood
only leave vasculature if they have a signal to bind to vasculature and leave
the first signal in this process is mediated by selectins, a second signal is then needed by integrins such as ICAM
process of neutrophils squeezing out of vasculature is call diapedesis
chemoattractants such as inflammatory cytokines or through fragments of bacteria draw neutrophils to site of action through chemotaxis
neutrophils then phagocytose pathogen and cause respiratory burst
neutrophils can also degranulate and release things such as matrix metallic proteases which cause a local antibacterial effect
neutrophils then die by apoptosis and are cleared by macrophages
describe process of respiratory burst
also known as oxidative burst
reaction catalysed by NADPH oxidase
NADPH oxidase has 6 protein subunits
all are phox proteins except for Rac2
when neutrophil is activated p22phox and gp91phox are activated, NADPH is oxidised and the electron is transferred to the phagosome
once electron is transferred to phagosome it combines with oxygen to form superoxide radicals which then end up forming hyrogen peroxide
an enzyme called myeloperoxidase converts hydrogen peroxide to bleach (HOCl-hypochlorous acid)
what is chronic granulomatous disease
neutrophil dysfunction due to dysfunction of NADPH oxidase
flow cytometry plot can be used to determine which subunit is causing malfunction of NADPH oxidase
causes lots of abscesses
treated with bone marrow transplant
is a primary ID
what are secondary immunodeficiencies caused by
can be due to malnutrition; protein/calorie malnutrition and lack of dietary elements such as iron/zinc
can be due to loss of cellular/humoral components; such as lymphocytes passively lost into the intestine as in intestinal lymphangiectasia, proteins such as antibodies can be lost to urine in nephrotic syndrome
tumours can also cause them by effecting the immune system
cytotoxic drugs/radiation: damage immune cells during cancer treatment
also malaria and diabetes and HIV
how are biologics used to treat autoimmunity
used to treat autoimmune diseases, suppress one particular part of immune system
try to mimic primary immunodeficiencies
example: JAKinibs (inhibit JAKs)
JAKs are molecules in immune cells which signal downstream of many types of receptors such as cytokine receptors and interferon receptors
JAKs activate STAT proteins, which shuttle to nucleus and act to promote genes
side affects are more susceptible to infections
what is mechanism of HIV, how is it treated
binds to receptors on T cells such as CD4 or CCR5 and causes cell death
over time the host shows increased levels of virus and decreased levels of CD4 cells
antiviral therapy keeps level of virus lower but does not completely destroy it
how are immunodeficiencies treated
antibiotics, immunoglobulins, cell replacement (bone marrow and thymus transplants) and gene therapy
