B lymphocytes and antibodies Flashcards
Interleukins vs interferons
between leukocytes vs interferes with viral replication
Innate cytokines: IF- alpha, beta and gamma
Inhibit viral infections
When cells can sense that their ribosomes have been “taken over” by viruses, this triggers the release of alpha and beta cytokines
- interferon binds ot receptors on cells around the infected cell and induce in them a change of gene expression often referred to as transient virus resistant state where their ribosomes are now difficult to take over. Non-specific response because acting on ribosomes
- affects NKC’s in the blood that up regulate their ability to recognise changes to associate with virus infection and kill those infected cells before the infection has completed its cycle
Innate cytokines: IL-1, IL-6, TNF-alpha
pro inflammatory (est bacterial infections) Wound healing and tissue repair: fibroblast proliferation, bone resorption, prostaglandin and collagenase synthesis, neuroendocrine effects
Adaptive cytokines
IL-1
T cell activation
B cell activation
adaptive cytokines
IL-2
T cell proliferation
NK cell activation
adaptive cytokines
IL-4, IL-5, IL-6
B cell differentiation antibody class switching
Adaptive cytokines
IFNgamma
Antiviral
Macrophage activation
NK cell activation
MHC up regulation
Il-8
C-X-C motif (alpha chemokines)
Neutrophil migration
Map-1, MIP-1alpha
c-c motif (beta chemokines)
Allergic inflammation
Haematopoietic cytokines
G-CSF, M-CSF, GM-CSF
Lineage specific control
Haematopoietic cytokines
IL-3 (multi-CSF)
proliferation of many lineages in bone marrow
Haematopoietic cytokines
IL-5
Eosinophil growth and activation (allergy)
Haematopoietic cytokines IL-7
Erythroblast and megakaryocyte growth
B cell ontogeny in bone marrow
What is the purpose of Haematopoietic cytokines?
just like EPO signals for more RBC production when you’re at high altitude, HC’s stimulate increased WBC production for when you need them
antibody structure
two identical light (constant and variable region) and heavy chains (3 constant and 1 variable)
Hinge region, disulphide bonds the CH2 domain has the ability to bind to some of the complement components
and the bottom part (CH2 and CH3) often called the FC region
How do we label light vs heavy chain isotopes
light
- kappa
- lambda
Heavy
- mu
- gamma
- alpha
- delta
- epsilon
What is the antibody class defined by?
by heavy chain IgM IgG IgA IgD IgE
Ouchterlony electrophoresis
allows you to analyse different serums in the blood
put spots on blood on agar plate and proteins will separate according to charge , can see what type on immunoglobulin e.g. gamma the patient is missing
Rabbit anti-human antiserum added to central trough, get diffusion to form precipitation lines
Antibodies around birth
from around 3 moths conception to about 8months post birth babe protected by maternal IgG
From one month post birth to 1 year babe’s IgG levels rise to 80% that of an adults
IgM levels start to increase a 7 months conception
IgA starts around 2 months old and takes a lot longer to get to adult levels
Where are B lymphocytes active?
secondary lymphoid organs e.g. spleen tonsils
b cell colonel activation
antigens pas through secondary lymphoid organs and select out B cells with high affinity for those antigens This binding leads to the first signal to the B cell to say you've recognised something the B cell then internalises that antigen and re expresses peptides derived from it on class II MHC Helper T cells do the co-stimulator conversation and various cytokines The B cell then proliferates and differentiates into effectors which secrete antibodies specific to the antigen that induced the response (plasma cells) And also a population of memory cells that replace the original naive B cell
Why memory cells?
Have the same specificity and immunoglobulin as the original B cell but theres more of them they’re longer lived, they recirculate and ultimately repopulate all our secondary lymphoid organs
Less fussy about the helper signals they require so they can be activated more quickly and in a more sustained way
Antibody effects: blocking and neutralisation
Attachment and entry (viruses, parasites)
Main protective effect of secretory IgA
Toxins (tetanus, diphtheria)
Immobilising bacterial flagella
Other Antibody effects
Agglutination
- clumping to assist phagocytosis
Opsonisation = enhancement of phagocytosis
Antibody dependant cellular cytotoxicity
Complement activation
Antibody dependant cell mediated cytotoxicity
enhancing ability of K (killer) cells to bind to target, because the antibodies attach the two together
K cells aren’t phagocytic but release granules from their cytoplasm that kill the cell that the antibodies are bound to
Large granular leukocytes properties
- killer cells, by recognising virus infected cells
2. finding antibody targets and bound to bad cells and killing the cells attached
Complement activation
antibodies band to bacterial cell surface antigens which causes a shape change in the antibody, the CH2 domain then becomes accessible to a set of inactive complement blood proteins that assemble themselves around that CH2 domain, to make an enzyme that then acts on the central component of the complement cascade called C3, C3 is cleaved into two fragments C3a affects blood vessel permeability, the C3b fragment is very chemically reactive and covalently attaches to anything close by, supposedly bacteria.
C3b has two functions
1. it has a link to phagocytes through their CR1 receptor so it can enhance phagocytosis
2. relates fragments that attract neutrophils to the site e.g.C5a fragment
3. a place where the “late components” can aggregate and breach the bacterial cell surface membrane
