QUESTIONS:

Caso # 1

Ursula did not respond to candida and mumps antigens, which are common
recall antigens, with a delayed-type hypersensitivity reaction. Give a possible
explanation.

En inmunologa, anergia es un estado de los linfocitos en el cual stos, pese a
estar presentes, no son activos.

The CD8 T cells secrete the cytokines IL-10 and LT and thereby suppress antigen
presentation by macrophages. IL-10 and LT suppress not only the M. leprae-
specific T cells but also neighboring T cells, leading to global hyporesponsiveness.

Which cytokine might be beneficial to a patient with lepromatous leprosy?

Cytokines with the potential to inhibit TH2 and induce a TH1 response are IL-2,
IFN-, and IL-12.

Describe the mechanism for Ursulas hypergammaglobulinemia.

The cytokines produced in TH2 responses lead to enhanced immunoglobulin
production. IL-4 induces isotype switching to IgE and increased production of IgG4
and IgE. IL-10 stimulates the production of IgG1 and IgG3, whereas IL-5
stimulates immunoglobulin production globally.

Why would Ursula be prone to asthma?

When she encounters a new antigen, her immune system will be awash with IL-4,
triggering a TH2 response to that antigen. This TH2 response with its associated
IL-4 production leads to an IgE response. Because asthma and other atopic
diseases are TH2-driven diseases involving IgE production, Ursula has a higher
risk of developing asthma.

Caso # 2

How do you explain the alarming increase in the incidence of mycobacterial
infections in patients with AIDS?

Mycobacteria, particularly atypical mycobacteria, are ubiquitous in the
environment, and any infection is normally contained by T-cell action. AIDS,
however, is characterized by a marked reduction in the number of CD4 TH1 cells.
Hence the production of IFN- is compromised, and patients with AIDS have
difficulty in activating their macrophages and clearing mycobacteria.


Clarissa Dalloway and her cousins had positive tuberculin skin tests. Would
you have predicted this?

The delayed-type hypersensitivity reaction is provoked by a few T cells that are
specific for tuberculin. After binding antigen, these T cells secrete chemokines that
nonspecifically recruit macrophages and other inflammatory cells. The secretion
and action of these chemokines are not dependent on IFN-. It is therefore not
surprising that Clarissa and her cousins developed positive tuberculin skin tests.

Clarissa and her cousins also did not develop granulomas as a result of
infection with atypical mycobacteria. On one occasion mycobacteria were
surprisingly cultured from Clarissas blood. What do these observations tell
us?

Granulomas form where there is local persistence of antigen, antigen-specific T
cells, and activated macrophages. These children could not activate their
macrophages, so it is not surprising that they did not form granulomas.
Granulomas can be beneficial in that they wall off and prevent the spread of
microorganisms. These children could not do that and we find the mycobacteria
spreading via the bloodstreama highly unusual finding in mycobacterial disease.
However, granuloma formation is preserved in patients with autosomal recessive
partial IFN-R1 deficiency and in patients with IL-12R1 deficiency.

Clarissa also had a problem with salmonella, but she had no problem with
pneumococcal infection or with any viruses, such as chickenpox. How do
you explain this?

Infection with pyogenic bacteria such as pneumococci is controlled and terminated
by antibody and complement. In fact Clarissa had a very high level of IgG (1750
mg dl1), probably as a result of increased IL-6 production induced by the chronic
mycobacterial infection. Most viral infections, such as chickenpox, are terminated
by cytotoxic CD8 cells. Activation of these cells is not dependent on IFN-.
However, there is evidence from mice that a lack of the IFN- receptor increases
susceptibility to certain viruses, including vaccinia virus and lymphocytic
choriomeningitis virus. Salmonellae take up residence as an intracellular infection
of macrophages and become inaccessible to antibody and complement; they can
be destroyed in this site only when macrophages are activated by IFN-.