immunology 2 buse
TRANSCRIPT
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T Cells
Tc cells are CD8+, Th cells are CD4+
CD = cluster of differentiation
Expressed by various cells at particularstages of differentiation
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T Cell Receptors
Similar to Abs
Contain constant & variable regions
Mediate Ag recognition
Found on cell surface of T cell, but is not
secreted
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Major Histocompatability
complex T cells cannot recognize Ag alone
Ag must be presented in conjunction with
major histocompatability complex (MHC)
proteins
In humans called human leucocyte antigens
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MHC proteins are glycoproteins found on
cell surface
Vary from 1 individual to another & serve
as a label
2 classes, MHC I & MHC II are involved in
Ag processing Differ in structure, location & function
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MHC Ifound on all nucleated cells
Important in in presenting endogenous Ag,
eg virus to Tc cells
Endogenous Ags - produced within cytosol,
eg viral proteins in an infected cell
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MHC IIfound only on immunocompetent
celss such as macrophages & B cells
Present exogenous Ag to Th cells
Exogenous Agtaken up by endocytosis,
found in vesicles within cells
Eg bacteria & their products taken up by
macrophages
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Generation of Ab Diversity
Vast range of Ab-producing cells
exist, independent of exposure to any
specific Ag
Presence of a given Ag stimulates
production of a particular Ab or set of Abs
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Vaccination
Primary & Secondary Immune Responses
o
Following initial stimulation of a responseby particular Ag, memory cells specific to
that Ag are formed
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o On 2nd encounter response is faster &
stronger
-Memory cells are activated by Ag
-Become Ab secreting plasma cells
-Form further memory cells
o Basis of vaccination
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Principle of Vaccination
Non-pathogenic organism primes the
immune system so that on encounter with
pathogen, a protective response is generated
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During 1o challenge, stimulated B & T cells
proliferate & differentiate to give effector
cells + memory cells
Memory cells are long-lived & proliferatemore rapidly
o Facilitate rapid control of subsequent
infections
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Passive Immunization
Preformed Abs are transferred torecipient, eg.
o Natural maternal Abs
o
Artificial immune serum such as horseantivenin
Protects against snake biteShort-term protection
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Active Immunization
Protective immunity & immunologicmemory are elicited, eg.
o Natural infection such as flu virus
o Artificial infection such as vaccines-Attenuated organisms
-Inactivated organisms
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Route of Administration of Ag
Influences type if immune response
1. Systemic Response
Vaccine is introduced by injection
Increase of circulating Abs & specific T
cells
2. Mucosal Response
Vaccine is introduced orally or byrespiratory route
IgA predominates
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Uses of Adjuvants
Certain substances, which when
administered simultaneously with a specific
Ag, will enhance the immune response to
that Ag
Eg Aluminium Salts (hydroxyl, phosphates)
-1st safe & effective cpds to be used in
human vaccines
-Promote good Ab response, but poor CMI
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Attributes of a Good Vaccine
1. Ability to elicit the appropriate immune
response for a particular pathogen-Tuberculosis- CMI
-Most bacterial & viral infections- Abs
2. Long-term protection
-Ideally single dose-life long immunity
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3. Safety
-Non-pathogenic
-No side effects
4. Stable
-Should maintain immunogenicity
o Despite adverse conditions prior to
administration
5. Cheap
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Vaccine Production
In developing a vaccine, consider the branchof immune system to be activated
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Humoral immunity
o epitopes must be accessible to B-cell
receptors
o represent immunodominant epitopes
of infectious agent
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CMI
o vaccine should be capable of
maximizing presentation of Ag with Class I
MHC molecules
o Must undergo transient growth in
recipient
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Live Attenuated Organisms
-Virulence artificially reduced by in vitro
culture
i. Under adverse conditions, eg low To
ii. Selection of mutants which
replicate poorly in human host
-Often single dose reqd
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Replication of vaccine strain in host
i. Reproduces many features of w.t infection
ii Does not cause clinical disease
-Induces both humoral & CMI
Long-lived
-May revert to virulent form
Eg. Bacillus Calmette-Guerin (BCG)-an attenuated
Mycobacterium bovis (Tuberculosis)
-Viral particles causing measles or mumps
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Inactivated (Killed) Organisms
Virulent pathogen inactivated by:
o Irradiation with gamma rayso Chemicals such as formaldehyde orb-propiolactone
Produces mainly humoral immunity
o Poor immunogenicity
Requires multiple boosters
o Short-lived
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More stable
o Organisms need not be viable
o
Can withstand adverse storage conditions
Cannot revert to virulent form
o Safer
o Cannot replicate in host & cause disease
Eg.
o Cholera (bacterial)
o Influenza (viral)
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HIV Vaccine?
Problems
High mutation rate of HIV
Need for both CMI & humoral immunity
Lack of good animal model
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Trial Vaccines
Recombinant peptides, gp120
DNA vaccines
Live attenuated virus??
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Immunochemical Techniques
Techniques that use the interaction between
antibody (Ab) and antigen (Ag) to detect or
quantitate either Ab or Ag.
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Ab-Ag interaction is specific
-Ab to HIV reacts with HIV but not with flu virus
Examples
Anti-insulin Abs are used to quantify the amount
insulin in a serum sample
Bovine serum albumin (BSA) is used to test for
the presence of anti-BSA Abs in a rabbitimmunized with BSA
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Enzyme linked immunosorbent assay
(ELISA)
Detection reagent is an enzyme, which
converts a colourless substrate to coloured
product
Detected by simple eye or read by a
colorimeter
Can be used to assay for Ab or ag, can label
either Ab or Ag
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Assay Design
Many different variations on assay design
Solid phase for assay is usually a 96-well
microtitre plate which binds protein non-
specifically
Enzymes used mainly HRP or AP, which act on
a wide range of colourless substrates to givecoloured products
Small, do not interfere with Ab-Ag interaction
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ELISA for Ab to HIV
Coat plate with Ag
Block surface
Add serum sample
Add E-labelled anti-human Ab
Add colourless substrate
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Situations where Ab detection is inappropriate
Window period
Newborn with HIV+ mother
Solution Detect virus rather than immune response
eg PCR to detect viral RNA