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)
Lysozyme contains:
-defensins
(antimicrobial
peptides);
-hydrolases
(destructive enzymes,
e.g. proteases and
phospholipases);
-oxidative enzymes
(make hypochlorite
and reactive oxygen
species)
Phagocytes and Toll-like receptors (TLRs)
-Neutrophils and Monocytes/macrophages have TLRs, a type of pattern
recognition receptor, which bind to MAMPs
* binding of MAMPs to
TLRs triggers downstream
pathways.
* For example, MAMP-
TLR binding in
macrophages
activates NF-kB, a
transcription factor,
which results in
increased production
of cytokines for
macrophage activation
and inflammation
Examples of microbial defenses against phagocytosis
- Haemophilus influenzae and Bacillus anthracis have anti-phagocytic
capsules – the capsule prevents phagocytosis. - Mycobacterium tuberculosis inhibits fusion of the lysosome with the
phagosome, so the bacteria has a safe place to live inside a macrophage - Listeria and Shigella bacteria escape from the phagosome and divide
in the cytoplasm of host cells. These bacteria then use the host cell’s
cytoskeletal proteins to propel them into neighboring cells. (see A-H below)
Two Branches of Adaptive Immunity
1.Humoral immunity: carried out by antibodies produced by
B lymphocytes
* most effective at defending against bacterial toxins,
bacteria, and viruses circulating in the body, before they
have entered cells
2.Cell-mediated immunity: carried out by cytotoxic T
lymphocytes (CTLs)
* most effective when antigens are already inside host
cells and inaccessible to antibodies; for example, cell-
mediated immunity is involved in killing virus-infected
cells
* helper T lymphocytes are important for activating both of
the above types of immunity
What is an antigen?
- Antigen: a substance the body identifies as foreign (non-
self).
–Many antigens are proteins or glycoproteins, but some are
polysaccharides. Proteins tend to be stronger antigens than
polysaccharides because they have a more complex structure.
–A microbe usually has many different antigens. Examples:
– capsular polysaccharides
– proteins on the outside of bacteria (e.g. flagellin, outer membrane
proteins, etc.)
Epitope
a region on an antigen that is specifically identified by antibodies or Cell receptors
Characteristics of adaptive immunity
- Specificity
* antibodies and T-cell receptors bind specifically to epitopes - Amazing diversity
* In total, B and T lymphocytes can recognize ~10 8 different epitopes.
* each antibody or T cell receptor recognizes just one epitope - Discrimination between “self” and “non-self”
* clonal deletion - B and T cells that bind to “self” are destroyed
during development and never make it out to circulation
* problems with distinguishing “self” from “non-self” result in
autoimmune disease - Memory
* quick secondary response to previously encountered antigens
* involves Memory B and T cells
* basis for vaccination
Primary Response
the immune response produced upon the first
exposure to a pathogen or antigen
Secondary Response
the immune response that occurs on a subsequent
exposure to that same pathogen or antigen
Immunological Memory
-The secondary response is faster and more efficient due to the presence of memory B and T cells - long-lived cells
that may persist for decades, ready for activation upon encounter with the
same antigen.
Ways in which antibodies help combat infectious diseases
-Neutralization: antibodies binds to toxins of viruses so they can’t attach to receptors on host cells(monoclonal)
-opsonization
-activate complement
-agglutination: antibodies bind to microbes or viruses forming clumps that are easily removed
Antibodies and opsonization
-like activated complement antibodies also act as opsonins to enhance phagocytosis
Complement activation
-most common way to activate complement is when complement proteins bind to MAMPs
also activated when antibodies bind to antigens
MHC
-important for T cell activation
-MHC class 1 proteins: expressed on the surface all nucleated cells of the body
-MHC class II proteins: expressed only on the surface of professional antigen presenting cells
-the MHC proteins bind to peptides from antigens; thus peptide MHC complex is recognized by the T cells
Helper T cells
-helper T lymphocytes (CD4 T cells) are activated when their T cell receptors bind to antigen+MHC class II
-have a critical role in producing cytokines that activate and induce proliferation of B cells
CTLs
-an activated CTL recognize an infected cell when the T cell receptor binds to antigen + MHC class I on the infected cell
-the infected cell is directly killed by the CTL by releasing perforin and granzymes which together induce apoptosis
