IMMUNITY THE ABILITY TO RESIST DISEASE. NONSPECIFIC VS SPECIFIC /toc.htm

IMMUNITY

THE ABILITY TO RESIST DISEASE

NONSPECIFIC VS SPECIFIC

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NONSPECIFIC

• 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

• LARGE

• COMPLEX

• PROTEINS

• NUCLEOPROTEINS

• POLYSACCHARIDES

• GLYCOLIPIDS

ANTIGENIC DETERMINANT SITES

• SITES ON ANTIGEN THAT CAUSE PRODUCTION OF ANTIBODY

• MONOVALENT

• MULTIVALENT

• HETEROPHILE OR HETEROLOGOUS

HAPTENS

• 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

• IgA

• IgD

• IgE

• IgG

• IgM

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

STRUCTURE OF ANTIBODY MOLECULE

ANTIBODY SUBCLASSES

• Ig A

• Ig G

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

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

• 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

• 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

• TRACE AMOUNTS IN SERUM

• MAINLY FOUND ON B CELLS

• REGULATES IMMUNE SYSTEM

• MONOMER

• MAY PLAY ROLE IN ELIMINATING SELF-REACTIVE AUTOANTIBODIES

IMMUNOGLOBULIN E

• LESS THAN 1% OF ANTIBODY

• SKIN SENSITIZING

• ANAPHYLACTIC

• BINDS TO MAST CELLS AND BASOPHILS

• FIGHTS PARASITES

ANTIBODY DIVERSITY

• 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

• INITIAL CHALLENGE

• LAG PHASE

• LOG PHASE

• PLATEAU

• PASTEUR PHASE

• LOW ANTIBODY AFFINITY

SECONDARY IMMUNE RESPONSE

• 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

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M/Monoclonals.html

IMMUNOTOXINS

CHIMERIC MONOCLONAL ANTIBODIES

• 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

• 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

• 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

• 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 ANTIBODY-

ANTIGEN

• 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

• STREPTOKINASE-STREPTODORNASE

• TRICHOPHYTON• MUMPS• DIPTHERIA-TETANUS

TOXOID• STREPTOKINASE-

STREPTODORNASE• 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

• 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 CELLHELPER T CELLB 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 100-10,000 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

• 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

• 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

• 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 ANTI-INFLAMMATOR 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 ANTIGEN-

PRESENTING 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

• 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

CYTOTOXIC T LYMPHOCYTES THEN TRAVEL THROUGHOUT THE BODY

BINDING TO INFECTED CELLS

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 CELL-MEDIATED 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