Immunology An Overview The only Principle of Immunology Learn on your own: Tolerance Clinical Immunology Self-Test Questions: A: 1 B: 1 - 4 C: 1 - 3 D: both E: 1 The only Principle of Immunology for which there is no ambiguity: Every Principle of Immunology has Ambiguity Overview of Immune System

Respiratory tract cilia of innate defenses Our immune defense has two branches 1. ‘Innate’ defenses First lines of defense Rapid response Defend in a general way -- not pathogen specific Usually sufficient 2. ‘Acquired’ defenses Last line of defense Pathogen specific Creates immunity Slower onset These systems closely interact Respiratory tract cilia of innate defenses Antibody molecule of Acquired defenses ILR - Immunology - 2

Four characteristics distinguish Acquired vs Innate responses Recognition of pathogens A few common “warning signals” Millions of pathogen-specific antigens Specificity of response General response to pathogens Response is to specific antigens Speed of response Seconds to hours Hours to days Memory of encounter None Can yield future immunity B-cells -- attack extracellular pathogens; toxic molecules Upon activation release AG-specific antibodies T-cells 1) hornmonally regulate immune system 2) attack intracellular pathogens -- kill cells T-cells as “MHC restricted” -- only bind to peptide fragments “presented” by other cells CD4 cells: upon activation secrete cytokines -- needed for activation of B-cells and T-cells CD8 cells: upon activation attack infected body cells ILR - Immunology - 4

Overview of Immune System What are the types of Innate Immunity? I. Non-induced mechanisms “Barriers to infection” -- 1st line of defense Anatomical Mechanical Cilia and mucus Skin wounding Overview of Immune System

Overview of Immune System Innate Immunity… II. Induced mechanisms Physiological, e.g., fever Cellular , e.g., phagocytosis Enzymatic, e.g., complement Receptor-mediated Broadly specific -- recognize “danger signals” -- PAMPs Responses phagocytosis pathogen killing antigen presentation cytokine production Anatomical Skin & epithelial layers: a formidable barriers to infection -- tough and impervious -- look how readily infection sets in following wound Ciliated epithelial cells: (eg. of trachea) serve same purpose Body fluids -- Saliva, tears and mucous secretions -- wash away potential invaders before colonization can begin Physiological Body temperature alone makes body unsuitable for certain pathogens -- ANTHRAX used to be a common disease of farm animals -- chickens have an innate immunity to bacterium -- due to higher body temperature pH of stomach & female reproductive tract -- lethal to many common pathogens Cellular Phagocytic cells (macrophages, neutrophils) granulocytes, etc Chemical/enzymatic -- bile, H2O2, free radicales -- lysozyme, proteases, other enzymes http://lpi.oregonstate.edu/infocenter/phagocytosis.html Overview of Immune System

Microbes can cause infections outside or inside of cells Always Intracellular: Viruses Intra- or extra- cellular: Bacteria Usually extracellular: Fungi, Protozoa, worms Adenovirus infected cell Listeria infected cell Listeria ILR - Immunology - 2

Humoral There are two “arms” of the Acquired Immune System? Attack extracellular pathogen and toxins B-cells ------> antibodies Cell-mediated 1) Attack infected body cells & cancerous cells T-killer cells T-cells T-helper cells 2) Hormonal regulation (Cytokines) ILR - Immunology - 2

Antibodies are produced by the Humoral arm of the acquired immune system Involves B-cells Attack pathogens outside of cells Have B-cell receptors (BCR) -- a type of antibody ILR - Immunology - 4

T-cells possess T-cell Receptors Similar to Antibodies -- antigen-specific -- one type per cell -- created by gene rearrangements However, -- less specific than antibodies -- less diverse (fewer types) -- never are released -- only bind to antigens on MHC ILR - Immunology - 4

T-helper cells and T-killer cells bind to different types of MHC Killer-T cells -- bind to AG on MHC-I -- attack infected & cancerous cells Helper-T cells -- bind to AG on MHC-II -- hormonally regulates immune response Macrophages, Dendritic cells, B-cells ILR - Immunology - 4

Overview of Immune System What are the two types of antigen-presenting cells? “Professional” AG-presenting cells “Non-professional” -- via MHC-I or MHC-II -- All nucleated body cells -- can present antigen to TH and TC cells -- only present to Cytotoxic T-cells Examples -- only via MHC-I -- dendritic cells & -- response is cell destruction -- macrophages -- B-cells -- (other IM cells) Overview of Immune System

Overview of Immune System Upon activation Naïve immune cells become Effector cells B-cells become: Plasma cells TH cells become: TH effector cells -- activate other cells Tc cells become: Cytotoxic lymphocytes (CTLs) Overview of Immune System

Overview of Immune System What happens when lymphocytes are activated? “Clonal Selection” Antigen recognition Cell activation Memory cells Immunological memory Primary vs Secondary responses Overview of Immune System

Overview of Immune System How do immune cells communicate? Extensive cell-cell contact Membrane protein interaction Immune synapse Hormonal exchange Cytokines Interleukins Interferons Chemokines etc Endocrine Paracrine Autocrine Overview of Immune System