1 basic concepts in immunology
TRANSCRIPT
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BASIC CONCEPTSIN IMMUNOLOGY
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The perfect world
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The real world
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IMMUNOLOGYKEYS
Immunity: resistance to disease
Immune System: the collection of cells, tissuesand molecules that mediate the resistance
Immune Response: the response made by host to defend itself against
foreign substances
The coordinated work of these cells and molecules
The Physiological Function: preventand eradicate
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DEFENCE AGAINST INFECTION
A. Physical barriers
B. Innate immunity
C. Adaptive immunity
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BODYDEFENSE
1. quick healing if broken
2. Skin
Fatty acid on the skin
3. Tight epithelial junction
4. Self cleaning
Coughing sneezing
Mucous & air flow in the
RT
Urine flow in the UT
Diarrhea and vomiting
Saliva, sweat & tears
5. In-hostile environment
PH (stomach and urine)
Anti-microbial peptides Defensins by epithelial cells
Cryptidins by intestinal
epithelial cells
Surfactant factors in the RT
The presence of normal flora Competetion
Secretion of antibacterial
substances (Colicins)
Enzymes lysozymes
A. Physical barriers (mechanical, chemical & microbial)
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BODYDEFENSES
B. Innate immunity Consist of chemical and cellular defense mechanism First line of defense Lacks the ability to recognize certain pathogens Lacks the ability to provide specific protective immunity that
prevents re-infection (no memory) Triggered immediately Focusing of these mechanisms to site of invasion (inflammation) if inflammation does not remove invaders, Adaptive immunity
get activated
C. Acquired (adaptive immunity) development of immunological memory. Specificity Is generated by clonal selection of lymphocytes (theory- Fig 1)
Takes time Strengthen with second exposure primary response vs
secondary response (Fig 2)
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THEPRINCIPLEMECHANISMSOF
INNATEANDADAPTIVEIMMUNITY
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MECHANISMSOFADAPTIVEIMMUNITY
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CLONALSELECTIONTHEORY- FIGURE 1
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HISTORY
Early human societies Outbreaks
many died
survivals remain healthy on subsequent outbreaks
Smallpox- Variola major ~40-80% mortality
Variola minor 5-10% mortality
Rinderpest (cattle plaque)
Jenner-1798 used cowpox or vaccinia ---1979eradicated - Fig 3
Cowpox and canine distemper (failed)
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BY 1979 WHO DECLAREDSMALLPOXERADICATED (FIG 3)
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HISTORY
Pasteur-1880s- vaccine against Fowl cholera in chickens (Pasteurella
multocida)
Old culture protect accidentally allowed to age
Birds remain healthy Second infection with fresh P. multocida no disease
Virulent vs avirulent
Anthrax & rabies vaccine
Salmon in the USAalso dead organism could be
used as a vaccine
Robert Koch: infectious disease caused bymicroorganism (pathogens) each responsible for aparticular disease (pathology)
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HISTORY
Serum can neutralize toxins and can protect Antibodies
Tetanus toxin is antigen.
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THECOURSEOFATYPICALADAPTIVEIMMUNE
RESPONSE- FIGURE 2
Lag phase 2
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Important principle of Humoral
immunity
After single injection no Ab is detectable for several days Lag
period.
Abfirst detectable about one week post injection, and climbs for
10-14 days before declining again and disappeared within fewweeks primary response.
Second dose injection, 2 days lag period. Faster response, high
level of Ab, and more prolonged protection up to months or years.
memory cells.
Third dose response??
Negative response????
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IMPORTANTPRINCIPLEOF CELL-
MEDIATEDIMMUNITY
Destruction and removal of abnormal cells, cancer cells,
virus infected cells, and graft rejection.
First-set reaction: 7-10 days.
Second-set reaction: 1-2 days, and more powerful.
Lymphocye.
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TERMS
Immune responseAntibody
Antigen
Antigenicity
ImmunogenicityAntigenic determinant (Epitopes)
Haptens
Opsonization
Antigen presentation Phagocytosis
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IMMUNOLOGYKEYS
Immune response: the response made by host to defend itselfagainst foreign substances
Tolerance: immune system able to recognize its own cellas not foreign, and not elicit immune response
Antibody is a protein that binds specifically to a substance (antigen)
all antibodies have the same basic structure
produced by cells known as plasma cells
binds to and neutralizes foreign substances (pathogens) and prepare themto be engulfed
Phagocytosis : Active process rounded a particle matter(internalization) by cells - usually referred to as phagocytic cells(phagocytes)
Haptens: small molecule
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IMMUNOLOGYKEYS Opsonization: alteration of the surface of a pathogen or
other particles so that it can be ingested by phagocytes
Antigen: any molecule that can bind specifically to antibody.
not all antigens can generate antibody
those antigen that can generate antibody are calledimmunogens.
Antigenic determinant: a portion of an antigen that isbound to a given antibody (also called epitope).
Antigen presentation: describes the process by whichthe antigen displayed as a peptide fragments bound to amolecule known as MHC Major histocompatibility complexfound on the surface of a cell.
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ANTIGENICITY VS IMMUNOGENICITY
Antigenicity: the ability of molecule to be recognized by a
product of immune system. Size, complexity, stability, degradability, and foreignness.
Immunogenicity: the ability of molecule to elicit animmune response.
Antigenicity, foreignness
Plastic and Stainless steel??
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Lipid and nucleic acids are a poor antigenic
Simplicity, instability, rapidly degenerated, Act as Haptens.
Bacterial antigens:
Cell wall: enodtoxin
Capsule: K antigen
Pili:
Flagella: flagellin protein, H antigen
Exotoxin: secreated by bacteria.
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DETERMINANTS RECOGNIZEDBYTHE
INNATE IMMUNE SYSTEM
Adaptive Immune System Discrete Determinants ( )
Reacts with a specific pathogen
Innate Immune System Broad Molecular Patterns
Reacts with a variety of pathogens
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DETERMINANTS RECOGNIZEDBYTHE
INNATE IMMUNE SYSTEM
PAMPs Pathogen Associated Molecular Patterns
PRRs Pattern Recognition Receptors
Biological
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PAMP
PRR
Biological
Consequence of
Interaction
Microbial cell wall
components
Complement Opsonization;
Complement
activation
Mannose-
containing
carbohydrates
Mannose-binding
protein
Opsonization;
Complement
activation
Polyanions Scavenger receptors Phagocytosis
Lipoproteins of
Gram + bacteriaYeast cell wall
components
TLR-2 (Toll-like
receptor 2)
Macrophage
activation;Secretion of
inflammatory
cytokines
CpG islands orCG islands (CGI) are genomic regions that contain a high frequency of CpGsites. The " " in C G refers to the hos hodiester bond between the c tosine and the uanine
http://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Cytosinehttp://en.wikipedia.org/wiki/Guaninehttp://en.wikipedia.org/wiki/Guaninehttp://en.wikipedia.org/wiki/Cytosinehttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/CpG_site -
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PAMP PRR
Biological
Consequence of
Interaction
Viral double
stranded RNA
TLR-3 Production of
interferon
(antiviral)
LPS
(lipopolysaccharideof Grambacteria
TLR-4 Macrophage
activation;Secretion of
inflammatory
cytokines
Flagellin (bacterialflagella)
TLR-5 Macrophageactivation;
Secretion of
inflammatory
cytokines
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PAMP PRR
Biological
Consequence of
Interaction
U-rich single
stranded viral RNA
TLR-7 Production of
interferon
(antiviral)
CpG containing
DNA
TLR-9 Macrophage
activation;
Secretion of
inflammatory
cytokines
CpGoffrequencyhighacontainthatregionsgenomicare(CGI)islandsCGorislandsCpGguaninetheandcytosinethebetweenbondphosphodiesterthetorefersCpGin"p"The.sites
http://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/Guaninehttp://en.wikipedia.org/wiki/Cytosinehttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Phosphodiester_bondhttp://en.wikipedia.org/wiki/Cytosinehttp://en.wikipedia.org/wiki/Guaninehttp://en.wikipedia.org/wiki/CpG_sitehttp://en.wikipedia.org/wiki/CpG_site -
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Viral antigens:
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Cell-Surface antigens:
Blood group Ag: A, B. O,
Histocompatibility Ag:MHC1, MHC2
The major histocompatibility complex (MHC) is a set of cell
surface molecules encoded by a large gene family in all
vertebrates. MHC molecules mediate interactions of
leukocytes, with other leukocytes or body cells.
Clusters of Differentiation: CD4, CD8, .
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Cross Reactivity
Anti-A
Ab
Ag A
Anti-A
Ab
Ag B
Shared epitope
Anti-A
Ab
Ag C
Similar epitope
Cross reactions