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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
10May06 KLVadheim Lecture 2 2
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)
10May06 KLVadheim Lecture 2 3
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
10May06 KLVadheim Lecture 2 4
Combination vaccines
• DT
• DTaP
• DTaP-HepB-IPV
• HepA-HepB
• Hib-HepB
• MM
• MMR
• MMRV
10May06 KLVadheim Lecture 2 5
The Bare Minimum Immunology
MedCh 401 Spring 2006
Lecture 2
10May06 KLVadheim Lecture 2 6
Immunology• The science of differentiating self from non-
self
• Defense against invaders– Bacterial– Viral– Fungal– Parasitic– Particulate (e.g., slivers)
10May06 KLVadheim Lecture 2 7
Immune system characteristics
• Specificity
• Memory
• Tolerance
10May06 KLVadheim Lecture 2 8
Blood cells
• RBCs - carry oxygen
• WBCs - immune cells– lymphocytes– Natural Killer cells– Polymorphonuclear leukocytes (PMNs)– macrophages
10May06 KLVadheim Lecture 2 9
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
10May06 KLVadheim Lecture 2 10
Some General Immune Responses
• Fever
• Malaise
• Inflammation
• Localized erythema
10May06 KLVadheim Lecture 2 11
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)
10May06 KLVadheim Lecture 2 12
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.
10May06 KLVadheim Lecture 2 13
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
10May06 KLVadheim Lecture 2 14
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
10May06 KLVadheim Lecture 2 15
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
10May06 KLVadheim Lecture 2 16
Innate immunity II
• Normal flora– Staphylococcus aureus on skin– E. coli in gut– Candida in vaginal tract– Corynebacteria diphtheriae in laryngeal
passage
10May06 KLVadheim Lecture 2 17
Innate Immunity III
• Macrophages– Kupffer cells - liver– microglia - CNS– mesoangial cells - kidney– osteoclasts - bone
• Natural killer cells
• PMNs (and other WBCs)
10May06 KLVadheim Lecture 2 18
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
10May06 KLVadheim Lecture 2 19
Innate Immunity V
• Dendritic cells– Langerhans cells– Interstitial dendritic cells– Interdigitating dendritic cells– Circulating dendritic cells
10May06 KLVadheim Lecture 2 20
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
10May06 KLVadheim Lecture 2 21
Acquired immunity II
• Active– Develop and recover from disease
• Passive– Transplacental maternal antibodies (IgG)– Maternal antibodies in human milk (IgA)
10May06 KLVadheim Lecture 2 22
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
10May06 KLVadheim Lecture 2 23
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
10May06 KLVadheim Lecture 2 24
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
10May06 KLVadheim Lecture 2 25
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
10May06 KLVadheim Lecture 2 26
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
10May06 KLVadheim Lecture 2 27
Primary v. Secondary Immune Responses
IgG
IgM
Antibody Conc.
Time after immunization
10May06 KLVadheim Lecture 2 28
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)
10May06 KLVadheim Lecture 2 29
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