adaptive immunity - b cell Flashcards
b cells are part of the — immune system as they have —- response
they produce – which is crucial to fight pathogens ( mainly extracellular pathogens)
- adaptive
- antigen specific
- antibodies
-BCR are found in the cell —- receptor or b cells and they recognise antigen in —- form
-anitgen recognition cause b cell – where they — and differentiates into —
each plasma cell product trillions of —-
- the — are the secreted form of the BCR (which is a membrane bound immunoglobulin molecule )
- antibodies are secreted into — and – which triggers effector response
- cell surface antigen receptor
- biological form ( protein carbs lipids polysaccharides )
- b cell activation
- proliferates
- differentiates into plasma cells
- antibodies ( aka immunoglobin aka ig)
- antibodies
- circulation
- mucosal membranes
life cycle of b cells :
1- b cell development occurs in — and its – to antigen exposure:
* BCR rearrangement
* Selection process
* Now known as Naïve B cells
2- b cell activation occurs in — and its — antigen exposure :
* B cell is ACTIVATED
* Differentiation into
plasma cells
3- b cell function occurs in— and its – to recognition antigen
- bone marrow aka primary lymphoid antigen
- prior
- lymph nodes . spleen aka 2ndart lymphoid tissues
- initial
- peripheral tissues where needed
- response to
( check slide 9 )
- A membrane bound IgM is also called the —
- It is composed of— chains and —- chains
and —- chains - They are assembled to form a — structure
- The heavy and light chains are attached via—- bonds
- The — region is the variable ‘antigen-binding site’
- The — region is the constant region
- BCR
- 4 polypeptides
- 2 heavy chains (H) and 2 light chains ( L)
- Y
- disulfied bonds
- v region
- c regions
- At any one time we have millions of B cells in our body, each having a
BCR with a different—- for antigen - How? During B cell development—- of BCR genes (VDJ
recombination) occurs and variable BCRs with unique specificities are
generated! - —–– randomly combine V(D)J genes to form VDJ or VJ
segments →—- different combinations!!!!!
- specifity
- gener rearrangement
- CDJ recombination
- 10 power 11
b cell activation occurs in 2 ways:
1- — > which use antibody class isotope-switched high affinity antibodies , memory b cells , long lived plasma cells
2- —> mainly IgM ,low affinity antibodies , short lived plasma cells
- T cell dependent ( as follicular b cells )
- T cell independent ( as b-1 cells , marginal zone b cell )
b cell activation requires — signals
1- singnal : — binding to BCR
*B cell antigen receptor will recognise—- (protein, carbohydrate, lipid, polysaccharide)
*Triggers—- of antigen
*B cells excellent—- and—-
*If T-independent, the recognition of an antigen is — to activate the B cells to produce— levels of IgM antibodies (no second signal)
*If T-dependent (i.e. protein antigen), peptides are presented on MHC class —
*Up-regulation of CD40 a co-stimulatory receptor
*Up-regulation of cytokine receptors
2d signal:
use — help
* ACTIVATED —- will recognise antigen presented by B cells
* The T cell upregulates costimulatory molecules —- which binds to —on —
* The production of— drive B cell proliferation and differentiation
- 2 signals
- antiges
- antigens
- phagocytosis
- phagocytes and APC
- enough
- low
- class ii
- T cell help
- helper T cells
- CD40L
- CD40
- b cells
- cytokines
- —- are secreted proteins which recognise — on the surface of pathogens using their antigen binding site within the variable regions
*—- can be any biological molecule –protein, carbohydrate, lipid, polysaccharide - The—- region activates different effectors (complement proteins or innate immune cells) that eliminates these microbes and toxins
- The ‘type’ of— region defines the isotype of an antibody
- antibodies
- epitopes
- epitopes
- constant
- constant
( info : The “epitope” is the specific part of the antigen that is
recognised by T and B cell receptors)
b cell function occurs in — where needed and the functions include :
- peripheral tissue
1- neutralisation of microbes n toxins by igG igA
2- opsonisation and phagocytosis of microbes IgG
3- antibodies dependent cellular cytotoxicity IgG (igE)
4- phagocytosis of mcuorbes opsonisation w complement fragment ( c3b) , activation of complement (IgG , igM)
5- inflammation
6- lysis of microbes
antibodies structural features:
1. —–: recognises antigen and binds incredibly tightly – Incredibly specific – can distinguish between very similar epitopes
2. ——:where — protein binds to start the classical complement cascade
3.binding site for —- Macrophages, mast cells,basophils, NK cells, neutrophils and eosinophils all have Fc receptors that will recognise the
Fc portion of an antibody and
bind helps antibody function
- anitgen binding site
- complement biding site
- C1q
- immune cells
( check slide 23 structure sssosooso important )
b cell activation results in :
- antibodies secretion
- isotope switching where only when T cell dependent
- affinity maturation when only T cell dependent
- memory b cell only when T cell dependent
—- anything the immune system recognises as non self
antigen
- — is the first antibody secreted upon infection
- But B cells can isotype switch into making ——- isoforms as required
- During isotype switching the antigen binding site remains —- but the constant region of the heavy chain is —-
- The process of isotype switching is induced by —– interaction and—- released by T helper cells
- Each isotype has a slightly different function as discussed later
- IgM
- igG igA igE igD
- same
- replaced
-CD40-CD40L - cytokines
—- complement activation
—- oponiszation , phagocytpsis , complement activation , neonatal immunity ( placental transfer )
—– immunity against helminths , mast cells degranulation ( immediate hypersensivity )
—- mucosal immunity ) transpot IgA through epithelia )
IgM
IgG ( most skilled ) IGG1 IGG3
IgE , IgG4
- IgA
- —- is the process by which the
affinity of antibodies produced in response to an antigen increases with— or—- exposure - With repeated exposures to the same antigen, a host will produce antibodies of successively—- affinities
- A secondary response can produce antibodies with several fold — affinity than in a primary response
- one way this occurs is by —- in the variable antigen binding region of the antibody
- affinity maturation
- prolonged
- repeated
- great
- great
- random mutation
pathogens neutralisation :
* Antibody neutralization of microbe and toxins
* Binds microbes/toxins and makes them —to enter cells
* Neutralization function of antibody
requires only the —- regions of antibodies, not the — region
* Very efficient at preventing —
- too bulky
- antigen binding region
- not Fc region
- viral infection
- Antibodies can “coat” microbes and make it easier for— to recognise them
- The opsonised microbe will bind to —- on the phagocytes
- This leads to efficient phagocytosis and killing of the internalised microbe
- phagocyte
- antibody specific receptors
( Neutrophils, Macrophages and dendritic cells all have Fc receptors for IgG and phagocytose IgG coated pathogens)
complement activation:
Antigen binding site and complement recognition sites needed
* Antibody binds to pathogen surface (typically IgG/IgM)
* Complement binding site exposed
* Get activation of the complement cascade (classical pathway), generating products that can:
- Attract leukocytes → —-
- Opsonise microbes →—-
- Cause assembly of the MAC → —
- inflammation
- promotes phagocytosis
- lyse bacteria
antibody dependent cellular cytotoxity:
* —- cells and other —bind to antibody-coated cells and destroy these cells
* NK cells express FcγRIII receptor which binds to IgG attached to the surface of a cell
* NK cells discharges — to kill opsonised cell
* Some therapeutic antibodies use this mechanism to kill —-
- nk cells and other leukocyte
- granules
- cancer cells
- Most— are too large to be
phagocytosed
*— antibodies are generated against the worms - IgEs bind to (“prime”) the surface of either —- or —- (via Fcε receptors)
- When the worm antigens bind to their
specific IgE antibodies, this perturbs the
membrane of the mast cells/eosinophils - These cells —- , releasing their
contents, which can kill the worms - Mast cells , histamine and proinflammatory mediators; eosinophils – lytic granules and
proinflammatory mediators
- helminth
- IgE
- mast cells or estinophils
- degranulates
antibody classes:
they have – types of heavy chains
* most abundant Ig in the body; only antibody class that can cross
placenta; involved in all antibody functions aka —-
* Secreted at mucosal surfaces; blocks pathogen entry; involved in
neutralisation; IgA immunity acquired via colostrum and milk aka —-
* On naïve B cells; first Ig to be secreted; involved in complement activation aka —
* Part of antigen receptor on naïve B cell surface; unclear role (binds mast
cells and basophils and drive the production of anti-microbial peptides) aka —
* Attaches to mast cells and eosinophils; implicated in worm expulsion and
classic allergic responses aka —-
- 5 ( gamma alpha mu delta epsilon )
IgG
IgA
IgM
IgD
IgE
( check slide 36)
read:
B cell/Antibody Deficiencies
Common Variable Immune Deficiency (CVID)
* Characterised by low antibody levels, specificially IgG, IgM and
IgA
* Symptoms vary but recurrent infections of the lungs and
gastrointestinal tract are more common
Selective IgA Deficiency
* Most common immunodeficiency
* Failure of B cells to differentiate into IgA producing plasma cells
* At least 1/3 patients are asymptomatic (as IgM can compensate)
X-linked agammaglobulinemia (XLA)
* Caused by a mutation in a protein involved in B cell
development → Absent B cells
* Recurrent bacterial infections
