Immunodeficiency Flashcards
what is the difference between primary and secondary autoimmune disease
primary - inherent defect usually genetic
secondary - immune system affect due to external causes or disease
describe the hierarchy of the immune system
immune syetem - innate and adaptive
innate - barrier and chemical, pathogen recognition, cellular (phagocytes and NK), complement
adaptive - hunoral (antibodies and B cells0 and cellular (B and T cells)
what are 5 causes of immunodeficiency
breakdown of physical barriers - CF (lack of lung secretion) protein loss malignancy drugs infection (HIV/TB)
give 5 examples of drugs that have a secondary association with autoimmune disease
steroids - suppress immune system DMARDS - anti rheumatic Rituximab - against B cells anti-convulsants myelosuppressive
what is the role of neutrophils and macrophages in the innate immunity
neutrophils are short lived
macrophages are long lasting (start as monocytes then mature in bone marrow to macrophages)
east bacteria and fungi
what type of acid is found din a lysosome to form phagolysosome complex
hypochlorous acid
what quality about neutrophils and macrophages allow them to recognise pathogens associated molecular patterns (PAMPS)
the innate cells have pathogen recognition receptors unique to pathogens to differentiate from human cells
give an example of a PAMP
liposaccharide
give an example of a type of PRR and examples within that subset of recognition
TLR - toll like receptors are PRR
TLR3 - recognise viral RNA
TLR4 - liposacchrides
TLR5 - recognises flagellum
what is the role of MyD88 and IRAK4
released on phagocytosis after PRR activation on innate cells which release more inflammatory mediators
why is it strange to have normal levels of WBC’s during bacterial infection
should have increases in WBC to attack infection
which shows deficiency in B cell recruitment or activation which may infer an innate system issue
what is the clinical presentation of IRAK4 deficiency and how do you treat it
can recognise the bug but cannot cause an inflammatory response - recurrent infection strep/staph
prophylactic antibiotics or IV immunoglobin if severe
how do you differentiate between MyD88 deficiency and IRAK4
genetic testing
how do you create hypochlorous acid in the lysosome
O2 - superoxide via reduction (electron donation to O2)
what is a granuloma
collection of macrophages
what is the common problem associated with cells which causes chronic granulomatous disease
macrophages will eat pathogen but can’t destroy and NADPH complex can donate electron to produce lysosome acid
what genetically in chronic granulomatous disease
X linked - affects men mainly
what is the treatment of chronic granulomatous disease
haemopoitic stem cell transplant and prophylactic antibiotics
how do you test to see if a phagocyte is dysfunction in producing effective hypochlorous acid
relays on reduction
eg test neutrophils - nitro blue tetrazolium reduction - healthy neutrophils go clear but purple mean they are dysfunctional
which part of the immune system is complement within
innate
what are the three types fo complement pathways
classical
alternative / MBL
describe in terms of C proteins the classical compliant pathway
antibody dependant (adaptive help) antibody attaches to microbe C1 binds to this and cleaves C4 into C4a/b + C2 into C2a/b
then C4b and C2a bind to C4a2b (c3 convertase)
this cleaves C3 into C3a/b
C3a causes inflammation
C3b contends with c3 convertase = C4b2a3b (C5 convertase)
this cleaves c5 in c5a/b
c5b recruits c6/7/8 which then binds with C9 in microbe membrane
what is the role of C3a C4a and C5a in complement
dilation of arterioles, release of histamine from mast cells and chemotaxis of phagocytes
what is the role of C3b in complement
opsonisation of microbes to help phagocytosis
what is the role of c5b C6 C7 C8 C9
form MAC complex which causes cytolysis of cell via perforation
how do you test complement function
patients serum should Clyde sheep erythrocytes via classical pathway
what would a deficiency in C2 or C4 cause
autoimmunity SLE or myositis
what would a deficiency in MAC complex cause
repeated bacterial meningitis (N. meningitis)
what Th cell tends to cause more atopic diseases
TH2
makes a lot of IgE
what three ways to antibodies neutralise toxins
neutralise them
clump together
opsonise
activate complement
what would a defect in Brutons tyrosine kinase cause
no b cell maturation in the bone marrow so no antibodies are made
name 4 types of B cell defects
CVID
IgA deficiency
X linked hyper IgM syndrome
transient hypogammaglobulaemia of the infant
how do these drugs affect the immune system riturximab methotrexate ciclosporin/azathiprine prednisolone
antibody against cd20 for B cell cancers
hits fast growing cells like neutrophils and macrophages
work of B/T cells
works on large part of immune
what type of cell does HIV kill
CD4 cells
what is SCID and what causes it
no T cells
defect in critical T cell receptors
loss of communication - MHC2 deficiency in B cells
metabolic - adenosine deaminase deficiency
what do problems in these types of cells cause phagocyte complement antibodies T cells
PRR - IRAK4 - recurrent pneumonia
recurrent bacterial meningitis
recurrent sinopulmonary infection
SCID, and HIV causes some complications with T cells
