When the immune system goes wrong

A system able to attack can also attack the wrong thing, or stop attacking altogether. Three categories of failure illuminate its normal working.

Allergies: a disproportionate reaction

   HARMLESS antigen (pollen, dust mite, peanut)
              |
              v
   EXCESSIVE immune response
              |
              v
   sneezing, hives, asthma -> up to anaphylactic shock

Strictly speaking the system does not mistake its target: it reacts to a real but harmless one, with an intensity out of all proportion to the danger. The damage comes from the response, not the allergen.

Allergies have risen sharply in industrialised countries over fifty years. The hygiene hypothesis offers an explanation: an immune system little challenged in childhood would calibrate its responses poorly. It is supported by several studies — children raised on farms are markedly less allergic — without being proven.

Autoimmunity: a sorting error

   the system attacks the SELF, mistaking it for non-self

type 1 diabetes     destruction of the insulin-producing pancreatic cells
multiple sclerosis  attack on the sheath of neurons
rheumatoid arthritis attack on the joints

These diseases show, negatively, the importance of self-tolerance: during maturation, lymphocytes recognising the body's own molecules are normally eliminated. Let that sorting fail, and the system turns on its host.

Immunodeficiencies

CONGENITAL   genetic defect, rare
ACQUIRED     HIV, chemotherapy, immunosuppressants, malnutrition

HIV is particularly instructive: it infects the helper T lymphocytes, the cells that coordinate the entire adaptive response. By destroying the conductor, it paralyses the orchestra.

   helper T cells destroyed
        |
        v
   neither B nor cytotoxic T cells properly activated
        |
        v
   opportunistic infections by normally harmless germs

AIDS therefore does not kill directly: it lets other infections do so.

Transplants and rejection

A transplant is non-self: the system treats it as an intruder.

   graft with a different MHC  ->  recognised as foreign  ->  REJECTION

Hence two requirements: finding a donor with a compatible MHC, and giving immunosuppressants for life. These create a permanent dilemma — too few, and the graft is rejected; too many, and the patient becomes vulnerable to infection.

Antibiotics and antivirals: do not confuse them

ANTIBIOTIC   acts on BACTERIA (wall, ribosomes, bacterial DNA)
             -> NO effect on viruses

ANTIVIRAL    blocks a step of the viral cycle
             -> far harder to design: the virus uses the machinery
                of our own cells

Taking an antibiotic for flu or a cold is therefore useless — and harmful: it destroys the flora and selects resistant bacteria. Antibiotic resistance is now one of the leading health threats identified by the WHO, with projections of several million annual deaths by 2050.

Summary

• Allergy: excessive response to a harmless antigen; the damage comes from the response.
• Autoimmunity: the system attacks the self, through lost tolerance.
• Immunodeficiency: HIV destroys the helper T cells that coordinate the response.
• Transplant: a different MHC causes rejection; hence immunosuppressants.
• Antibiotics have no effect on viruses.
• Their needless use selects resistant bacteria.