LECTURE #2 INNATE IMMUNITY

After studying lecture #2, you should be familiar with the following concepts.
1. Self Versus Non-Self. During our lifetimes we face countless assaults from any
number of microbial, viral, parasitic and fungal invaders. Thus, an effective immune
system requires a detection system that can reliably discriminate between pathogenic
non-self cells without inducing immune responses against healthy self cells. As we
will see, there are two very distinct forms of this immune surveillance system.
2. Innate Immunity. The innate immune response is the first line of defense against
invading microbes and is the sole recognizable immune system in the overwhelming
majority of multicellular organisms. The entire repertoire of the innate immune system is
encoded within the germline and innate immune responses do not change upon repeat
exposure to an infectious or toxic agent. In innate immunity, microbial detection
proceeds through the recognition of generic microbial molecules (Pathogen Associated
Molecular Patterns (PAMPs)) by host Pattern Recognition Receptors (PRR).
3. Inflammation. Inflammation is an immediate consequence of PAMP detection by a
PRR. Inflammation involves reorganization of the vasculature at the site of infection to
permit the influx of leukocytes to the site of infection.
4. Macrophages. Macrophages are an important cell type that gets recruited to the site
of infection during inflammation. Macrophages arise from bone marrow stem cells and
circulate in the blood as monocytes. Monocytes are recruited to the site of infection
where they differentiate into macrophages. Macrophages are highly phagocytic cells that
counter microbial proliferation at the site of infection.
5. Phagocytosis. Phagocytosis is the process whereby dedicated phagocytes
(neutrophils, monocytes, macrophages) digest and destroy invading microbes. Surface
PRRs on phagocytes bind PAMPs on microbes and initiate a complex series of cellular
events that results in internalization of the microbe by the phagocyte in a vesicle known
as a phagosome. The phagosome fuses with a second vesicle known as the lysosome
to form a phagolysosome. In the phagolysosome, lysosomal enzymes and reactive
oxygen/reactive nitrogen species combine to eliminate the ingested microbe.
6. Cytokines and Chemokines. Active macrophages also release cytokines and
chemokines to induces secondary immune responses. Chemokines are small shortrange molecules that attract additional lymphocytes such as B cells and T cells (B and T
cells will be discussed later). Cytokines are small regulatory molecules that drive multiple
features of immune responses (e.g. differentiation, inflammation, proliferation,
apoptosis).
Prepared by E. Foley