Immunology core 4- B cells and antibodies

Adaptive immunity

The body's 3rd line of defence involving B and T cells and antibodies - highly specific and takes days to weeks to activate

Innate immunity

2nd line of defence present from birth involving complement neutrophils and macrophages - activates within hours or days

Physical and chemical barriers

The 1st line of defence including skin and mucous membranes

Why gene rearrangement is needed

Without it only around 300 antibodies could be made - with VDJ recombination and somatic hypermutation billions can be produced

BCR structure

Y-shaped protein with two heavy chains two identical light chains and two identical antigen binding sites - membrane anchored on B cells

Antibody vs BCR

An antibody is a soluble BCR lacking the hydrophobic transmembrane sequence - secreted rather than membrane bound

TCR structure

Membrane protein made of two chains alpha and beta with one antigen binding site and a transmembrane region

Two-signal activation rule

Both B and T cells require two signals to activate ensuring antigen specificity and preventing autoimmunity

Tolerance

The process of clearing self-reactive lymphocytes to prevent autoimmunity

T cell positive selection

In the thymic cortex T cells reactive to MHC survive and those not reactive to MHC undergo apoptosis

T cell negative selection

In the thymic medulla T cells reactive to self-antigens are apoptosed and those that do not react to self carry on maturation

Dendritic cell role in T cell activation

Dendritic cells phagocytose pathogens process them into peptide fragments load them onto MHC molecules and present them to T cells in the lymph nodes

Antigen processing

Unfolding and cleaving the pathogen's macromolecular structures into shorter peptide fragments inside the APC

Antigen presentation

Displaying processed peptide fragments bound to MHC molecules on the cell surface for T cell recognition

Cytotoxic T cells CD8

Recognise viral peptide bound to MHC class I and kill infected cells directly

T helper cells CD4

Recognise bacterial peptide bound to MHC class II and activate macrophages while regulating antibody production by B cells

T regulatory cells

Suppress activation of naive T cells and produce regulatory cytokines to prevent overactivation chronic inflammation and autoimmunity

Memory T cells

Long-lived cells that mediate immunological memory - more sensitive to their specific antigen and respond rapidly upon reinfection

MHC class I pathway

Presents intracellular antigens such as viral proteins made in the cytoplasm to cytotoxic CD8 T cells

MHC class II pathway

Presents extracellular or vesicular antigens such as phagocytosed bacteria to helper CD4 T cells

B cell maturation site

The bone marrow where B cells undergo gene rearrangement and selection before leaving as naive B cells

B cell activation by T helper cells

T helper cell binds CD40 on B cell via CD40L and releases cytokines such as IL-2 which drive B cell proliferation and differentiation

Clonal selection

Only B cells whose BCR binds the specific antigen are activated and proliferate producing clones with identical BCRs

Plasma cells

Differentiated effector B cells specialised in secreting large quantities of soluble antibodies - they no longer express BCRs on their surface

Memory B cells

Long-lived B cells that retain antigen information and upon reinfection rapidly differentiate into plasma cells producing faster and stronger antibody responses

B regulatory cells

Immunosuppressive B cells that inhibit proliferation of T cells and inflammatory cells to support anti-inflammation

Follicular B cells

Circulate between secondary lymphoid organs searching for their specific antigen and upon finding it differentiate into plasma cells with T cell co-stimulation

IgM

First antibody secreted after B cell activation - pentameric and excellent at activating the classical complement pathway

IgG

Monomeric antibody that neutralises viruses opsonises pathogens and crosses the placenta providing passive immunity to the foetus

IgA

Dimeric antibody found in mucosal secretions such as saliva and breast milk - traps pathogens at mucosal surfaces and does not activate classical complement

IgE

Monomeric antibody that binds mast cells and triggers histamine release - involved in allergic responses and defence against parasites

IgD

Monomeric antibody found at very low serum concentrations - mainly functions as the BCR on naive B cells alongside IgM

Fab region

Fragment antigen binding - the two identical arms of an antibody where antigen binds containing the variable regions

Fc region

Fragment crystallisable constant region that interacts with immune cells such as macrophages and is constant within an antibody class

Neutralisation

Antibodies bind pathogenic antigens or toxins blocking them from entering or harming host cells

Opsonisation

Antibodies coat a pathogen flagging it for phagocytosis by macrophages and other phagocytes

Complement activation by antibodies

Antigen-antibody complexes activate the classical complement pathway leading to phagocytosis lysis or inflammation

VDJ recombination

Gene rearrangement of V D and J segments in the heavy chain and V and J in the light chain during B cell maturation - creates a unique antigen binding site before antigen is encountered

Somatic hypermutation

Introduces point mutations to the variable regions in the germinal centre after antigen stimulation - selects for B cells with the highest antigen affinity

Isotype switching

Replaces the constant region DNA of IgM with another class such as IgG IgA or IgE without changing the variable region - mediated by AID in germinal centres giving the same antigen specificity with different effector function

Autoimmunity

When self-reactive lymphocytes attack the body's own tissues - e.g. in type 1 diabetes where T cells attack pancreatic beta cells

Allergy and hypersensitivity

An inappropriate immune response to a harmless antigen such as IgE-mediated mast cell degranulation in hay fever releasing histamine

Germinal centre

A structure within lymph nodes where B cells undergo somatic hypermutation isotype switching and fate decisions to become plasma cells or memory cells

Affinity maturation

The process by which somatic hypermutation followed by selection produces B cells with progressively higher affinity antibodies over the course of an infection