【Western medicine diagnotics question】CHP3 Clinical immunology

CHP3 Clinical immunology

1. How lymphocytes (especially B) can maintain receptors on their surfaces? Is this genetically related? If so, when the lymphocytes are first exposed to the antigens, how could the antigen receptor be synthesized? 

Is there a mutation within the nuclei of these lymphocytes when they learn to make the receptors? If there is, can you explain how this occurs?

B cells differentiate from lymphoid cells in the bone marrow in a way that allows them to express an antigen receptor on the surface permanently. The expression of the receptor is a definition of B cells and is a result of the differentiation pathway. The antigen receptor varies from one immature B cell to another. There are billions of different receptors, but any B cell will express only one type of receptor. The antigen does not ‘design’ the receptor; rather, a clonal B cell that recognizes the antigen (very few B cells will recognize a given antigen) will proliferate in response to the antigen and signals from T cells. 

As the B cells proliferate and differentiate further, the DNA region that codes for the antigen receptor undergoes mutation, and cells with mutations that recognize the antigen better are selected for further development, while those that do not recognize the antigen die.

2. What is the mechanism of nuclear factor-κB (NFκB) causes cancer?

NFκB is a transcription factor that alters cell behaviour. It inhibits apoptosis and increases cell proliferation by increasing the production of tumour necrosis factor (TNF-α).

3. What are the diseases associated with hypocomplementaemia and which complement deficiency in particular?

The following are the major patterns of deficiency:

• C3, C1q and factors H and I: susceptibility to capsulated bacteria, also systemic lupus erythematosus (SLE)-like syndrome
• C5-9: susceptibility to disseminated neisserial infections
• C1 esterase deficiency: hereditary angio-oedema.

4. What is meant by ‘B lymphocytes are sensitive to clonal deletion’?

Clonal deletion occurs during the development of immune tolerance. Clonal deletion occurs when lymphocytes of a particular specificity are lost when in contact with ‘self’ or an extrinsic antigen. Thus, clonal deletion can help protect individuals against autoimmunity.

5. What are the immunological implications of ‘bare lymphocyte syndrome’/MHC deficiency?

In the bare lymphocyte syndrome, a rare recessive condition, major histocompatibility complexes are not expressed. The clinical manifestation is of severe combined immune deficiency (SCID). Patients present in infancy with viral, bacterial, fungal and protozoal infections that are difficult to control because of poor immunity.

6. Please explain oligoclonal and monoclonal.

‘Oligoclonal’ antibodies are produced by more than one clone (family) of cells, but not by as many as are involved in the production of polyclonal antibodies. 

‘Monoclonal’ indicates that the antibodies are produced by a single clone of cells.

7. How do you define autoimmune disease?

Autoimmune disease happens when the body's natural defense system can't tell the difference between own cells and foreign cells, causing the body to mistakenly attack normal cells.

In autoimmune disorders, the body generates immune responses against its own tissues, producing autoreactive T cells and autoantibodies. In normal development, T and B lymphocytes that recognize ‘self’ antigens are deleted in the thymus and bone marrow (central tolerance). Those that escape are suppressed by regulatory T cells in the circulation.

8. Why is dexamethasone not routinely used instead of prednisolone, which is almost universally used routinely in autoimmune diseases, or other indications for steroids? Is it because dexamethasone lacks the mineralocorticoid activity seen with prednisolone and therefore does not cause salt/water retention and hypertension?

Dexamethasone has very high glucocorticoid activity and therefore needs careful monitoring to avoid side-effects. Most trials on the use of corticosteroids have been performed with prednisolone, hence its common use.

9. Can high doses of dexamethasone be used in acute relapses of multiple sclerosis (MS) in place of pulse methylprednisolone? If so, what is the recommended dosage?

All trials in MS are with methylprednisolone (1 g daily for 3 days), so it is better to use this agent.

10. What is meant by ‘pus cell’ and is this term synonymous with neutrophils?

Yes; the pus cell is a neutrophil.

Neutrophils, also known as polymorphonuclear leukocytes (PMNs), have long been considered as the short-lived, nonspecific white cells that form pus-and also happen to kill invading microbes.

11. Can dendritic cells migrate into lymph nodes? Immunology textbooks state that these initial blood monocytes infiltrate inflamed tissue. Is the professional antigen-presenting cell the dendritic cell that enters lymph nodes?

Dendritic cells can change their expression of chemokine receptors and migrate from the mucosa to the lymph nodes. Dendritic cells are of several types and are similar to monocytes (myeloid dendritic cells), plasma cells (plasmacytoid) and follicular cells, which are probably not of haemopoeitic origin.

12. How often should treatment with azathioprine be monitored with liver enzymes and a full blood count?

Many advocate monthly monitoring, but on long-term azathioprine 3-monthly will often suffice.

13. What is the most specific liver enzyme or function test for monitoring azathioprine therapy?

Serum transferases: measurement of thiopurine methyltransferase (TPMT) levels before starting therapy can predict patients who will have a toxic reaction to azathioprine.

14. Do you agree or disagree that the dose of azathioprine should be adjusted according to the dose that lowers lymphocytes to 0.8 × 109/L?

We normally use a dose of 2 mg/kg and stick to it unless there are problems.