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recognize the pathogen with the aid of dendritic cells. Full-blown adaptive
immune responses thus require several days. Here I show you the major cellular
components involved in innate immunity. Some of them engulf pathogens;
Macrophages, neutrophils, dendritic cells. They are called phagocytes and others
act as effector cells, releasing bactericidal proteins or proteins that can kill
microbes, and some act as cytokine producing cells. Cytokines, such as G-CSF, IL
means interleukin, IL-1, IL-6. They mediate inflammatory and immune reactions,
and are principal mediators of communication between cells of the immune
system. A recent addition to the innate immune system is a group of cells, here,
innate lymphoid cells or ILCs. We know now that there are, at least, three types of
ILCs. They all secrete cytokines that can activate immune cells including T and B
lymphocytes. So, in this system, you have many different kinds of cells and they
secrete bactericidal proteins and cytokines. Most ... Quite few of them are called
interleukins.
Recognizing Invaders Part 2
The complement system is made up of over 25 proteins and protein fragments,
which assist the ability of antibodies and phagocytic cells to clear pathogens from
an organism. They are normally produced by the liver cells and circulate as
inactive precursors in the blood. When infection occurs, microbial products may
activate proteases in the system, which cleave specific proteins to release
cytokines, and this amplifies a cascade of further cleavages. The end-result of
this activation cascade is massive amplification of the response and activation of
the membrane attack complex on the surface of the pathogen, which leads to
killing of microbes. Complement proteins are inactive until they are cleaved by a
protease, which in turn, converts the proteins into a protease. For instance,
binding of an antibody to a pathogen triggers the complement activation through
the so-called classical pathway. And the antibody bound to the pathogen can
activate C1, which activates C2 and C4, which activates C3 and C5, which leads
to the sequential activation of C6, C7, C8 and C9, which finally results in the
formation of the membrane-attack complex or MAC on the surface of the
pathogen. The MAC in turn functions as a channel, allowing the passage of ions
and small molecules, which causes osmotic swelling and killing of the pathogen
or infected cells. Alternatively, when a complement component C3 binds to the
microbial cell surface, this activates a number of other complement proteins in
sequence. This is called an alternative pathway. Some of the products induce
blood vessel dilatation, histamine release from mast cells, recruitment of
phagocytes. Some of them induce promotional microbial phagocytosis and killing
locally. Now, in addition to the classical pathway and the alternative pathway,
there is another complements activation pathway - the lectin pathway. Upon
activation of complement proteins through these pathways, now, inflammatory
leukocytes are recruited to the site of infection, phagocytosis by the activated
leukocytes is promoted, and pathogens are killed at the site of infection. So, you
can see now how important the complement system is as a component of the
innate immune system.
PAMPs or DAMPs, and forms oligomers with an adaptor protein and an inactive
form of caspase-1, which leads to activation of caspase-1, which in turn activates
IL-1. IL-1 is constitutively produced in inflamed cells as inactive form. But
activated caspase-1 activates IL-1 to induce acute inflammation. And Toll-like
receptor signaling also enhances this process. So, upon sensing of PAMPs and
DAMPs, NLRP-3 oligomerizes with an adaptor protein and inactive form of
caspase-1. Once recruited, caspase-1 is activated, and cleaves pro-IL-1 (inactive
from of IL-1), to generate biologically active IL-1. And IL-1 induces acute
inflammation and causes fever. And among these proinflammatory cytokines, you
have IL-1, IL-18, TNF (tumor necrosis factor), and Interleukin-6 and so on.
effector function and migrate mainly to lymph nodes. In contrast, effector cells
are usually cycling and live only for days. Activated B cells secrete antibodies,
whereas helper T cells secrete cytokines, and cytotoxic T cells can kill microbeinfected cells. On the other hand, memory cells are quiescent, live long, but have
no effector function, migrating through the lymph nodes and bone marrow.
MHC and peptide meet and are delivered to the cell surface, and finally presented
to T cells. This is the MHC class I pathway. In contrast, when microbes are
endocytosed, they enter the endocytic vesicle and are degraded into peptides in
infected cells. Because class II molecules enter the same vesicles, they bind to
these peptides and are transported to the cell surface. In this case, a T cell
subset expressing CD4 recognizes the MHC-peptide complex. So, once again, the
first event is, here, antigen uptake, followed by antigen processing and then you
have MHC biosynthesis, and peptide-MHC association, and finally these peptides
are presented on cell surfaces to be recognized by T cells. This is the MHC class
II pathway.