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    FinalEffector Cells

    Uploaded by

    agarwalkeshav1947

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    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd

    FinalEffector Cells

    Uploaded by

    agarwalkeshav1947
    10 views42 pages

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    © © All Rights Reserved

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    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    10 views42 pages

    FinalEffector Cells

    Uploaded by

    agarwalkeshav1947

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 42

    Effector Cell Responses

    Antibody and Cell


    Mediated
    Introduction to Effector Cell Responses
    • HI Effector
    • Ab Class dependent: IgG vs IgM
    • FcR of Ab determines Cell Type activated
    • Intracellular pathogens: No access to Ab
    • Tumors: Escape Ab Response
    • Cell Mediated Response: Th & Tc
    • Ag specific & Ag Non specific
    • Ag Specific: Lymphocytes
    • Ag Non specific: NK cells & Myeloid lineage cells
    • Cooperation of HI & CMI: ADCC
    Antibody Mediated Effector Functions

    • Neutralization: Inactivate
    • Opsonization: Enhanced phygocytosis
    • Agglutination: Clumping
    • Complement fixation: MAC & anaphylotoxins
    • Antibody-dependent cell-mediated cytotoxicity
    • Degranulation:
    Neutralization
    • Block entry
    • Gp120 of HIV binds CD4
    • Influenza expresses
    Hemagglutinin that binds
    Glycoprotein on epi. cells
    • Neutralizing Ab
    • Tetanus toxoid
    • Snake bite
    • Genetic variants
    Agglutination of Streptococcus pneumonia by
    antibodies in nasal secretions
    • Multiple ag binding site/ab: IgA vs IgM
    • Diff. Infection
    • Clearance
    • cillia
    • Peristalysis: mucus)
    • Prevents colonization
    • Bacteria: Red
    • Nasal cells: blue
    Degranulation
    Antibody Mediated Effector Functions

    • Neutralization: Inactivate
    • Opsonization: Enhanced phygocytosis
    • Agglutination: Clumping
    • Complement fixation: MAC & anaphylotoxins
    • Antibody-dependent cell-mediated cytotoxicity
    • Degranulation:
    Antibody-dependent cell-mediated cytotoxicity (ADCC)

    • Cells that have


    cytotoxic potential
    (NK cells,
    macrophages, etc)
    express receptors for
    Fc portion of antibody
    Functions of Fc Receptors
    Fc Receptor Structures, Expression
    Patterns, and in Vivo Functions
    Revision of Final Effector Cells
    IgM
    • Primary Immune Response
    • Low affinity: No affinity
    maturation
    • Circulating are Decavalent but
    surface bound divalent
    • Complement fixation
    • Agglutination
    IgG
    • Most common in serum
    • Most Diverse:IgG1, , IgG2, IgG3,
    and IgG4
    • Opsonization
    • Complement activation
    • Monomeric
    IgA
    IgA
    • Present in secretions
    • IgA1 and IgA2
    • No complement fixation
    • Highly glycosylated Binds to bacterial polysach.
    • Agglutination
    • Ag clearance
    • Special feature: Secretory chain
    • Binds Poly Ig Receptor
    • Long Half life: Fc region is resistant to many of the proteases
    • Fc region is resistant to many of the microbial proteases (evasion
    mechanisms)
    IgE

    • Role in allergy and asthma


    • protection against parasitic worms
    • Protozoa
    • Venoms
    • degranulation of eosinophils and
    basophils
    • histamine and proteases that
    damage pathogens
    • Inflammation
    IgD
    • Extremely low level
    • higher levels: respiratory tract
    • Binds: Respiratory bacterial and
    viral pathogens
    • bind to basophils and mast
    cells→ Antimicrobial peptide &
    cytokines
    Therapeutic antibodies (Animation)
    Therapeutic Antibodies
    Therapeutic antibodies
    • How Monoclonal Antibodies Treat Cancer - Bing video
    Cell Mediated Immunity

    • Important in detecting and eliminating cells that harbor intracellular pathogens

    • Antigen specific
    • CD8+ and CD4+ T cells
    • Nonspecific cells
    • NK cells, non-lymphoid types such as macrophages, neutrophils, and eosinophils
    Effector Responses
    • Importance of these become evident when system is defective
    • Di George Syndrome
    • Born without thymus, lack T cell component
    • Can fight extracellular pathogens but have issues with intracellular pathogens (viruses,
    intracellular bacteria)

    • Effector T cells express variety of effector molecules


    • CTLs or Tc cells, CD8+
    • Class I MHC restricted
    Effector phase of CTLs
    • CTL-Mediated Death
    • Conjugate formation of CTL with infected cell
    • Membrane attack
    • CTL dissociation
    • Target cell destruction

    Granules contain perforin


    Stages in CTL-mediated killing of target cells
    mechanisms: Granules

    • lymphocyte-specific protein tyrosine kinase (Lck)


    Conjugate formation between CTL and target
    cell & reorientation of CTL cytoplasmic
    CTL-mediated pore
    Fas/FasL-mediated cytolysis
    (even in lacking granzymes & perforins)
    Fas Ligand Fas (CD95)
    • Transmembrane protein on • Present on target cells
    CTLs • Its cross linking induces
    • In cells lacking death
    granzyme/perforins mediate • Apoptosis induced in Target
    death
    • localizes in the granule
    membrane
    • Cross links Fas on target
    • TNF family molecule
    Induction of Apoptosis
    • Mediated by Caspase group of enzymes
    • cysteine proteases
    • cleave after an aspartic acid residue
    • Caspase: Cysteine, aspartate, protease
    • Present in inactive form → Proteolytic cleavage →
    Activation
    • Sequential cascade of events → systematically
    disassemble the target cell
    • Two types
    • Initiator caspases
    Fas/FasL-mediated cytolysis
    Time course of responses to viral infection
    Natural Killer Cells (NK)
    • Defend against viruses, other intracellular pathogens, and
    tumors
    • Produce important cytokines:
    • IFN-γ:Enhances the phagocytic, microbicidal, and antigen
    presentation
    • TNF-α, GMCSF and chemokines
    • Lymphoid cells
    • Share early lineage to T cells
    • NK cells don’t develop exclusively in thymus
    • Killing of target cell is similar to that of CTL
    Natural Killer Cell Activity
    Balance of Activating and Inhibitory Signals
    Missing Self Hypothesis
    NK cells kill targets by processes similar to CTLs
    END
    Experimental Assessment of CML
    • Mixed Lymphocyte Reaction (MLR)
    • T lymphocytes from 2 donors undergo extensive
    proliferation when mixed
    • Each donors’ MHC is the antigen
    • If MHC is same on both donors’ cells then there is
    no reaction
    • If MHC is different, each donors’ T cells will react
    to each other and will proliferate
    • Degree can be measured by adding [3H]-Thymidine to
    culture and monitoring uptake into DNA
    Experimental Assessment of CML
    • Cell-mediated
    lympholysis
    • Target cells are labeled
    intracellularly with 51Cr
    (will not pass out of
    the cell unless cell is
    lysed)
    • If there is cell-
    mediated cytotoxicity,
    then 51Cr will be
    detected

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