Download W12

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

Vaccine wikipedia , lookup

Molecular mimicry wikipedia , lookup

Transcript
Fate of the Immunogen
 Equilibrium phase
 Catabolic decay phase
 Immune elimination phase
• Clearance after 2o exposure
– More rapid onset of immune
elimination phase
Amount of Circulating Ag (%)
 Clearance after 1o exposure
Equilibrium Phase
100
75
50
Catabolic
Decay Phase
Immune
Elimination
Phase
25
2
4 6 8 10 12
Days after Injection
Kinetics of the Ab Response
T-dependent Ag; 1o Response
LAG
LOG
PLATEAU
DECLINE
Ab Titer
• Lag phase
• Log phase
• Plateau phase
• Decline phase
Ag
Days After Immunization
Kinetics of the Ab Response
• Lag phase
• Log phase
• Plateau phase
• Decline phase
Ab Titer
T-dependent Ag; 2o Response
1o Ag
2o Ag
* Specificity
Days After Immunization
Kinetics of Ab Response to
T-independent Ags
 4 Phases
IgM Ab
 No secondary
response
Ab Titer
 IgM antibody
1o Ag
2o Ag
Days After Immunization
Milestones in immunization
3000BC
Evidence
of sniffing
powdered small pox
crust in Egypt
2000BC
Sniffing
of small pox
crust in China
 1500BC
 Turks introduce
variolation
1700AD
Introduction
of variolation
in England and later in the
US
1780AD
Edward
Jenner discovers
small pox vaccine
 1885AD
 Pasteur discovers rabies
attenuated vaccine
Edward Jenner
Discovery of small pox vaccine
Modern era of the vaccine
1920s
Diphtheria and
Tetanus
1960s
Mumps measles
and rubella virus
Sabin polio
1934
Pertussis
1955
Salk polio
1985
Haemophilu
s
1990s
Hepatitis and
varicella
Different modes of acquiring immunity
Immunity
Innate
Acuired
Passive
Artificial
Natural
Active
Artificial
Natural
Passive Immunity
Natura
l
Artificia
l
Placental
transfer of IgG
Antibodies or
immunoglobulins
Colostral
transfer of IgA
Immune cells
Passive Immunization
disease
antibody
source
indication
diphtheria, tetanus
human, horse
prophylaxis, therapy
vericella zoster
human
immunodeficiencies
gas gangrene,
botulism, snake
bite, scorpion sting
horse
post-exposure
rabies,
human
post-exposure
hypogammaglobulinemia
human
prophylaxis
Active Immunization
Natural
Artificial
Attenuated
organisms
killed organisms
exposure to subclinical infections
sub-cellular
fragments
toxins
others
Live Attenuated Vaccines
polio*
not used in std.
schedule
measles, mumps & rubella
Varicella zoster
children with no history
of chicken pox
hepatitis A
not required in
SC
yellow fever
Military and travelers
tuberculosis
not used in this country
Recommended Childhood
Immunization Schedule (2002)
Complement
Discovered in 1894 by
Bordet
It represents lytic
activity of fresh serum
Its lytic activity
destroyed when
heated at 56C for 30
min
Complement functions
Host benefit:
opsonization to enhance phagocytosis
phagocyte attraction and activation
lysis of bacteria and infected cells
regulation of antibody responses
clearance of immune complexes
clearance of apoptic cells
Host detriment:
Inflammation, anaphylaxis
Pathways of complement activation
CLASSICAL
PATHWAY
antibody
dependent
LECTIN
PATHWAY
ALTERNATINE
PATHWAY
antibody
independent
Activation of C3 and
generation of C5 convertase
activation
of C5
LYTIC ATTACK
PATHWAY
A damage to host mediated by preexisting immunity
to self or foreign antigen
Types of hypersensitivity reactions
Type I:
Type II:
Type III:
Type IV:
anaphylactic or immediate
cytotoxic
Immune complex
cell mediated or delayed
Type-I hypersensitivity
The common allergy
Anaphylaxis can be fatal
Sensitization against allergens
B cell
TH1
Histamine, tryptase,
kininegenase, ECFA
Leukotriene-B4, C4, D4,
Newly
prostaglandin D, PAF
synthesized mediators
Type II hypersensitivity
role of neutrophils
Complement
mediated
lysis
ADCC
frustrated
phagocytosis
Type II hypersensitivity
role of neutrophils
B cell
TH1
Histamine, tryptase,
kininegenase, ECFA
Leukotriene-B4, C4, D4,
Newly
prostaglandin D, PAF
synthesized mediators
Type III hypersensitivity
Serum
sickness
mediated
by immune
complexes
Type III hypersensitivity mechanism
Type III hypersensitivity mechanism
Type III hypersensitivity
the role of immune complex size
Type IV hypersensitivity
 Delayed reaction
 36 to 48 hours
 Characterized by induration
and erythema
 Also known as cell mediated
hypersensitivity
 Tuberculin test is the most
common example
Delayed hypersensitivity reactions
type
time of
reaction
clinical
appearance
histology
antigen and site
contact
dermatitis
48-72
hours
eczema
T cells, later
macrophages
epidermal: heavy
metals, poison ivy,
rubber, latex
tuberculin
48-72
hours
local
induration
lymphocytes,
monocytes
intradermal:
tuberculin,
lepromin, etc.
granuloma
21-28
days
hardening
M, giant cells,
epitheloid cells,
fibroblasts
persistent antigen
stimulus, chronic
infection
Mechanism of damage in contact
hypersensitivity
M
APC
TH1
IL2,
TNF,
IFN
IL2
TNF,
IFN/
NO2
M
NK
LAK
preTc
Tc
Comparison of hypersensitivity
reactions
characteristic
Type-I
Type-II
Type-III
Type-IV
antibody
IgE
IgG, IgM
IgG, IgM
none
antigen
Exogenous
cell surface
soluble
cellular
response
time
15-30 min.
Min.-hrs
3-8 hours
48-72 hours
or longer
appearance
Weal & flare
Lysis &
necrosis
Erythema
& edema
Erythema &
induration
histology
baso- and
eosinophils
Ab and
complement
PMN and
complement
Monocytes &
lymphocytes
transfer with
antibody
antibody
antibody
T-cells
examples
hay fever,
asthma
pemphigus,
Goodpasture
farmers’
lung, SLE
TB test, poison
ivy, granuloma
Immunodeficiency
Two major types of immunodeficiency
diseases
Secondary immunodeficiencies
 immunodeficiency resulting from infections
and other diseases
 immunodeficiency resulting from iatrogenic
causes
 immunodeficiency due to aging or malnutrition
Primary immunodeficiency
 Inherited immunodeficiencies
Immunologic defects caused by HIV
infection
Cellular abnormalities
 decrease in CD4 T cells (reversal of CD4/CD8
ratio)
Functional abnormalities
 increased susceptibility to infections particularly
intracellular pathogens
 decrease in cell mediated immunity
 decrease in the NK cell functions
Primary immunodeficiency diseases
 Stem cell defect
 Reticular dysgenesis
 T and B cell defect
 severe combined immunodeficiency


X-linked
 IL2 receptor -chain
autosomal
 adenosine deaminase (ADA)
 purine nucleoside phosphorylase (PNP)