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Transcript
Humoral Immunity Ajith Sominanda Department of Anatomy The need of a humoral immunity • Microorganisms multiply in the fluid compartments i.e. ECF and blood, therefore needs a soluble agent to act on ! • Antibodies stick to microorganisms in the fluid compartments of the body A magnet coated with iron dust A bacteria coated with antibodies Components in the Humoral immunity Cellular component • B cells • Plasma cells • T cells • Macrophages Molecular component • Immunoglobulins (Antibodies) • Complement proteins B cell • B cells are lymphocytes and mature in the bone marrow. • Express immunoglobulin receptor (IgM or IgD) on the cell surface called B cell receptor (BCR). • Different types of B cells are found (Naïve, Activated, Memory) • B cells secrete antigen specific immunoglobulins which circulate as antibodies. IgM or IgD Plasma cell • Fully differentiated B cells form Plasma cells and secrete antibodies • Has a different morphology and adapted to Secretory function Antibodies Structure of a typical antibody (IgG molecule) 1. Globular proteins in the serum are immunoglobulins 2. Typical immunoglobulin molecule consists of a) 2 heavy chains (450-600 a.acids) b) 2 light chains (230 a.acids) 3. These are cross linked by disulphide bonds Immunoglobulin molecule has Two functional regions 1. Variable region (‘V’ region) For antigen binding 2. Constant region (‘C’ region) For effector functions of antibodies • Complement activation • Fc receptor activation • Placental transfer Antigen binding site Antigen CDR Complementarity determinant Region Specific B cell produces specific antibodies against a specific antigen Process Specific of B cell Somatic produces recombination specific antibodies in B cell nucleus against produces a specific this Antibody antigendiversity Types (Classes) of antibodies Comparison of antibody classes Humoral Immune Response (sequence of events in antibody mediated immunity) Humoral Immune Response Antigen binding to BCR & B cell Activation Proliferation of B cells (clonal expansion) Antibody production by plasma cells Effector mechanisms of antibodies 1. Neutralization 2. Opsonization 3. Complement activation 1. B cell activation •Antigenic stimulation / Binding starts the B cell activation •First signal is sent through BCR •Second signals are sent through coreceptors (CD 40/40L) Types of B cell activation T cell independent activation T cell dependent activation Signaling that occurs during cell-cell interaction: comparison between ‘APC-T cell’ and ‘B cell-T cell’ For T cells second signal is delivered by a professional antigen-presenting cell such as dendritic cell. For B cells (right panel), the second signal is usually delivered by an activated T cell. 2. B cells proliferation and differentiation 1. 1st signalling through Ag-BCR 2. 2nd signalling through CD40-CD40L 3. IL4 drives B cells to proliferate 2. B cells proliferation and differentiation Cont.. During B cell proliferation, mutations (somatic hyper mutation) generate many clones of B cells bearing surface BCRs with different affinities towards the same antigen 2. B cells proliferation and differentiation Cont.. In the lymph node germinal centers, high affinity B cells are selected and differentiated into plasma cells Primary Immune response • Immune response which occurs by activation of naïve B cells by encountering the relevant antigen for the first time • Takes some time to mount this immune response (714 days) • Produces IgM antibodies • Disappears rapidly • Produces memory B cells • Indicates an acute infection Initial Humoral Immune Response ‘’The Primary Immune Response’’ Antigen binding to Naïve B cells B cell Activation Proliferation of B cells (clonal expansion) Antibody production by plasma cells Secondary Immune response • Subsequent encountering of the same antigen by memory B cells produces antibodies rapidly and in a larger quantity (titer) • The type of antibody is IgG (class switching has occurred) • Indicates the protective immunity • May last a longer period Primary Immune Responses Naïve B cell Activated B cell Plasma cell Secondary Immune Responses Memory B cell Activated B cell Plasma cell Primary and Secondary Immune Responses 3. Effector Mechanisms of antigen bound Antibodies 1. 2. 3. Neutralization i.e. Toxines Fc mediated phagocytosis i.e. activation of Macrophages and ploymorpho nuclear leukocytes Complement activation Effector Function: Fc receptor activation by antigen-antibody complex Fc receptor Just before the END 1. IgG A. is the major type of antibody in serum B. is a multivalent antibody C. can activate the complement cascade D. can cross the placenta 2. IgM A. is a divalent antibody B. is the first antibody synthesized in a primary infection C. Found on surface of B cell D. activates complements 3. IgE A. is at high concentrations in the blood B. is found on mast cells C. plays a role in allergic responses D. produced in parasitic infestation 4. IgA A. is present in the secretions of mouth and intestinal tract B. is a pentavalent antibody C. can activate the classical complement cascade D. both a and c Q: Discuss the following aspects in relation to routine childhood vaccination: 1. Antigens and adjuvents 2. Booseter doses Good to know stuff Comparison of B cell and T cell BCR TCR CD19 CD40 CD3 CD40L Antigen binding yes yes Antigen binding receptor BCR TCR Co-stimulatory molecules Yes yes Co-stimulatory partner T cell APC Cell marker / identity CD19 CD3 Comparison of Antigen processing and presentation: B cell as an APC The end