B cells Flashcards
(22 cards)
Role of Antibodies?
Activate B cells
Neutralisation
Activate complement
Opsonisation
ABCC
Types of Antibodies and roles?
IgG:
- Serum
- Late after infection
IgM:
- Low affinity but high avidity
- Arises early in infection
- Complement activation
IgA:
- Mucosal protection
IgE:
- Helminth
- Allergy
IgD:
- B cell surface
Theory of clonal selection?
Population of lymphocytes
Each recognizes 1 antigen
On exposure to antigen the cell able to recognize it divides rapidly
Results in a clone of lymphocytes able to deal with invading pathogen
B cell developmental stages?
Common lymphoid progenitor
- -> B cell linage
- -> VDJ rearrangement
- -> Negative selection
Occurs in BM
Role of Rag-1 and Rag-2?
Drive heavy and light chain rearrangement
Role of VDJ rearrangement?
Allows the random generation of antigen receptors for the specific immune system
–> unique specificity of each cell
Occurs in light and heavy chains in B cells
Role of negative selection?
Screens for autoimmunity in immature B cells
Highly cross linking self-Ag = deletion
Receptor editing = stops autoreactivity
Explain the process of B-cell Activation
B cells recirculate through LNs, spleen and MALT until encounter with specific Ag
Ag is presented to T-cell with MHC-II
T-cell –> B-cell:
- Activation and Proliferation
- Somatic hypermutation and isotype switching
- Differentiation into memory B cell or plasma cell
What is somatic hypermutation?
Mutation of immunoglobulin genes during B cell proliferation
–> cells with increased affinity for Ag
Occurs in germinal centres
What is isotype switching?
Activated B cells change surface Ig expression
Caused by changes in immunoglobulin genes at switch regions
Results in IgM –> IgG etc
Role of memory B cells?
Long lived B cells
Surface Ig expressing, usually Isotype switched
- -> faster response to secondary challenge
- -> minimal T cell help
Role of Plasma cells?
Migrate to BM where they secrete Ab for long time
Diseases resulting from lack of antibody response?
Recurrent sinopulmonary and gut infections
Polysaccharide-encapsulated pyogenic organisms:
- Strep pneumoniae
- H. Influenzae
- Strep. pyogenes
- B. Catarrhalis
Staph aureus
Giardia Lamblia
Camplyobacter jejuni
Clinical features of CVID
Recurrent sinopulmonary infections
Recurrent GIT infections
Sprue-like syndrome
Skin infections
Autoimmunity:
- Cytopenias- ITP, AIHA
- Thyroid
- Pernicious anaemia
Lymphoma - NHL
Stomach cancer
Splenomegaly and lymphadenopathy
Allergic disease
Amyloidosis
Diagnosis of CVID?
IgG low
IgA or IgM low
Normal B and T cell counts
Hypogammaglobulin on EPG
Treatment of CVID?
IVIG
Empiric antibiotics
Avoid live vaccines
Genetic causes of CVID?
PIK3CD
LRBA
CTLA4
What is X-Linked agammaglobulinaemia?
X linked genetic disease
Loss of Brutons TYR kinase
Nil B cells or Ig
Nil lymphoid tissue
Onset of infections at 6 months
Malabsorption and RA
Treat with IVIG
IgA deficiency?
Due to dysregulation of Ig isotype class switching
Most asymptomatic
Can get recurrent mucosal infections - sinopulmonary and giardiasis
Associated with
- Atopy
- IBD and coeliac disease
- Other autoimmune diseases
Can have anaphylaxis to IgA containing blood products
IgG subclass deficiency?
Controversial
Associated with IgA deficiency
Recurrent sinopulmonary infections
May require IVIG
Specific antibody deficiencies?
Recurrent URTIs
Normal Ig levels and B cell levels
Don’t respond to vaccinations
Which IL is responsible for B and T cell development from stem cells?
IL-3
