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Flashcards in B cells Deck (22):
1

Role of Antibodies?

Activate B cells

Neutralisation

Activate complement

Opsonisation

ABCC

2

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

3

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

4

B cell developmental stages?

Common lymphoid progenitor
--> B cell linage
--> VDJ rearrangement
--> Negative selection

Occurs in BM

5

Role of Rag-1 and Rag-2?

Drive heavy and light chain rearrangement

6

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

7

Role of negative selection?

Screens for autoimmunity in immature B cells

Highly cross linking self-Ag = deletion
Receptor editing = stops autoreactivity

8

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

9

What is somatic hypermutation?

Mutation of immunoglobulin genes during B cell proliferation
--> cells with increased affinity for Ag

Occurs in germinal centres

10

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

11

Role of memory B cells?

Long lived B cells
Surface Ig expressing, usually Isotype switched

--> faster response to secondary challenge
--> minimal T cell help

12

Role of Plasma cells?

Migrate to BM where they secrete Ab for long time

13

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

14

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

15

Diagnosis of CVID?

IgG low
IgA or IgM low
Normal B and T cell counts

Hypogammaglobulin on EPG

16

Treatment of CVID?

IVIG
Empiric antibiotics

Avoid live vaccines

17

Genetic causes of CVID?

PIK3CD
LRBA
CTLA4

18

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

19

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

20

IgG subclass deficiency?

Controversial
Associated with IgA deficiency

Recurrent sinopulmonary infections

May require IVIG

21

Specific antibody deficiencies?

Recurrent URTIs

Normal Ig levels and B cell levels

Don't respond to vaccinations

22

Which IL is responsible for B and T cell development from stem cells?

IL-3