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ACQUIRED – SPECIFIC – ADAPTIVE IMMUNITY. DUAL SYSTEM: HUMORAL ANTIBODIES – SOLUBLE PROTEINS IN BLOOD, MUCUS, MILK, SALIVA, LYMPH BIND BACTERIA & AID PHAGOCYTOSIS, BIND & INACTIVATE VIRUSES, TOXINS
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ACQUIRED – SPECIFIC – ADAPTIVE IMMUNITY DUAL SYSTEM: HUMORAL ANTIBODIES – SOLUBLE PROTEINS IN BLOOD, MUCUS, MILK, SALIVA, LYMPH BIND BACTERIA & AID PHAGOCYTOSIS, BIND & INACTIVATE VIRUSES, TOXINS CELL MEDIATED IMMUNITY – IMMUNE CELLS SEEK OUT AND DESTROY HUMAN CELLS EXPRESSING FOREIGN ANTIGENS E.G., PATHOGENIC VIRUSES
DISCRIMINATION BETWEEN SELF AND NON-SELF, RESPONDS ONLY TO FOREIGN MATERIAL • DIVERSITY – SPECIFIC ANTIBODIES WHICH RECOGNIZE TRILLIONS OF SPECIFIC, DIFFERENT STRUCTURES • SPECIFICITY – IMMUNITY DIRECTED AT ONE UNIQUE PATHOGEN • MEMORY – RESPONDS QUICKLY TO RE-EXPOSURE • SELF-LIMITING – DOES NOT OPERATE UN-CONTROLLED
HUMORAL IMMUNITYCELL-MEDIATED IMMUNITY CIRCULATING, SOLUBLE CELLS WHICH SPECIFICALLY PROTEINS, ANTIBODIES ATTACK HOST CELLS INFECTED (GAMMA GLOBULINS) BY SOME VIRUSES OR FUNGI REACT WITH BACTERIA, AND TUMOR CELLS SOME VIRUSES, TOXINS B LYMPHOCYTE DEFICIENCY T LYMPHOCYTE DEFICIENCY AGAMMAGLOBULINEMIA DiGEORGE SYNDROME BACTERIAL INFECTIONS VIRAL INFECTIONS SCID –SEVERE COMBINED IMMUNODEFICIENCY DISEASE B AND T LYMPHOCYTE DEFICIENCY LETHAL
HEMATOPOESIS- T AND B CELL ORIGINS
THE DEVELOPMENT AND FUNCTION OF B AND T LYMPHOCYTES
CLONAL SELECTION • NAÏVE LYMPHOCYTE POPULATION CONTAINS CELLS WITH POTENTIAL TO RESPOND TO ALL IMAGINABLE ANTIGENS • INTRODUCING A SPECIFIC ANTIGEN STIMULATES SPECIFIC LYMPHOCYTES WHICH CAN RESPOND TO THAT ANTIGEN TO: • PROLIFERATE & PRODUCE A HUGE POPULATION OF THEMSELVLES WHICH • SYNTHESIZE SOLUBLE ANTIBODIES - HUMORAL • OR ACT AS CYTOTOXIC CELLS – CELL MEDIATED IMMUNITY
HUMORAL IMMUNITY • ANTIGENS - CAUSE ANTIBODY SYNTHESIS AND CELL- MEDIATED RESPONSE • FOREIGN – • HIGH MOLECULAR WEIGHT >10,000 • DEGRADABLE BY HOST BACTERIAL OR FUNGAL CELL SURFACE PROTEINS CAPSID PROTEINS OF VIRUSES ENVELOPE PROTEINS OF ENVELOPED VIRUSES BACTERIAL TOXINS POLLEN, DUST, DANDER, BLOOD CELLS OF PERSONS NOT OF SAME BLOOD GROUP ANTIGENIC DETERMINANTS – SMALLER STRUCTURES ON SURFACES OF ANTIGENS, AS AMINO ACID SIDE CHAINS ON PROTEIN SURFACE, RECOGNIZED BY ANTIBODIES - EPITOPES
ANTIGENS ARE NUMEROUS AND DIVERSE EPITOPES – SMALL FRAGMENTS OF LARGE MOLECULES POOR ANTIGENS – LOW MW NON-DEGRADABLE
ANTIBODIES • SOLUBLE PROTEINS RECOGNIZE AND BIND ANTIGENS (ANTIGENIC DETERMINANTS) SPECIFICALLY • CIRCULATE IN BLOOD, LYMPH, PRESENT IN MUCUS, TEARS, SALIVA, MOTHER’S MILK • SYNTHESIZED IN RESPONSE TO FOREIGN ANTIGEN • REACTION WITH PATHOGEN PROVIDES SPECIFIC IMMUNITY BACTERIAL CELLS – BORDETELLA PERTUSSIS (WHOOPING COUGH) INCREASED PHAGOCYTOSIS EFFICIENCY NON-ENVELOPED VIRUS – POLIO –VIRUS NEUTRALIZATION (INACTIVATION) TOXINS – CLOSTRIDIUM TETANI TOXIN - INACTIVATION
IMMUNOGLOBULIN (ANTIBODY) STRUCTURE
IMMUNOGLOBULIN CLASSES IgG GAMMA HEAVY CHAIN, MONOMERIC, VALENCE 2, 80%, FLUIDS, TOXINS, OPSONIN, TRANSPLACENTAL IgM MU HEAVY CHAIN, PENTAMERIC, VALENCE 10, 5-10%, FIRST, MEMBRANE BOUND ON B CELLS, ACTIVATE COMPLEMENT IgA ALPHA HEAVY CHAIN, MONOMERIC, SECRETED, VALENCE 4, 5-15%, MUCOUS MEMBRANES, PROTECTS SURFACES IgD DELTA HEAVY CHAIN, MONOMERIC, VALENCE 2, <1%, B CELL SURFACE, RECOGNIZES ANTIGENS IgE EPSILON HEAVY CHAIN, MONOMERIC, VALENCE 2, <1%, IMMUNE DISORDER – ANAPHYLAXIS (ALLERGY)
IMMUNOGLOBULIN G IMMUNOGLOBULIN M
B CELL ACTIVATION – BECOME PLASMA CELL - SECRETE SPECIFIC ANTIBODIES EACH B CELL HAS ONE RECEPTOR – IMMUNOGLOBULIN – IgM SPECIFIC FOR ONE AND ONLY ONE ANTIGENIC DETERMINANT B CELL BINDS TO ANTIGEN (ANTIGENIC DETERMINANT) WHICH ITS RECEPTOR RECOGNIZES (CAN BIND) BINDING – SIGNAL TRANSDUCTION ACTIVATES THAT B CELL T HELPER CELLS FUNCTION TO STIMULATE: • PROLIFERATION OF THAT B CELL PRODUCING HUGE POPULATION OF B CELLS OF THAT SPECIFICITY • & DIFFERENTIATION – BECOME PLASMA CELLS, PRODUCE ANTIBODY OR BECOME MEMORY CELLS
THE MEMBRANE BOUND B-CELL RECEPTOR
T HELPER CELL ROLE IN ANTIBODY SYNTHESIS NAÏVE TH0 CELLS EXPRESS RECEPTORS, SPECIFIC FOR ANTIGENIC DETERMINANTS, AND CD4 CO-RECEPTOR BIND ANTIGENIC DETERMINANT PRESENTED ON ANTIGEN- PRESENTING MACROPHAGE/DENDRITIC CELL ACTIVATED, BECOME TH2, CLONAL SELECTION TH2 CELL RECEPTORS BIND ACTIVATED B CELLS EXPRESSING SAME ANTIGENIC DETERMINANT STIMULATE CLONAL SELECTION OF THOSE B CELLS & DIFFERENTIATION INTO PLASMA CELLS PUMPING OUT LIFE-SAVING ANTIBODIES
THE ROLE OF THE T-CELL RECEPTOR PROTEIN IN T-HELPER CELL ACTIVATION
T-DEPENDENT ANTIGEN TRIGGERING of a B CELL 1. ANTIGEN PRESENTING MACROPHAGE (OR DENDRITIC CELL) PROCESSES FOREIGN MATERIAL, PRESENTS EPITOPE BOUND TO MHC CLASS II AND NAIVE B CELL IMMUNOGLOBULIN RECOGNIZES THAT SAME EPITOPE ON OTHER INVADER CELLS; PROCESSES IT, PRESENTS SAME EPITOPE BOUND TO MHCII 2. T HELPER CELL TH0 RECEPTOR- IMMUNOGLOBULIN SPECIFIC FOR THAT EPITOPE CO-RECEPTOR CD4 BINDS EPITOPE BECOMES T HELPER CELL TH2 CLONAL SELECTION 3. B CELL DISPLAYING THAT EPITOPE RECOGNIZES TH2 ABLE TO BIND THAT EPITOPE B CELL PRESENTS EPITOPE FOREIGN INVADER B CELL NAIVE MHCII BINDS TH IMMUNO- GLOBULIN ABLE TO RECOGNIZE THAT EPITOPE INGESTS INVADER PROCESSES DISPLAYS EPITOPE IN MHCII 4. THOSE B CELLS STIMULATED TO PROLIFERATE & DIFFERENTIATE TO PLASMA CELLS (PUMP OUT SPECIFIC ANTIBODIES) OR MEMORY CELLS SIGNAL FOR B CELL
ANTIBODY PRODUCTION AND KINETICS
FORMATION OF GENE FOR IMMUNOGLOBGULIN LIGHT CHAIN PRODUCTION
FORMATION OF A GENE FOR THE HEAVY CHAIN OF AN ANTIBODY MOLECULE
ANTIBODY DIVERSITY HOW CAN A PERSON SYNTHESIZE 10e13 DIFFERENT ANTIBODIES? • REARRANGEMENT OF ANTIBODY GENE SEGMENTS IN PRECURSORS OF B CELLS – COMBINATORIAL JOINING GENE SPLICING IMMUNOGLOBULIN GENE FRAGMENTS ON SAME CHROMOSOME • GENERATING DIFFERENT CODONS DURING GENE SPLICING • SOMATIC MUTATIONS
IMMUNOGLOBULIN GENE SPLICING LIGHT CHAINS: MANY V, J, AND SOME C REGIONS IN PRECURSOR B CELLS RECOMBINATION BY SPECIFIC ENZYMES SPLICES OUT VARIOUS REGIONS, JOINING ONE V, ONE J, AND ONE C REGION IN DEVELOPING B CELLS IN BONE MARROW HEAVY CHAINS: MANY V, D, J, AND SOME C REGIONS IN PRECURSORS SIMILAR COMBINATORIAL JOINING
CONSEQUENCES OF ANTIGEN-ANTIBODY BINDING