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IMMUNITY
THE ABILITY TO RESIST
DISEASE
NONSPECIFIC VS SPECIFIC
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http://www.gsbs.utmb.edu/microbook
/toc.htm
NONSPECIFIC
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PHYSICAL BARRIERS
CHEMICAL BARRIERS
CELLULAR BARRIERS
INFLAMMATION
FEVER
SPECIFIC IMMUNITY
• IMMUNE CELLS RECOGNIZE
FOREIGN ANTIGENS
• DIRECTLY OR INDIRECTLY
ELIMINATE THEM
ACQUIRED IMMUNITY
NATURAL VS ARTIFICIAL
ACTIVE VS PASSIVE
NATURALLY ACQUIRED
ACTIVE IMMUNITY
• DUE TO ANTIGENIC STIMULUS FROM
INFECTION
• ANTIBODIES
• SENSITIZED LYMPHOCYTES
• SHORT TERM TO LONG TERM
• MEMORY CELLS MADE
NATURALLY ACQUIRED PASSIVE
IMMUNITY
• ANTIBODIES TRANSFERRED FROM
MOTHER TO INFANT
• ACROSS THE PLACENTA
– Ig G
– SHORT TERM IMMUNITY
• IN THE CLOSTRUM AND MILK
– IgA
– AS LONG AS BABY IS NURSING
• NO MEMORY CELLS ARE FORMED
ARTIFICIALLY ACQUIRED
ACTIVE IMMUNITY
• VACCINATIONS/IMMUNIZATION
– KILLED OR WEAKENED MICROBES
– INACTIVATED TOXINS
– COMPONENTS OF CAPSIDS, CAPSULES
OR OTHER MICROBIAL COMPONENTS
– VECTOR VACCINES
• MEMORY CELLS ARE FORMED
ARTIFICIALLY ACQUIRED
PASSIVE IMMUNITY
• TRANSFER OF ANTIBODIES FROM
SOME OTHER ORGANISM
• SHORT TERM IMMUNITY
• NO MEMORY CELLS FORMED
ANTIGENS
• ANTIBODY GENERATING
MOLECULES
• IMMUNOGENS/ALLERGENS
• SELF VS NONSELF
• MARKERS ON CELLS, PROTEINS,
VIRUSES AND ETC
CHARACTERISTICS OF
ANTIGENS
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LARGE
COMPLEX
PROTEINS
NUCLEOPROTEINS
POLYSACCHARIDES
GLYCOLIPIDS
ANTIGENIC DETERMINANT
SITES
• SITES ON ANTIGEN THAT CAUSE
PRODUCTION OF ANTIBODY
• MONOVALENT
• MULTIVALENT
• HETEROPHILE OR HETEROLOGOUS
HAPTENS
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SMALL ORGANIC MOLECULES
NOT ANTIGENIC BY ITSELF
MUST BIND TO CARRIER MOLECULE
PENICILLIN
NICKEL
CELLS OF THE SPECIFIC
IMMUNE RESPONSE
LYMPHOCYTES
LYMPHOCYTE FUNCTION
B CELL
B CELLS
• MADE IMMUNOCOMPETENT IN
FETAL LIVER AND BONE MARROW
PLASMA CELLS
• DERIVED FROM B CELLS
• RESPOND TO ANTIGEN BY
SECRETING ANTIBODIES
• HUMORAL DEFENSE
• DEFEND AGAINST BACTERIA,
BACTERIAL TOXINS AND VIRUSES
FOUND IN BODY TISSUES
PLASMA CELL
ANTIBODIES
• GLYCOPROTEINS
• GAMMA GLOBULIN PORTION OF
SERUM
• DIFFER IN MOLECULAR SIZE,
STRUCTURE, CHARGE, AMINO ACID
COMPOSITION AND CARBOHYDRATE
COMPOSITION
• FIVE CLASSES
IMMUNOGLOBULINS
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IgA
IgD
IgE
IgG
IgM
CHARACTERISTICS OF
ANTIBODIES
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MOST ARE BIVALENT
CRYSTALIZABLE FRAGMENT (Fc)
ANTIBODY BINDING FRAGMENT (Fab)
FOUR POLYPEPTIDE BONDS
LIGHT AND HEAVY CHAINS
HEAVY CHAINS DETERMINE CLASS
FLEXIBLE HINGE REGION
STRUCTURE OF ANTIBODY
MOLECULE
ANTIBODY SUBCLASSES
• Ig A
• Ig G
FUNCTION OF
IMMUNOGLOBULINS
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ALL ARE BIFUNCTIONAL
Fab BINDS TO ANTIGEN
Fc BINDS TO COMPLENT AND CELLS
DOES NOT LEAD TO DIRECT
DESTRUCTION
• MARKS CELL FOR DESTRUCTION
• ACTIVATES NONSPECIFIC RESPONSES
IMMUNOGLOBULIN
CLASSES
IMMUNOGLOBULIN G
• MAJOR Ig IN SERUM
• 70-75 % OF IMMUNOGLOBULIN POOL
• ACTS AGAINST BACTERIA AND
VIRUSES
• OPSONIZING AND NEUTRALIZING
• ACTIVATES COMPLEMENT
• CROSSES PLACENTA
SUBCLASSES OF IgG
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Ig1
Ig2
Ig3
Ig4
VARY IN COMPOSITION AND
NUMBER AND ARRANGEMENT OF
DISULFIDE BONDS
IMMUNOGLOBULIN M
• ABOUT 10 % OF IMMUNOGLOBULIN
POOL
• FOUND ONLY IN SERUM
• MONOMERS, PENTAMERS,
HEXAMERS
• JOINING CHAINS
• FIRST ANTIBODY PRODUCED
• FOUND ON B CELL MEMBRANES
FUNCTION OF IgM
• FIRST ANTIBODY PRODUCED IN PRIMARY
IMMUNE RESPONSE
• AGGLUTINATES
• ACTIVATES COMPLEMENT
– BY CLASSICAL PATHWAY
• OPSONIZES
• MONOMERIC FORMS ARE FOUND ON
SURFACE OF B LYMPHOCYTES
– ACT AS RECEPTORS FOR ANTIGEN
IMMUNOGLOBULIN A
• 15 % OF POOL
• MAINLY DIMER IN SERUM
SECRETORY IgA
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SECRETORY IMMUNE SYSTEM
SPECIAL SECRETORY COMPONENT
GI TRACT
RESPIRATORY TRACTS
GENITOURINARY TRACT
SALIVA
TEARS
SWEAT
FUNCTION OF IgA
• PROTECTS BODY SURFACES
• IMMUNE EXCLUSION
• BINDS TO TO ANTIGENS IN LAMINA
PROPRIA
• ACTIVATES COMPLEMENT BY
ALTERNATIVE PATHWAY
IMMUNOGLOBULIN D
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TRACE AMOUNTS IN SERUM
MAINLY FOUND ON B CELLS
REGULATES IMMUNE SYSTEM
MONOMER
MAY PLAY ROLE IN ELIMINATING
SELF-REACTIVE AUTOANTIBODIES
IMMUNOGLOBULIN E
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LESS THAN 1% OF ANTIBODY
SKIN SENSITIZING
ANAPHYLACTIC
BINDS TO MAST CELLS AND
BASOPHILS
• FIGHTS PARASITES
ANTIBODY DIVERSITY
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REARRANGEMENT OF EXONS
SOMATIC MUTATIONS
POST TRANSCRIPTIONAL EDITING
INDEPENDENT ASSORTMENT OF
LIGHT AND HEAVY CHAINS
ANTIBODY SPECIFICITY
• INFINITE NUMBER OF ANTIBODIES
POSSIBLE
• BASED ON B CELL CLONES
CLONAL SELECTION
THEORY
• SMALL SET OF CELLS THAT CAN
RESPOND TO ANTIGEN
• ALL ARE PRESENT IN FETUS
• ANTIGEN SELECTS THE
APPROPRIATE CLONE
• EFFECTOR AND MEMORY CELLS ARE
PRODUCED
PRIMARY ANTIBODY
RESPONSE
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INITIAL CHALLENGE
LAG PHASE
LOG PHASE
PLATEAU
PASTEUR PHASE
LOW ANTIBODY AFFINITY
SECONDARY IMMUNE
RESPONSE
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ANAMNESTIC RESPONSE
PROVIDES IMMUNITY
CLONES OF B OR T MEMORY CELLS
SHORTER LOG PHASE
HIGH ANTIBODY AFFINITY
SPECIAL TYPES OF
ANTIBODIES
POLYCLONAL VS
MONOCLONAL ANTIBODIES
http://users.rcn.com/jkimball.ma.ultra
net/BiologyPages/M/Monoclonals.ht
ml
IMMUNOTOXINS
CHIMERIC MONOCLONAL
ANTIBODIES
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PART HUMAN --- PART MOUSE
VARIABLE REGION—MOUSE
CONSTANT REGION HUMAN
66% HUMAN
LESS TOXIC
HUMANIZED ANTIBODIES
• THE ANTIGEN BINDING SITE IS THE
ONLY PORTION OF THE ANTIBODY
THAT CONTAINS MOUSE PROTEINS
• 90% IS HUMAN
FULLY HUMAN ANTIBODIES
• TRANSGENIC MICE
• GENETICALLY MODIFIED MICE
CONTAIN HUMAN ANTIBODY GENES
• WOULD PRODUCE FULLY HUMAN
ANTIBODIES
• MIGHT BE POSSIBLE TO PRODUCE
THEM TO MATCH THE SPECIFIC
PATIENT
CATALYTIC ANTIBODIES
• USED TO TRANSFORM SIMPLE
COMPOUNDS
– BLOOD CLOTS INHEART
ANTIBODY FUNCTION
• ACTIVATION OF
COMPLEMENT
• TOXIN
NEUTRALIZATION
• VIRAL
NEUTRALIZATION
• AHERANCE INHIBITION
• PARASITIC INFECTIONS
• ANTIBODY
DEPENDENT CELL
MEDIATED
CYTOTOXITY
• OPSONIZATION
• REGULATING
INFLAMMATION
• IMMUNE COMPLEX
FUNCTION OF COMPLEMENT
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MEDIATE INFLAMMATION
CHEMOTAXIS
PHAGOCYTE ACTIVATION
CYTOLYSIS
OPZONIZATION
ACTIVATION OF OTHER IMMUNE
CELLS
COMPLEMENT ACTIVATION
• COMPLEMENT MAKES UP A MAJOR
PORTION OF SERUM
ACTIVATORS OF THE
ALTERNATE PATHWAY
• MOLECULES WITH REPEATING
CHEMICALS STRUCTURES
• ENDOTOXINS
• POLYSACCHARIDES
• LIPOPOLYSACCHARIDES
• TEICHOIC ACID
• Ig A
ACTIVATION BY THE
CLASSICAL PATHWAY
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Ig M
IgG1
IgG2
IgG3
ANTIGEN ANTIBODY COMPLEXES
COMPLEMENT IS A MAJOR
REGULATOR OF THE
INFLAMMATORY RESPONSE
TOXIN NEUTRALIZATION
• BLOCKS ABILITY OF TOXIN TO
ENTER CELL OR ATTACH TO
CELL RECEPTORS
• ANTIBODIES ARE CALLED
ANTITOXINS
VIRAL NEUTRALIZATION
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IgG
IgM
IgA
BIND TO VIRUSES IN
EXTRACELLULAR FLUID AND
INACTIVATE THEM
• C4B AIDS IN THIS PROCESS
ANTIBODIES THAT BLOCK
ADHERANCE
• SECRETORY Ig A
• PROTECTS AGAINST PATHOGENS ON
MUCOSAL SURFACES
ANTIBODY-DEPENDENT
CELL-MEDIATED
CYTOTOXICITY
• NATURAL KILLER CELLS
• DESTROYS CELLS BY CYTOLYSIS OR
BY CYTOTOXIC MEDIATORS
ADDC DEATH BY APOPTOSIS
APOPTOSIS
ADDC CYTOLYSIS
ANTIBODIES THAT FIGHT
PARASITIC INFECTIONS
• IgE
• EOSINOPHILS ARE INVOLVED ALSO
OPSONIZATION
• COATING WITH ANTIBODIES
• COATING WITH ANTIBODIES AND FIXED
COMPLEMENT
• INCREASES PHAGOCYTOSIS OR CAUSES
EXTRACELLUAR DESTRUCTION IF TO BIG
FOR PHAGOCYTOSIS
• IgG1
• IgM
OSPSONIZATION AND
INTRACELLULAR DESTRUCTION
OPSONIZATION AND
EXTRACELLULAR DESTRUCTION
ANTIBODIES AND THE
INFLAMMATORY RESPONSE
• MAY BE TRIGGERED BY SPECIFIC OR
NONSPECIFIC IMMUNE SYSTEM
• IgE ANTIBODIES ON MAST CELLS
• C3a AND C5a OF THE COMPLEMENT
SYSTEM
IMMUNE COMPLEX
FORMATION BY ANTIBODYANTIGEN
• PRECIPITATION
• AGGLUTINATION
HEMAGGLUTINATION
ANTIBODIES IN THE LAB
SETTING
• IN VIVO TESTING
• IN VITRO TESTING
IN VIVO TESTING
• ALLERGY TESTING
IMMEDIATE
DELAYED (T-CELL)
IMMEDIATE TESTING
• WITHIN 20 MINUTES
• USED FOR RESPIRATORY ALLERGIES
DELAYED TESTING
• CELL MEDIATED
TESTING
• FOOD ALLERGIES
• CONTACT DERMATITIS
• CANDIDA ALBICANS
• TRICHOPHYTON
• MUMPS
• DIPTHERIA-TETANUS
TOXOID
• STREPTOKINASESTREPTODORNASE
• TRICHOPHYTON
• MUMPS
• DIPTHERIA-TETANUS
TOXOID
• STREPTOKINASESTREPTODORNASE
• TUBERCULIN
ANTIGENS
• HISTOPLASMA
TUBERCULIN
ANTIGENS
T B TESTING
POSITIVE TB TEST
IN VITRO TESTING
AGGLUTINATION
• DIRECT AGGLUTINATION
WIDAL TEST
• LATEX AGGLUTINATION TEST
HUMAN CHORIONIC GONADOTROPIN
• HEMAGLUTINNATION
• ANTIBODY TITER
COMPLEMENT FIXATION
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WASSERMAN TEST
VIRAL DISEASES
FUNGAL DISEASES
RICKETTSIAL DISEASES
CHLAMYDIAL DISEASES
PROTOZOAL DISEASES
ELISA TESTS
• ENZYME LINKED IMMUNOSORBENT
ASSAY
• LABELED ENZYMES LINKED TO
ANTIGENS OR ANTIBODIES
• HELIOBACTER PYLORI
• SYPHILIS
• BRUCELLOSIS SALMONELLOSIS
• CHOLERA
NEUTRALIZATION
REACTIONS
• DETERMINES WHETHER TOXINS OR
VIRUSES HAVE BEEN INACTIVATED
BY ANTIBODY
• CLOTRIDIUM BOTULINUM
• MANY VIRAL DISEASES
B CELL BIOLOGY
ANTIGEN SPECIFIC ---T DEPENDENT
POLYCLONAL --- T INDEPENDENT
T DEPENDENT ANTIGEN
TRIGGERING
• REQUIRES:
ANTIGEN PRESENTING CELL
HELPER T CELL
B CELL
• MAINLY PROTEINS AND HAPTENS
B CELLS AND T CELLS
ACTIVATE ONE ANOTHER
ALL THE IMMUNE
RESPONSES THAT PRODUCE
IgA, IgE AND IgG ARE T
DEPENDENT ANTIGEN
TRIGGERED
B CELL DIFFERENTIATION
• AFFINITY MATURATION
• CLASS SWITCHING
• FORMATION OF PLASMA AND
MEMORY CELLS
AFFINITY MATURATION
• DURING HUMORAL
IMUNE RESPONSE
AFFINITY OF THE
ANTIBODIES TO
ANTIGEN
INCREASES 10010,000 TIME
CLASS SWITCHING
• ADDITIONAL REARRANGEMENT OF
THEIR HEAVY CHAIN GENE
SEGMENTS CAN OCCUR.
• PRODUCES IgG, IgA AND IgE
T INDEPENDENT ANTIGEN
TRIGGERING
• NOT ALL ANTIBODY RESPONSES
REQUIRE T CELL HELP.
• POLYMERIC
• TUMOR PROMOTING AGENTS
• ANTI-IMMUNOGLOBULIN (ANTI Ig)
• BACTERIAL LIPOPOLYSACCHARIDES
T INDEPENDENT ANTIGEN
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T INDEPENDENT 1
T INDEPENDENT 2
GENERALLY WEAKER
NO MEMORY CELLS FORMED
IgM PRIMARY ANTIBODY
T INDEPENDENT TYPE 1
• LIPOPOLYSACCHARIDE BACTERIAL
CELL WALL COMPONENTS
• MOST ARE MITOGENS--POLYCLONAL
• CAN ACTIVATE UP TO ONE THIRD OF
ALL B CELLS WHEN PRESENT AT
HIGH LEVELS
T INDEPENDENT TYPE 2
• POLYMERIC MOLECULES
• BACTERIAL CELL WALL
POLYSACHARIDES
• POLYMERIC PROTEINS
• DOES NOT REQUIRE DIRECT T
HELPER CELL INVOLVEMENT
• REQUIRES T HELPER CYTOKINES FOR
CLASS SWITCHING
DIFFERENCES BETWEEN
T DEPENDENT AND
T INDEPENDENT TRIGGERING
T INDEPENDENT IS THE MAIN
IMMUNE RESPONSE IN
INFANTS UNTIL AGE TWO
CHEMICAL MEDIATORS OF
THE IMMUNE RESPONSE
CYTOKINES
• MEDIATE BOTH SPECIFIC AND
NONSPECIFIC IMMUNE RESPONSE
• GENERAL TERM
• PRODUCTS OF ONE CELL
POPULATION THAT AFFECTS
ANOTHER
TYPES OF CYTOKINES
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MONOKINES
LYMPHOKINES
INTERLEUKINS
CHEMOKINES
FUNCTIONS OF CYTOKINES
• MEDIATE NONSPECIFIC IMMUNITY
• ACTIVATE EFFECTOR CELLS
• MEDIATE MATURE CELL ACTIVATION,
DIFFERENTIATION, GROWTH AND
BEHAVIOR
• MEDIATE IMMATURE GROWTH AND
DIFFERENTIATION
CYTOKINE EFFECTS ON
NONSPECIFIC IMMUNITY
• INTERFERON ALPHA
• INTERFERON BETA
INTERFERON ALPHA
• PRODUCED BY MACROPHAGES AND
MONOCYTES
• INDUCES THE ANTIVIRAL STATE
• INCREASES EXPRESSION OF CLASS I
MHC MARKERS ON MACROPHAGES
• INCREASES EXPRESSION OF Fc
RECEPTORS ON MACROPHAGES
• ACTIVATES NATURAL KILLER CELLS
INTERFERON BETA
• PRODUCED BY FIBROBLASTS INDUCES
ANTIVIRAL STATE
• MODULATES ANTIBODY PRODUCTION
• INDUCES DIFFERENTIATION OF
FIBROBLASTS
• STIMULATES EXPRESSION OF MHC
MARKERS
• ENHANCES SECRETION OF INTERLEUKIN 1
alpha AND TUMOR NECROSIS FACTOR BY
MACROPHAGES
INTERLEUKIN 1
• MEDIATES BOTH SPECIFIC AND
NONSPECIFIC IMMUNITY
• PRODUCED BY A VARIETY OF CELLS
• STIMULATES T HELPER CELLS
INPRESENCE OF ANTIGEN
• ATTRACTS PHAGOCYTES IN
INFLAMMATORY RESPONSE
• STIMULATES HYPOTHALAMUS AND
CAUSES FEVER
– ENDOGENOUS PYROGEN
CHEMOKINES
• PARACRINE
• LOW WEIGHT MOLECULES
• MEDIATES INFLAMMATORY
RESPONSE
• INDUCES MIGRATION OF WHICHT
BLOOD CELLS INTO INFECTED OR
DAMAGED AREAS
TUMOR NECROSIS FACTOR
ALPHA
• ONE OF THE MAJOR CYTOKINES
THAT MEDIATES THE HOST
RESPONSE TO GRAM NEGATIVE
BACTERIA
• RELEASED BY MONONUCLEAR
PHAGOCYTES
– DUE TO STIMULATION OF
LIPOPOLYSACCHARIDE
ACTIONS OF TUMOR NECROSIS
FACTOR ALPHA
• STIMULATES AN INCREASE IN B CELLS
• INITIATES LEUKOCYTE ADHERANCE TO
VASCULAR ENDOTHELIUM
• STIMULATES OTHER MONONUCLEAR
PHAGOCYTES TO SECRETE INTERLEUKINS
1, 6 OR 8
• STIMULATES THE HYPOTHALMUS TO
INDUCE FEVER
– ACTS AS AN ENDOGENOUS PYROGEN
• IS CYTOTOXIC TO TUMOR CELLS
TUMOR NECROSIS CHEMOKINES
AND INTERLEUKIN 1 ROLE IN
EXTRAVASATION
INTERFERON GAMMA
• PRODUCED BY
– T HELPER CELLS, CYTOTOXIC CELLS AND NATURAL
KILLER CELLS
• AMPLIFIES ACTIVATION OF T HELPER CELLS
• INCREASES THE EXPRESSION OF MHC
MOLECULES
• PROMOTES DIFFERENTIATION OF BOTH T AND B
CELLS
• REGULATES THE RELEASE OF Ig FROM CELLS
• PROMOTES MATURATION OF CYTOTOXIC T CELLS
• INDUCES ANTIVIRAL STATE
• ACTIVATES MACROPHAGES, NEUTROPHILS AND
NATURAL KILLER CELLS
MIGRATION INHIBITION
FACTOR
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PRODUCED BY MACROPHAGES
ACTIVATES MACROPHAGES
PREVENTS MIGRATION FROM SITE
SECRETION INDUCED BY TUMOR
NECROSIS FACTOR,
LIPOPOLYSACCHARIDES AND OTHER
FACTORS
INTERLEUKIN 2
• PRODUCED BY HELPER T CELLS
– FOR SHORT PERIOD AFTER ACTIVATION BY ANTIGEN
• MEDIATES THE ACTIVATION, GROWTH AND
DIFFERENTIATION OF MATURE LYMPHOCYTES
• TRIGGERS THE POLIFERATION OF T HELPER AND
CYTOTOXIC T CELLS
• CAN INDUCE THE SYNTHESIS OF INTERFERON
– INDIRECTLY ACTIVATES NATURAL KILLER CELLS
• STIMULATES THE GROWTH OF CERTAIN B CELLS
• HAS BEEN USED AGAINST CERTAIN CANCERS
– RENAL CELL CARCINOMA
– MALIGNANT MELANOMA
INTERLEUKIN 3
• COLONY STIMULATING FACTOR
• STIMULATES PROLIFERATION OF
STEM CELLS IN BONE MARROW
• INFLUENCES DIFFERENTIATION OF
BONE MARROW CELLS
– MAST CELLS, MACROPHAGES AND
GRANULOCYTES
INTERLEUKIN 8
• CHEMOATTRACTANT FOR PHAGOCYTES
AND OTHER IMMUNE CELLS TO SITE OF
INFLAMMATION
• ALSO CALLED NEUTROPHIL ACTIVATING
FACTOR
• SECRETED BY A VARIETY OF CELLS
• CONSIDERED A CHEMOKINE
• PRIMARILY MEDIATE THE ACTIVATION
AND MIGRATION OF NEUTROPHILS INTO
THE TISSUES FROM BLOOD STREAM
INTERLEUKIN 10
• SECRETED BY T HELPER 2 CELLS
AND T REGULATOR CELLS
• INTERFERS WITH THE ACTIVATION
OF T HELPER 1 CELLS
• INHIBITS CYTOKINE PRODUCTIN BY
MACROPHAGES
• MAINLY PLAYS AN ANTIINFLAMMATOR ROLE
INTERLEUKIN 12
• INVOLVED IN THE DIFFERENTIATION OF T
HELPER CELLS
– T HELPER 1 REPONSE
• ENHANCES CYTOTOXIC ACTIVITY OF
NATURAL KILLER CELLS AND CYTOTOXIC
T LYMPHOCYTES
• BLOCKS THE FORMATION OF NEW BLOOD
VESSELS BY INDUCING THE PRODUCTION
OF INTERFERON GAMMA
T CELL BIOLOGY
RESPOND TO MHC MARKERS
MHC MOLECULES
• FOUND ON ALL NUCLEATED CELLS
• ALSO CALLED HUMAN LEUKOCYTE
ANTIGENS (HLAs)
• CLASS I
• CLASS II
• CLASS III
– ASSOCIATED WITH COMPLEMENT
SYSTEM
CLASS I & II MHC
STRUCTURE
• TWO PROTEIN CHAIN
• GROOVE INTO WHICH PEPTIDE
MOLECULES CAN BE INSERTED
– WHICH MAY OF MAY NOT CAUSE A
IMMUNE RESPONSE
SOURCES OF MHC CLASS I & II
ANTIGEN PROCESSING
ENDOGENOUS VS EXOGENOUS
CLASS I MHC MOLECULES
• ENDOGENOUS ANTIGENS
• PEPTIDES THAT ORIGINATE IN THE
CYTOSOL
• PEPTIDES AND MHC CLASS I COMBINE
• CARRIED TO PLASMA MEMBRANE
• DISPLAYED TO PASSING CD 8+ CELLS
CELLS ARE CONSTANTLY TAKING
INVENTORY OF ITS CELLULAR
PRODUCTS
• PROTEOSOMES CHOP OF VARIOUS
PROTEINS IN CELL INTO PEPTIDE
EPITOPES
– SERIES OF PEPTIDES
– APPROIMATELY 8-10 AMINO ACIDS
LONG
EXAMPLES OF ENDOGENOUS
ANTIGENS
• PRODUCED WITHIN CELLS OF THE BODY.
– VIRAL PROTEINS PRODUCED DURING VIRAL
REPLICATION
– PROTEINS PRODUCED BY INTRACELLULAR
BACTERIA SUCH AS RICKETTSIAS AND
CHLAMYDIAS DURING THEIR REPLICATION
– PROTEINS THAT HAVE ESCAPED INTO THE
CYTOSOL FROM THE PHAGOSOME OF
PHAGOCYTES SUCH AS ANTIGEN-PRESENTING
CELLS
– TUMOR ANTIGENS PRODUCED BY CANCER
CELLS
– SELF PEPTIDES FROM HUMAN CELL PROTEINS.
PROTEINS THAT HAVE ESCAPED INTO
THE CYTOSOL FROM THE PHAGOSOME
OF PHAGOCYTES SUCH AS ANTIGENPRESENTING CELLS
CLASS II MHC MOLECULES
• EXOGENOUS ANTIGEN
• BROUGHT INTO ANTIGEN
PRESENTING CELL BY ENDOCYTOSIS
• DIGEST IN PHAGOLYSOSOME
• FRAGMENTS COMBINE WITH
PREFORMED MHC CLASS II
• DISPLAYED ON PLASMA MEMBRANE
• RECOGNIZED BY CD4 + CELLS
FORMATION OF MHC CLASS II
• EXAMPLES
–
–
–
–
–
BACTERIA
FREE VIRUSSE
YEASTS
PROTOZOA
TOINS
CLASSES OF MHC
MOLECULES
•
•
•
•
A, B, C, AND D
CLASS I--A, B AND C
CLASS II-- D GROUP
MHC MOLECULES ARE ALSO
INVOLVED IN SUSCEPTIBILITY T
PARTICULAR INFECTIOUS AND
NONINFECTIOUS DISEASES
T CELLS
• SECRETE CYTOKINES
• ATTACK VIRUS INFECTED CELLS
• ATTACK HOST CELLS WITH
INTRACELLULAR PARASITES
• ATTACK CANCER CELLS
• CELL MEDIATED IMMUNITY
T CELLS
• MADE
IMMUNOCOMPETENT
IN FETAL THYMUS
• FOUND IN BLOOD
AND LYMPH SYSTEM
TYPES OF T CELLS
T HELPER, CTYOTOXIC T CELLS
AND REGULATOR
CD 4 T HELPER CELLS
• DO NOT DIRECTLY KILL THE CELL
• CAN ENLARGE AND DIVIDE
– INCREASES NUMBER OF T4 CELLS
• CAN SECRETE CYTOKINES
– INHIBITS PATHOGEN
– RECRUIT OTHER CELLS
• T HELPER 1, T HELPER 2 AND T
HELPER 0
T HELPER CELLS
• Th 1
– RECOGNIZE ANTIGEN PRESENTED BY
MACROPHAGES
– INITIATE CELL MEDIATED IMMUNITY
– PRODUCE IL-2, INTERFERON GAMMA,
LYMPHOTOXIN, AND TUMOR NECOSIS
FACTOR BETA
• PROLIFERATION OF T 8 LYMPHOCYTES
• DIFFERENTIATION INTO CYTOTOXIC T
LYMPHOCYTES
• ACTIVATION OF CYTOTOXIC T LYMPHOCYTES
• ACTIVATION OF NATURAL KILLER CELLS
• PROLIFERATION OF T 4 LYMPHOCYTES
T HELPER CELLS
• T HELPER 2
• RESPOND TO ANTIGENS PRESENTED BY B
LYMPHOCYTES (AS ANTIGEN PRESENTING
CELLS)
• PRODUCE INTERLEUKINS 2, 4, 5, 10 AND 13
–
–
–
–
–
STIMULATE ANTIBODY PRODUCTION
STIMULATE DIFFERENTIATION INTO PLASMA CELLS
ENABLE
CLASS SWITCHING
ACTIVATE EOSINOPHILS AND INCREASE IgE
• TO FIGHT HELMINTHS AND ARTHROPODS
T HELPER CELLS
• BALANCE BETWEEN T HELPER 1 AND
T HELPER 2 PLAYS A ROLE IN HOW
WELL THE CELL FIGHTS CERTAIN
INFECTIONS
T REGULATOR CELLS
• FORMERLY KNOWN AS SUPPRESSOR
T CELLS
• MAY OR MAY NOT EXIST
• THEIR FUNCTION IS TO SUPRESS THE
ACTIVITY OF OTHER T CELLS
ACTIVATION OF T HELPER
CELLS
• NEED ANTIGEN PRESENTING CELLS
DISPLAYING TYPE II MHC MARKERS
• T HELPER CELLS ARE CLASS II
RESTRICTED
– ONLY INTERACT WITH CELLS PRESENTING
CLASS MHC II MOLECULES
• B CELLS, DENDRITIC CELLS, AND MACROPHAGES
ANIMATION OF T 4 HELPER
CELLS ACTIVATION
ANIMATION OF THE EFFECTS
OF INTERLEUKIN 2
ACTIVATION OF CYTOTOXIC
T CELLS
• NEED ANTIGEN PRESENTING CELLS
DISPLAYING TYPE I MHC MARKERS
– CD8 CYTOTOXIC CELLS ARE CLASS I
RESTRICTED
• ONLY RESPOND TO CLASS I MHC MARKERS
ANIMATION OF CD8 CYTOTOXIC T
CELL ACTIVATION
• COMBINATION OF T CELL RECEPTOR
AND CD8 MARKERS WITH MHC
CLASS I MARKERS ON MACROPHAGE
ACTIVATE CYTOTOXIC T CELL AND
LEADS TO ITS DIFFERENTIATION
INTO A CYTOTOXIC T LYMPHOCYTE
EFFECTS OF INTERLEUKIN 2
SECRETED BY HELPER T CELLS ON
ACTIVATED CYTOTOXIC T CELLS
• ONCE ACTIVATED SIGNALS AND
CYTOKINES FROM T HELPER 1 CELLS WILL
LEAD TO PROLIFERATION OF CD8 CELLS
AND THEIR DIFFERENTIATION INTO
CYTOTOXIC T LYMPHOCYTES
• CYTOTOXIC T CELLS DO NOT DISPLAY
INTERLEUKIN 2 RECEPTORS UNTIL THEY
ARE ACTIVATED
– ONLY CYTOTOXIC T LYMPHOCYTES CAN KILL
OTHER CELLS
• NIAVE CYTOTOXIC T CELLS CANNOT
ANIMATION OF ACTIVATED
CYTOXIC T CELL PROLIFERATION
ANIMATION OF DIFFERENTIATION
INTO CYTOTOXIC T LYMPHOCYTES
CYTOTOXIC T LYMPHOCYTES THEN
TRAVEL THROUGHOUT THE BODY
BINDING TO INFECTED CELLS
• THEY ONLY BIND TO THOSE CELLS THAT
DISPLAY A MHC CLASS I MARKER WITH THE
SAME ANTIGEN THEY ARE SPECIFIC FOR
• THEY BIND TO THE MHC CLASS I MARKER
AND RELEASE PERFORIN, GRANZYMES AND
CHEMOKINES THAT TRIGGER EITHER LYSIS
OR APOPTOSIS
APOPTOSIS
OTHER ACTIVITIES OF T
HELPER CELLS
T HELPER 1 CELLS ALSO
ACTIVATE MACROPHAGES
• BINDING OF MACROPHAGE TO T HELPER 1
CAUSES SECRETION INTERFERON
GAMMA BY T HELPER 1 CELLS
• INTERFERON BINDS TO RECEPTORS ON
MACROPHAGE
• INTERFERON GAMMA ACTIVATES
MACROPHAGE
– PRODUCES MORE HYDROLYTIC ENZYMES IN
LYSOSOME
– PRODUCES MORE NITIC OXID
– PRODUCES MORE TOXIC OXYGEN RADICALS
T HELPER CELLS ALSO ACTIVATE
NATURAL KILLER CELLS
• IL-2 AND IFN GAMMA PRODUCED BY
T helper 1 CELLS ACTIVATE NATURAL
KILLER CELLS
AQUIRED IMMUNE
TOLERANCE
• TOLERANCE INDUCTION
• BODY’S ABILITY TO MAKE
ANTIBODIES AGAINST NONSELF
ANTIGENS WHILE TOLERATING SELF
ANTIGENS
• ESTABLISHED EARLY IN EMBRYONIC
LIFE
NULL CELLS
• LACK SPECIFIC
SURFACE
MARKERS
• NATURAL KILLER
CELLS
• PART OF
NOSPECIFIC
IMMMITY
NATURAL KILLER CELLS
•
•
•
•
•
•
SMALL POPULATION
NONSPECIFIC
NULL CELLS
DESTROY TUMORS
VIRUS INFECTE CELLS
FUNGI, BACTERI, PROTOZOA, AND
HELMINTHS
• IMMUNE SURVEILLANCE
HOW NATURAL KILLER
CELLS WORK
• ACTIVATED BY INTERFERONS AND
INTERLEUKIN 2
• CALCIUM DEPENDENT SEQUENCE
• INSERT PERFORIN 1 INTO TARGET
• RELEASE LYSOSOMAL SECRETIONS
– CAUSES LYSIS OR APOPTOSIS
INTERACTION OF A NATURAL
KILLER CELL WITH A NORMAL
BODY CELL
INTERACTION OF A NATURAL
KILLER CELL WITH A CELL NOT
DISPLAYING MHC CLASS I MARKERS
APOPTOSIS
• PROGRAMED CELLULAR DEATH
NATURAL KILLER CELLS
INTERACTIONS ARE PART OF
NONSPECIFIC IMMUNITY
SUPERANTIGENS
• BACTERIAL PROTEINS
• STIMULATE IMMUNES SYSTEM
MORE EXTENSIVELY
• NONSPECIFICALLY STIMULATE T
CELLS
• INDUCE MASSIVE CYTOKINE
PRODUCTION
HYPERSENSITIVITIES
•
•
•
•
ALLERGIES
EXAGGERATED IMMUNE RESPONSE
IMMEDIATE OR DELAYED
MAIN DIFFERENCE IN HOW IMMUNE
SYSTEM RESPONDS
TYPE I ANAPHYLACTIC
HYPERSENSITIVITY
• IgE ANTIBODY
• MAY BE HEREDITARY DISPOSITION
• IgE BINDS TO BASOPHIL AND MAST
CELLS
• T DEPENDENT IMMUNITY
• SUBSEQUENT EXPOSURE WILL
CAUSE MAST CELLS AND BASOPHILS
TO DEGRANULATE
SYSTEMIC ANAPHYLAXIS
• LARGE MAST CELL DEGRANULATION
IN SHORT TIME
• SMOOTH MUSCLE CONSTRICTION IN
BRONCHIOLES
• ARTERIOLE DILATION
• INCREASED VASCULAR
PERMEABILITY
CAUSE OF DEATH
•
•
•
•
REDUCED VENOUS RETURN
REDUCED BLOOD PRESSURE
CIRCULATORY SHOCK
ASPHYXIATION
POSSIBLE CAUSES
• DRUGS
• ANTISERA
• INSECT VENOM
LOCALIZED ANAPHYLAXIS
•
•
•
•
ATOPIC
ALLERGIC RHINITIS
BRONCHIAL ASTHMA
FOOD ALLERGIES
PREVENTING TYPE I
RESPONSES
• REPLACE IgE RESPONSE WITH IgG
RESPONSE
• SERIES OF ALLERGEN SHOTES
• EFFECTIVE ABOUT 65 TO 75% WITH
INHALED ALLERGENS
TYPE II CYTOTOXIC
HYPERSENSITIVITIES
• DESTRUCTION OF HOST CELLS
• LYSIS OR TOXIC MEDIATORS
• ANTIBODY MEDIATED CELLMEDIATED CYTOTOXICITY
• IgG OR IgM
• DIRECTED AGAINST TISSUES OR
CELL SURFACES
• INTERACT WITH COMPLEMENT
EXAMPLES
• BLOOD TRANSFUSIONS WITH
WRONG BLOOD TYPE (ABO)
• HEMOLYTIC DISEASE OF THE
NEWBORN
• DRUG INDUCED HEMOLYTIC ANEMIA
DRUGS THAT CAN INTIATE A
TYPE II HYPERSENSITIVITY
• PENICILLIN
• QUINIDINE
• METHYLDOPA
TYPE III IMMUNE COMPLEX
HYPERSENSITIVITY
• FORMATION OF IMMUNE
COMPLEXES
• NORMALLY REMOVED BY
RETICULOENDOTHELIAL SYSTEM
• EXCESS MAY ACCUMULATE
• ACTIVATES COMPLEMENT
EXAMPLES OF TYPE III
HYPERSENSITIVITIES
• SERUM SICKNESS
• DRUG REACTIONS
• POSTSTREPTOCOCCAL
GLOMERULONEPHRITIS
• SYSTEMIC LUPUS ERYTHEMATOSUS
• RHEUMATOID ARTHRITIS
• GOODPASTURE’S SYNDROME
• FARMERS LUNG
ASPERGILLOSIS
GLOMERULAR NEPHRITIS
TYPE IV CELL MEDIATED
HYPERSENSITIVITY
•
•
•
•
T CELL MEDIATED
USUALLY TAKES DAYS TO OCCUR
MEDIATED BY CYTOKINES
CAUSES EXTENSIVE TISSUE
DAMAGE
EXAMPLES OF TYPE IV
• INTRACELLULAR PARASITE
MYCOBACTERIUM
• TB TEST
• SOME AUTOIMMUNE DISEASE
• CONTACT DERMATITIS
• KILLING OF CANCER CELLS
• TRANSPLANT REJECTION
AUTOIMMUNE DISORDERS
• FAILURE TO RECOGNIZE SELF
ANTIGENS
AUTOIMMUNITY VS
AUTOIMMUNE DISORDER
FACTORS THAT AFFECT
AUTOIMMUNE DISORDERS
•
•
•
•
VIRUSES
GENETICS
ENDOCRINE SYSTEM
PSYCHONEUROIMMUNOLOGICAL
MORE COMMON IN OLDER
PEOPLE
TRANSPLANT REJECTION
• ISOGRAFTS
• ALLOGRAFTS
• XENOGRAFTS
MECHANISMS OF TISSUE
REJECTION
• T CELL IMMUNITY IS ACTIVATED
• CYTOTOXIC T CELLS KILL TISSUES
• T HELPER CELLS RELEASE
CYTOKINES
• NATURAL KILLER CELLS ALSO
INVOLVED
IMPORTANCE OF MHC
MARKERS
• CLASS I MHC MARKERS
• 77 MHC MOLECULES CODED FOR BY
FOUR GENES
• ATTEMPT TO MAKE AS CLOSE A
MATCH AS POSSIBLE
CYCLOSPORIN.
TACROLIMUS AND OTHER
DRUGS GIVEN TO SUPPRESS
T CELL IMMUNITY
IMMUNODEFICIENCIES
PRIMARY/CONGENITAL
VS
SECONDARY/ACQUIRED
PRIMARY/CONGENITAL
IMMUNODEFICIENCY
• CHRONIC GRANULOMATUS DISEASE
• COMMON VARIABLE
HYPOGAMMOGLOBULEREMIA
• DI GEORGE’S SYNDROME
• SEVERE COMBINE
IMMUNODEFICIENCY DISEASE
CHRONIC GRANULOMATOSUS
DISEASE
• RECURRENT INFECTIONS
• DEVELOPMENT OF INFLAMMATORY
CELLS
– IN LYMPH NODES, LUNGS, BONES AND SKIN
• INHERITED LACK OF NADPH OXIDASE IN
NEUTROPHILS
– THEY ARE UNABLE TO KILL INGESTED
MICROBES
Di GEORGE’S SYNDROME
• THYMUS FAILS TO DEVELOP
• NO T CELL IMMUNITY
– CELL MEDIATED
– T DEPENDENT HUMORAL IMMUNITY
• GENERALLY DIE OF VIRAL
INFECTION
BRUTON-TYPE
AGAMMAGLOBULEMAI
• INHERITED DEFECT USUALLY INHERITED
BY BOYS
• CANNOT MAKE ANTIBODIES
• SUFFER RECURRENT BACTERIAL
INFECTIONS
• DO HAVE CELL MEDIATED IMMUNITY
• IMMUNOGLOBULIN DEFICIENCIES
USUALLY OCCUR IN ONLY ONE Ig CLASS
– IgA IS MOST COMMON
SEVERE COMBINED
IMMUNODEFICIENCY DISEASE
• SCIDs
• NEITHER B OR T CELLS ARE
PRODUCED
• BOY IN THE BUBBLE
SECONDARY
IMMUNODEFICIENCIES
•
•
•
•
•
•
•
ACQUIRED AFTER BIRTH
CANCER
STRESS
DIABETES
MALNUTRITION
CERTAIN ENVIRONMENTAL TOXINS
HIV