Immunology Flashcards
is there immunological memory in the innate response?
no
only in acquired response
which types of immune response can distinguish self from non cell?
acquired
when does innate and acquired response occur?
innate = 0-96 hrs acquired = >96hrs
which response is germline encoded?
innate
can therefore act quicker
what do regulatory T cells do?
secrete cytokines that dampen down response
which type of response is autoimmune disease most associated with?
acquired
slide 4
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what do Th1 cells do?
activate macrophages via IFN gamma
TFH cell function?
helps activate B cells
occurs in germinal centre
B cells vs T cells?
B cells see and bind to any type of antigen
T cells have to see peptide only antigens - presented by MHC I or II
what does CD8 do once activated by helper T cells?
differentiate into cytotoxic cells
migrate from lymph nodes into infected site and directly kill infected cells (ones that express antigenic peptides)
what are plasma cells?
effector B cells that secrete antibodies which bind to opsonised pathogens to induce phagocytosis
also activate complement
which antibody important in type 2 and 3 hypersensitivity?
IgG
what is autoimmunity?
presence of adaptive immune responses against self tissue
what gives different polypeptides that group to form different antigen receptors?
random rearrangement of antigen receptor genes
means everyone has some self reactive immune cells/antigen receptors
how are self reactive immune cells filtered?
tested in lymph nodes
killing mechanism for self reactive T and B cells but some can escape so secondary mechanism needed
what si the second mechanism?
regulatory T cells
destroy most of the remaining self reactive cells and those that are left aren’t really effective
what causes development of autoimmune disease?
defective filtering of self reactive immune cells - breakdown of tolerance system?
what is the tolerance system?
general term means failure to amount an immune response
central tolerance = process of eliminating developing B or T cells that are reactive to self
describe the pathogenesis of autoimmunity?
genetic susceptibility > initiating event > breakdown of self tolerance and loss of immune regulation > activation of auto-reactive T and B cells > hypersensitivity reactions > autoimmune phenomena or disease
what gene mutation can cause problems/deficiency with regulatory T cells?
FOXP3
leads to deficiency of reg T cells
HLA (MHC) genes on chromosome 6
causes problems with binding of MHC and antigenic peptide
which MHC is presented by all cells?
MHC I
additional MHC II on antigen presenting cells
sex hormone genes (females higher rates of autoimmunity)
how many MHC types presented on antigen presenting cells?
12?
6 from each parent?
how can polymorphism of HLA genes affect immunity?
lots of variants
so some variants like to present certain peptides (like self peptides) more than other variants so can be more likely to develop autoimmune disease
what environmental factors can initiate autoimmunity?
molecular mimicry
incurrent infections
tissue damage (release of previously hidden self antigens which aren’t shown at time of cell production/filtering)
superantigens
slide 11 table
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what drives most autoimmunity diseases?
hypersensitivity reactions
classic picture of myasthenia gravis?
droopy eyelid
muscle weakness
fatigue
reversible symptoms
what is myasthenia gravis?
autoimmune neuromuscular disorder
auto-reactive antibodies (IgG) bind with acetylcholine receptors on muscle cells
function of ACH recptor?
expressed at neuromuscular junction
postsynaptic
involved in contraction
who gets myasthenia gravis and what causes it?
any age
most unknown cause but thymic tumour and HLA associations sometimes
how does myasthenia gravis present clinically?
insidious onset
first symptoms usually eye
fatigue and muscle weakness
can first appear in/after pregnancy or with anaesthtic administration
what cells are involved in myasthenia gravis?
CD4 Th cells
AChR protein antigens activate auto reactive B cells
what is early onset MG associated with?
increased adaptive immune response in thymus
key MHC class II presenting cells?
dendritic
macrophages
how does MG develop?
- CD4 T cells activated by unfolded AChR subunits expressed by thymic epithelial cells
- effector Th cells stimulate auto-reactive B cells to produce anti-AChR antibodies
- Thymic Myoid cells are attacked by these antibodies and release AChR-immune complexes
- these complexes activate other antigen presenting cells, perpetuating the response
what can AChR antibodies do?
prevent binding of ACH at neuromuscular junction by binding to the ACh receptor
causes defect in nerve impulse at NMJ leading to impaired contraction
eventually the receptors are destroyed altogether
Bind complement leading to destruction of muscle end plate (type HS)
how can AChR activate complement and what is the result of this?
antibody binding to the AChR activates the complement cascade, resulting in formation of the membrane attack complex (MAC) and localised destruction of the post synaptic membrane
this leads to a simplified post synaptic membrane which lacks the normal deep folds and has a flat surface
how is MG treated via increasing neurotransmission?
anti-cholinesterase agens - stops breakdown of ACh
how is MG treated through reducing autoimmunity?
immunosuppressive drugs
plasmapheresis
IV immunoglobulin
Eculizumab
what is Eculizumab?
monoclonal antibody
binds to C5b so it cant be cleaved and membrane attack complex cant be formed
inhibits complement
how can surgery be used for MG?
thymectomy
- if MG associated with thymus cancer
what type of gene encodes for HLA proteins and what is the significance of this?
highly polymorphic gene
allows for different HLA variants, some of which bind to different peptide antigens
