Fate of the Immunogen

Clearance after 1o exposureEquilibrium phaseCatabolic decay phaseImmune elimination phase

• Clearance after 2o exposure

– More rapid onset of immune elimination phase

Immune Elimination

Phase

Days after Injection2 4 6 8 1210

Am

oun

t of

Cir

cula

tin

g A

g (%

)

25

75

100

50

Equilibrium Phase

Catabolic Decay Phase

Kinetics of the Ab ResponseT-dependent Ag; 1o Response

• Lag phase

• Log phase

• Plateau phase

• Decline phase Ag

D a y s A f t e r I m m u n i z a t i o n

A b

T i

t e

r

LAG LOG DECLINEPLATEAU

Kinetics of the Ab ResponseT-dependent Ag; 2o Response

* Specificity

• Lag phase

• Log phase

• Plateau phase

• Decline phase

1o Ag 2o Ag

D a y s A f t e r I m m u n i z a t i o n

A b

T i

t e

r

Kinetics of Ab Response toT-independent Ags

4 PhasesIgM

antibodyNo

secondary response

1o Ag 2o Ag

D a y s A f t e r I m m u n i z a t i o n

A b

T i

t e

r

IgM Ab

1500BC Turks introduce

variolation

1885AD Pasteur discovers rabies

attenuated vaccine

3000BCEvidence of sniffing powdered small pox crust in Egypt

2000BCSniffing of small pox crust in China

1700ADIntroduction of variolation in England and later in the US

1780ADEdward Jenner discovers small pox vaccine

Edward Jenner

Discovery of small pox vaccine

1920s

Diphtheria and Tetanus

1934

Pertussis

1955

Salk polio

1960s

Mumps measles and rubella virus

Sabin polio

1990s

Hepatitis and varicella

1985

Haemophilus

Different modes of acquiring immunityDifferent modes of acquiring immunity

Innate

A r ti f ic ia l N a tu ra l

P ass ive

A r ti f ic ia l N a tu ra l

A ctive

Acuired

Im m unity

Innate

A r ti f ic ia l N a tu ra l

P ass ive

A r ti f ic ia l N a tu ra l

A ctive

Acuired

Im m unity

Natural Artificial

Colostral transfer of IgA

Placental transfer of IgG

Antibodies or immunoglobulins

Immune cells

Passive ImmunityPassive Immunity

 disease  indicationantibody source

Passive ImmunizationPassive Immunization

human, horsediphtheria, tetanus prophylaxis, therapy

vericella zoster human immunodeficiencies

gas gangrene, botulism, snake bite, scorpion sting

horse post-exposure

rabies, human post-exposure

hypogamma-globulinemia

human prophylaxis

Active ImmunizationActive Immunization

Natural Artificial

exposure to sub-clinical infections

Attenuated organisms

killed organisms

sub-cellular fragments

toxins

others

tuberculosisnot used in this country

polio*not used in std. schedule

measles, mumps & rubella yellow fever

Military and travelersVaricella zoster

children with no history of chicken pox

hepatitis A

not required in SC

Live Attenuated VaccinesLive Attenuated Vaccines

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 phagocytosisphagocyte attraction and activationlysis of bacteria and infected cellsregulation of antibody responsesclearance of immune complexesclearance of apoptic cells

Host detriment:Inflammation, anaphylaxis

CLASSICALPATHWAY

ALTERNATINEPATHWAY

activationof C5

LYTIC ATTACKPATHWAY

antibodydependent

LECTINPATHWAY

antibodyindependent

A damage to host mediated by preexisting immunity to self or foreign antigen

Types of hypersensitivity reactionsTypes of hypersensitivity reactions

Type I: anaphylactic or immediateType II: cytotoxicType III: Immune complexType IV: cell mediated or delayed

Type I: anaphylactic or immediateType II: cytotoxicType III: Immune complexType IV: cell mediated or delayed

Type-I hypersensitivityType-I hypersensitivity

The common allergy

B cell

Histamine, tryptase, kininegenase, ECFA

Leukotriene-B4, C4, D4, prostaglandin D, PAF

Newly

synthesized mediators

TH1

Complement mediated

lysis

ADCCfrustrated

phagocytosis

B cell

Histamine, tryptase, kininegenase, ECFA

Leukotriene-B4, C4, D4, prostaglandin D, PAF

Newly

synthesized mediators

TH1

Type III hypersensitivityType III hypersensitivity

Serum sicknessmediated by immune complexes

Type III hypersensitivitythe role of immune complex size

Type III hypersensitivitythe role of immune complex size

Type IV hypersensitivityType 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 reaction 36 to 48 hours Characterized by

induration and erythema Also known as cell

mediated hypersensitivity

Tuberculin test is the most common example

persistent antigen stimulus, chronic infection

M, giant cells, epitheloid cells, fibroblasts

hardening21-28 days

granuloma

intradermal: tuberculin, lepromin, etc.

lymphocytes, monocytes

local induration

48-72 hourstuberculin

epidermal: heavy metals, poison ivy, rubber, latex

T cells, later macrophageseczema

48-72 hours

contactdermatitis

antigen and sitehistologyclinical appearance

time of reaction

type

APC

IL2, TNF , IFN

TH1

IL2 TNF , IFN /

N O 2

NK

M M

LAK

preTc

Tc

Type-IVType-IIIType-IIType-Icharacteristic

Comparison of hypersensitivity reactionsComparison of hypersensitivity reactions

TB test, poison ivy, granuloma

farmers’ lung, SLE

pemphigus, Goodpasture

hay fever, asthma

examples

antibody IgE IgG, IgM IgG, IgM none

antigen Exogenous cell surface cellularsoluble

response time

15-30 min. Min.-hrs 3-8 hours 48-72 hoursor longer

appearance Weal & flare Lysis & necrosis

Erythema & edema

Erythema & induration

baso- and eosinophils

Ab and complement

histology PMN andcomplement

Monocytes & lymphocytes

T-cellsantibodyantibodyantibodytransfer with

Two major types of immunodeficiency diseasesTwo major types of immunodeficiency diseases

Secondary immunodeficiencies immunodeficiency resulting from

infections and other diseases immunodeficiency resulting from

iatrogenic causes immunodeficiency due to aging or

malnutritionPrimary immunodeficiency

Inherited immunodeficiencies

Secondary immunodeficiencies immunodeficiency resulting from

infections and other diseases immunodeficiency resulting from

iatrogenic causes immunodeficiency due to aging or

malnutritionPrimary immunodeficiency

Inherited immunodeficiencies

ImmunodeficiencyImmunodeficiency

Immunologic defects caused by HIV infectionImmunologic defects caused by HIV infection

Cellular abnormalitiesdecrease 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

Cellular abnormalitiesdecrease 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 diseasesPrimary immunodeficiency diseasesStem cell defect

Reticular dysgenesisT and B cell defect

severe combined immunodeficiency X-linked

IL2 receptor -chain autosomal

adenosine deaminase (ADA) purine nucleoside phosphorylase (PNP)

Stem cell defectReticular dysgenesis

T and B cell defectsevere combined immunodeficiency

X-linked IL2 receptor -chain

autosomal adenosine deaminase (ADA) purine nucleoside phosphorylase (PNP)