L95: Adaptive Immunity II Flashcards
What are the two major cells of lymphoid organs?
- T-cells;
- B-cells.
Where do B-cells mature?
Bone marrow
Where are B-cells found?
- Circulation (blood and lymph);
- Lymphoid organs.
On what surface are antigens recognised by B-cells?
B-cell receptors (BCR)
What, effectively, is a BCR?
Antibody
What are plasma cells?
Activated B-cells
What do plasma cells produce?
Antibodies
What molecules recognise antigens?
- T-cell receptors (TCR);
- B-cell receptors (Immunoglobins [Ig]);
- Major histocompatibility complexes (MHC proteins).
What enables variation of antigen reception?
Multiple genes encoding for antigen receptors (TCR, Ig, MHC)
What is the general structure of an antibody (immunoglobin- Ig)?
- Y-shaped;
- Heavy chain and light chain duplex;
- Fab (antigen-binding) region: variable;
- Fc (constant) region: constant.
What are the different classes of antibodies?
5 classes:
- IgA;
- IgD;
- IgE;
- IgG (1-4);
- IgM.
What are IgAs and what do they target?
- Immunoglobulin A;
- Found in secretions such as tears, saliva, mucus;
- Attack pathogens before they gain entry to internal tissues.
What are IgDs and what do they target?
- Immunoglobulin D;
- Found on the surface of B-cells (BCR);
- Can bind to antigens in ECM.
What are IgEs and what do they target?
- Immunoglobulin E;
- Attack individual molecules found on the surface of basophils and macrophages (e.g. pollen);
- Allergen response;
- Stimulate histamine release.
What are IgGs and what do they target?
- Immunoglobulin G;
- 80% of immunoglobulins;
- Attack pathogens (bacteria, viruses etc.).
What are IgMs and what do they target?
- Immunoglobulin M;
- BCR;
- Macroglobulin (large in size);
- Function early on in the immune response;
- IgM to IgG response.
What is the IgM to IgG response?
- IgMs released after first encounter with antigen;
- IgM production declines as IgG production accelerates.
What are the three effector functions of antibodies?
- Neutralisation;
- Opsonisation;
- Complement activation.
(all to prevent bacterial or viral adhesion)
What is opsonisation?
Antibodies sticking to the surface of pathogens to promote phagocytosis by phagocytes or destruction
Where are the B-cells produced?
Bone marrow
Where are the B-cells specialised?
Bone marrow
What happens at each development stage of B-cells?
Rearrangement of immunoglobulin heavy and light chains
Where do B-cells migrate to?
Lymphoid organs
What is a BCR?
Antibody
What do heavy chains comprise of?
- V, variable;
- D, diversity;
- J, joining genes.
What do light chains comprise of?
- V, variable;
- J, joining genes.
What are the main types of immature B-cells?
IgM
What are the main types of mature B-cells?
IgG (still naive)
What is negative selection?
Selection of B-cells to ensure there is no self-antigen reaction. If reaction, not selected, apoptosis.
How are B-cells activated?
- Thymus-dependent (TD), T-cell help OR;
- Thymus-independent (TI).
Where does B-cell activation mainly happen?
Lymphoid organs
What is the type of B-cell activation dependent on?
Antigen
What does B-cell activation lead to?
A rise in the number of plasma cells (antibody factories)
What are the stages of TD B-cell activation?
- Interaction between T-cell and BCR with CD40 and CD40L co-receptor binding;
- Cytokines released from Th cells induce proliferation;
- Generation of plasma cells, which produce antibodies;
- Production of memory cells;
- Plasma cells initially produce IgM, before class switching to IgG.
By what process does class-switching happen?
Gene rearrangement
What is affinity maturation?
The increased binding strength of an antibody to an antigen after repeated exposure
What is avidity?
The ability of antibodies to form complexes (antibody-antibody binding)
How does the affinity of an antibody to an antigen effect the immune response?
Greater affinity = greater response
Which B-cell response (TI or TD) leads to an immunological memory?
TD
What are the stages of TI B-cell activation?
- Direct binding of antigen (LPS) to BCR;
- B-cells differentiate into plasma cells and produce IgM.
Which B-cell response (TI or TD) is stronger?
TD
Explain the basis of vaccination.
- Based on an immunological response developed in the primary response to exposure to an antigen;
- Primary response is slow, IgM acts early but these cells undergo class-switching to IgG;
- Primary response leads to the generation of memory T and B-cells;
- Upon second exposure there is a pool of cells waiting to respond immediately;
- Cells are also primed (IgG rather than IgM) so the response is stronger.
How does a secondary response differ to a primary and what influences this?
- Stronger and quicker response;
- Stronger because cells are primed (IgG rather than IgM);
- Quicker as a pool of cells are ready to respond immediately.
What other molecules are required for cross talk?
Co-receptors CD40 and CD40L
What is immunologic tolerance?
A state of immune unresponsiveness to certain antigens (self/ commensals etc.)
What type of response is immunologic tolerance?
Active and specific
What type of immune cells (adaptive) are tolerised?
Both, B and T-cells but it is more important to tolerise T-cells
Why is it more important to tolerise T-cells?
Most B-cells can’t make antibodies without T-cells so immune response would most likely be stopped before self-reaction
What are the two types of tolerance?
Central and peripheral
Where does central T-cell tolerance happen?
Thymus (positive and negative selection)
Where does peripheral T-cell tolerance happen?
Out with the thymus and bone marrow, i.e. tissues and lymphoid organs (T-cell activation)
Explain peripheral T-cell tolerance?
- 3 signal process;
- Both signals 1 and 2 must happen before signal 3;
- If signal 1 but no 2, anergy;
- If signal 1 and 2 but no 3, apoptosis;
- Tregs also block self-binding.
Where does central B-cell tolerance happen?
Bone marrow (negative selection ONLY)
Where does peripheral B-cell tolerance happen?
Secondary lymphoid organs
Why is a B-cell self-reaction less likely to happen than a T-cell self-reaction?
Self-reactive B-cells still require help from self-reactive T-cells (independently tolerated)
When does central tolerance happen?
During the development of B and T-cells
How are autoimmune diseases initiated?
Branch of tolerance
Give three examples of autoimmune diseases.
- Psoriasis;
- Rheumatoid arthritis;
- Graves’ disease (thyroid);
- Hashimoto’s thyroiditis;
- Lupus;
- Sjogren’s syndrome;
- Chron’s disease;
- Multiple sclerosis;
- Type-1 diabetes.
