Foreign activators Flashcards
what are foreign activators
non-self molecules (which originate outside the body), recognised by the immune system
example of FAs
microbes, allergens, foreign tissue
foreign activators are not
small like other chemical
- molecules with a size less than several thousand daltons are poorly recognised
which type of FAs are recognised well
proteins and polysaccharides
how does the immune system recognise FAs
receptors
example of FA and receptor interactionn
APC initially comes into contact with FA- presenting it on its surface to a T ell, which produces cytokines
cytokines work by
switching on other immune cels
making other cells more effective
signals to other parts of the immune system to signal in certain ways
when the immune system fails
consequence of immune system not recognising FAs
what if the immune system over responds to self or non self antigens
e.g. autoimmune diseases or sepsis
when the immune system fails to respond
e.g. AIDs
two arms of Immune system
innate
adaptive
innate immunity
- epithelial barriers
- phagocytes, dendritic cells, complement, NK cells
adaptive immuntity
- B cells- antibodies
- T cells - effector T cells
I and A systems are
constantly talking to eachother
in both arms of the immune system FAs are recognised by
receptors
innate immune response occurs within
a few hours or days after exposure to FA
examples of innate receptors
soluble receptors
- secreted from cells found in the blood, plasma, lymph, mucosal section
cell surface receptors
- found on macrophages neutrophils, lymphocytes ad other somatic cells
innate receptors are
encoded in germline- limited diversity
- a finite list of antigens can be recognised
innate receptors typically only
recognise structures common to different molecules e.g. LPS in gram neg bacteria
Adaptive receptors are much
more powerful, focused and targeted
Cell surface receptors of adaptive system
- T and B cells
-
soluble receptors of adaptive
blood, plasma, lymph, mucosal secretions
adaptive receptors typically
recognise structures unique to different molecules
Innate receptors recognise
PAMPs- recognised to PRR
although the innate system can only react to a certain number of common FAs
this enables it to act quickly
examples of FAs which the innate can respond to
- cell wall components= peptidoglycan, lipopolysaccharide, phospholipomannans
- nucleic acids e.g. viruses
- flagellin
- conserved stress proteins
- -> NOT FOUND IN HUMANS
examples innate soluble receptors
- natural antibodies
- comlement
- pentraxins
- collectins
- ficolins
examples of innate cell receptors
TLR
Nod-Like receptors
Rig like receptors
C Type lectin like receptors
How is self recognition avoided
-innate system tends to recognised molecules which are never found in mammals e.g. lipopolysaccharide, phospholipomannans, peptidoglycan etc
Toll like receptors structure
extracellular domain (ligand recognition) and intracellular domain (signalling)
process of TLR activation
1) recognition of bacterial molecule by TLR (by horseshoe part)
2) dimerisation of the TLR
3) signalling and inflammatory response e.g. NF-kB
if too many TLRs become activated
sepsis- one balancing act
receptors are also involved in signalling betwen
cells of the immune system
cytokines
chemical signals that reg the immune system
sepsis
consequence of infection by microorganism, systemic overwhelming infection, causes coalition of blood- over production of signals)
- positive feedback loop
why was the Spanish flu so devastating and mainly affected 20/30 yr olds
due to their bodies having the strongest immune system- over reactive immune system and cytokines causing mortality
example of experimental drug which was intended to activate T cells
TGN1412- an antibody ro CD28 on T cells.
- when it reached human trials many people became unwell even at 500 the concentration
- had been tolerated well by the weaker immune system of animals
an adaptive receptors recognise..
antigens that are unique to an individuals pathogen
- takes time to develop and mature but can provide a vy powerful protective response
antibodies
soluble receptors of adaptive immune system
most common types of proteins recognised by adaptive immune system
proteins and polysaccharides
the adaptive immune system has …… than the innate
less of a requirement for a panel of diff receptors
types of adaptive soluble receptors
natural antibodies, compliment, pentraxins, collecting, folicins
where does the myriad of antibodies each specific for a diff epitope come from?
- b- cell possesses gene for one antibody type that recognises one epitope
diff antibodies recognise
diff epitopes
different antibodies are produced via
random recombination of germ cells
antibodies are the most important
soluble receptorefector
how is self-recognition avodided
-clonal deletion eliminates self-recognition by the adaptive response
where do B cells mature
bone marrow
how does clonal deletion ensure self-recognition is avoided
bone marrows mature in the bone marrow, where self antigens are present
- B cells which produce antibodies against these antigens (epitopes) are deleted
adaptive system receptors have potentially
infinite adaptability to recognise discrete features
