Adaptive Immunity 2 Flashcards
what do B cells communicate with?
T cells
what do B cells produce?
antibodies
what does clonal expansion lead to?
generation of two subsets
what are plasma cells?
great big antibody factories
why are memory B cells important?
to mount a quicker antibody response to any subsequent infections
where do B cells mature?
in the bone marrow
where are B cells found?
they circulate in the blood and lymph and are found in large numbers in lymphoid organs
how do B cells recognise antigens?
through B cell receptor (BCR) which is the actual antibody (IgM or IgD)
what does diversity in BCR mean?
potential to respond to numerous antigens
once B cells are activated what do they change into?
plasma cells (antibody factories)
what are the three main receptors of adaptive immunity?
T cell receptor, B cell receptor and MHC
what does multiple genes encoding allow?
the development of a repertoire of receptors with wide specificity
which immunoglobulins can be B cell receptors?
IgM or IgD
what are the five different immunoglobulins produced by B cells
IgG, IgE, IgD, IgM and IgA
what is the most prominent antibody in the human body?
IgG
how many subsets can IgG be divided into?
4
how many subsets can IgA be divided into?
2
what is IgM capable of doing?
binding multiple antigens
what are the regions of B cell receptors?
constant and variable
what are the chains that B cell antibodies have?
light and heavy chains
what are the three main functions for antibodies in the human body?
neutralisation, opsonisation and initiation of complement
what is the primary goal of antibodies?
to prevent microbial activity and aid removal of threat from host
what is opsonisation?
the coating of pathogens by antibodies or complement proteins
what can opsonisation of pathogens by antibodies lead to?
phagocytosis, antibody dependent cellular cytotoxicity, mast cell degranulation
what complement pathway do antibodies initiate?
classical
what is the steps of antibody depended cellular cytotoxicity?
antibodies bind antigens on the surface of target cells, NK cell CD16 Fc receptors recognise cell-bound antibodies, cross-linking of CD16 triggers degranulation into a lytic synapse, tumour cells die by apoptosis
which antibodies give the greatest response in the classical pathway?
IgG and IgM
what is each B cell development stage defined by?
rearrangements of the immunoglobulin heavy and light chain genes
where do B cells go once they are in the periphery?
they migrate to secondary lymphoid organs
what does B cell development generate?
diversity
what are the steps of B cell development from being a stem cell?
stem cell - lymphoid progenitor - pro-B cell - early pre-B cell - late pre-B cell - immture B cell - mature B cell - either plasma cell OR memory B cell
what must the B cell be to be in the periphery?
mature
what genes does the heavy chain involve?
V, D, J
what genes does the light chain involve?
V and J
what is the main immature B cell receptor?
IgM
what receptors do mature B cells express?
IgM and IgD
where are IgM and IgD found on mature B cells?
the surface
what type of selection do B cells go and whereabouts?
negative selection in the bone marrow
what happens to self-reacting B cells?
macrophages engulf and remove them
what does selection ensure?
that there is no reactivity against self antigens
what are the major functions of antibody?
prevention of microbial adhesion, activation of complement, neutralisation of toxin, opsonisation to promote phagocytosis
what does diversity of antibody specificity involve?
gene-rearrangements during development
what type of B cells are antigen naive?
mature B cells
what are the two types of B cell activation?
thymus-depended antigens and thymus-independent antigens
what are thymus-dependent antigens?
antigens which require T cell help
what are thymus-independent antigens?
antigens which don’t require T cell help
where does B cell activation occur?
lymph nodes
what does activation of naive B cells result in?
the rise of plasma cells
how many signals are required for thymus independent antigen activation?
1 (antigen directly attach to B cell receptors leading to downstream signalling) but a second may exist
how many signals are required for thymus dependent antigen activation?
2 (co-stimulatory molecules on T helper cells and cytokines)
what does T cell and BCR interactions require?
co-receptor binding (CD40 to CD40L)
what do cytokine signals released from T helper cells induce?
proliferation
what does antigen dependent B cell activation generate?
a pool of plasma cells which produce antibody and memory B cells
what do plasma cells initially produce?
IgM
what antibody is produced by plasma cells once class-switched from IgM?
IgG
with the antigen independent B cell activation is antibody response stronger or weaker than antigen depended B cell activation?
weaker
what does antigen independent B cell activation NOT lead to?
generation of memory B cells (no long term immunity)
what does the activation of B cells lead to?
class switching
why does class switching take place?
because IgM response is weak
how does class switching occur?
by gene rearrangement but antigen binding site remains the same
what does repeated exposure to antigen cause?
affinity maturation - the antibody has increasing affinity for antigen
what does affinity mean?
strength of binding of single antibody to antigen
what does avidity mean?
ability of antibodies to form complexes
what antibody is bivalent?
IgG
what antibody is decavalent?
IgM
with regards to IgM, what is its affinity and avidity?
low affinity and high avidity
what does avidity give and what does it take into account?
it gives a measure of the overall strength of an antibody-antigen complex and takes into account valency of an antibody-antigen interaction
what is valency?
the amount of antigen binding sites
what are the characteristics of IgG?
highest opsonisation and neutralisation activities, classified into four subclasses (IgG1, IgG2, IgG3, IgG4)
what are the characteristics of IgM?
produced first upon antigen invasion, increases transiently
what are the characteristics of IgA?
expressed in mucosal issues, forms dimers after secretion
what is the characteristics of IgD?
unknown function
what is the characteristics of IgE?
involved in allergy
where is IgA secreted?
oral cavity, oesophagus and small intestine
what does cross talk between B and T cells lead to?
generation of both arms of the adaptive immune response
what are both the arms of the adaptive immune response?
humoral and cellular immunity
what are germinal centres?
hubs for T cell and B cell cross talk and proliferation and differentiation, and somatic hypermutation
what is somatic hypermutation?
the response of an immune cell to external stimuli from an antigen
what does antigen exposure lead to?
immunological memory
what does the presence of memory T and B cells mean?
that upon second exposure the immune system can respond much faster
what antibody produces a more effective response immediately?
IgG
summarise the basic principle of vaccination
B and T cells, antigen exposure leads to immunological memory, memory B and T cells ensure a faster response on second exposure, primed cells produce a more effective IgG response immediately
what does the higher antigen affinity of IgG mean?
the secondary response is much more specific
what is immune tolerance?
the immune system can become dysfunctional and in a state of immune unresponsiveness to a particular antigen or set of antigens
what is immunological tolerance?
an active response to a particular antigen and it can happen in B and T cells
what are the two main types of tolerance?
central and peripheral
where does central tolerance occur?
in the primary lymphoid organs (thymus and bone marrow)
where does peripheral tolerance occur?
outwith the thymus and bone marrow
what are immunogens?
antigens that elicit immune responses
what do tolerogens induce?
an unresponsive state
what are the two types of central tolerance selection for T cells?
positive and negative
what does selection lead to?
the elimination of >90% of T cells
where does T cell selection occur?
in the thymus
what is the type of selection for B cells?
negative selection - B cells that bind strongly to self antigen are eliminated
where does B cell selection occur?
bone marrow
what does it mean if some tolerance mechanisms are dysfunctional?
autoimmunity/allergies
what is peripheral tolerance?
not all self-reactive T cells are eliminated however, peripheral tolerance prevents their activation
what does signal 1 but no signal 2 result in?
anergy
what does signal 1 and 2 but no signal 3 result in?
deletion by apoptosis
how can T regualtory cells directly block activity?
by binding antigen (both self and foreign antigen)
where does peripheral tolerance occur?
in the lymphoid organs
why do self reactive B cells become anergic in peripheral tolerance?
because most self-reactive T cells are eliminated and B cells do not receive T cell help
how do T cells help activate B cells?
antigen recognition induces expression of effector molecules by the T cell which activates the B cell
what does a breach of tolerance to self antigens or commensal organisms drive?
many autoimmune diseases
what does tolerance ensure?
the immune system does not attack slef antigens
why are central and peripheral tolerance checkpoints in place?
to prevent autoimmunity
