Initiation of Acquired Immune Responses - B cells Flashcards
What are the B cells the source of?
Soluble antibodies
How are T and B cells trained to not self destroy?
Usually they are destroyed or inactivated when they try to react with self-antigens
What is an antigen?
Any substance which can cause an adaptive immunity activating B and T cells
What is an antibody?
A protein that is produced in response to a particular antigen
What is between the heavy chain and the light chain of antibodies?
The variable antigen binding site
How many polypeptide chains do antibodies have?
4 - 2x light and 2x heavy
What do B cells use as receptors?
Membrane-bound antibodies to recognise and bind to antigens (IgM or IdD)
What are the 5 classes of antibodies?
IgM, IgG, IgA, IgE and IgD
Where do antigen specific T and B cells develop?
Primary lymphoid tissues - bone marrow (B cell), thymus (T cell) and spleen
What is the process of Transendothelial Migration?
Lymph flows into lymph nodes through afferent lymphatic vessels.
B and T cells enter lymph nodes through High Endothelial Venules (HEV).
B cells come through HEV straight into the lymphoid follicle
T cells come through HEV and stay in the T-cell area of the lymph node and interact with dendritic cells that come in through the afferent lymph
How do lymph and lymphocytes leave the lymph node?
Through the medullary sinus and then efferent lymphatic vessels. efferent lymph eventually get back into blood circulation via the subclavian vein
What happens when B cells are activated?
B cells clonal proliferate and differentiate in 2 types of effector cells - Plasma or Memory B cells
What are plasma cells (B)?
Produce and secrete soluble, antigen-specific antibodies
What are memory B cells?
Long lived cells that continue to circulate around the body
How do B cells encounter antigens?
Specialised cells within B cell zones can ‘trap’ opsonised antigen which express opsonin receptors
What happens once a B cell has encountered an antigen?
To become fully activated, B cells need to receive 2 signals to become fully activated and clonal proliferate - antigen and ‘helping’ cells
What do the proliferate cells from B cells form?
A secondary folic - the Germinal Centre (tends to be where cancers arise)
What happens when the B cells have proliferated sufficiently?
Stop proliferating and differentiate into antibody-secreting plasma cells, which recognise the same specific antigen as the original parent B cell
What are the first type of antibody secreted by plasma cells?
Low affinity (antigen-specific) IgM antibodies
What do T helper cells do?
Help production and secretion of ‘better’ antibodies from B cells that are reacting to protein antigens
How do T helper cells help produce better antibodies?
Switch from low to high affinity antibody production
Switch from producing IgM to IgG antibodies (or IgA or IgE) - IgG can act as an opsonin
B cells can differentiate into LONG-lived plasma cells
Stimulate production of antigen-specific memory B cells
What are the differences in antibody classes?
Different heavy chains (same basic structure and same antigen-specificity)
Why are long-lived plasma cells important?
Go from lymph node to bone marrow and remain secreting antibodies for years
How do antibodies help kill and eliminate pathogens?
Recognition function and effector function
What is recognition function?
Binding to antigen, mediated by variable region site
What is effector function?
Clearance mechanisms mediated interaction of the heavy chain constant region with effector molecules (complement and Fc receptors, Fc = fragmented crystal)
What does membrane bound IgM do?
Serves as the B cell antigen receptor
What is agglutination?
Clumping of particles caused by antibody molecules binding to antigens on the surface of two adjacent particles
What antibody classes mediated agglutination?
IgM and IgG
What does agglutination do?
Increases the efficacy of pathogen elimination by enhancing phagocytosis. Can also prevent viruses from binding to and infecting host cells
What activates the classical complement pathway?
The Fc region of IgM (only one required as it can bind many antigens at once) and IgG (several different ones must bind closely located antigens to recruit and activate C1) antibodies
What are the functions of IgG?
Agglutination, complement system activation, foetal immune protection, neutralisation, opsonisation and NK activation
What happens to IgG in the foetus?
Transported across the placenta into foetal blood circulation
How does IgG help on neutralisation?
Prevents viruses from infecting host cells and prevents microbial toxins from disrupting normal cell function though the binding of high affinity neutralising antibodies
Why are IgG good opsonins?
As phagocytes express a type of Fc receptor that binds specifically to the heavy chain of IgG
How are natural killer cells activated?
Innate immune reposone or adaptive immune response by IgG
What do membrane bound IgD do?
Serves as the B cell antigen receptor to activate B cell
Where is the monomeric form of IgA found?
In blood serum
What does the dimeric form of IgA do?
Neonatal defence and neutralisation at mucosal sites (present in secretory fluids)
Where are secreted IgA antibodies transported to?
Colostrum and breast milk in order to protect the GI tract of neonates
What does IgE do?
Trigger allergic response eg asthma and anaphylaxis
How many Fc sites must each C1 bind to for a stable interaction?
At least 2 - results in a conformational change in Fc exposing a binding site for complement proteins that ends in the production of a C3 cleaving enzyme