10May06KLVadheim Lecture 21 Types of Vaccines II

10May06 KLVadheim Lecture 2 1

Types of Vaccines IIType of vaccine Bacterial Viral

Live attenuated

Typhoid (Ty21a)BCG

Polio (OPV)Influenza (FluMist)MeaslesMumpsRabies (old)RotavirusRubellaVacciniaVaricellaYellow Fever

Whole

PlagueCholeraAnthraxPertussis (old)

Japanese Encephalitis VirusPolio (IPV)Hepatitis ARabies (HDCV and PCECCV)Influenza (old)

Toxoids DiphtheriaTetanus

Subunits Pertussis (new) InfluenzaProtein

Recombinant HepB

Pure MeningococcalPneumococcalTyphoid Vi

Inactivated/Killed

Fractional

Polysaccharide

Conjugated HibMeningococcal


Types of Vaccines IIIType of

AdministrationBacterial Viral

Intramuscular DiphtheriaTetanusPertussis (whole cell)Acellular PertussisPlaguePneumococcalTyphoid Vi

Hepatitis AHepatitis BHaemophilus influenzae bMost FluRabies

Subcutaneous AnthraxMeningococcalPneumococcal

Japanese Encephalitis VirusMeaslesMumpsRubellaPolio (IPV)VaricellaYellow Fever

Intradermal BCG Vaccinia (Smallpox)Rabies (HDCV for pre-exposure vaccine)

Inhaled FluMist

Oral RotavirusTy21a

Polio (OPV)


The Perfect Vaccine• 100% effective• Oral dosage form• No adverse effects• Highly immunogenic

– life-long immunity from a single dose

– no boosters required

• Cheap• Stable at room temperature

– no cold chain required


Combination vaccines

• DT

• DTaP

• DTaP-HepB-IPV

• HepA-HepB

• Hib-HepB

• MM

• MMR

• MMRV


The Bare Minimum Immunology

MedCh 401 Spring 2006

Lecture 2


Immunology• The science of differentiating self from non-

self

• Defense against invaders– Bacterial– Viral– Fungal– Parasitic– Particulate (e.g., slivers)


Immune system characteristics

• Specificity

• Memory

• Tolerance


Blood cells

• RBCs - carry oxygen

• WBCs - immune cells– lymphocytes– Natural Killer cells– Polymorphonuclear leukocytes (PMNs)– macrophages


The immune system is...

• General and specific

• Innate (natural) and acquired (adaptive)

• Active and passive– Natural and artificial

• Cell-mediated and humoral

• Primary and secondary immune responses


Some General Immune Responses

• Fever

• Malaise

• Inflammation

• Localized erythema


Essential Concepts• Active

– Produced by one’s own immune system, e.g., development and recovery from disease

– More permanent (years)

• Passive– Produced by other humans or animals and

infused, injected, ingested or absorbed into recipient

– Transient (weeks to months)


Active Immunity

• Natural– Host produces

antibodies in response to infection

– Host develops protective response to live viral vaccine

• Artificial– Host produces

protective immune response to killed cells, detoxified toxins, etc.


Passive Immunity

• Natural– Placental transfer of

maternal antibodies (IgG)

– Transfer of maternal antibodies via nursing (IgA)

• Artificial– injection of immune

serum from person who has recovered from disease

– transfusion of hyperimmune serum from animal


Summary

Immune response to disease

Response to live vaccinee.g., MMR

Natural

Response tokilled vaccine

or detoxofied toxin

Artificial

Active

Maternal antibodies:Transplacental (IgG)

Breast milk (IgA)

Natural

Immune orHyperimmune

Serum

Artificial

Passive

Im m une System


Innate immunity

• Surface barriers– Skin– Ciliary action of respiratory epithelia– Mucus in respiratory and urogenital tracts– Acid pH of skin secretions– Lysozyme in tears, saliva, perspiration– Extreme acidity of stomach


Innate immunity II

• Normal flora– Staphylococcus aureus on skin– E. coli in gut– Candida in vaginal tract– Corynebacteria diphtheriae in laryngeal

passage


Innate Immunity III

• Macrophages– Kupffer cells - liver– microglia - CNS– mesoangial cells - kidney– osteoclasts - bone

• Natural killer cells

• PMNs (and other WBCs)


Innate Immunity IV

• Complement system– Enzyme cascade– Not antigen-specific– Enhances phagocytosis– Stimulates inflammation, increasing capillary

permeability to increase plasma and complement flow to injury

– Can directly lyse cells


Innate Immunity V

• Dendritic cells– Langerhans cells– Interstitial dendritic cells– Interdigitating dendritic cells– Circulating dendritic cells


Acquired Immunity I• Cell-mediated - these are lymphocytes

– T cells• TH2 (Helper) CD4+ - activate T and B cells

• TH1 (DTH) - role in allergies

• TC (Cytotoxic) CD8+, aka CTLs - kill cells with foreign Ag on the surface

• Memory

– B cells• Plasma cells (produce antibodies)

• Memory B cells


Acquired immunity II

• Active– Develop and recover from disease

• Passive– Transplacental maternal antibodies (IgG)– Maternal antibodies in human milk (IgA)


Summary

Su rfac e B ar r ie rs C o m p le m e n t sy s tem N orm al flo ra M a cro p ha g esN a tu ral K iller ce lls

P M N sD e nd r itic ce lls

In n a te

T H 1

T H 2

T C

M e m o ry T c e lls

T ce lls

A P C s

M e m o ry B c e lls

B C e lls

C e ll-m e d ia ted

IgM

IgG

IgA

IgD

IgE

A n tibo d ies

H u m o ral(B ce lls to P lasm a c ells)

A c qu ired

Im m u n e sy stem


Variability of the immune response

• Avidity (binding affinity)– low for recent infections– high for secondary immune responses

• Specificity– low for primary immune responses– high for secondary immune responses


Immunoglobulins

• IgA - primary antibody in secretions; half-life ~5 days

• IgM - primary antibody response; half-life 5-10 days

• IgG - secondary antibody response; half-life 21-24 days

• IgD - found on B cell surfaces

• IgE - bound to mast cells; amplifies immune response


Antibody functions• Opsonization - coating Ag with Ab enhances

phagocytosis• Steric hindrance - bind to surfaces of

microorganisms and prevent attachment to cells• Toxin neutralization• Agglutination and precipitation - bind to surface

of microbes and precipitate them; reduces number of infectious units and enhances phagocytosis


Antibody functions II• Complement activation

– induces inflammatory response– attracts phagocytes to site of infection– opsonizes cells with foreign antigens– lyses some bacteria and viruses

• Antibody-dependent cell cytotoxicity - IgG enables Natural Killer cells to recognize and kill opsonized target cells


Primary v. Secondary Immune Responses

IgG

IgM

Antibody Conc.

Time after immunization


When good things go bad...• Allergies

– Hay fever– Delayed-type hypersensitivity– Anaphylaxis

• Autoimmunity– MS (CNS) – Amyotrophic Lateral Sclerosis (ALS; -motor

neurons of spinal cord)– Primary biliary cirrhosis (liver)


Terms to Know• Anaphylaxis• Antigen• Antibodies

– types

– functions

• Antigen-presenting cells

• Allergen

• Complement• WBC v. RBC• T and B Memory cells• Natural v. artificial

responses• Active v. Passive

responses • B, T and Plasma cells• Phagocyte

Documents

10May06KLVadheim Lecture 21 Types of Vaccines II