IMMUNITY

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IMMUNITY

• THE ABILITY TO RESIST DISEASE

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NONSPECIFIC VS SPECIFIC

• http//www.microbiologytext.com/
• http//www.gsbs.utmb.edu/microbook/toc.htm

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NONSPECIFIC

• PHYSICAL BARRIERS
• CHEMICAL BARRIERS
• CELLULAR BARRIERS
• INFLAMMATION
• FEVER

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SPECIFIC IMMUNITY

• IMMUNE CELLS RECOGNIZE FOREIGN ANTIGENS
• DIRECTLY OR INDIRECTLY ELIMINATE THEM

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ACQUIRED IMMUNITY

• NATURAL VS ARTIFICIAL
• ACTIVE VS PASSIVE

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NATURALLY ACQUIRED ACTIVE IMMUNITY

• DUE TO ANTIGENIC STIMULUS FROM INFECTION
• ANTIBODIES
• SENSITIZED LYMPHOCYTES
• SHORT TERM TO LONG TERM
• MEMORY CELLS MADE

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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

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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

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ARTIFICIALLY ACQUIRED PASSIVE IMMUNITY

• TRANSFER OF ANTIBODIES FROM SOME OTHER ORGANISM
• SHORT TERM IMMUNITY
• NO MEMORY CELLS FORMED

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ANTIGENS

• ANTIBODY GENERATING MOLECULES
• IMMUNOGENS/ALLERGENS
• SELF VS NONSELF
• MARKERS ON CELLS, PROTEINS, VIRUSES AND ETC

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CHARACTERISTICS OF ANTIGENS

• LARGE
• COMPLEX
• PROTEINS
• NUCLEOPROTEINS
• POLYSACCHARIDES
• GLYCOLIPIDS

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ANTIGENIC DETERMINANT SITES

• SITES ON ANTIGEN THAT CAUSE PRODUCTION OF
  ANTIBODY
• MONOVALENT
• MULTIVALENT
• HETEROPHILE OR HETEROLOGOUS

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HAPTENS

• SMALL ORGANIC MOLECULES
• NOT ANTIGENIC BY ITSELF
• MUST BIND TO CARRIER MOLECULE
• PENICILLIN
• NICKEL

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CELLS OF THE SPECIFIC IMMUNE RESPONSE

• LYMPHOCYTES

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LYMPHOCYTE FUNCTION

• B CELL

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B CELLS

• MADE IMMUNOCOMPETENT IN FETAL LIVER AND BONE
  MARROW

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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

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PLASMA CELL
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ANTIBODIES

• GLYCOPROTEINS
• GAMMA GLOBULIN PORTION OF SERUM
• DIFFER IN MOLECULAR SIZE, STRUCTURE, CHARGE,
  AMINO ACID COMPOSITION AND CARBOHYDRATE
  COMPOSITION
• FIVE CLASSES

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IMMUNOGLOBULINS

• IgA
• IgD
• IgE
• IgG
• IgM

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CHARACTERISTICS OF ANTIBODIES

• MOST ARE BIVALENT
• CRYSTALIZABLE FRAGMENT (Fc)
• ANTIBODY BINDING FRAGMENT (Fab)
• FOUR POLYPEPTIDE BONDS
• LIGHT AND HEAVY CHAINS
• HEAVY CHAINS DETERMINE CLASS
• FLEXIBLE HINGE REGION

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STRUCTURE OF ANTIBODY MOLECULE
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ANTIBODY SUBCLASSES

• Ig A
• Ig G

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FUNCTION OF IMMUNOGLOBULINS

• 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

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IMMUNOGLOBULIN CLASSES
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IMMUNOGLOBULIN G

• MAJOR Ig IN SERUM
• 70-75 OF IMMUNOGLOBULIN POOL
• ACTS AGAINST BACTERIA AND VIRUSES
• OPSONIZING AND NEUTRALIZING
• ACTIVATES COMPLEMENT
• CROSSES PLACENTA

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SUBCLASSES OF IgG

• Ig1
• Ig2
• Ig3
• Ig4
• VARY IN COMPOSITION AND NUMBER AND ARRANGEMENT OF
  DISULFIDE BONDS

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IMMUNOGLOBULIN M

• ABOUT 10 OF IMMUNOGLOBULIN POOL
• FOUND ONLY IN SERUM
• MONOMERS, PENTAMERS, HEXAMERS
• JOINING CHAINS
• FIRST ANTIBODY PRODUCED
• FOUND ON B CELL MEMBRANES

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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

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IMMUNOGLOBULIN A

• 15 OF POOL
• MAINLY DIMER IN SERUM

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SECRETORY IgA

• SECRETORY IMMUNE SYSTEM
• SPECIAL SECRETORY COMPONENT
• GI TRACT
• RESPIRATORY TRACTS
• GENITOURINARY TRACT
• SALIVA
• TEARS
• SWEAT

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FUNCTION OF IgA

• PROTECTS BODY SURFACES
• IMMUNE EXCLUSION
• BINDS TO TO ANTIGENS IN LAMINA PROPRIA
• ACTIVATES COMPLEMENT BY ALTERNATIVE PATHWAY

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IMMUNOGLOBULIN D

• TRACE AMOUNTS IN SERUM
• MAINLY FOUND ON B CELLS
• REGULATES IMMUNE SYSTEM
• MONOMER
• MAY PLAY ROLE IN ELIMINATING SELF-REACTIVE
  AUTOANTIBODIES

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IMMUNOGLOBULIN E

• LESS THAN 1 OF ANTIBODY
• SKIN SENSITIZING
• ANAPHYLACTIC
• BINDS TO MAST CELLS AND BASOPHILS
• FIGHTS PARASITES

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ANTIBODY DIVERSITY

• REARRANGEMENT OF EXONS
• SOMATIC MUTATIONS
• POST TRANSCRIPTIONAL EDITING
• INDEPENDENT ASSORTMENT OF LIGHT AND HEAVY CHAINS

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ANTIBODY SPECIFICITY

• INFINITE NUMBER OF ANTIBODIES POSSIBLE
• BASED ON B CELL CLONES

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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

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(No Transcript)
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PRIMARY ANTIBODY RESPONSE

• INITIAL CHALLENGE
• LAG PHASE
• LOG PHASE
• PLATEAU
• PASTEUR PHASE
• LOW ANTIBODY AFFINITY

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SECONDARY IMMUNE RESPONSE

• ANAMNESTIC RESPONSE
• PROVIDES IMMUNITY
• CLONES OF B OR T MEMORY CELLS
• SHORTER LOG PHASE
• HIGH ANTIBODY AFFINITY

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SPECIAL TYPES OF ANTIBODIES
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POLYCLONAL VS MONOCLONAL ANTIBODIES

• http//users.rcn.com/jkimball.ma.ultranet/BiologyP
  ages/M/Monoclonals.html

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IMMUNOTOXINS
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CHIMERIC MONOCLONAL ANTIBODIES

• PART HUMAN --- PART MOUSE
• VARIABLE REGIONMOUSE
• CONSTANT REGION HUMAN
• 66 HUMAN
• LESS TOXIC

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HUMANIZED ANTIBODIES

• THE ANTIGEN BINDING SITE IS THE ONLY PORTION OF
  THE ANTIBODY THAT CONTAINS MOUSE PROTEINS
• 90 IS HUMAN

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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

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CATALYTIC ANTIBODIES

• USED TO TRANSFORM SIMPLE COMPOUNDS
• BLOOD CLOTS INHEART

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ANTIBODY FUNCTION

• ACTIVATION OF COMPLEMENT
• TOXIN NEUTRALIZATION
• VIRAL NEUTRALIZATION
• AHERANCE INHIBITION
• PARASITIC INFECTIONS

• ANTIBODY DEPENDENT CELL MEDIATED CYTOTOXITY
• OPSONIZATION
• REGULATING INFLAMMATION
• IMMUNE COMPLEX

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FUNCTION OF COMPLEMENT

• MEDIATE INFLAMMATION
• CHEMOTAXIS
• PHAGOCYTE ACTIVATION
• CYTOLYSIS
• OPZONIZATION
• ACTIVATION OF OTHER IMMUNE CELLS

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COMPLEMENT ACTIVATION

• COMPLEMENT MAKES UP A MAJOR PORTION OF SERUM

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ACTIVATORS OF THE ALTERNATE PATHWAY

• MOLECULES WITH REPEATING CHEMICALS STRUCTURES
• ENDOTOXINS
• POLYSACCHARIDES
• LIPOPOLYSACCHARIDES
• TEICHOIC ACID
• Ig A

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ACTIVATION BY THE CLASSICAL PATHWAY

• Ig M
• IgG1
• IgG2
• IgG3
• ANTIGEN ANTIBODY COMPLEXES

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COMPLEMENT IS A MAJOR REGULATOR OF THE
INFLAMMATORY RESPONSE
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TOXIN NEUTRALIZATION

• BLOCKS ABILITY OF TOXIN TO ENTER CELL OR ATTACH
  TO CELL RECEPTORS
• ANTIBODIES ARE CALLED ANTITOXINS

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VIRAL NEUTRALIZATION

• IgG
• IgM
• IgA
• BIND TO VIRUSES IN EXTRACELLULAR FLUID AND
  INACTIVATE THEM
• C4B AIDS IN THIS PROCESS

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ANTIBODIES THAT BLOCK ADHERANCE

• SECRETORY Ig A
• PROTECTS AGAINST PATHOGENS ON MUCOSAL SURFACES

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ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY

• NATURAL KILLER CELLS
• DESTROYS CELLS BY CYTOLYSIS OR BY CYTOTOXIC
  MEDIATORS

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ADDC DEATH BY APOPTOSIS
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APOPTOSIS
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ADDC CYTOLYSIS
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ANTIBODIES THAT FIGHT PARASITIC INFECTIONS

• IgE
• EOSINOPHILS ARE INVOLVED ALSO

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OPSONIZATION

• COATING WITH ANTIBODIES
• COATING WITH ANTIBODIES AND FIXED COMPLEMENT
• INCREASES PHAGOCYTOSIS OR CAUSES EXTRACELLUAR
  DESTRUCTION IF TO BIG FOR PHAGOCYTOSIS
• IgG1
• IgM

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OSPSONIZATION AND INTRACELLULAR DESTRUCTION
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OPSONIZATION AND EXTRACELLULAR DESTRUCTION
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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

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IMMUNE COMPLEX FORMATION BY ANTIBODY-ANTIGEN

• PRECIPITATION
• AGGLUTINATION HEMAGGLUTINATION

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ANTIBODIES IN THE LAB SETTING

• IN VIVO TESTING
• IN VITRO TESTING

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IN VIVO TESTING

• ALLERGY TESTING IMMEDIATE DELAYED
  (T-CELL)

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IMMEDIATE TESTING

• WITHIN 20 MINUTES
• USED FOR RESPIRATORY ALLERGIES

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DELAYED TESTING

• CELL MEDIATED TESTING
• FOOD ALLERGIES
• CONTACT DERMATITIS
• CANDIDA ALBICANS
• TRICHOPHYTON
• MUMPS
• DIPTHERIA-TETANUS TOXOID
• STREPTOKINASE-STREPTODORNASE

• TRICHOPHYTON
• MUMPS
• DIPTHERIA-TETANUS TOXOID
• STREPTOKINASE-STREPTODORNASE
• TUBERCULIN ANTIGENS
• HISTOPLASMA TUBERCULIN ANTIGENS

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T B TESTING
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POSITIVE TB TEST
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IN VITRO TESTING
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AGGLUTINATION

• DIRECT AGGLUTINATION WIDAL TEST
• LATEX AGGLUTINATION TEST HUMAN CHORIONIC
  GONADOTROPIN
• HEMAGLUTINNATION
• ANTIBODY TITER

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COMPLEMENT FIXATION

• WASSERMAN TEST
• VIRAL DISEASES
• FUNGAL DISEASES
• RICKETTSIAL DISEASES
• CHLAMYDIAL DISEASES
• PROTOZOAL DISEASES

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ELISA TESTS

• ENZYME LINKED IMMUNOSORBENT ASSAY
• LABELED ENZYMES LINKED TO ANTIGENS OR ANTIBODIES
• HELIOBACTER PYLORI
• SYPHILIS
• BRUCELLOSIS SALMONELLOSIS
• CHOLERA

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NEUTRALIZATION REACTIONS

• DETERMINES WHETHER TOXINS OR VIRUSES HAVE BEEN
  INACTIVATED BY ANTIBODY
• CLOTRIDIUM BOTULINUM
• MANY VIRAL DISEASES

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B CELL BIOLOGY

• ANTIGEN SPECIFIC ---T DEPENDENT
• POLYCLONAL --- T INDEPENDENT

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T DEPENDENT ANTIGEN TRIGGERING

• REQUIRES ANTIGEN PRESENTING CELL HELPER T
  CELL B CELL
• MAINLY PROTEINS AND HAPTENS

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B CELLS AND T CELLS ACTIVATE ONE ANOTHER
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ALL THE IMMUNE RESPONSES THAT PRODUCE IgA, IgE
AND IgG ARE T DEPENDENT ANTIGEN TRIGGERED
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B CELL DIFFERENTIATION

• AFFINITY MATURATION
• CLASS SWITCHING
• FORMATION OF PLASMA AND MEMORY CELLS

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AFFINITY MATURATION

• DURING HUMORAL IMUNE RESPONSE AFFINITY OF THE
  ANTIBODIES TO ANTIGEN INCREASES 100-10,000 TIME

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CLASS SWITCHING

• ADDITIONAL REARRANGEMENT OF THEIR HEAVY CHAIN
  GENE SEGMENTS CAN OCCUR.
• PRODUCES IgG, IgA AND IgE

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T INDEPENDENT ANTIGEN TRIGGERING

• NOT ALL ANTIBODY RESPONSES REQUIRE T CELL HELP.
• POLYMERIC
• TUMOR PROMOTING AGENTS
• ANTI-IMMUNOGLOBULIN (ANTI Ig)
• BACTERIAL LIPOPOLYSACCHARIDES

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T INDEPENDENT ANTIGEN

• T INDEPENDENT 1
• T INDEPENDENT 2
• GENERALLY WEAKER
• NO MEMORY CELLS FORMED
• IgM PRIMARY ANTIBODY

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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

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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

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DIFFERENCES BETWEEN T DEPENDENT AND T
INDEPENDENT TRIGGERING

• T INDEPENDENT IS THE MAIN IMMUNE RESPONSE IN
  INFANTS UNTIL AGE TWO

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CHEMICAL MEDIATORS OF THE IMMUNE RESPONSE
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CYTOKINES

• MEDIATE BOTH SPECIFIC AND NONSPECIFIC IMMUNE
  RESPONSE
• GENERAL TERM
• PRODUCTS OF ONE CELL POPULATION THAT AFFECTS
  ANOTHER

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TYPES OF CYTOKINES

• MONOKINES
• LYMPHOKINES
• INTERLEUKINS
• CHEMOKINES

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FUNCTIONS OF CYTOKINES

• MEDIATE NONSPECIFIC IMMUNITY
• ACTIVATE EFFECTOR CELLS
• MEDIATE MATURE CELL ACTIVATION, DIFFERENTIATION,
  GROWTH AND BEHAVIOR
• MEDIATE IMMATURE GROWTH AND DIFFERENTIATION

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CYTOKINE EFFECTS ON NONSPECIFIC IMMUNITY

• INTERFERON ALPHA
• INTERFERON BETA

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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

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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

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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

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CHEMOKINES

• PARACRINE
• LOW WEIGHT MOLECULES
• MEDIATES INFLAMMATORY RESPONSE
• INDUCES MIGRATION OF WHICHT BLOOD CELLS INTO
  INFECTED OR DAMAGED AREAS

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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

100
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

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TUMOR NECROSIS CHEMOKINES AND INTERLEUKIN 1 ROLE
IN EXTRAVASATION
102
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

103
MIGRATION INHIBITION FACTOR

• PRODUCED BY MACROPHAGES
• ACTIVATES MACROPHAGES
• PREVENTS MIGRATION FROM SITE
• SECRETION INDUCED BY TUMOR NECROSIS FACTOR,
  LIPOPOLYSACCHARIDES AND OTHER FACTORS

104
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

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INTERLEUKIN 3

• COLONY STIMULATING FACTOR
• STIMULATES PROLIFERATION OF STEM CELLS IN BONE
  MARROW
• INFLUENCES DIFFERENTIATION OF BONE MARROW CELLS
• MAST CELLS, MACROPHAGES AND GRANULOCYTES

106
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

107
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 ANTI-INFLAMMATOR ROLE

108
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

109
T CELL BIOLOGY

• RESPOND TO MHC MARKERS

110
MHC MOLECULES

• FOUND ON ALL NUCLEATED CELLS
• ALSO CALLED HUMAN LEUKOCYTE ANTIGENS (HLAs)
• CLASS I
• CLASS II
• CLASS III
• ASSOCIATED WITH COMPLEMENT SYSTEM

111
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

112
SOURCES OF MHC CLASS I II

• ANTIGEN PROCESSING
• ENDOGENOUS VS EXOGENOUS

113
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

114
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

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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.

116
PROTEINS THAT HAVE ESCAPED INTO THE CYTOSOL
FROM THE PHAGOSOME OF PHAGOCYTES SUCH AS
ANTIGEN-PRESENTING CELLS
117
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

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FORMATION OF MHC CLASS II

• EXAMPLES
• BACTERIA
• FREE VIRUSSE
• YEASTS
• PROTOZOA
• TOINS

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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

120
T CELLS

• SECRETE CYTOKINES
• ATTACK VIRUS INFECTED CELLS
• ATTACK HOST CELLS WITH INTRACELLULAR PARASITES
• ATTACK CANCER CELLS
• CELL MEDIATED IMMUNITY

121
T CELLS

• MADE IMMUNOCOMPETENT IN FETAL THYMUS
• FOUND IN BLOOD AND LYMPH SYSTEM

122
TYPES OF T CELLS

• T HELPER, CTYOTOXIC T CELLS
• AND REGULATOR

123
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

124
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

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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

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T HELPER CELLS

• BALANCE BETWEEN T HELPER 1 AND T HELPER 2 PLAYS A
  ROLE IN HOW WELL THE CELL FIGHTS CERTAIN
  INFECTIONS

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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

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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

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ANIMATION OF T 4 HELPER CELLS ACTIVATION
130
ANIMATION OF THE EFFECTS OF INTERLEUKIN 2
131
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

132
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

133
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

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ANIMATION OF ACTIVATED CYTOXIC T CELL
PROLIFERATION
136
ANIMATION OF DIFFERENTIATION INTO CYTOTOXIC T
LYMPHOCYTES
137
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

138
APOPTOSIS
139
OTHER ACTIVITIES OF T HELPER CELLS
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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

141
T HELPER CELLS ALSO ACTIVATE NATURAL KILLER CELLS

• IL-2 AND IFN GAMMA PRODUCED BY T helper 1 CELLS
  ACTIVATE NATURAL KILLER CELLS

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AQUIRED IMMUNE TOLERANCE

• TOLERANCE INDUCTION
• BODYS ABILITY TO MAKE ANTIBODIES AGAINST NONSELF
  ANTIGENS WHILE TOLERATING SELF ANTIGENS
• ESTABLISHED EARLY IN EMBRYONIC LIFE

143
NULL CELLS

• LACK SPECIFIC SURFACE MARKERS
• NATURAL KILLER CELLS
• PART OF NOSPECIFIC IMMMITY

144
NATURAL KILLER CELLS

• SMALL POPULATION
• NONSPECIFIC
• NULL CELLS
• DESTROY TUMORS
• VIRUS INFECTE CELLS
• FUNGI, BACTERI, PROTOZOA, AND HELMINTHS
• IMMUNE SURVEILLANCE

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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

146
INTERACTION OF A NATURAL KILLER CELL WITH A
NORMAL BODY CELL
147
INTERACTION OF A NATURAL KILLER CELL WITH A CELL
NOT DISPLAYING MHC CLASS I MARKERS
148
APOPTOSIS

• PROGRAMED CELLULAR DEATH

149
NATURAL KILLER CELLS INTERACTIONS ARE PART OF
NONSPECIFIC IMMUNITY
150
SUPERANTIGENS

• BACTERIAL PROTEINS
• STIMULATE IMMUNES SYSTEM MORE EXTENSIVELY
• NONSPECIFICALLY STIMULATE T CELLS

151

• INDUCE MASSIVE CYTOKINE PRODUCTION

152
HYPERSENSITIVITIES

• ALLERGIES
• EXAGGERATED IMMUNE RESPONSE
• IMMEDIATE OR DELAYED
• MAIN DIFFERENCE IN HOW IMMUNE SYSTEM RESPONDS

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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

154
SYSTEMIC ANAPHYLAXIS

• LARGE MAST CELL DEGRANULATION IN SHORT TIME
• SMOOTH MUSCLE CONSTRICTION IN BRONCHIOLES
• ARTERIOLE DILATION
• INCREASED VASCULAR PERMEABILITY

155
CAUSE OF DEATH

• REDUCED VENOUS RETURN
• REDUCED BLOOD PRESSURE
• CIRCULATORY SHOCK
• ASPHYXIATION

156
POSSIBLE CAUSES

• DRUGS
• ANTISERA
• INSECT VENOM

157
LOCALIZED ANAPHYLAXIS

• ATOPIC
• ALLERGIC RHINITIS
• BRONCHIAL ASTHMA
• FOOD ALLERGIES

158
PREVENTING TYPE I RESPONSES

• REPLACE IgE RESPONSE WITH IgG RESPONSE
• SERIES OF ALLERGEN SHOTES
• EFFECTIVE ABOUT 65 TO 75 WITH INHALED ALLERGENS

159
TYPE II CYTOTOXIC HYPERSENSITIVITIES

• DESTRUCTION OF HOST CELLS
• LYSIS OR TOXIC MEDIATORS
• ANTIBODY MEDIATED CELL-MEDIATED CYTOTOXICITY
• IgG OR IgM
• DIRECTED AGAINST TISSUES OR CELL SURFACES
• INTERACT WITH COMPLEMENT

160
EXAMPLES

• BLOOD TRANSFUSIONS WITH WRONG BLOOD TYPE (ABO)
• HEMOLYTIC DISEASE OF THE NEWBORN
• DRUG INDUCED HEMOLYTIC ANEMIA

161
DRUGS THAT CAN INTIATE A TYPE II HYPERSENSITIVITY

• PENICILLIN
• QUINIDINE
• METHYLDOPA

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TYPE III IMMUNE COMPLEX HYPERSENSITIVITY

• FORMATION OF IMMUNE COMPLEXES
• NORMALLY REMOVED BY RETICULOENDOTHELIAL SYSTEM
• EXCESS MAY ACCUMULATE
• ACTIVATES COMPLEMENT

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EXAMPLES OF TYPE III HYPERSENSITIVITIES

• SERUM SICKNESS
• DRUG REACTIONS
• POSTSTREPTOCOCCAL GLOMERULONEPHRITIS
• SYSTEMIC LUPUS ERYTHEMATOSUS
• RHEUMATOID ARTHRITIS
• GOODPASTURES SYNDROME
• FARMERS LUNG

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ASPERGILLOSIS
165
GLOMERULAR NEPHRITIS
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TYPE IV CELL MEDIATED HYPERSENSITIVITY

• T CELL MEDIATED
• USUALLY TAKES DAYS TO OCCUR
• MEDIATED BY CYTOKINES
• CAUSES EXTENSIVE TISSUE DAMAGE

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EXAMPLES OF TYPE IV

• INTRACELLULAR PARASITE MYCOBACTERIUM
• TB TEST
• SOME AUTOIMMUNE DISEASE
• CONTACT DERMATITIS
• KILLING OF CANCER CELLS
• TRANSPLANT REJECTION

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AUTOIMMUNE DISORDERS

• FAILURE TO RECOGNIZE SELF ANTIGENS

169
AUTOIMMUNITY VS AUTOIMMUNE DISORDER
170
FACTORS THAT AFFECT AUTOIMMUNE DISORDERS

• VIRUSES
• GENETICS
• ENDOCRINE SYSTEM
• PSYCHONEUROIMMUNOLOGICAL

171
MORE COMMON IN OLDER PEOPLE
172
TRANSPLANT REJECTION

• ISOGRAFTS
• ALLOGRAFTS
• XENOGRAFTS

173
MECHANISMS OF TISSUE REJECTION

• T CELL IMMUNITY IS ACTIVATED
• CYTOTOXIC T CELLS KILL TISSUES
• T HELPER CELLS RELEASE CYTOKINES
• NATURAL KILLER CELLS ALSO INVOLVED

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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

175
CYCLOSPORIN. TACROLIMUS AND OTHER DRUGS GIVEN TO
SUPPRESS T CELL IMMUNITY
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IMMUNODEFICIENCIES

• PRIMARY/CONGENITAL
• VS
• SECONDARY/ACQUIRED

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PRIMARY/CONGENITAL IMMUNODEFICIENCY

• CHRONIC GRANULOMATUS DISEASE
• COMMON VARIABLE HYPOGAMMOGLOBULEREMIA
• DI GEORGES SYNDROME
• SEVERE COMBINE IMMUNODEFICIENCY DISEASE

178
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

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Di GEORGES SYNDROME

• THYMUS FAILS TO DEVELOP
• NO T CELL IMMUNITY
• CELL MEDIATED
• T DEPENDENT HUMORAL IMMUNITY
• GENERALLY DIE OF VIRAL INFECTION

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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

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SEVERE COMBINED IMMUNODEFICIENCY DISEASE

• SCIDs
• NEITHER B OR T CELLS ARE PRODUCED
• BOY IN THE BUBBLE

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SECONDARY IMMUNODEFICIENCIES

• ACQUIRED AFTER BIRTH
• CANCER
• STRESS
• DIABETES
• MALNUTRITION
• CERTAIN ENVIRONMENTAL TOXINS
• HIV