The document discusses various methods of immune regulation, including both immunosuppressive drugs and immunopotentiation techniques. It describes several classes of immunosuppressive drugs like corticosteroids, thiopurines, alkylating agents, cyclosporine, and tacrolimus that work by suppressing cytokines, inhibiting cell division, or blocking T-cell activation. The document also covers methods to potentiate the immune system through cytokines, adoptive immunotherapy, or vaccination. It outlines several immunological assays used in clinical practice like measuring immunoglobulins, radioimmunoassays, ELISAs, and analyzing complement levels and DNA through techniques like PCR.

1. Immune Regulation
Themba Hospital FCOG(SA) Part 1 Tutorials
By Dr N.E Manana

2. INTRODUCTION
• The immune system in general responds appropriately to the
presence of foreign antigens.
• However, there are certain diseases that arise from either a defective
or overresponsive immune system on the part of the host.
• Two major therapeutic approaches are possible: either
immunosuppression or immunopotentiation of the immune system

3. Immunosuppressive Drugs
• Table 3.1

4. Immunosuppressive Drugs
Corticosteroids
• Modulate inflammation by suppressing cytokine- and chemokine-
encoding genes, which inhibits the activation and recruitment of
inflammatory cells
• The side effects of steroids are numerous and often depend on both
the dose used and duration of treatment.
• These include an increased susceptibility to infection, osteoporosis,
and growth disturbances in children, as well as gastric ulcers,
hypertension, acne, and hirsutism

5. Immunosuppressive Drugs
• The development of the thiopurines in the 1950s ushered in a new
group of immunosuppressive agents, the most important of them
being azathioprine
• It is inactive until it is metabolized in the liver and takes three to four
weeks to be effective.
• The metabolites work by inhibiting DNA synthesis in dividing cells
(such as activated lymphocytes).
• Like many other drugs, it has side effects, mainly in bone marrow
toxicity, and long-term use eventually results in granulocytopenia and
thrombocytopenia

6. Immunosuppressive Drugs
• Another group is the alkylating agents, of which cyclophosphamide is one
of the best examples.
• This drug also requires activation by the liver. It inhibits cell division and
can suppress antibody production, and it decreases delayed-type
hypersensitivity
• Methotrexate, which inhibits cell division by disrupting folic acid
metabolism, has similar immunomodulatory effects
• Cyclosporin, a naturally occurring fungal metabolite, also inhibits T-cell
activation and cell-mediated immunity
• Tacolimus is a newer-generation drug with a similar mechanism of action.

7. OTHER IMMUNOSUPPRESSIVE METHODS
• There are a number of instances in which antibodies have been used
to suppress the immune response
• Among the earliest measures has been the use of anti-RHD antibodies
• More recently, monoclonal antibodies are being used to suppress the
immune system
• Antibodies that target the immune system can target cell surface
molecules on T or B cells or can target soluble mediators of
inflammation such as cytokines
• Other methods of immunosuppression are plasmapheresis or plasma
exchange

8. IMMUNOPOTENTIATION
• Chronic infections such as HIV and hepatitis C are characterized by an
inability of the host to control viral replication
• The ability to potentiate the host immune response to control chronic
infections is an important goal and is under active investigation.
• At least some types of cancer can be controlled by the host immune
system, so potentiation of the host immune system may prove useful
in treating these cancers
• There are three principal ways to potentiate the immune response in
humans: through cytokines, adoptive immunotherapy, or vaccination

9. IMMUNITY
• The two ways to achieve immunity are actively and passively
• Active immunity is achieved when exposure to a foreign stimulus triggers
an immunological response to the agent by the host
• Artificial active immunization is the administration of an immunogen as a
vaccine
• Vaccines may be live organisms, killed organisms, or modified toxins.
• Although no vaccine is ideal and each has its problems

10. CYTOKINE IMMUNOMODULATION
• There is increasing interest in targeting T cells or the cytokine
regulators to regulate the elimination of autoreactive T cells, tumor
cells, and the maintenance of a specific memory response to these
pathogens
• Such immune responses are normally regulated by cytokines, and the
activities of the cytokines have a high degree of redundancy.
• There are several distinct differences in the functions of IL-2 and IL-5.
IL-2 is involved in checkpoints or brakes on the immune system.

11. • Figure 3.4

12. Immunological Techniques
• Laboratory tests vary widely in clinical immunology.
• Some are essential for diagnosis while others are useful in subclassifying
disorders
• These tests do vary in their sensitivity and specificity.
• Some assays are quantitative in that they produce precise results
• Qualitative assays are less specific and will give answers such as normal–
abnormal, or positive–negative results

13. ANTIBODY PRODUCTION
• Antibodies for various tests can be produced in a number of different
ways
A. Polyclonal antibodies: Many mammals have been used to produce
antibodies
B. Monoclonal antibodies

14. IMMUNOLOGICAL ASSAYS
• The introduction of automated machines to measure
immunoglobulins and other proteins has proceeded rapidly in recent
decades.
• Precise measurement of serum immunoglobulins is an essential
cornerstone in this area and is important for repeated and serious
infections
• The main principle behind this test is related to the formation of
immune complexes between the antibody and a given antigen.
• These tests primarily use polyclonal antibodies for each antigen since
monoclonal antibodies do not form immune precipitates because
there are too few relevant epitopes

15. Radioimmunoassay and Enzyme Linked
Immunosorbent Assays (ELISAs)
• The use of these highly sensitive assays in human disease has virtually
exploded in the past two decades
• They can be used to detect the levels of a given antibody or hormone
in human serum, and they are extremely sensitive methods of
detecting low levels of autoantibodies.
• Once the serum or purified antibody or antigen to be tested is placed
in the well, a second radio labeled antihuman IgG antibody is placed
in the well
• After appropriate binding and further washes, the degree of activity
of the antibody to a given antigen can be determined

16. Complement Assays
• Perhaps the most useful assays for complement are the
immunochemical assays of C3 and C4.
• The alternative and classical modes of complement breakdown, a low
C3 and C4 but normal factor B suggest that activation of the classical
pathways has occurred
• Examples would be patients with systemic lupus erythematosus or
vasculitis
• In contrast, if C3, C4, and factor B are all low, the alternative pathway
is also activated via either feedback loops or simultaneous activation
• This would point to a gram negative bacteremia.

17. • FIGURE 2.5

18. DNA ANALYSIS
• Known unique segments of nucleic acid sequences can be used as
DNA probes to determine the presence of complementary sequences
of DNA in a sample from a given patient
• The probe, which is a single strand of a given DNA, is presented to the
target DNA, which is composed of thousands of nucleotides
• The complementary strands from target and probe DNA will anneal to
each other, a process known as DNA hybridization
• The high affinity of the probe for a complementary segment in the
target DNA is the most specific intermolecular interaction between
biological macromolecules

19. • FIGURE 2.6

20. POLYMERASE CHAIN REACTION (PCR) ASSAY
• FIGURE 2.7

21. Thank you