almost know (4) Flashcards
L19- Passive immunisation?
Occurs naturally by transfer of maternal antibodies (Abs) (IgG) across the placenta
or in breast milk
Abs (IgG and IgA) present in breast milk or across the placenta.
Protection against: diptheria, mumps, measles etc for first 6 months of life
Protective immunity can be conferred by the administration of specific
antibodies collected from actively immune individuals (humans or animals)
VariZIG (Varicella Zoster Immune Globulin (Human)) is a sterile
lyophilised preparation of purified human immunoglobulin G (IgG)
containing antibodies to varicella zoster virus, VZV (chickenpox). It
provides passive immunisation for non-immune individuals exposed to VZV,
reducing the severity of varicella infections
Injection with preformed specific antibodies
Protection against: Hepatitis A, rabies, tetanus
Injection with antitoxin (antibodies) can be live-saving
Protection against: botulism, snake / spider bite (poisonous)
Passive immunisation protection for patient is short-lived because the immunisation
does not induce active immunological memory and only lasts
as long as the injected antibody persists in the body
L19- Live, attenuated or inactivated/killed
bacterial and viral vaccines? + problem?
Effective vaccines are composed of intact microbes that are treated in such
a way that they are attenuated OR killed, so they no longer cause disease,
while retaining their immunogenicity
Advantage of attenuated microbial vaccines is that they elicit all the innate and
adaptive immune responses (both humoral and T cell mediated)
However, the inactivated (killed) bacterial vaccines generally induce limited
protection and are effective for only short periods
Live, attenuated viral vaccines are usually more effective e.g. polio, measles,
and yellow fever.
Early approach for producing attenuated viruses was repeated passage in cell
culture
More recently, temperature-sensitive and gene deletion mutants have been
generated
Viral vaccines often induce long-lasting specific immunity, so immunisation of
children is sufficient for lifelong protection
So good cus they activate innate and adaptive-memory b and t cells produced. The innactibated killed are not as potent, limited protection, do not have long lasting effects.
Learn examples of pathogens associated with vacines
Attenuated: formed in lab through repeat passage in cell culture.
In live-attenuated
vaccines, like the
measles, mumps, and
rubella shot, weakened
viruses incorporate their
genetic instructions into
host cells, causing the
body to churn out viral
copies that elicit
antibody and CD4 and
CD8 T cell response
The major concern with attenuated viral or bacterial vaccines is safety
The live-attenuated oral polio vaccine has nearly eradicated the disease, but in
rare cases the virus in the vaccine is reactivated and itself causes serious polio
Success of worldwide vaccination is creating the unusual problem that the
vaccine-induced disease, although rare, could become more frequent than the
naturally acquired disease! So vacine can be infectous.
Solution? reverting to the killed virus vaccine to complete the eradication
program (or 3rd generation vaccines)
A widely used inactivated vaccine of considerable public health importance is
the influenza or flu vaccine. Influenza viruses are grown in chicken eggs
Innactivated vaccine: Flu shot: Trivalent inactivated (killed) vaccine given intramuscularly
3 of the most frequently encountered influenza strains are selected every year
and incorporated into this vaccine
L19- Immunisation?
Immunisation: “process whereby a person is made immune or resistant to an infectious
disease, typically by the administration of a vaccine”
(World Health Organization, WHO)
(Process of conferring increased resistance or decreased susceptibility to infection)
A procedure designed to increase concentrations of antibodies (b cells)
and/or effector T cells which are protective against infectious agents
(and cancer)
Can be performed before exposure to infection organisms
= immunoprophylaxis or prophylactic vaccination
(designed to prevent disease from developing in healthy individuals) given before exposure e.g: infant vaccinations
Or during an active infection (or cancer) = therapeutic vaccination
(designed to treat an existing infection or cancer by strengthening
the body’s natural anti-microbial/viral or anti-tumour immune response)
The best vaccines are those that stimulate the development of long-lived
plasma cells that produce high-affinity antibodies as well as memory B cells -
humoral immune responses induced by the germinal centre GC reaction which
requires help provided by antigen-specific CD4+ T follicular helper cells
Live, attenuated or inactivated/killed
bacterial and viral vaccines?
Effective vaccines are composed of intact microbes that are treated in such
a way that they are attenuated OR killed, so they no longer cause disease,
while retaining their immunogenicity
Advantage of attenuated microbial vaccines is that they elicit all the innate and
adaptive immune responses (both humoral and T cell mediated)
However, the inactivated (killed) bacterial vaccines generally induce limited
protection and are effective for only short periods
Live, attenuated viral vaccines are usually more effective e.g. polio, measles,
and yellow fever.
Early approach for producing attenuated viruses was repeated passage in cell
culture
More recently, temperature-sensitive and gene deletion mutants have been
generated
Viral vaccines often induce long-lasting specific immunity, so immunisation of
children is sufficient for lifelong protection
So good cus they activate innate and adaptive-memory b and t cells produced. The innactibated killed are not as potent, limited protection, do not have long lasting effects.
Learn examples of pathogens associated with vacines
Attenuated: formed in lab through repeat passage in cell culture.
In live-attenuated
vaccines, like the
measles, mumps, and
rubella shot, weakened
viruses incorporate their
genetic instructions into
host cells, causing the
body to churn out viral
copies that elicit
antibody and CD4 and
CD8 T cell response
L3- alternative pathway?
initiated by spontaneous hydrolysis of c3 to c3(h20) (fluid-phase c3 convertase) that binds to factor B, allowing factor D to cleabe factor B to Bb and Ba.
note: c3(h20)Bb is fluid phase c3 convertase.
amp: a
c3b binds to the pathogen surface for oponisation. c3b interacts with factor B, so factor D cleaves factor b into alternative c3 convertase (c3bBb). factor P stabilises this complex on pathogen surface enhancing the cleavage of more c3 into c3a and c3b. c3bBbC3b is alternative c5 convertase which then cleaves more c5.
L3- c5a and c3a?
c5a anc 3a: enhance inflammation and attract immune cells to the site of infection e.g: for phagocytosis by macrophages and neutrophils. bind to receptors on mast cells and basophils for the release of histamine and other proinflammatory factors (fact check).
c3a«c5a (c5a greater potency and activity). they act on c5a and c3a receptors on:
endothelial cells- cause muscle contraction, increased vascular permeability and promoting adhesion molecule expression.
mast cells- cause histamine release (fever and allergic reaction), pathogen recognition and cytokine
macrophages, monocytes and granulocytes such as neutrophils: chemotaxis to attact these cells, cause phagocytosis and degranulation of mast and basophils.
T cell- promote their activation (by promoting antigen presenting cell activation (macrophages) and promote their resolution.
c3b and c5b are highly reactive and non specific so can bind to host tissue. regulation protects self tissue from a complement attack.
- there is short-half life of the activated thioester so rapid degranulation of c3b/c4b so activation of proteins only on pathogen surface
- tight reg of activation pathways (DAMPS -damage associated molecular patterns and TLR co signal needed
- there is complement regulation on host tissue
L3- complement effectors for opsonisation?
c3b and (c4b) bind to complement receptors (CR).
MACROPHAGES- CR1, LIGAND- C3b
MONOCYTE: CR2, LIGAND: iC3b
B CELLS- CR3, LIGAND: C3dg
PMN (neutrophils), LIGAND (c4b)
EFFECT- PHAGOCYTOSIS IN THE PRESENCE OF C5a
L3- Complement regulation?
(SOLUBLE IN PLASMA) C1 inibitor: inhibits the classical and mbl preventing c1r and c1s and masps from activating the complement cascade.
(SOLUBLE) C4bp: regulate the classical and mbl pathway by binding to c4b so preventing c3 convertase formation
(SOLUBLE) factor H: REG alt by binding to c3b preventing c3bBb formation and promoting its degradation
( MEMBRANE BOUND) DAF (dissosication accelerating factor) : accelerates dissaosication of c3/c5 convertase in all pathways so stops cascade early. binds to c3b in alt and c4b in classical and mbl (factcheck)
(MEMBRANE BOUND) CR1: helps break down c3b and c4b to prevent further activation of complement.
(SOLUBLE) Factor I: chops the complement proteins and changes its shape to make it more susceptible to truncation. a protease.
(MEMBRANE BOUND): properdin (factor p) : an activator that stabilises the complement by binding and enhances the survival of the complement on membrane. in the alternative pathway.
(MEMBRANE BOUND): CD46: membrane co factor protein. acts as a co factor to factor i to cleave c3b and c4b. releases c3f so c3b becomes ic3b.
(MEMBRANE BOUND): CD59: prevents mac formation by inhibiting c9 insertion in the membrane so stops lysis.
(SOLUBLE) PROTEIN S: co factor. inhibits mac assembly. stabilises c5b complexes in the fluid phase preventing binding to host membranes.
L6- Proteosome structure + substrates?
first: alpha subunit, beta subunit, alpha subunit. converts proteins to be degraded to peptides. protosome is: 26S. 20S core: 4 stacks of 7 proteins. 7 diff alpha and 7 diff beta subunits. 3x beta subunits have active sites. these cleave amino acids. in an immune reaction some subunits get swapped by ifn-y. more efficient to generate more peptides. 19S regulator: ubiquitin - recognising proteins tagged with ubiquitin and unfolds so can enter catalytic core of proteosome. total of 6 active sites per proteosome
chymotrypsin-like: cleavage after hydrophobic residues.
trypsin-like: cleavage after basic residues.
post-acidic or caspase-like: cleavage after acid residues..
L6- Peptides after protesome?
longer than those presented by mhc class 1. further trimmed by amino-peptidase in the cytosol and er. emino-peptideases: ERAAP (IN ER): trims 15aa to 8-10aa. induced by ifn-y. inhibition reduces cell surface expression of mhc class 1.
transported to ER BY TAP: -transporter associated with antigen processing (TAP) pumps peptides to er.
-heterodimer of tap1 and tap2 proteins with 8 transmembrane domains. belong to ABC family (ATP-binding casette) of transporters.
- present in ER membranes.
TAP transports 8-15aa long peptides- have basic or hydrophobic cooh- termini
