A summary of innate and acquired immunity General iology INNATE IMMUNITY Rapid responses to a broad range of microbes Course No: NG00 Credits:.00 External defenses Invading microbes (pathogens). The Immune System Repetition Internal defenses Skin Phagocytic s Mucous membranes Antimicrobial proteins Secretions (low ph) Inflammatory response (physical barriers) ACQUIRED IMMUNITY Slower responses to specific microbes Natural killer s (ular and chemical mechanisms) Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Prof. Dr. Klaus Heese The System system: Functions: ) Remove excess interstitial fluid; ) Transport of dietary lipids; ) Specific immunity (as compared to non-specific immunity). Lymph is essentially recycled blood plasma The lymphatic system has multiple interrelated functions: - It is responsible for the removal of interstitial fluid from tissues - It absorbs and transports fatty acids and fats (lipids) as chyle from the digestive system - It transports white blood s to and from the lymph nodes into the bones - The lymph transports presenting s (APCs), such as dendritic s, to the lymph nodes where an immune response is stimulated.
Primary lymphoid organs The central or primary lymphoid organs generate lymphocytes from immature progenitor s. The thymus and the bone marrow constitute the primary lymphoid tissues involved in the production and early selection of lymphocytes. Secondary lymphoid organs Secondary or peripheral lymphoid organs maintain mature naive lymphocytes and initiate an adaptive immune response. The secondary/peripheral lymphoid organs are the sites of lymphocyte activation by. Activation leads to clonal expansion and affinity maturation. Mature lymphocytes recirculate between the blood and the peripheral lymphoid organs until they encounter their specific. The lymphatic system plays an active role in defending the body from pathogens 4 vessels return lymph to the blood via two large ducts that drain into veins near the shoulders. Interstitial fluid bathing the tissues, along with the white blood s in it, continually enters lymphatic capillaries. Adenoid Tonsil Lymph nodes Spleen Peyer s patches (small intestine) Tissue s Interstitial fluid vessel capillary lood capillary Fluid inside the lymphatic capillaries, called lymph, flows through lymphatic vessels throughout the body. Secondary lymphoid tissue provides the environment for the foreign or altered native s (s) to interact with the lymphocytes. It is exemplified by the lymph nodes, and the lymphoid follicles in tonsils, Peyer's patches, spleen, adenoids, skin, etc. that are associated with the mucosa-associated lymphoid tissue (MALT). Appendix vessels Lymph node Masses of lymphocytes and macrophages Within lymph nodes, microbes and foreign particles present in the circulating lymph encounter macrophages, dendritic s, and lymphocytes, which carry out various defensive actions. Lymphocyte Development as part of acquired immunity Lymphocytes arise from stem s in the bone marrow Newly formed lymphocytes are all alike but they later develop into s or s, depending on where they continue their maturation Lymphoid stem one marrow Thymus primary lymphoid organ s Depending on their source peptide s are handled by different classes of MHC s Class I MHC s, found on almost all nucleated s of the body display peptide s to cytotoxic s Infected Antigen fragment Class I MHC receptor A fragment of foreign protein () inside the associates with an MHC and is transported to the surface. The combination of MHC and is recognized by a, alerting it to the infection. lood, lymph, and lymphoid tissues (lymph nodes, spleen, and others) secondary lymphoid organ (a) Cytotoxic
s Class II MHC s, located mainly on dendritic s, macrophages, and s display s to helper s general overview of T (CD4/CD8) activation Th/Th Tc Microbe Antigenpresenting A fragment of foreign protein () inside the associates with an MHC and is transported to the surface. The combination of MHC and is recognized by a, alerting it to the infection. Antigen fragment Class II MHC receptor Figure 4.9b (b) Helper Antigen presentation stimulates s to become either "cytotoxic" CD8+ s or "helper" CD4+ s. Helper s produce CD4, a surface protein that enhances their binding to class II MHC complexes on -presenting s Activation of the helper then occurs Activated helper s secrete several different cytokines that stimulate other lymphocytes The role of helper s in acquired immunity After a dendritic engulfs and degrades a bacterium, it displays bacterial fragments (peptides) complexed with a class II MHC on the surface. A specific helper binds to the displayed complex via its TCR with the aid of CD4. This interaction promotes secretion of cytokines by the dendritic. Dendritic Dendritic Peptide Class II MHC TCR CD4 Helper Cytokines Cytotoxic Proliferation of the, stimulated The s in this clone by cytokines from both the dendritic secrete other cytokines and the itself, gives rise to that help activate s a clone of activated helper s and cytotoxic s. (not shown), all with receptors for the same MHC complex. Helper T Cells: A Response to Nearly All Antigens Cell-mediated immunity (attack on infected s) Humoral immunity (secretion of antibodies by plasma s) The activated cytotoxic secretes proteins that destroy the infected target A specific cytotoxic binds to a class I MHC complex on a target via its TCR with the aid of CD8. This interaction, along with cytokines from helper s, leads to the activation of the cytotoxic. Cytotoxic TCR Class I MHC Target infected s, cancer s, and transplanted tissues Perforin Granzymes CD8 Peptide The activated releases perforin s, which form pores in the target membrane, and proteolytic enzymes (granzymes), which enter the target by endocytosis. Pore The granzymes initiate apoptosis within the target s, leading to fragmentation of the nucleus, release of small apoptotic bodies, and eventual death. The released cytotoxic can attack other target s. Released cytotoxic Apoptotic target Cancer Cytotoxic
Dendritic Cells : Center of the Immuniverse How can we use Dendritic Cells as therapeutic Vaccines? Methods - obtain DC from patient blood - Load DC with tumor components - Return DC to patients Humoral and -mediated immunity defend against different types of threats The roles of the major participants in the acquired immune response Humoral immune response Cell-mediated immune response Mechanism of action -dependent activation Acquired immunity includes two branches: i) the humoral immune response involves the activation and clonal selection of s, resulting in the production of secreted antibodies, ii) the -mediated immune response involves the activation and clonal selection of cytotoxic T-s First exposure to Antigens engulfed and Antigens displayed Intact s displayed by dendritic s by infected s Activate Activate Activate Secreted cytokines activate Helper Cytotoxic Gives rise to Gives rise to Gives rise to Active and Plasma Memory Memory Active memory s s cytotoxic cytotoxic helper s s s T mammals immature s are formed in bone marrow Secrete antibodies that defend against pathogens and toxins in extraular fluid Defend against infected s, cancer s, and transplanted tissues 4
Mechanism of action - -dependent activation Activation of s is aided by cytokines and binding to helper s; the clonal selection of s generates antibodysecreting plasma s, the effector s of humoral immunity After a macrophage engulfs and degrades a bacterium, it displays a peptide complexed with a class II MHC. A helper that recognizes the displayed complex is activated with the aid of cytokines secreted from the macrophage, forming a clone of activated helper s (not shown). A that has taken up and degraded the same bacterium displays class II MHC peptide complexes. An activated helper bearing receptors specific for the displayed binds to the. This interaction, with the aid of cytokines from the, activates the. Antibody-Mediated Disposal of Antigens The binding of antibodies to s is also the basis of several disposal mechanisms; it leads to elimination of microbes by phagocytosis and complement-mediated lysis inding of antibodies to s inactivates s by The activated proliferates and differentiates into memory s and antibody-secreting plasma s. The secreted antibodies are specific for the same bacterial that initiated the response. Viral neutralization (blocks binding to host) and opsonization (increases phagocytosis) Agglutination of -bearing particles, such as microbes Activation of complement system and pore formation Complement proteins acteria Virus Macrophage Precipitation of soluble s MAC Peptide Pore Class II MHC CD4 TCR Cytokines Helper Activated helper Soluble s Secreted antibody Clone of plasma s s Endoplasmic reticulum of plasma Clone of memory s The Allergic Response Enhances Antibodymediated mechanisms of disposal Phagocytosis Foreign Leads to Cell lysis Macrophage asophil activation: both Ca and C5a have anaphylatoxin activity, directly triggering degranulation of mast s / basophils as well as increasing vascular permeability and smooth muscle contraction. IgE Allergen Histamine Granule Mast IgE antibodies produced in On subsequent exposure to the Degranulation of the, response to initial exposure same allergen, IgE s triggered by cross-linking of to an allergen bind to attached to a mast recogadjacent IgE s, receptors on mast s. nize and bind the allergen. releases histamine and other chemicals, leading to allergy symptoms. 5