4. Innate and Adaptive Immunity - Tagged.pdf

Innate and Adaptive Immunity DR KAYE This Photo by...

Innate and Adaptive Immunity DR KAYE This Photo by Unknown author is licensed under CC BY-NC-ND. What’s it all about?  The Players…. Dendritic cells (DCs), named for their probing, 'tree-like' or dendritic shapes, are responsible for the initiation of adaptive immune responses and hence function as the 'sentinels' of the immune system.... DCs are bone marrow (BM)-derived leukocytes and are the most potent type of antigen- presenting cells. The Players….. NK cells– Lymphocytes that recognize and kill virus-infected cells and tumor cells by cytotoxic agents granzyme and perforin. a. They have (1) cell receptors that bind bacteria fimbria proteins and (2) receptors that recognize (MHC) class molecules. b. antibody-dependent cellular cytotoxicity (ADCC) – NK cell assists ab attachment c. NK cells are primary sources of gamma IFN, a potent antiviral cytokine  Phagocyctic cells Phagocytic cells include (1) monocytes, macrophages, PMNs, dendritic Cells. The phagocytic toxins include defensins, cathelicidin, lactoferricin and selectin which promotes endothelial attachment. The Phagosome is an endocytic vesicle its low pH immobilize bacteria; superoxide, peroxide, nitrous oxide and peptides to kill. Macrophages attach the Fc portion of an antibody and activate the C3 component of complement. Cytokines …hormones of the immune system Any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells. Cytokines Cytokines are small proteins that regulate inflammation. There are two groups: Signalers: TNF, Interleukin 1,6,12,23 Chemokines: Direct chemotaxis Cytokines are released from macrophages together with prostaglandins (lipid esp. clotting) and leukotrienes(esp.allergy). Their Effects include micro vessel dilation, edema, fibrin and adhesions. Induces chemotaxis and chemokine release to recruit monocytes and neutrophils from the blood into sites of infection. Innate Components (42)Tabulated Cells PMN, Monocytes/Macrophages Natural Killer cells, Dendritic cells, Langerhans Proteins Complement,Cytokines, chemokines, transferrin, lactoferrin, defensins, lysozymes Microbial Sensors TLR- Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) that initiate the innate immune response by sensing conserved molecular patterns for early immune recognition of a pathogen NOD-like receptors (NLRs) The nucleotide-binding oligomerization domain-like receptors are intracellular sensors of pathogen- associated molecular patterns (PAMPs) that enter the cell via phagocytosis RIG-I-like receptors (retinoic acid-inducible gene I-like receptors, RLRs) are a family of molecules that are expressed inside cells in order to sense viruses More Microbial Sensors  Helicases - are enzymes that bind and may even remodel nucleic acid or nucleic acid protein complexes. They unpack the bacterial genes  MDA-5 –(melanoma differentiation-associated protein 5) is a RIG- I-like receptor with a pattern recognition receptor capable of detecting viruses. More Microbial Sensors  Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes.... PAMPs activate innate immune responses, protecting the host from infection, by identifying some conserved nonself molecules. Antigen Presenting Cells  Dendritic cells, macrophages , B- lymphocytes  APC’s phagocytose then present the identifier protein (epitope) to  Immature lymphocytes. This is required for chemotaxis(IL8), migration, ingestion, and microbial killing. APC’s maturing lymphocytes Opsonins  Opsonization (antibodies that coat the surface of bacteria to increase recognition and phagocytosis. Opsonin's include IgG, mannose binding lectin, and C3b products.  (1) antibody alone can act as opsonin;  (2) antibody plus antigen can activate complement via the classic pathway to yield opsonin; and  (3) opsonin may be produced when the alternative pathway is activated and C3 is generated  Complement  The complement system function includes lysis of infectious organisms, activation of inflammation, opsonization and immune clearance  Complement consists of 30 proteins found in the serum or on the membrane of selected cells.  There are three complement pathways, Classical(ag-ab), Alternative (Factor B,D,I), and Lectin(mannose on bacteria) which lyse the pathogen directly, or release complement fragments that can interact directly with T and B lymphocytes for their cytokines or directly using anaphylatoxins C5a and C3a. Complement The complement cascade. Each pathway results in the formation of MAC (membrane attack complex), leading to cell lysis. Complement provides protection from pathogens by four mechanisms:  (1) cytolysis (MAC), MAC Taxi On View  (2) chemotaxis  (3) opsonization  (4) vasodilation and vascular permeability.  Interferons  Interferons (IFN) produced by NK and TL’s to defend against virus infections and adjust cell growth, differentiation, gene transcription, and translation.  Three groups: alpha beta and gamma  All inhibit gene regulating viral growth.  MHC-II stimulates helper CD4 TLs which in turn increases NK cells to produce interferon Symptoms and Signs  Adaptive Immunity  Cellular response  T and B Lymphocytic activation  Humoral Response  Plasma cell proliferation  Antibodies T Cells Functions of T cells.  (1) CD4 T cells can become T helpers ex. Th1, Th2, Th17, or T reg cells (after APC presents the MHC-II molecule).  Th1 cells can produce cytokines (IL-2, IFN-a) interleukin and interferon, activate macrophages, or trigger B cell switching to IgG synthesis.  Th2 cells activate mast cells and eosinophils and trigger B-cell switching to IgE synthesis.  Th17 cells can produce IL-17 triggering production of IL-8 and recruitment of neutrophils and macrophages. Treg cells produce TGF-b and IL-10, which can suppress immune responses.  (2) CD8 T cells function as cytotoxic T cells. (after APC present MHC-I molecule) Antigen Recognition –the epitope Antigen Recognition –the epitope Killer CD8 cells destroy infected cell if MHC-I presents foreign peptide Helper CD4 cells use APC’s MHC-II super ag peptide to induce B cells antibody production  Cell Activation –T cell receptor (TCR) Co-stimulatory receptors As the TCR recognizes a small part of the antigen (called peptide), this ensures the specificity of the response; only T cells that recognize this antigen will be activated. The second signal (called co-stimulatory signal) is provided by a costimulatory molecule for regulation and structural stability Summary: Cellular Response Working Together Antibodies  Antibody production: When antigen interacts with B cell via the presenting T cell complex (CD4+MHC-II), the B cell is stimulated to divide and form a clone under the effect of IL2,4,5,6. The B cell differentiates into plasma (that secrete antibody) and memory cells.  Antibody Functions  Functions of antibody: Antibody can enhance phagocytosis, induce neutralization of viruses and bacterial toxins, and participate in complement-mediated lysis and ADCC.  Both light chain types occur in all classes of immunoglobulins (IgG, IgM, IgA, IgD, IgE), but any one immunoglobulin molecule contains only one type of L chain. The amino terminal portion of each L chain contains part of the antigen-binding site. Heavy (H) chains are distinct for each of the five immunoglobulin classes and are designated (gamma), ì (mu), á (alpha), (delta), and d (epsilon). Antibody Response Hypersensitivity Reactions:  Type I, Immediate: IgE antibody is induced by the allergen and binds via its Fc receptor to mast cells and eosinophils. After encountering the antigen again, the fixed IgE becomes cross-linked, which induces degranulation and release of mediators, especially histamine.  Type II: Antigens on a cell surface combine with antibody, which leads to complement-mediated lysis (eg, transfusion or Rh reactions) or other cytotoxic membrane damage (eg, autoimmune hemolytic anemia) ex.Penicillin ag-ab on RBC.  Type III, Immune Complex: Antigen-antibody immune complexes are deposited in tissues, complement is activated, and PMNs are attracted to the site, causing tissue damage.  Type IV, Delayed: T lymphocytes, sensitized by an antigen, release cytokines upon second contact with the same antigen. The cytokines induce inflammation and activate macrophages. Assignment  Assignment: Explain why AIDS is an immune deficiency. Be specific giving details on the weak parts of the innate and adaptive responses that are exploited by opportunistic infections. Acronyms  PAF- platelet activating factor  GM-CSF Granulocyte Macrophage Colony stimulating factor  IL – Interleukin  ACE – Angiotensinogen converting enzyme  DAMP- Damage associated molecular proteins  IFN- Interferon  CD- Cluster of differentiation  MHC- Major histocompatibility complex  Ig - Immunoglobulin  PAMP= Pathology associated molecular pattern (protein)  TNF- Tumor necrosis factor  NK – Natural killer  ADCC- Antibody dependent cellular cytotoxity