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Adaptive & Innate Immunity The Immune Response and Immunity • Immune response ▫ Innate (non-specific) ▫ Adaptive (specific): Primary: when encountering the microorganism for the first time. Secondary: in recurrent infections (memory) Acquisition of Immunity ▫ Natural: - active - passive ▫ Artificial: - active - passive Naturally Acquired Immunity • Active: ▫ Acquired through contact with microorganisms (infection). ▫ Provides long term protection. • Passive: ▫ Antibodies pass from mother to fetus across placenta or in breast milk (IgG) ▫ Provides immediate short term protection (few months) Artificially Acquired Immunity • Active: ▫ Antigens introduced through vaccination. ▫ Provides long term protection. • Passive: ▫ Induced by the transfer of antibodies ▫ Referred to as: Immune serum globulins(ISG), immune globulins (IG) or gamma globulins ▫ Provides immediate short term protection active natural passive adaptive active immunity artificial innate passive Adaptive immunity Humoral Cell mediated B lymphocytes T lymphocytes Antibodies Cytokines Extra cellular infections Intra cellular infections Soluble mediators of the immune system: Immunoglobulins Cytokines Interferons Complement Immunoglobulins Immunoglobulins (Ig): • Are gamma globulins (proteins) of defined specificity for different epitopes that make up antigens. • They are produced by plasma cells (differentiated B cells) N epitopes Immunoglobulins are divided into five classes: • Three major classes ( IgG, IgM, IgA). • Two minor classes (IgD and IgE). Basic Structure of Immunoglobulin: • The immunoglobulin molecule consists of four polypeptides chains: two heavy (H) and two light( L) chains fastened together by disulfide bonds. N • Heavy chains consist of two different domains (constant, and variable). • Light chains also have two different domains (constant, and variable). • A light chain variable domain and a heavy chain variable domain together form a pocket that constitutes the antigen-binding region (Fab). • The flexibility of Ig is associated with the presence of hinge region. • Heavy chains are designated by using of Greek letters (μ, γ, α, δ, and Є), and the immunoglobulins produced are IgM, IgG, IgA, IgD, and IgE, respectively. • The light chain consists of two kappa(κ) or two lambda(λ) chains. Immunoglobulins Isotypes: IgG • IgG accounts for approximately 75-85% of the total serum Ig • It is the most abundant antibody produced during secondary humoral immune response. • Have monovalent affinity. • It is the only class that can cross the placenta. IgG structure: • n IgM: • Found either as a B cell bound monomer or as a secreted pentamer. • Present on B lymphocyte surfaces. • Normally secreted as a J-chain containing pentamer with molecular mass of 900 KD. • Form ~ 5-8 % of normal serum immunoglobulin. • Dominates in early primary immune response. • Anti-A and Anti-B blood groups. • Complement fixation. • Multivalent avidity (10 antigens). IgM Structure: • n IgA: It accounts for 10-16% of serum Igs. Most abundant in saliva, tears, intestinal mucus, bronchial secretions, milk, prostatic fluid (body fluids & secretions). Called secretory IgA The predominant Ig produced in Peyer’s patches (illume submucosa), tonsils and other submucosal lymphoid tissue. It has two subclass: in IgA1: Monomer in the serum. IgA2: Dimer when secreted (secretory IgA). IgA1: IgA2 ratio in blood is 5:1 IgD • Has a Molecular weight of 180 KD. • Present on B-cell surface. IgE: Form less than 1% of total serum Igs. A unique high affinity Fc receptor on mast cell and basophils. (bounded) Great role in allergy, through cross linking and release of histamine from mast cells and basophils. play a role in helminths infection. Summary • There are 5 isotypes of immunoglobulins. • IgG is the most abundant in serum, the most important in secondary infections and the only one that can cross the placenta. • IgM is the most important in the primary exposure and in complement fixation. • The secretory IgA is most important in immunity in body secretions, submucosa and lumens. • IgD is bounded to the surface of B cells. • IgE is bounded to the mast cells and basophils and is the most important in allergic reactions and helminths infestation. Primary & Secondary Antibody Response • Primary Response ▫ Following the first exposure to an antigen, there is a slow rise in IgM followed by a slow rise in IgG • Secondary Response ▫ Following exposure to previously encountered antigen, there is a rapid rise in IgG and slow or no rise in IgM Molecules of Cellular Interaction: Cytokines: are low-molecular weight soluble protein messengers that are involved in : • Cellular interaction; inflammatory response in innate and adaptive immunity. • Cellular growth, differentiation, and repair mechanism. Cytokines are produced by a wide variety of immune and non-immune somatic cells. Cytokines produced by lymphocytes are known as lymphokines. Cytokine IL-1 N IL-2 • N IL-4, IL-5 IL-10, IL13 TNF-α TNF-β Cellular Targets Source Macrophage, T cell, B cell, B cell End. CD4 cell (TH1) CD4 cell (TH2) TH2, CD8 cells T cell, B cell, NK cell, Mac. B cell, T cell, Eos B cell, TH2, Mac. Function Leukocyte activation, End. Adhesion T cell proliferation. Differentiation of TH2 and B cell Inhibits IL-2, and INFγ. Down reg. IL-12 Mac, PMN, Mac, PMN, T, Inflammatory Mediator. T, B cells. End. Lymphocytes Wide Variety Inflammatory Mediator. Cytokines and Immune cells interaction: N Interferons (IFNs): are low molecular weight soluble proteins. • Activated by presence of intracellular pathogens such as viruses ,bacteria, and parasites or tumor cells. • Released by lymphocytes and other somatic Non-immune cells. • Major Action: - Anti-Viral infection. - Fight Tumors. N Interferons N Cellular Source Targets Function INF-α Lymphocytes, Epithelium, fibroblasts. Wide variety of cells. -Up-regulates MHC Class I. -Inhibit viral proliferation INF-β Epithelium, fibroblasts. Wide variety of cells. Up-regulates MHC Class I. Inhibit viral proliferation INF-γ CD8*& CD4*T cells, and NK cells. T , B, M, NK, End. Anti-Viral. Anti-Parasitic. Enhances MHC Class I and II expression. Complement system: Complement system: series of soluble enzymes and proteins (C1,C2…….C9) that function in both innate and adaptive immune response against pathogens. Complement activation can be initiated via: ▫ Alternative pathway. ▫ Classical pathway ▫ Mannan-binding lectin pathway. Alternative pathway: • Activation of the alternate pathway started from C3 in the presence of the microbe, and continue tell activation of membrane attack complex (MAC) Classical pathway of Complement: • Starts by antigen - antibody interaction which enables C1 binding and continue tell MAC activation. Mannan-binding lectin pathway • Lectins are proteins that bind to carbohydrates. • Mannan is polymer of the sugar mannose. • This pathway is activated by binding of mannan-binding lectin (MBL) to certain microbes, and continue tell MAC formation. • N The Complement Anaphylatoxins: • The small fragments (C3a, C4a, C5a) generated in the alternative and the MBL pathway act as anaphylotoxins. • They attract and activate some cells (neutrophils, phagocytes and mast cells) to the site of infection to produce an inflammatory reaction. Mechanism of Inflammation: N