Immunity Introduction PDF

Immunity & Pathogenesis: an overview 1 2 3  Learning Objectives At the end of the lecture students should be able to understand and explain the following: – Innate immunity 1. Inflammatory response 2. Phagocytosis 3. Co...

Immunity & Pathogenesis: an overview 1 2 3  Learning Objectives At the end of the lecture students should be able to understand and explain the following: – Innate immunity 1. Inflammatory response 2. Phagocytosis 3. Complement system 4. Interferons – Adaptive immune system 1. Humoral immune response 2. Cell-mediated immune response 3. Immune tolerance 4. Types of adaptive immunity 4  3 Lines of Defense 1. Nonspecific surface defenses – structural, mechanical & biochemical 2. Innate immune defenses Both depend on leukocytes 3. Adaptive immune defenses & plasma proteins 5 Both Immunities: Innate and Adaptive  Innate  Adaptive Natural immunity, non-specific mechanisms Specific, acquired immunity by which pathogens are recognized & – develops after exposure to a suitable responded to antigen – or after transfer of antibodies or lymphocytes from an immune donor Activationof Complement – microbe attacking proteins (C1-C9, etc.) Humoral and Cellular Adaptive Immunities in blood, lymph & EC fluid Humoral: B cells Cellular: T cells Phagocytosis – leukocytes that destroy microbes via _Antigens are molecules recognized by adaptive immune system phagocytosis – proteins, most are strong antigens – polysaccharides, weak antigens Inflammation _Antibodies – specialized proteins produced by B cells – circulate in blood recognizing & binding to microbes, foreign proteins or toxins a.k.a. immunoglobulins (Ig) 6  Innate vs. Adaptive Immunity Characteristic Innate Immunity Adaptive Immunity Speed of response Rapid, within a few hours Slow, days to weeks to act Variation over time No change over lifetime Changes with exposure to microbes & foreign substances Means of recognising Class of molecules Unique molecules on particular pathogens shared by groups of pathogens (e.g. cholera microbes (e.g. LPS) enterotoxin) Number of molecules Only a few Almost infinite number recognised Change during response Constant Improves during response 7 Leukocytes (white blood cells) 8 Innate Immunity 9  Innate Immunity  Innate Natural immunity, non-specific Inflammation (IL6) triggers Liver to release mechanisms by which pathogens are recognized & responded to acute phase proteins (inc complement molecules) Activation of Complement – microbe attacking proteins (C1-C9, etc.) in blood, lymph Three ways to activate the & EC fluid complements (called Complement Cascade Activation); Phagocytosis  All three cascades are – leukocytes that destroy independent but converge to a microbes via phagocytosis common pathway with subsequent: Inflammation 1-Recruitment of inflammatory cells (e.g C5a) For further inflammation, histamine release, phagocytosis 2-Oponization of pathogens coating of microbe with C3b, binds to complement receptors on phagocytes, recognized as foreign & ingested 3-Formation of Membrane Attack Complex (MAC) kills microbes by “putting holes” in plasma membrane 10  Phagocytosis  Innate Recognition, ingestion (by engulfing) & digestion of microbes & foreign particles by phagocyte Natural immunity, non-specific mechanisms by which pathogens are Phagocytes recognized & responded to – Macrophages: long lived, residence in tissues – Neutrophils: short-lived, most abundant white blood cell Activation of Complement – microbe attacking proteins Recognition & adherence (C1-C9, etc.) in blood, lymph – Phagocyte cell surface receptors recognize a specific foreign molecule (e.g. LPS, & EC fluid peptidoglycan) & bind to foreign cell – Opsonins Complement molecules attach to foreign cell Phagocytosis increase adherence – leukocytes that destroy microbes via phagocytosis Inflammation 11   Innate Inflammation Natural immunity, non-specific mechanisms Fluid accumulation in affected tissues by which pathogens are recognized & responded to Reaction to injury Activation of Complement – Symptoms: redness, swelling, pain, heat – microbe attacking proteins (C1-C9, etc.) in blood, lymph & EC fluid Inflammatory stimulus Phagocytosis – Damage to tissue: injury, infection, disordered immune – leukocytes that destroy microbes via phagocytosis response Inflammation Attracting/stimulating phagocytes Altering capillaries – activate phagocytes _dilation causes increased – increased phagocytosis blood flow _↑ leukocytes & complement – margination proteins adhere to capillary wall _erythema (redness of tissue) – diapedesis _↑ permeability, enabling Pass through endothelial leukocytes to enter affected lining, dissolve basement tissue membranes & enter tissue 12  Acute Inflammation & Repair Response to infection – inflammatory mediators – stimulated capillaries – activated phagocytes – pus dead microorganisms & tissue Clean-up – phagocytic cells neutrophils & macrophages – eliminate dead cells microbes, tissue, foreign particles Repair – return to normal – tissue damage, scarring, permanent damage 13  Innate_Interferons (Defense Against Viral Infections) Group of naturally occurring proteins, that ‘interfere’ with viral replication Act as chemical messengers between cells Induce healthy neighboring cells to become more resistant to viral infection 14  Innate_Natural Killer Cells (Defense Against Viral Infections) Kill infected or altered cells – Many viruses ↓ expression of host cell surface proteins (e.g. MHC class I complex) – NK cells kill host cells lacking these proteins Interferon stimulation ↑ killing effectiveness Also produce cytokines – Stimulate macrophage 15 Adaptive Immunity 16 Both Immunities: Innate and Adaptive  Innate  Adaptive Natural immunity, non-specific mechanisms Specific, acquired immunity by which pathogens are recognized & – develops after exposure to a suitable responded to antigen – or after transfer of antibodies or lymphocytes from an immune donor Activationof Complement – microbe attacking proteins (C1-C9, etc.) Humoral and Cellular Adaptive Immunities in blood, lymph & EC fluid Humoral: B cells Cellular: T cells Phagocytosis – leukocytes that destroy microbes via _Antigens are molecules recognized by adaptive immune system phagocytosis – proteins, most are strong antigens – polysaccharides, weak antigens Inflammation _Antibodies – specialized proteins produced by B cells – circulate in blood recognizing & binding to microbes, foreign proteins or toxins a.k.a. immunoglobulins (Ig) 17 Humoral Immune Response 18  Humoral Immune Response Mounted by B cells Each individual B cell is only able to produce 1 kind of antibody – surface antibody acts as an antigen receptor (10 trillion (1013) B cells 100 million distinct antibodies) Antigen receptors – Recognize small part of antigen Epitope or antigenic determinant 19 Antibody Structure Y-shaped molecule No separate gene encodes each antibody 4 peptide chains type – 2 identical heavy chains – 2 identical light chains – disulfide bridges connect  Gene rearrangement multiple copies of each 2 antibody fragments gene segment Fab (antigen binding) different – variable region combinations of Fc (constant) those segments 5 classes of antibodies – share similar constant regions  Pairing of heavy/light chains form antigen- binding site 20  Clonal Selection 1. One specific B cell recognizes a specific epitope (antigen) – only cell which reacts with antigen epitope becomes activated 2. B cell proliferation – each cell recognizes same antigen – Effector cells B cells, plasma cells – Memory cells reserve for future recognition  Plasma cells – produce antibodies specific for same antigen epitope many antibodies produced by each B cell 21  Class of Immunoglobulins Type Secreted Form Proportion Location Function IgA Monomers & 15-20% Blood, milk, saliva, tears Protection at potential entry dimers sites IgD Monomers