The haematopoietic tree, B lymphocytes and antibodies Flashcards
Innate immunity
Inbuilt/hardwired from birth
Triggered by molecules unique to invading pathogens (PAMPs)
Pathogen-associated molecular patterns (PAMPs)
N-formylated peptides
Lipopolisaccharide
Mannose
N-formylated peptides
Released from bacteria
Recognised by specific N-formyl peptide receptors on neutrophils.
Allows neutrophils to chase and capture bacteria.
Lipopolisaccharide
Component of gram negative bacterial cell walls, recognised by specific toll-like receptors on immune cells, stimulates immune cell recruitment and activation.
Mannose
Component of bacterial cell walls that is recognised by mannose binding lectin triggering the activation of the complement pathway.
Adaptive immunity
Most well known
Involves specific identification and destruction of pathogens precisely desgined and targeted by B and T lymphocytes and antibodies
Lymphatic system
Lymph nodes - in groin, armpits, neck and other sites. Critical sites from which lymphocytes are mohilised.
Invaders are brought back to nodes by antigen presenting cells via lymphatic drainage.
Bacteria
Usually present outside cells thus detectable by antibodies
Viruses
Usually present knside cells thus not detectable by antibodies
Tumour cells
Multiple strategies to evade detection/destruction by immune system
Macrophages and neutrophils
Efficient killers with no intelligence
Engulf bacterial invaders decorated with antibodies with the help of complement pathway.
Other cells types (eosinophils and mast cells) are designed to evict larger invaders like parasites.
NK cells
Destroy cells that do not present class I MHC on their cell surface ie tumour cells.
Antibodies (humoral immunity)
B cells contribute to adaptive immunity by becoming plasma cells which generate antibodies
Antibodies bind to extracellular pathogens to ljmit spread of infection
Self-reactive antibodies - deleted as they emerge from bone marrow, cause of autoimmunity
Non-reactive antibodies - die quickly, no helpful for fighting pathogens
Pathogen reacting antibodies - expand and proliferate
4 major postulates of clonal selection hypothesis
- Each B lymphocyte can only make one type of Ig
- Each B cell will take the Ig it makes and present them on their cell membrane with the specificity bearing side facing outwards so it is accessible to pathogens
- Only those B cells that bind to the antigen can develop into antibody secreting plasma cells which go on to proliferate and synthesize lots of antibody molecules which are then secreted into blood
- The specificity of the antibody is exactly the same as that which was on the surface of the B cells.
Ig structure
Two light and two heavy chains covalently linked by disulphide bonds.
Variable domains in the heavy chain and light chain comhine to form the antigen binding site
Heavy chain consistent region has 3 domains and a hinge region. The light chain also has a consistent domain.
The varible domains on light and heavy chains inludde 3 hypervariable complementarity determining regions (CDRs)
CDRs are the main regions responsible for antigen recognition and antibodies variability.
Antibody isotopes
IgM
IgG
IgE
IgA
IgM
5/6 Ig units covalently linked by disulphide bonds
Found in serum and secretory immunoglobulins
10/12 antigen binding sites
High avidity for antigens
Very efficient in activatjng complement
IgG
Found in serum and breast milk
Can cross placenta, protects developing foetus in utero
Dominant serum Ig following sevond exposure to pathogen
4 subclasses based on relative abundance in serum
IgE
Least abundant Ig in serum but can trigger most powerful immune reactions
Important in allergic responses and fighting parasitic infections
Activates mast cells, mainly eosinophils.
IgA
Most abundant Ig in secretions (tears,saliva) and gut mucosal lining
Di and tri meric forms resistant to digestion and degradation.
Works by binding to and smothering pathogen.
How does antibody binding fight invaders?
Neutralisation by agglutination (smothering)
Opsonization and phagocytosis
Activation of complement pathway
Antibody directed cellular cytotoxicity.
Fighting large parasite
IgEemployed to activate two cell types via activation of FCe receptors on mast cells and eosinophils
Mast cells release preformed granules. These mediators function to expel the invader by triggering sneezing,itching,muscular contraction.
Eosinophils arrive later, are recruited to the site of infection by chemokines (secreted by mast cells). They release cytotoxic granules onto foreign particles.
Non specific so can cause collateral damage to host cells (injury response)
