Humoral Immunity Humoral Immunity and Complement

Transfer of non-cell components of blood-- Robert Beatty antibodies, complement MCB150 Humoral immunity = antibody mediated

B Cell Activation of T-dependent antigens B cell Antigens

T cell dependent B cell antigens T cell independent Majority of antigens. Do not require thymus. Most protein antigens. No memory. T cell help required for B cell activation and antibody production.

T-cell dependent antigens T-cell independent antigens

1 B Cell Activation T-dependent antigens Location of B Cell Activation

Antigen activated B cells remain in T cell zones of LN. Linked Recognition Maximize contact of Need T cell epitope along with B cell epitope to B cells with T cells. get antibody response.

B cells get help from T cells, help = CD40Ligand and IL-4.

Clonal proliferation In Follicles Isotype Switching

Affinity maturation

Somatic hypermutation

2 T cell Independent Antigens B cell mitogens (e.g. LPS) B-1 cells At low levels normal immune response to LPS Activated by repeating CHO epitopes that provide crosslinking At high levels LPS can cause non-antigen specific to induce antigen uptake and activation. activation of B cells. Mitogen effect

Antigen specific immune response Lower affinity, lower numbers, no memory. Primarily IgM.

Antibody Effector Functions Opsonization Neutralization Antibody Effector Functions Enhancement of phagocytosis Neutralizing abs block active site for adherence, entry into host cell, or active site of toxin

Neutralizing antibodies are usually high affinity and primarily IgG.

3 Antibody-dependent cell-mediated Complement Activation cytotoxicity (ADCC) Antibody Effector Functions Antibody Effector Functions

Antibody binds to pathogen or infected target cell. Fc portion of antibody binds to Fc receptors of a cytotoxic cell.

Antibody binds to antigen…….complement binds. Kill, kill, kill…….

Which we will talk about in great detail---- very shortly.

ADCC of target cell with bound antibody by activated NK cells

Control of Antibody Effector Functions Location of Antibody Isotype Influences Function Fc Receptors

IgA Mucosal Fc γ Receptors – opsonization and ADCC IgG Tissues/blood crosses placenta FcRα1 for IgA – opsonization and ADCC IgE Parasitic, mast cells FcεR1 on Mast cells – can prolong life of IgE (role in hypersensitivity) IgM Peritoneum, tissues,

4 Complement Complement Classical Pathway Pathways

C1q binds to 1 IgM molecule

OR

2 IgG molecules

Complement Classical Pathway Classical Pathway Q: Why don't Complement proteins bind to antibodies in serum or lymph fluid?

C1q binds to

2 IgG molecules

Staple form of IgM Planar form of IgM Answer: Antibodies only expose Fc domain for Complement binding when bound to antigen.

5 C1qr2s2 Classical Pathway Classical Pathway

Once C1q binds to antibodies it provides site for serine proteases C1s and C1r to bind. C1 cleaves C4 and C2. Full C1 molecule is made of 1 C1q with C4b and C2b stay bound to cell surface 2C1r and 2 C1s molecules. to form C3 convertase (cleaving C3).

Formation of Membrane Attack Complex Membrane Attack Complex (MAC)

Once C5b is bound then C6, C7, C8 all bind to attract multiple C9s. C9is pore-forming protein.

6 Alternate Pathway

C3 spontaneously cleaves. C3b is bound. Factor B binds C3b-B is cleaved by D forms C3bBb. C3bBb is a C3 convertase stabilized by Properdin. Amplification making more C3b. C3bBb3b is C5 convertase.

Biological Functions of C' Biological Functions of C' Lysis of pathogen of infected cell Opsonization Complement Receptors initiate other functions of C'

CRs vs FcRs

7 Biological Functions of C' Biological Functions of C' Clearance of Immune complexes Inflammation

Proteins that Regulate and Inhibit Proteins that Regulate and Inhibit Complement Complement

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