The Immune System Unit 04 2025 PDF

THE IMMUNE SYSTEM CELLS and EVENTS IN AN IMMUNE RESPONSE  Learning Objectives Describe cells and effector molecules of immune system Differentiate between innate and adaptive immunity Describe the production and role of T cells Describe the production and role of B cells Explain th...

THE IMMUNE SYSTEM CELLS and EVENTS IN AN IMMUNE RESPONSE  Learning Objectives Describe cells and effector molecules of immune system Differentiate between innate and adaptive immunity Describe the production and role of T cells Describe the production and role of B cells Explain the association between MHC antigens & T cells Elaborate on the process of inflammation Describe different types of hypersensitivity  The Immune System of Vertebrates u Cells of the immune system arise from pluripotent stem cells u Two main lines The lymphoid lineage ü produces lymphocytes ü two main types: T cells and B cells The myeloid lineage ü produces phagocytes and other cells ü Two basic kinds: monocytes and ü polymorphonuclear granulocytes or leukocytes (neutrophil, basophil, eosinophil) Immune Response  Innate Immunity q Innate responses tend to be more generic and nonspecific because the cells do not express receptors specific to one particular antigen q The cells that function in innate immunity do not utilize immunological memory q The innate defenses include humoral factors and cells, anatomical barriers, resident flora, secretion/body fluid  Host Defenses in Innate Immunity Humoral factors and Acute-Phase Reactants: Complement proteins, CRP, Lactoferrin, Lysozyme, Pepsin, Stomach acidity Anatomical barriers: Cilia, Mucus, Skin Resident Flora: Many nonpathogenic bacteria Cells: Antigen presenting cells, Basophils, Eosinophils, Mast Cells, Natural Killer cells, Phagocytes  Types of Acute-Phase Reactants PROTEIN RESPONSE NORMAL INCREASE FUNCTION TIME CONCENTRATION (HOURS) (MG/DL) C-reactive protein 4–6 0.5 1,000X Opsonization, complement activation Serum amyloid A 24 5 1,000X Activates monocytes and macrophages Alpha1-antitrypsin 24 200–400 2–5X Protease inhibitor Fibrinogen 24 200–400 2–5X Clot formation Haptoglobin 24 40–290 2–10X Binds hemoglobin Ceruloplasmin 48–72 20–40 2X Binds copper and oxidizes iron Complement C3 48–72 60–140 2X Opsonization, lysis  Cells of Innate Immunity q Phagocytes: Engulf antigens that are outside cells (extracellular) into a vacuole where antigens are destroyed – i.e. Monocytes in the blood ü Destroy antigen inside phagocytic vacuole q Monocytes circulate in the blood ü Has some phagocytic capability but not as effective as in its mature form (Macrophage) ü Can migrate to tissue but is short lived q Macrophages ü Develop from blood monocytes in tissues and are long-lived. q Neutrophils (phagocytic) ü Represent over 90% of the circulating granulocytes  Cells of Innate Immunity cont q Basophils (circulating cells) least common of the granulocytes, possess IgE receptors, release histamine to make blood vessels permeable to other cells, contain the anticoagulant heparin that prevents blood from clotting too quickly. ü Stain dark blue with hematoxylin and eosin stains. ü Play a part in ecto-parasite infections (ticks) and allergies. ü May also regulate activity of T cells and mediate the magnitude of the secondary immune response (Anamnestic response).  Cells of Innate Immunity cont q Eosinophils (granulocyte found mostly in tissue, parasite fighter) recognize parasites, mostly helminths via an intermediary IgE attached to the parasite. ü They attach themselves via the IgE and release Major Basic Protein and Eosinophil Cationic Protein which are toxic to the helminth. ü Stain bright red with hematoxylin and eosin stains.  Cells of Innate Immunity cont u Mast Cells and Basophils: increase vascular permeability(less than 0.2% of circulating leucocytes) o Mast cells reside in connective tissues and mucous membranes, and regulate the inflammatory response u Natural Killer Cells: Destroy infected cells (e.g., virally infected cells) o Found normally without exposure to antigens o Can kill a variety of transformed or virus-infected cells. u Antigen Presenting Cells: (Dendritic Cells, Macrophages and B cells) Activate T-cells which then release cytokines that initiate pathogen specific immune response. The major cells of innate immunity Phagocytosis Antigen presentation Antigen Presenting Cells (APCs) Proteins eaten by APCs are broken down to small pieces (peptides), which are loaded on special receptors (MHCs) and transported to the cell surface. Peptide+MHC complex can be recognized by a T cell and that interaction can lead to an adaptive immune response.  Receptors: PRRs and PAMPs Pathogen-Recognition Receptors (PRRs) on immune cells recognize molecules called pathogen-associated molecular pattern (PAMPs) unique to infectious organisms PRRs found on: Macrophages and dendritic cells, neutrophils, eosinophils, monocytes, mast cells, T cells, and epithelial cells Once PRRs bind with PAMPs, phagocytic cells are activated One example of PRR is Toll-like receptors (TLR)  Adaptive Immunity v Adaptive immunity is that component of the immune system that adapts-depending on the antigens that it encounters. v As a general rule, when a pathogen is outside the cell, (bacteria, virus, parasite, fungus) the key players will be phagocytes (innate), B cells (lymphocytes) and antibodies (adaptive). v B cell activation requires specific CD4+ T cells (TH2) and their cytokines (adaptive). ü Characterized by more rapid, stronger memory response.  Lymphocytes Two different kinds of lymphocytes serve different functions qT cells ü Differentiate initially in the thymus qB cells ü In mammals, differentiate in fetal liver, spleen and the adult bone marrow ü In avians, B cells differentiate in an organ found only in birds the bursa of Fabricius  Cells of Adaptive Immunity q B cells and Plasma cells (Anamnestic or secondary immune response) ü Produce Antibodies q CD4+ T cells produce cytokines that: ü Enhance production of cytotoxic molecules in the phagocyte (TH1) ü Regulate activation of antigen presenting cells (Innate) ü Induce proliferation of NK cells (Innate) q Cytotoxic T cells ü Lyse Infected Cells (Virally infected cells)  B Cells u The B cell antigen-specific receptor is an antibody molecule on the B cell surface, and recognizes whole antigens only, without any need for antigen processing. u The antigen-specific receptor is a membrane bound antibody – the membrane immunoglobulin.  T Cell Thymocyte v Progenitor T cells migrate to the thymus to become mature T cells hence are known as thymocytes while in the thymus. v Once out of the thymus some will seed secondary lymphoid tissue (spleen, lymph node or Mucosa-associated lymphoid tissue or MALT) but most will re-circulate (immunosurveillance) between blood and lymphoid tissue until they die or encounter antigen. v T cells leave the thymus as either CD4+ T cells or as CD8+ T cell  T Cells q Takepart in Cell-mediated immunity (cellular immunity) and humoral immunity where antibody plays a subordinate role and they contribute to all other aspects of immunity.  T Cells Two broad classes: v CD4+ T cells main function is secreting cytokines needed for regulation of all immune responses and for combating extracellular pathogens (Helper T Cell) v CD8+ T cells main role is to destroy infected (intracellular pathogens) cells (Killer T cell or Cytotoxic T cell)  T Cells and MHC T cells recognize a “non-self” target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and presented in combination with a “self” receptor called a major histocompatibility complex (MHC) molecule. Antigen presenting cells: u Dendritic cells u Macrophages uB cells  T Cells and MHC q CD8 + T cells only recognize antigens coupled to Class I MHC molecules (Self). q CD4+ T cells only recognize antigens coupled to Class II MHC molecules (Self). q Class I MHC is found on a variety of cell types while Class II MHC is primarily found on antigen presenting cells.  CD8+ T Cell u CD8+ T Cells are the sub-group of T cells that kill cells infected with intracellular pathogens, or that are otherwise damaged or dysfunctional.  CD4+ T cell q CD4+ T cells are the subgroup of T cells that release cytokines that influence the activity of many cell types. q Cytokine signals produced by helper T cells enhance the microbicidal function of macrophages and the activity of killer T cells. Adaptive immunity: humoral and cellular responses CD4 (helper) T cell CD8 (killer) T cell T cell receptors only recognize antigens presented on MHC molecules Regulatory T cells (Tregs)  Normal IR: Process of Inflammation Body’s overall reaction to tissue injury due to physical or chemical agents, invasion by an infectious agent Cardinal signs and symptoms: Rubor (erythema/redness due to vasodilation) Calor (heat given off by ↑blood flow) Tumor (edema/swelling due to ↑ fluid/exudate) Dolor (pain caused by stimulation of nerve endings) Initiation of Local Inflammatory Response  Hypersensitivity Four types of hypersensitivity reactions are recognized. All require an initial sensitization phase. First three occur within 24 hours qI – Allergy (Immediate) Pollen-Ab IgE mainly q II – Antibody dependent cytotoxic hypersensitivity (