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INFECTION AND IMMUNITY

Major Areas
Definitionsof Immunity
Antibody dependent protective
mechanisms
Complement mediated protection
Cell mediated protective
mechanisms
Parasite and microbe evasion
immune stratagems
 Vaccines
Infection and Immunity
 Infants depend on maternal protective
antibodies, principally IgG, in the first 6-9
months in life.
 sIgA secretion in human colostrums and milk
confers maternal immunity to suckling infants.
 IgG crosses the placenta from the eighth week
of gestation by passive and active
transmission.
 Maternal IgG – Fc receptors on the placenta
syncytiotrophoblasts facilitate the active
transfer of the IgG antibodies.
 Maternal derived antibodies interfere with
vaccination of infants (measles, mumps and
rubella infections).
Immunity Profile
Sterile Immunity
 State of protection when all the
infectious agents are eliminated in the
host.
Premunition
 Low-grade infection providing
protection in subsequent asymptomatic
chronic infections
 Occurs in several infections, malaria
and diphtheria (Corynebacterium
diphtheria).
Immunity Profile cont
Concomitant Immunity
 Age dependent resistance to reinfection
directed at the early larval stages
 Adult forms unaffected (schistosomiasis,
filariasis and echinococcosis diseases).
Herd Immunity
 Community protection or resistance
conferred to susceptible proportion of
individuals in a vaccinated population
(>=95%) and
 Infection does not result in an epidemic
Innate Determinants of Immunity
Genetic Determinants
Physical Barriers
Soluble Factors
Cellular Components
Innate Mediated Factors

Innate immune responses involve


Genetics, anatomical barriers,
bacterial antagonisms
Pattern-recognition receptors (PRR)
Soluble factors
 Nonspecific defense chemicals,
complement proteins
Innate Mediated Factors cont
Cellular (cells) components
 Neutrophils, monocytes and
macrophages
 Basophils, mast cells and eosinophils
release inflammatory mediators.
Alternative pathway of complement
activation
 Provides defense against gram-
negative bacteria
Interferons inhibit viral replication and
activate inflammatory cells.
Genetic determinants of malaria immunity
Innate protection associated with
 Negative Duffy (a-b) blood groups
(Plasmodium vivax);
 Sickle cell trait A/S and glucose-6-
phosphate (G-6-PO4) dehydrogenase
deficiency.
 Plasmodium infected erythrocytes highly
susceptible to toxic oxygen intermediates
or radicals.
 Intracellular development of P.falciparum
in G-6-PO dehydrogenase deficient
Physical Barriers To Infection
Barrier site (first line of Activity
defense)
 Skin sweat  Flushing, organic acids

 Skin and GI tract natural  Compete for niches


fauna
 GI tract Peristalsis, low pH, bile
acid, flushing,
antibacterial peptides
 Lung tracheal cilia  Mucociliary elevation

 Nasopharynx, mucus and  Flushing, lysozymes


saliva, eye tears
Antimicrobial Peptides
Defensins and cathelicidins
 Protect against microbes
 Secreted by epithelial cells (skin, GIT,
genitourinary tract and nasal passages
and lungs) and recruited leukocytes
(neutrophils).
 Punch lethal holes facilitated by their
positive charges in penetrating the
bacterial membranes.
 Synergistically with cathelicidins confer
protection against microbes.
Events in Phagocytosis involve:
(1) Organism (bacterium) attaches to pseudopodia (long membrane evaginations) leading
to (2) Ingestion occurs forming phagosome that (3) Fuses with lysosome releasing
lysosomal enzymes into phagosome and (4) Digestion of ingested organism leading to (5)
Release of products from the cell.
Microbicidal Mechanisms
Associated with
 Assembly of NADPH oxidase
 Upregulation of cytochrome B558 in activated
neutrophils
 Production of ROI (superoxides, hydrogen
peroxide)
 Hydrogen peroxide reaction with chlorides

o Generates hypochloric acid (microbicidal


agent) and free chlorine
Macrophage Derived Factors and Activities
Products Activity

Metabolites:
Reactive oxygen intermediates Inflammation and intracellular
(ROI) killing
Reactive nitrogen Inflammation and intracellular
intermediates (RNI) killing
Eicosanoids, prostaglandins Regulation, inflammation
Cytokines:
leukotrienes Recruitment
Inflammation and activation of
IL-1, TNF-α, IL-6
Platelet activating factor platelets.
Th1 activation
IFN-α
IL-10 Th1 suppression, Th2 activation
IL-12, IL-18 Activation of NK and T cells
TGF- β Inflammation, tissue repair
Adhesion molecules:  
Fibronectin Opsonisation
Thrombospondin Adhesion, phagocytosis
Complement:
C3b, C4b and C2b  Opsonisation

Enzymes:
Lysozyme Degrades bacterial cell walls
Collagenase, elactase Matrix catabolism
Complement Mediated Protection
C3b-R and C4b-R mediated
opsonization and phagocytosis
C3b-R and C4b-R potentiation of
ADCC
MAC (C5b-9) mediated lysis and
neutralization
Complement AssociatedPhagocytosis
C3b-R and C4b-R mediated opsonization and
phagocytosis effective protective mechanism
against
Gram-positive bacterial infections
 Streptococcal (S. pyogenes and S.pneumoniae)
 Staphylococcal (S. aureus)
 Meningococcal (N.meningitidis)
 Plaque (Y.pestis); cryptococcal and anthrax
(B.anthracis).
C3b and C4b potentiate ADCC mechanisms against
various pathogens.
Membrane attack complex activity
Responsible for
 Neutralization of gram-negative bacteria
o E. coli, S. typhi, S. dysenteriae, N.
meningitides, N. gonorrhea),
 Damage of
o Filarial worms (microfilariae),
o Tapeworms (protoscolices of E. granulosus)
and
o Amastigotes of leishmania parasites.
Antibody Dependent Mechanisms
Inhibitionof epithelial
attachment
Neutralization activity
Fc-R mediated opsonization and
phagocytosis
Fc-R potentiation ofADCC
importance of antibody – mediated mechanisms

Depend on host-parasite interactions.


 Acquired resistance gradual and
influenced by the parasite
development stages, species and
dosages.
 Exposure to plasmodium parasites
induces partial immunity dependent
on sporozoite, inoculum,species and
stage specific.
 Anti-circumsporozoite protection
ineffective against blood stage
infective merozoites and vice versa.
Inhibitory responses
In early schistosomiasis anti-egg
stage blocking antibodies inhibit
protective immunity against
cercariae.
o Young schistosomiasis patients
susceptible to cercarial infectivity
despite high anti-egg antibodies.
Inhibition of Epithelial Cell Attachment

sIgA and IgG prevent adherence onto


sub-epithelial mucosal surfaces by
bacterial infections
Cholera (Vibrio cholera);
Gonococcal (Neisseriae
gonorrhoea);
Streptococcal (Streptococcus
pneumoniae);
Dysentery (Shigella dysenteriae);
Neutralizing Antibody Activity
 Live microorganisms release diffusible
exotoxins, neutralized by sIgA and IgG
antibodies.
 IgG potent anti-toxin antibodies in tissue
spaces
 IgG mediate neutralizing activities by binding
exotoxin (antigenic determinants) or
receptors on target cells.
 In poliomyelitis, most neutralizing antibodies
directed at virus protein polypeptide 1 (VP1)
 In parainfluenza virus and adenovirus
infections raised against haemagglutinin and
Neutralizing Antibody Activity cont
Mechanism effective against various pathogens
o Gram-negative bacteria (S. typhi, K.
pneumoniae, V. cholerae, E. coli,
S.dysenteriae);
o Gram-positive bacteria (Cl.tetani, S.
pyogenes, C. diphtheria and S.aureus)
o Viruses( CMV, RSV, parainfluenza, HBV and
HIV.
o Infective protozoan stages (merozoites and
sporozoites)
o Anti-merozoite antibodies neutralize acute
manifestation of malaria.
Neutralizing Antibody Activity cont
Species specific protective IgG in multiple
malaria infections
 Inhibit invasion of normal
erythrocytes thru blocking
glycophorin receptors (merozoite
receptors on erythrocytes)
 Prevent infected erythrocyte entry
into vascular endothelium (heart,
brain and kidney venules parasite
sequester to avoid spleen immune
attack)
Ab Mediated Opsonization and Phagocytosis
Opsonic antibodies facilitate Fc-R mediated
phagocytosis important against
bacterial infections
o Streptococcal (S. pneumoniae)
o Staphylococcal meningococcal
(N.meningitidis)
o Plague (Yersinia pestis),
o Cryptococcal (C. neoformans) and
anthrax (Bacillus anthracis);
Opsonization and phagocytosis
Protozoan infections
o Malaria (P.falciparum),
o Trypanosomiasis (T.rhodesiense);
Echinococcosis (E.granulosus
protoscolices);
Viral infections (HBV).
Antibody Dependent Cell Mediated Cytotoxicity
(ADCC)
 Target organism or parasite killing due to
released cytotoxic factors
o Perforins,
o Lymphotoxins and
o Neutral serine proteases)
 Eosinophil derived cytotoxic peroxidase (EPO),
eosinophil cationic protein (ECP) and major
basic protein (MBP) mediate killing
 ADCC effective against helminthic infections
o Schistosomulae (S. mansoni and S. haematobium)
o Microfilariae (W.bancrofti and Onchocerca volvulus)
during natural oncocerciasis infections
Antibody Dependent Cellular Cytotoxity (ADCC) Mechanism:
Cytotoxic cells express Fc-R for the Ig bound onto the target and
damage it as explained in the text.
Cell Mediated Immunity (CMI)
Mechanisms
Cell Mediated Immunity Mechanisms
Cytotoxic T lymphocytes (CTL)
Macrophage mediated
cytotoxicity
NK cell cytotoxicity
Delayed type hypersensitivity
(DTH)
Cytotoxic T Cells (CTL)
CTL mediate antigen – specific, class
1MHC – restricted cytotoxicity against
o All viruses, obligate intracellular bacteria
(Chlamydia) and some protozoa (T. gondii).
o Induce apoptosis targets and then dissociate
to bind and kill other target cells.
Specific CTL CD8 mediate protective immunity in
o Viral and protozoan infections (influenza and
malaria)
o Influenza virus infected cells lysed by CTL.
CTL Cont
Disease progression correlates with T cell
responses and IgM-anti-HCV antibodies.
Intracellular development of parasites
 P. falciparum inhibited by CTL and
 Cytokines (TNF, IL-6 and C-reactive
proteins)
 Sporozoites induce CTL that
o Recognize plasmodium parasite antigens on
the surface of malaria infected hepatocytes
o Damaged by the parasite specific CD8+ CTL.
Macrophage Mediated Cytotoxicity
CTL derived γ-IFN efficiently activate mφ to
fuse their phagosomes and lysosomes
more
o Increase synthesis of NO, ROI, antimicrobial
peptides and IL-12.
Activated mφ increase phagocytic,
metabolic oxygenation and respiratory
burst activity.
o Microbicidal mechanisms involve
• Oxygen dependent damage eg H2O2
• Myeloperoxidase-halogen system with production
of HCL03 and enhanced free chlorine.
Mφ Cyt Cont
Macrophage mediated cytotoxicity involve ROI
(H2O2 and superoxides, oxidant stress, potent
against
 Obligate intracellular parasites in mφ
(L.donovani and T. gondii);
 Plasmodium parasites in red blood cells
(intraerythrocytic death);
 Mycobacterial (M.tuberclosis and M.Leprae)
 Staphylococcal (S.aureus) and salmonella
(S.typhi) infection
NK Mediated Cytotoxicity (NK Cyt)
Th1 cytokines (IL-2 and IFN-γ) activate NK cells
 Releasing pore-forming proteins (perforins),
proteolytic enzymes (granzymes) and
chemokines leading to apoptosis.
NK provide early defence against
 Intracellular
infections (herpex group
viruses, Leishmania and Listeria).
 Primed NK cells kill viral and tumour cells by
apoptosis (low or no MHC Ag expression-target)
 ADCC mediated by killer (K) cells, a sub-
population of NK cells.
Delayed Type Hypersensitivity (DTH)
Confer host protection against
 Bacteria

o Mycobacterial infections (M.leprae;


M.tuberclosis);
o Chlamydia species;
o Syphilis (Treponema pallidum infection)
o Staphylococcal (S. aureus) and salmonella
(S.typhi) infections;
 Obligate intracellular parasites (L.donovani, L.
aethopica and T. gondii);
 Fungal infections ( mucocutaneous candidiasis
and coccidiomycosis)
DTH in Leshmaniasis
Cutaneous leishmaniasis disease pattern.
 Allergic response in one extreme characterized
hyperactivity to parasite antigens with few or
no parasites (L.tropica) infection.
 Other extreme patients are anergic with
multiple disseminated parasite filled ulcers and
little spontaneous (L.aethiopia )infection.
 In between, an optimal DTH,a single sore leads
to a spontaneous cure mediated by the DHT
DTH Leshmaniasis cont
Protected individuals demonstrate
Primed CD4+ T cells, activated
macrophages, giant cells and
absences of bacteria.
Immunosuppressed patients have
Increased replication of bacteria in
macrophages
Elevated CD8 T suppressor cells.
Parasite and Microbe Immune Evasion Stratagems
Privilegedanatomical site
Antigenic variation and
camouflage/mimicry
Impairment of phagocytic cell
associated functions
Latency infections and modulation of
antigens.
Promotion of Epithelial Attachment
Commensals in epithelial surfaces
(nasopharynx, colon) and
pathogenic agents (Neisseria
gonorrhoea) fail to induce protective
sIgA
Bacteria periodically changes pilin
surface antigens.
Epithelial attachment cont
 Helicobacter pylori survive in worst
environment (pH -1.4) by converting urea
into ammonia neutralizing acid and virus
in salivary glands.
Disruption of epithelial cells
o Helicobacteria pylori secreted proteins
or receptors used by
o Streptococcus pneumoniae in the
nasopharynx for transporting IgA
and IgM antibodies
Intracellular Infection
Intracellular infection facilitate avoiding
antibodies eg
Herpes viruses, measles virus,
mycobacteriae, brucellae,
Cryptococcus neoformans,
Plasmodium, leishmaniae,
trypanosomes and toxoplasmas or
spread directly from host cell to the
other.
Physical Barriers
Some parasites and microbes develop cell
walls or physical barriers against
immune attack.
Encystment strategy employed in E.
granulosus, G. lamblia and
E.histolytica infections.
E. granulosus fibrous tissue
surrounds fluid filled capsule
containing protoscolices
Cell wall development
T.spiralis
and T.saginata larvae
surrounded by collagenous capsule
in the muscles, providing a physical
barrier.
Mycobacteria elaborate lipid rich cell
wall capsule resistant to lysosomal
enzymes.
Intracellular Infections
Malaria-infected erythrocytes express endothelial
cell receptors facilitating adherence in the
microvessels.
 Cerebral malaria uncommon in tolerant
children
 Parasitized erythrocytes sequester evenly and
thinly in various tissues
 Sporozoite in hepatocytes (liver anatomical
arrangement) provide physical barrier
o Prevent direct contact between hepatocytes
and erythrocytes
Intracellular Infection cont
 Leishmania proliferate and multiply
without triggering phagocyte respiratory
burst activity.
 Malaria uninfected red blood cells with
high glutathione activity avoid the
oxidant stress.
o P.falciparum infected erythrocytes
form spontaneous rosettes resistant to
oxidative killing
Antigenic drift
 A small change involving
point mutation or single
nucleotide alteration
resulting in a single
amino acid change
recognized by the
immune system
 In influenza virus point
mutations in the genes
coding for
Haemagglutinin and
Neuraminidase lead to
many changes in its
antigenic structure
Antigenic drift
Antigenic shift
Antigenic shift
A drastic change in antigenic structure that may be
due to genetic reassortment between human and
non-human viruses eg human and avian influenza
A
Antigenic Variation
Parasites in blood or interstitial fluid
evade attack through antigenic
variation through
Periodic alteration in
membrane surface parasite
epitopes
Different variant surface
glycoprotein expressed (VSG)
by trypanosomes
P. falciparum periodically alters
Antigenic var cont
Changes in HIV envelope proteins
through
 Coding errors mediated by
reverse transcriptase and
 High mutation rates during
replication
Antigenic Variation cont
Continuous change in the antigenic
repertoire facilitates evasion of potent
immune responses.
 Antigenic variation displayed by bacteria
(Neisseria gonorrhoea, intestinal bacteria).
 N. gonorrhoea possesses 50 distinct
glycoprotein and lipopolysaccharide antigens
and N. meningitidis expresses 10 antigenic
types (serotypes).
 Rhinoviruses with 82 and enteroviruses with 62
different antigens.
Antigenic Variation cont
Different antigens exists in
protozoan infections
 Plasmodium geographical
subpopulations or variants
responsible for antigenic variation in
malaria.
 Classic antigenic variation displayed
by trypanosome continuous change
of variable surface glycoproteins
(VSG)
Phagosome-Lysosome Fusion
Prevention of phagosome-lysosome fusion
allows
 Mycobacteria protected intracellular
location (M. tuberculosis and Salmonella
enterica)
 Bacteria release toxins and inhibitors,
(subvert mφ and neutrophil mediated
phagocytosis)
Phagosome-Lysosome Fusion cont
Capsular components (N. meningitides and
B. anthracis polysaccharides) anti-
phagocytic.
 S. aureus infections, sIgA mediates anti-
phagocytic activity through binding to
IgG – Fc receptor sites
o Diminishes Fc – R mediated
opsonization and phagocytosis.
Phagocytosis Interference
Parasites interfere with process of
phagocytosis and the activation of
oxidative killing mechanisms.
T.gondii parasites replicate in
macrophages (inhibit phagosome –
lysosome fusion)
M. leprae and T. pallidum evolve cell
walls resistant to lysosomal acid
hydrolases and multiply in the
cytoplasm.
Phagosome inteferance
Chlamydia enter directly into the
cytoplasm and avoid phagosome-
lysosome fusion.
Trypanosome cruzi rupture from the
phagolysosomes, avoid low pH and
high concentration of lysosomal
hydrolases.
Phagocytosis Interference cont
Plasmodium parasites
synthesize histidine rich
proteins (HRP),
o Potent
ROI inhibitors or
scavengers
Bacterialcapsules serve as anti-
phagocytic shields (S.
pneumoniae and S. aureus)
Inhibition of sIgA Protease Activity
IgA protease and fabulation involve IgA 1
splitting at the hinge region results in
 Fab fragments that attach onto surfaces
of organisms preventing binding of other
antibodies (Neisseriae, Haemophilus
influenzae).
 Gram-positive bacteria(Streptococcus
pyogenes) secrete proteolytic enzymes
which degrade Igs
Antigenic Mimicry/Camouflage
Antigenic mimicry/camouflage involves
incorporation of host proteins
 Schistosomes, coated with ABO and HLA
antigens (escape ADCC mediated by IgE)
 Larva stages of T.spiralis and
E.granulosus acquire Igs on wall
surfaces
 Viral influenza utilizes antigenic
camouflage strategy
Molecular mimicry
Parasitegenome encodes host- like
gene sequences expressed on their
surfaces (larval trematode stages).
Decoy Receptor – Mediated Endocytosis

Intracellular pathogens employ receptor-


mediated endocytosis to gain entry into
the host cell through
 Expression of surface decoy ligand for
receptor on target cell leading to binding
and tricked engulfing of microbes
 EBV binds receptors on B cells, HIV
attaches on CD4+ cells, T cells and mφs
 Influenza haemagglutinin binds
carbohydrate expressed on target cell
surfaces.
Receptor-mediated endocytosis
Allows
 Bacteria (Salmonella typhi) to enter the
host cell and
 M. tuberculosis binds C3 forming C3
convertase (opsonizes it for
phagocytosis).
Avoidance of CD8+ CTL activity
Dormancy or latency and inhibition
of synthesis of class 1 MHC
molecules eg
HSV synthesizes few proteins
during dormancy
CMV synthesizes proteins that
degrade class 1 MHC
molecules
Multiple Hosts
 Multiple hosts- parasites complete life
cycles by sequentially infecting one or
more alternate hosts (P.vivax and S.
mansoni).
 Parasites cause acute illness of short
duration and finding other hosts (measles
and influenza)
o Prevented through herd immunity leading to
reduction in the number of susceptible targets
to sustain an epidemic.
Multiple Hosts cont
Chronic infection
Evade immune response (malaria,
trypanosomiasis, tuberculosis,
leprosy and schistosomiasis)
Commensalism
 Microorganisms live harmlessly in the
body (commensalism) or benefit the host
(mutualism) thru
o Periodically changing surface antigens and
coats itself with a polysaccharide capsule.
Antigenic Modulation/Capping
Phenomenon

Capping by antibodies achieved when


 Combines with microbial antigens, form
complexes and move or
 Redistribute through the fluid medium of
the host cell membrane to form a cap or
cluster at one pole and
 Are either shed into the environment or
endocytosed, hydrolysed in the
lysosome (measles virus, T. gondii and
leishmaniae)
Immunosuppression
A profound or graded depression of
immune responses.
Involve disruption of the lymphoid
organ architecture (trypanosomes,
HIV and CMV
Direct damage of immunocytes
(CMV)
Immunosuppression
 Result in markedly decreased antibody
responses, reactivation and multiplication of
infectious agents.
 Impairment in specific antibody production

-anergic leishmaniasis (L.aetropica)


infected patients.
o Chronic HBV infections, antibody
responses markedly suppressed and poor
 In HIV infection profound decrease of CD4,
CD8, and anti-viral factors occur
Long Latency Period
HIV and HBV associated with
 Long incubation periods without clinical
expression of the disease.
 Quiescent or dormant period associated
with absence of immune response and
virus remains intact.
Reactivation occurs during :Pregnancy
o Organ transplantation
o Blood transfusion
o Or infection induced immune system
activation.
Vaccines
Vaccines
Vaccinationand Immunization
Vaccine Types
Vaccine Production
Most Widely Used Vaccines
Expanded Program of
Immunization
Vaccination and Immunisation
 Activeimmunization-stimulation of immune
system to develop its own immunity against
pathogens
 Edward Jenner showed cowpox (L. vaccines)
induced protection against smallpox
o Derived the concept of vaccination or
immunoprophylaxis.
 Passiveimmunity conferred from
administration of preformed antibodies (horse
serum or human)
o Provide immediate protection of short duration.
Vaccination and Immunisation cont
Active immunization involves the use of
 Live attenuated infectious agents;
 Detoxified killed bacterial extracts/secretions or
products.
 In many viral infections like influenza,
poliomyelitis, rabies, measles and mumps, both
procedures widely applied.
Unsuccessful immunization in neonates associated
 Poor polysaccharide antigens (bacterial capsule
polysaccharides)
 Neonates commonly infected with encapsulated
H. influenzae meningococci, pneumococci and
group B streptococci, responsible for high
Types of Vaccines
Inactivated vaccines killed organisms often with
formaldehyde e.g.,
 Prepared from killed entire organism (typhoid
vaccine and inactivated polio vaccine (IPV).
Attenuated vaccines: live organisms cultured to
reduce pathogenicity, retain antigenicity eg
 BCG, measles, mumps and rubella and oral
polio vaccine (OPV).
 Toxoids prepared from formaldehyde
denatured diphtheria and tetanus bacteria
toxins
Subunit vaccines
Purified surface molecules of pathogens eg
 HBsAg expressed in E. coli
 Purified capsular polysaccharides of 23
strains for S. pnuemoniae vaccine.
Most Widely Used Vaccines
Disease Vaccine Comments

Diphtheria Toxoid Often given to children in a single preparation


(DTP; the “triple vaccine”) or the now-
Tetanus Toxoid preferred DTaP using acellular pertusis

Pertusis Killed bacteria (“P”) or their purified


components (acellular pertusis = “aP”)
Polio Inactivated virus Inactivated polio vaccine: IPV (Salk)

Attenuated virus Oral polio vaccine: OPV (Sabin). Both


vaccines trivalent (types 1,2 and 3)
Hepatitis B Protein (HBsAg) from the surface of the virus Made by recombinant DNA technology

Diphtheria, tetanus, pertusis, polio and Uses acellular pertusis and IPV (Salk) Combination vaccine given in 3 doses to
hepatitis B infants
Measles Attenuated virus Often given as a mixture (MMR). Do not
increase the risk of autism.
Mumps Attenuated virus

Rubella Attenuated virus

Chicken pox (Varicella) Attenuated virus Caused by the variecella-zoster virus (VZV)

Influenza Heamagglutinins Contains heamagglutinins from the type A


and type B viruses recently in circulation

Attenuated virus Contains weakened viruses of the type B and


two type A strains recently in circulation

Pneumococcal infections Capsular polysaccharides A mixture of the capsular polysaccharides of


23 common types. Works poorly in infants.

7 capsular polysaccharides conjugated to Mobilizes helper T cells; works well in


protein infants
Live attenuated vaccine characte
 Possess the advantages of being cheap;
 Administered orally;
 Confer long life protective immunity that
mimics one acquired through natural
infections.
 Multiply in the recipient and increase
levels of the antigens and subsequent
antibody dependent mechanisms.
 Single dose adequate for the induction
of life long immunity.
Live vaccines characteristics
 Possess the advantages of being cheap;
 Administered orally;
 Confer long life protective immunity that
mimics one acquired through natural
infections.
 Multiply in the recipient and increase
levels of the antigens and subsequent
antibody dependent mechanisms.
 Single dose adequate for the induction
of life long immunity.
Inactivated or killed vaccines
 Require multiple applications
 More stable and possess safety
advantage if properly inactivated in
comparison to live vaccines.
Immunization coverage facilitated through
availability of heat-stable, single dose,
non-toxic and orally administered
vaccines.
Toxoid vaccine production
 Toxin produced from bacterial culture (C.
diphtheriae and CI. tetanus vaccines)
 Diphtheria toxoid and tetanus toxoid
formaldehyde-inactivated toxins
adsorbed onto aluminium salts for
increased immunogenicity.
 Toxoid tested for sterility, potency,
innocuity; specific toxicity, adjuvant
content, preservatives, content and
identity.
Live Vaccines Production
Viral vaccine production requires
 Use of either living tissue (human,
monkey and chicken embryos) or cell
lines as substrates for viral growth.
 Chicken embryo used for yellow fever and
influenza vaccines.
Human cells employed in the production of
o Rabies, measles, mumps, and rubella and
polio vaccines.
Attenuated BCG prepared from live culture
filtrate of M.tuberculosis bovis
Expanded Programme of Immunization (EPI)
Vaccines currently available include
o Meningococcus, rotavirus, HAV, HBV, rabies,
TB,
o Measles, mumps, poliovirus, varicella zoster,
o Tetanus, diphtheria, adenovirus, influenza,
yellow fever,
o Anthrax, cholera, plague, pneumococcus and
typhoid.
Global EPI include
o Polio, measles, neonatal tetanus, pertussis
(whooping cough), tuberculosis and hepatitis
B (National immunization schedule for
infants)
Schedule for Active Immunization of Children and Adults (Global EPI)

Age Vaccine

Birth Hepatitis B ( Hep B)

1-2 months Hep B

2 months Diphtheria and tetanus toxoids and cellular pertussis


(DTP), Haemophilus influenzae type b ( Hib),
inactivated polio (IPV) DTP, Hib, IPV, rotavirus ( RV).

4 months Hep B, DTP, Hib, IPV, Rv

6 months Oral polivirus vaccine (OPV), measles, mumps, rubella


MMR,

12-15 months Varicella vaccine for susceptible children

4-6 years DTP, OPV, MMR

11-12 years HepB, MMR, Varicella

25-64 years Measles, rubella

>65 years Influenza, meningitis and pneumonia


Kenya Expanded Programme of Immunization (KEPI)

Infant Age Vaccine

At birth (or before 2 weeks) B.C.G., Oral Polio


6 weeks (1.5 months or soon Oral Polio 1, + Pentavalent I
after) Oral Polio II, + Pentavalent
10 weeks (2.5 months or II
soon after) Oral Polio III + Pentavalent
14 weeks (3.5 months or III
soon after) Measles, Yellow fever*
9 months or soon after
*Yellow fever vaccine is only available in
Koibatek, Keiyo, Marakwet and Baringo
Districts of Rift Valley Province. Pentavalent
Vaccine = DPT + HBV + Haemophilus
influenza type B (Hib)
Polio Vaccine
Inactivated polio vaccine (IPV) and live attenuated
trivalent oral polio vaccine (TOPV)
 Induce neutralizing IgG and sIgA antibodies
effective against poliomyelitis.
 Major poliovirus protein antigen sites are VP1,
VP2 and VP3.
IPV (Salk vaccine) less efficient at inducing sIgA
in the respiratory and intestinal tract systems
 Provides individual protection against polio
paralysis.
TOPV,Sabin (Type I, II, III) confers efficient gut
humoral immunity but associated with risk of
paralysis.
Polio Vaccine cont
 Combination IPV and TOPV increases vaccine
efficacy in poliomyelitis control programmes.
 Profound proteolytic environment of intestinal
fluid alters the efficacy of live polio vaccines.
TOPV preferred due
 Low cost
 Ease of administration
 Superiority in conferring intestinal immunity
 Extended vaccine coverage through infection
of household and community contacts.
Meningitis Vaccine
Vaccine comprises 13 capsular
polysaccharide antigens
o Effective
against A and C
serogroups.
Natural meningococcal
infections
o Induceprotective anti-B group
polysaccharide antibodies.
Measles Vaccine
Measles vaccine the last one to
be given under the EPI schedule.
Newly developed vaccine
clinical trial -ISCOM (immune
stimulated complex)
o Measles virus proteins with
purified plant extract (saponin)
DTP Vaccine
Traditional DTP vaccine consists of three comp
 Detoxified tetanus toxoid; killed whole cell
pertussis and C. diphtheriae bacteria.
Acellular DTP vaccine contains either
 Filamentous haemagglutinin, pertactin and
pertussis toxin inactivated with formalin and
glutaraldehyde or
 One with filamentous haemagglutinin
pertactin and genetically detoxified pertussis
toxin.
Acellular DTP vaccines are fairly safe,
immunogenic and effective against pertussis.
Tuberculosis Vaccine
Live attenuated Bacille Calmette-Guerin contains
M. bovis.
 Vaccine only 50% - 80% effective against
severe childhood TB meningitis and miliary TB.
 BCG vaccination does not lead to low-level
infection
 No reliable immunological marker of protection
against tuberculosis
o Degree of protection not correlate with
tuberculin test sensitivity
Hepatitis B Vaccine
Plasma of symptomless carriers with hig(HBsAg)
 Inactivated through treatment with
formaldehyde, heat, pepsin or urea.
Recombinant DNA derived HBV vaccine
 Consist of hbsag particles expressed
recombinant DNA in the yeast (immunogenic,
effective and safe)
 Purified HbsAg particles adsorbed on
aluminium hydroxide and preserved with
thimmersol.
 HBV vaccine administered intramuscularly to
the individuals at risk of infection
Yellow Fever
 Not at the moment recommended for EPI.

 Contains freeze-dried live attenuated 17D


virus strain.
 Highly immunogenic and confers
protection for at least 10 years.
 Given to high-risk populations mainly in
Rift Valley Province (Keiyo, Koibatek,
Baringo and Marakwet).
Recombinant DNA vaccine
Recombinant DNA technique involves
 Cloning of genes coding for putatively protective
antigens
 Expression in and purification from prokaryotic
cells like Escherichia coli.
Safer, immunogenic and free from side effects
e.g.
 Recombinant vaccinia virus vaccines produced
by introducing foreign viral DNA into the vaccinia
DNA
 Hepatitis B, herpes simplex, rabies, and other
viral vaccines
Major advantages of these vaccines
 Low cost and ease of administration by multiple
pressures or by scratch technique
Synthetic Vaccines
Chemical synthesis of antigen involves
 Encoding by isolated genes,
 Sequenced and putative peptides
assembled eg
o Wholly synthetic vaccines explored for
malaria and diarrhoel diseases,
o New conjugate vaccine for
Haemophilus influenza type B, Hib.
Idiotypic Vaccines
 Idiotypic vaccines involve use of anti -idiotype
antibodies
o Serves as a mock antigen including
antibodies that recognize and block the
original antigen (idiotype).
 Elicit non-MHC restricted specific cellular
immunity
 Used as alternatives to polysaccharide derived
vaccines (normally poor immunogens for
antibody responses)
Internal image vaccines
Major advantages
Overcome constraints in vaccination
against some parasites and viruses
due to their antigenic variation
strategen to avoid immune attack.
Circumvent HLA restricted T cell
reactive vaccines (epitopes)
Subunit Vaccines
Purified surface molecules are
subunits of pathogens eg
 HBsAg expressed in E. coli
Purified capsular
polysaccharides of 23 strains
for S. pnuemoniae vaccine.

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