Immunology Flashcards
Innate Defenses
-present constitutively
-virtually identical among all members of the same species
Adaptive Defenses
-induced after contact with the invading organism
-reflect the experience of the individual
Physical and chemical barriers
-skin is a very effective physical barrier which few microbes can penetrate.
On skin, salt from sweat is present at high concentrations, which inhibits
growth of many microbes (remember: mannitol salt agar medium)
-mucous membranes - bathed with lysozyme and antimicrobial peptides
(also with antibodies)
-low pH of stomach acid kills many bacteria
-liquid currents in the digestive and urinary tracts flush out unattached
microbes
-lysozyme in body fluids like saliva and tears
Innate Defenses: Inflammation
-inflammation is often switched on when pathogens are present
-Phagocytes play a major role in removing microbes during inflammation
* phagocytes are white blood cells (leukocytes) that ingest and kill
microbes (we’ll talk more about them in a few slides)
* recruited to the site of microbial invasion by complement
chemotaxins and bacterial chemotaxins
How does the body know to switch inflammation on during microbial invasion?
When MAMPs are detected
MAMPs
- detected by the innate immune system when invading microbes are
present - about 1000 different MAMPS can be detected by the innate immune
system - sometimes called “PAMPs” (pathogen-associated), but “MAMPs” is
more accurate - MAMPs can bind to complement proteins and activate the
complement system - MAMPs can also bind to PRRs (Pattern recognition receptors) on
phagocytes such as neutrophils and macrophages
Examples of MAMPs
-flagellin
-pillin
-chitin
-murein
-LPS
-dsRNA
-uncapped RNA
f-met peptide
Innate Defenses: Complement System
-a system of ~30
soluble proteins,
usually inactive,
but can be
activated in a
proteolytic cascade
-people with
defects in
complement
function (due to
rare genetic
disorders) are
highly susceptible
to bacterial
infections or
autoimmune
diseases such as
lupus
- The most common way to activate complement is the “alternative
pathway,” triggered when complement proteins bind to MAMPs.
Phagocyte recruitment and inflammation
-activated complement proteins can act as complement chemotaxins to
recruit phagocytes to the site of infection, promoting inflammation
-also, bacteria release chemotaxins (e.g. peptides containing f-met) that
happen to advertise their presence and attract phagocytes
Opsonization
-activated complements acts as opsonin to enhance phagocytosis
-antibodies also act as opsonins and together antibodies and complement have additive effects on opsonization
MAC formation and cell lysis
-activated complement proteins can lyse cells or destroy virions directly by
forming the membrane attack complex (MAC), which forms pores in cell
membranes or viral envelopes
Examples of microbial defenses against complement
-Neisseria meningitidis hides its complement-activating MAMPs with a
thick capsule
-Salmonella has cell-surface components that prevent MACs from
forming
-Vaccinia virus (used to vaccinate against smallpox) encodes a protein
that binds to C4b and C3b, and thus inhibits complement activation
Phagocytes
-many types of cells can perform phagocytosis, but two groups of
“professional phagocytes” with roles in immunity are the leukocytes called
neutrophils and monocytes/macrophages
Neutrophils
-neutrophils (most numerous)
*short-lived cells (life span is a few weeks; terminally differentiated)
*move fast, responding rapidly and in large numbers to chemotaxins
Monocytes/macrophages
*long-lived
*monocytes that reside in tissues differentiate into macrophages
*arrive at the site of infection more slowly than neutrophils
*produce cytokines - secreted protein signals for communicating with
other cells of the immune system (e.g. cytokines activate phagocytes,
promote inflammation, and communicate with cells in the adaptive
defenses)