B AND T CELL MEDIATED IMMUNITY Flashcards
describe B cell development in the bone marrow from stem cells
stem cells… pro-b cells, pre-b cells… B cells
if B cells come into contact with antigens, what happens?
they can activate, proliferate and differentiate into memory cells and plasma cells
what do plasma cells do?
produce soluble antibodies and become long-term residents of the bone marrow
what are immunoglobulins
antibodies
what are the functions of antibodies?
recognise specific molecules, directly kill microbes, directly neutralise toxins, target phagocytes to microbes by opsonisation, regulate immune response, clear foreign antigens, involved in immunopathology and terminate the immune response
what are the 5 classes of antibody?
IgA, IgD, IgE, IgG, IgM
what makes these classes of antibodies different?
they all have different valencies (number of antibody binding sites) and different functions
what are the subclasses of IgG?
IgG1 IgG2 IgG3 IgG4
what is the valency of IgG?
2
what are the subclasses of IgA?
IgA1 and IgA2
describe the structure of an IgG?
made up of 4 polypeptide chains; 2 heavy chains and 2 light smaller chains. in each chain we have different domains. the terminal region is the antigen-binding site which recognises the epitopes.there is a hinge so the antibody is flexible.
what is an epitope?
a small number of amino acids on the antigen that is recognised by the antibody
why can different antibodies recognise different antigens?
the amino acids at the antigen binding site can change
what is affinity?
the strength of the binding action between 1 portion of an antibody and 1 antigen
what is avidity?
the overall strength of binding between the whole antibody and all antigens antigen
what is the variable region of the antibody? what is the constant region?
variable= terminal domain of the light and heavy chains constant= rest of antibody
what is the function of the constant region of an antibody?
to determine how a specific antibody will contribute to an immune response
why is it important that antibodies have a hinge?
so it can move/rotate/change shape
what is Fab?
Fragment Antigen Binding. the region on antibodies that binds to antigens
What is Fc?
Fragment Crystallizable region. the region of antibody that interacts with the cell surface receptors
what is somatic recombination?
it is how a progenitor lymphoid cell gains a specific antibody on its surface.
what happens in somatic recombination?
the gene is pulled together, a loop of DNA is excised and the strand of DNA is glued back together
why do antibodies have a fixed specificity for life?
as recombination only occurs once in the life of B cells
what is clonal selection?
a B cell expresses receptors specific to the distinct antigen, determined before the antibody ever encounters the antigen. Binding of Antigen to a cell activates the cell, causing a proliferation of clone daughter cells.
why don’t we normally see antibody responses until 2-4 days after an immune response?
due to the time taken for clonal selection and cell proliferation to occur
what is somatic hypermutation?
as cells begin to respond to antigens and proliferate, adjustment of affinity of the antibody can occur.
how do somatic hypermutations occur?
random mutations are introduced (driven by AID). the body selects the mutants that have a higher affinity and these can then proliferate
where do somatic hypermutations occur?
in the germinal centres of lymphoid tissue where B cells are proliferating vigorously.
What is isotype switching?
After immunization or infection, activated B cells can switch antibody isotope that they are expressing to change the effector function of the antibody, and improves its ability to eliminate the pathogen that induced the response
what stimulates isotype switching?
cytokines
what is the valence of IgM? How does this help them with their function?
- they are the largest antibody so can pick up large amounts of infection to mark for recognition by phagocytes. it protects surfaces in the systemic circulation
describe the structure of IgA?
it has a valency of 4 but has an accessory protein (secretory piece)
what is the function of IgA? how does it structure help?
it protects mucosal surfaces as its accessory protein allows it to cross epithelial barriers and enter mucosal sites
What is the function of IgE?
to protect barrier surfaces and tissue surfaces
describe the types of immunoglobulins we have from foetus to adult life
IgG is he only antibody that is transferred across the placenta. after birth we begin to develop more IgG and then IgM and then IgA.
what do follicular dendritic cells do?
They present antigens to potential memory cells, of which only B cells with high affinity B cell receptors can bind.
describe T cell dependant activation of B cells?
Antibodies recognise and process antigens and display them on their surfaces as MHC class II. T helper cells start producing and expressing IL-4 and CD40 receptors. Meanwhile, elsewhere, helper T cells recognise antigens and are activated and so T cell receptors. B and T cells come into close proximity, so T helper cells bind to the MHC complex as they recognise the antigen. Now T cells bind to antibodies using their CD40 ligand. T cells release IL-4 and these bind to Il-4 receptors on B cells and this is their signal to proliferate.
describe T cell formation from stem cells?
In the thymus T cell progenitors give rise to thermocytes which ll have different T cell receptors. A positive and negative selection will occur and 98% of T cells will die with the rest entering circulation
Describe the T cell receptor structure
2 polypeptide chains (alpha and beta- both similar molecular weight), a valency of 1. a transmembrane region
What do B cells use antibodies to recognise?
conformational epitopes- they look at the tertiary structure and recognise shape
what do T cells recognise?
linear epitopes. these are small sequences in linear arrangement
how do linear epitopes form?
antigen processing- phagosomes kill microorganisms and liberate fractions of molecules that can be bound and recognised by a T cell receptor
what are major histocompatibility complexes?
peptide shuttling proteins that transport peptides to surfaces of cells so they can be recognised by T cells
what is the structure of a class 1 MHC?
a single heavy chain, made up of 3 domains, bound to an accessory protein called beta 2 micro globulin
what is the structure of class 2 MHC?
2 polypeptide chains each with 2 domains
what are the differences between class 1 and 2 MHC molecules other than structure?
class 1 are expressed on all nucleated cells, present peptides to CD8+ T cells and surveil for virus infections class 2 are expressed on special antigen presenting cells, present peptides to CD4+ T cells and surveil for exogenous pathogens
