Medical Microbiology

Semester III
 Honoured as the "father of innate immunity

Metchnikoff discovered phagocytosis by macrophages and microphages as a critical host-

defense mechanism and thus is considered the father of cellular innate immunity. Ehrlich
described the side-chain theory of antibody formation and the mechanisms of how antibodies
neutralize toxins and induce bacterial lysis with the help of complement and thus is considered
one of the fathers of humoral adaptive immunity.
• Metchnikoff became interested in the study of microbes, and especially the immune
system. At Messina he discovered phagocytosis after experimenting on the larvae of
starfish.

• He first demonstrated the process when he inserted small citrus thorns into starfish
larvae, then found unusual cells surrounding the thorns. He realized that in animals
which have blood, the white blood cells gather at the site of inflammation, and he
hypothesised that this could be the process by which bacteria were attacked and killed
by the white blood cells.

• His theory, that certain white blood cells could engulf and destroy harmful bodies such
as bacteria

• He observed that leukocytes isolated from the blood of various animals were
attracted towards certain bacteria
• Metchnikoff discovered fungal infections causing insect death and became involved in the
biological control of insect pests through his student Isaak Krasilschik. They were able to make
use of green muscardine for control of insects in agricultural fields

• Green muscardine disease is the presentation of a fungal infection of insects caused by

members of the Metarhizium or Nomuraea species
• Metchnikoff also self-experimented with cholera that initially supported the probiotic
notion.

• To understand the differences in susceptibility to the disease, he drank a sample of cholera

but never got sick. He tested on two volunteers of which one was not affected while the
other almost died.

• He hypothesised that the difference in cholera infection was due to differences in intestinal
microbes, speculating that those who have plenty of beneficial ones would be healthier.
• Metchnikoff developed a theory that aging is caused by toxic bacteria in the gut and that
lactic acid could prolong life

• He also espoused the potential life-lengthening properties of lactic acid bacteria such as
Lactobacillus delbrueckii subsp. bulgaricus. This concept of probiotics, which he termed
"orthobiosis," was influential in his lifetime, but became ignored until the mid-1990s
when experimental evidence emerged
• Opsonization is an immune
process which uses opsonins to
tag foreign pathogens for
elimination by phagocytes.
Without an opsonin, such as an
antibody, the negatively-charged
cell walls of the pathogen and
phagocyte repel each other
 Metnikoff & Covid-19

• There is little evidence at present that tissue Macrophages express the ACE2
receptor required for direct infection.

• Tyrosine-phosphorylated receptors such as AXL play a role in recognition of

phosphatidyl serine expression by infected cells, as well as promoting the entry of
COVID19 as co-receptors to ACE2.

• It has been described age-related metabolic interactions between macrophages

and innate lymphoid cells which promote inflammasome activation. A contributory
role for the microbiome is suggested by the leakiness of the gut epithelium with
possible translocation of live bacteria or metabolic products with increasing
age,taking us back to Metchnikoff.

• Widespread tissue distribution of Macrophages and their migration through blood

and lymph, provide a Trojan horse mechanism, independent of ACE2 expression,
for monocytes and Macrophages to disseminate virus systemically to all major
organs of the body,