Immune System Flashcards
Compon4ents of the innate immune system
Physical epithelial and chemical barriers that keep infection out
Phagocytic cells such as macrophages which ingest microorganisms and kill them
Leukocytes such as mast cells, basophils, eosinophils, which provide important immunity against helmirth infection
Complement, which provides essential immunity against extracellular pathogens
Innate lymphoid cells such as NK cells
Components of adaptive
B lymphocytes which develop in bone marrow
T lymphocytes which develop in thymus
Kinetics of the immune response
The innate immune response is much faster when responding to infection
Innate immune response kicks into effect on day 0 - there are billions of innate cells that are capable of responding to infection, whereas adaptive immune response is much slower as there is only a handful of B cells and T cells at day 0 which show specificity for the pathogen- adaptive only really kicks in on day 7 of infection as it takes time for the right population of T cells and B cells which show specificity for the pathogen to undergo clonal expansion
Differences in receptors between innate and adaptive
Innate immune cells possess receptors called pattern recognition receptors
These receptors recognize PAMPS, which are structures shared by microbes but not present in eukaryotic cells
Each innate immune cell possesses many PRRs, and therefore can recognize many different PAMPS - thus each innate immune cell can recognize many pathogens
There is limited diversity within the PRR population - only about 100 PRRs
PRRS are encoded in the germline, and therefore their specificity is acquired in the genome
PRRs are broadly specific - they are able to distinguish bacterial species from viral species, but they are not very good at distinguishing different bacterial species from one another - TLR-4 recognizes LPS of gram negative but can’t tell whether the LPS comes from E.coli or salmonella
In contrast, each lymphocyte possess one unique receptor, and this receptor shows specificity for only a single pathogen - thus each lymphocyte can only recognize one specific pathogen
Are encoded in the germline, but specificity is inherited by somatic VDJ recombination of gene segments in lymphocyte receptor genes, with each recombination event giving rise to a new unique receptor that is able to recognize a different pathogen. This recombination helps to explain the large diversity in lymphocyte receptors - there are millions of lymphocyte receptors
Lymphocyte receptors are exquisetly specific - are able to discriiminate between closely related structures that only have few amino acid differences- eg your lymphocytes may protect you from this year’s influenza strain but not the next year’s
Adaptive immune system gives rise to B and T memory cells, which facilitate an immune response earlier in onset and greater in magnitude to secondary infection - however magnitude and onset of innate immune response remains same between primary and secondary infection - there is no memory generated
Physical barriers- infection
Skin - not great to live on as it is dry and has high concentrations of NACI - is also difficult to penetrate due to tough keratin layer- lysozymes in tears and secretions which can lyse bacteria, pH of vaginal tract and stomach which inhibit bacterial growth
Chemical barriers
Epithelial cells form physical barriers, but they also have an immune function
Epithelial cells have PRRS
When these PRRSare activated in response to pathogen, epithelial cell
- secretes chemokines and cytokines at basal surface which recruit immune cells to underlying tissue
- secrete antimicrobial substances such as defensins at the apical surface into the lumen
IL-22
ILC-3 and TH17 are located in lamina propria
These cells release IL-22, which stimulates epithelial cell proliferation and therefore allows for barrier integrity to be maintained, and defensin production
Mucociliary transport
Epithelial cells line airways
Among these epithelial cells are goblet cells, which secrete mucus that cover these epithelial cells
Pathogens can get stuck in this mucus
Epithelial cells have hairlike projections protruding from their apical surface called cilia
Cilia can beat in an asymmetric rhythm and move mucus containing stuck pathogens up the respiratory tract and out of it via the mouth/nose
Therefore mucociliary transport system prevents pathogens from invading deeper and getting into sterile organs
When are individuals susceptible to recurrent respiratory infections
Cystic fibrosis
Immotile cilia syndrome
When they are heavy smokers
Cystic fibrosis
caused by mutation in CFTR gene, which results in non-functional CFTR channels/absent CFTR channels at surface of cells, prevents transport of chloride ions, thus mucus becomes dehydrated and very thick and viscous - instead of trapping pathogens it has become the perfect place for bacteria to grow on
Complement
Are series of serum proteins produced by the liver
Are produced constituively
These serum proteins collectively form the complement biochemical pathway
Are proteases, can cleave and activate each other
Activation of complement
Alternate, Classical, Leptin
Alternate
Ancient non specific chemical reaction - no recognition event
C3 spontanoeusly hydrolyzes to form c3a and c3b
they interact with other proteins to form a c3 convertase
c3 convertase cleaves other c3 into c3a and c3b, which deposit on surface of microbe and interact with other proteins to formc5 convertase
c5 convertase cleaves c5 into c5a and c5b
Lectin
Mannose binding lectin receptor in serum recognizes and binds to lectin, a unique microbial carbohydrate
This activates MBL and the proteases associated with it - these proteases cleave c4 and c2
Cleaved c4 and c2 come together to form c3 convertase
c3 convertase cleaves cleaves c3 into c3 and c3b
C3a and c3b comes together with other proteins to form c5 convertase, which cleaves c5 into c5a and c5n
Classical
c1q receptor recognises antibody bound to antigen - it recognizes the conformational change that occurs in igG and igM antibodies as they bind to antigens
c1q binds to antibody antigen complexes
- these proteases cleave c4 and c2
Cleaved c4 and c2 come together to form c3 convertase
c3 convertase cleaves cleaves c3 into c3a and c3b
C3a and c3b comes together with other proteins to form c5 convertase, which cleaves c5 into c5a and c5n
