Lecture: Innate Immune Response | Biology PDF

**[Innate Immune Response]** What is the anatomy of the immune system? - It is localized in several body parts - Immune cells develop in bone marrow and thymus that are primary organs. - Immune responses occur in lymph nodes, spleen, appendix, and Peyer's patch, tonsils and adenoid...

**[Innate Immune Response]** What is the anatomy of the immune system? - It is localized in several body parts - Immune cells develop in bone marrow and thymus that are primary organs. - Immune responses occur in lymph nodes, spleen, appendix, and Peyer's patch, tonsils and adenoids that are secondary organs What are the components of innate Immunity? - Epithelial barriers, phagocytic cells, and soluble mediators (defensins, mannose binding lectin, complement, cytokines and chemokines) What are the characteristics of the localization of peripheral lymphoid tissue in the body? - Organized to optimize interactions between cells of the immune system and antigens. - Lymphoid tissues are classified into 2 groups: - Generative organs such as fetal thymus and fetal liver, and adult bone marrow that are involved in lymphopoiesis. - Peripheral lymphoid tissues: Sites where mature lymphocytes respond to foreign antigens. These include the lymph nodes (cervical, axillary, femoral and popliteal), spleen, and several mucosa-associated lymphoid tissues (MALT) that is a major site of immune response to mucosal pathogens. - Distribution of MALT throughout the body, including underneath the skin (cutaneous), gastrointestinal tract (Peyer's patches of the intestine) and the respiratory tract (pharyngeal tonsils). What are the lymphoid organs and tissues in the body involved in an immune response? - Primary System: Production of Lymphocytes - Thymus and Bone Marrow (site of hematopoiesis, together with early fetal liver) - Secondary system: lymphocytes encounter antigen - Spleen, lymph nodes, and Peyer's patch - Tertiary system: local effector sites - Skin, mucosal linings, lactating breast, secretory organs, omentum/ peritoneal cavity, liver, bone marrow - Ectopic site: site of inflammation Describe the organization of the lymph node - Lymph nodes receive all the extracellular fluid from the peripheral tissues and return it to the blood via the lymphatic vessels. - [Naïve T cells scanning APC surface:] Recognition of specific antigen results in stable conjugate formation, activation and differentiation into an effector T cell - Afferent lymphatics drain fluid from the tissues and carry antigen-bearing cells from infected tissues where they are trapped. - Clear segregation between B and T cell zones. - B cells concentrated in follicles, located at the periphery of each node. Those B cells responding to an antigen are present in the germinal center and are in a state of active expansion. - T cells present in the paracortex in close association with dendritic cells that present antigens to T cells. Describe the organization of the spleen - Same organization as a lymph node, but primary role in responses to blood-borne antigens.  What are the general criteria for an optimal immune response? - Organized lymphoid system is designed for the efficient activation of lymphocytes (by bringing antigen to 2° lymphoid organ and "exposing" circulating antigen-specific cells to the antigen). - Lymphocyte activation requires prior activation of the innate immune system which involves 2 signals: antigen (signal 1) and signal 2 which is induced by the innate response to the antigen. Antigen alone is insufficient. - Interaction of lymphocytes with other cells as well as antigen is necessary for optimal lymphocyte activation. What are the kinetics of an adaptive immune response? What is the timing of innate and adaptive Immunity? A diagram of a immune system Description automatically generated What are the characteristics of Innate Immunity? - Rapid (minutes to hours), no immunological memory - Innate cells do not proliferate in response (but can differentiate) - Receptors are not clonally distributed and encoded in the germ line - Discriminate foreign from "self" constituents using pattern recognition receptors, or PRRs (thus, lack fine specificity of lymphocyte receptors but are NOT non-specific) - PRRs recognize unique pathogen determinants (pathogen-associated molecular patterns, or PAMPs that include bacterial LPS, peptidoglycan, amongst others) - Innate cells release chemokines and cytokines - Chemokines attract cells to a site (out of blood, lymph, or within an organ) - Cytokines affect the behavior of cells (proliferation, differentiation, cytokine production) - Innate immune cell function is required for activation of adaptive immunity How can the innate and adaptive immune responses be differentiated? - Timing of response: Innate responses initiated rapidly and do not require prolonged period of induction. - Recognition of pathogens by innate responses can be due to preexisting broadly specific effectors, such as complement and phagocytic responses, that can kill pathogens directly. - Innate immune responses can be initiated upon recognition of unique pathogen determinants, called pathogen-associated molecular patterns, or PAMPs. Examples of PAMPs include bacterial lipopolysaccharide (LPS or endotoxin), bacterial peptidoglycan, unmethylated CpG dinucleotides in bacterial DNA - No memory. - Distinct from adaptive immune responses that are induced upon exposure to pathogens, are specific to the pathogen, and increase in magnitude upon each successive exposure. Describe hematopoiesis of the adaptive Immune system  Describe hematopoiesis in Innate Immune System Diagram of a cell membrane Description automatically generated with medium confidence What do pluripotent cells give rise to? - Common lymphoid progenitor (CLP) →progenitors of B, T cells and NK cells. - Common monocyte progenitor (CMP) →progenitors of monocytes, blood dendritic cells, neutrophils, eosinophils and basophils. Note: neutrophils, eosinophils and basophils are collectively termed granulocytes. What are the specific cells involved in the innate immune response? - NK cells: lack antigen specificity and do not express immunoglobulins or T cell receptors (different from B and T cells) - make up 10% of lymphocytes in the blood. - Detection of virus-infected cells (due to the lack of Class I MHC molecules) and release lytic granules and lyse virus-infected cells specifically. - Granulocytes: there are three types in the blood: - Neutrophils (aka polymorphonuclear neutrophils/PMNs): Irregular shaped nucleus; dense cytoplasmic granules. - These are one of three types of phagocytic cells in the blood. - Most abundant leukocyte in the blood numbering 4,000 -10,000 per µl, 40% of leukocytes - One of the first responders to infections and can phagocytose bacteria. - Form extracellular structures called NETS (neutrophil extracellular traps); made from chromatin and granule proteins that physically trap bacteria and fungi. - Short lifespans; die within hours of extravasation into tissues at sites of infection. - Eosinophils: recruited to sites of allergic inflammation and parasite infections. - Contain lots of lysosomes and are involved in killing of worm infections. - Basophils: circulating counterparts of tissue mast cells. - Involved in control of allergic reactions and IgE-mediated immediate hypersensitivity. - Monocytes→ macrophages - Differentiate into macrophages upon migration into tissues and can become cells such as microglia in CNS, Kupffer cells in liver, or alveolar macrophages in lung. Differentiation dependent on environmental cues. - One of three phagocytic cells in blood, but less abundant than neutrophils. There are \~500 -- 1000 per µl of blood. - Unlike neutrophils, these cells have rounded nuclei and lack large numbers of cytoplasmic granules BUT they contain acidic compartments with lots of proteases - Once migrated into tissues, can survive for an extended period. - Are antigen presenting cells and hence participate in both innate and adaptive immune responses. - Mast cells: like basophils in that they are involved in allergic responses and infections across epithelial surfaces. - Derived from monocytes (unlike granulocytes). - Primary function to degranulate cytoplasmic stores of histamine, prostaglandins, leukotrienes and cytokines such as TNFα. - Primary responders to asthma and anaphylaxis (bee stings). - Have receptors for class of antibodies called IgE. - Dendritic cells: Professional antigen presenting cells. - Most important APC for stimulating T cell functions. - Characterized by the presence of veiled processes or "dendrites" that emanate from the surface - Immature dendritic cells are migratory. - Phagocytic (engulf bacteria and kill them in lysosomes) and macro-pinocytic (take up extracellular fluid which is another mechanism for acquiring antigen). - Upon encountering pathogen, these cells "mature" and migrate to peripheral lymphoid tissues to initiate adaptive immune responses. - Play important roles in both innate and adaptive immune responses (like macrophages) What are antigen presenting cells? - B cells have antigen-specific receptors that allow these cells to internalize large amounts of antigens. - The three types of innate APCs: - Macrophages engulf extracellular bacteria, especially those coated by antibody, and process and present bacteria as antigens. - Mature dendritic cells that arise from immature dendritic cells after engulfment of bacteria or soluble antigen. - Neutrophils What is the process of phagocytosis (intracellular killing of microbes)? - Macrophages and neutrophils express many surface receptors that may bind microbes for subsequent phagocytosis; select examples of such receptors are shown. Microbes are ingested into phagosomes, which fuse with lysosomes, and the microbes are killed by enzyme and toxic substances produced in the phagolysosomes. These substances may also be released from phagocytes and kill extracellular microbes. NO, nitric oxide; ROS, reactive oxygen species.