Ch 43- Immune system

Function of Immune system To defend the body against disease Pathogens – agents of disease (bacteria, viruses, protists)

Immune system Non specific immunity (Innate immunity) All animals & plants have defenses effective immediately upon infection Specific immunity (Adaptive or Acquired immunity) All vertebrates have immunity after exposure to specific pathogens (slower response).

1. Non-specific (Innate) Immunity 1st line of defense: barrier Skin, mucous membrane, secretions 2nd line of defense: internal defenses Phagocytosis, natural killer cells, antimicrobial proteins, inflammatory response

Invertebrate defenses 1st barrier – exoskeleton made of chitin Digestive system is protected by a chitin-based barrier and lysozyme, an enzyme that breaks down bacterial cell walls The immune system recognizes bacteria and fungi by structures on their cell walls

Pathogen PHAGOCYTIC CELL Vacuole Lysosome containing enzymes Hemocytes - circulate within hemolymph and carry out phagocytosis, the ingestion and digestion of foreign substances including bacteria - also secrete antimicrobial peptides that disrupt the plasma membranes of fungi and bacteria

Non-specific immunity in Vertebrates Include barrier defenses, phagocytosis, antimicrobial peptides Unique to vertebrates: natural killer cells, interferons, inflammatory response

Barrier defenses Skin Mucous membranes Body secretions: saliva ,mucus, tears Low pH in skin & membranes

Phagocytosis “Cell eating” – white blood cells ingest invading pathogens Engulfs microbe & fuses with lysosyme to destroy it White blood cell attacking bacterium http://www.youtube.com/watch?v=qvGVoxdy-yM

This increases efficiency of phagocytes Phagocytes use Toll-like receptors (TLRs) that recognize molecular patterns characteristic of certain pathogens This increases efficiency of phagocytes i.e. one type recognizes double stranded RNA (in viruses) Flagellin – protein found in bacteria flagella

Types of phagocytes in mammals 2 main types: Neutrophils – short lived white blood cells move through bloodstream Macrophages – largest phagocytes Found fixed in parts of lymphatic system (spleen, lymph nodes, thymus) Some travel throughout body

Other cells Dendritic cells – phagocytic - in tissues, stimulate adaptive immunity Eosinophils – (low phagocytic) help defend against multicellular invaders, release destructive enzymes Natural killer cells Destroy virus-infected body cells, cancer cells Attack cells membrane, so cell lyses

Lymphatic system A network of vessels that distributes lymph through the body Lymph nodes hold many macrophages help trap foreign substances

Thymus Adenoid Tonsils Lymphatic vessels Spleen Lymph nodes Lymph node Blood capillary Interstitial fluid Tissue cells Lymphatic vessel Masses of defensive cells

Antimicrobial proteins Proteins involved in attacking microbes or stopping their reproduction Lysozyme- present in tears & saliva, mucous Complement proteins – 30 serum proteins – carry out steps to lyse microbes Interferons – secreted by virus-infected cells, induce neighboring cells to produce chemicals to inhibit viral reproduction

Inflammatory response Response to cut or entry of microorganisms Area becomes inflamed, red, swollen Result of chemical signals- From invader Nearby mast cells release histamines – released by body cells in response to injury Histamines dilate capillaries and increase permeability, so fluid & clotting elements leave can enter site

Acute inflammatory response http://www.youtube.com/watch?v=suCKm97yvyk

Inflammatory response Pathogen Splinter Mast cell Macro- phage Capillary Red blood cells Neutrophil Signaling molecules Movement of fluid Phagocytosis

Clotting begins Other cells release chemokines, which attract phagocytes to area Phagocytes consume pathogens & debris Pus - a fluid rich in white blood cells, dead pathogens, and cell debris from damaged tissues http://www.youtube.com/watch?v=CmbWE3jLUgM&list=UUDwoLF9pXx4RgB7BgmsnY0w

2. Specific Immunity Specific immune responses to particular microorganisms Found in vertebrates Lymphocytes – type of white blood cells 2 types: T cells – mature in thymus B cells – mature in bone marrow

Antigens Substances that can elicit a response from a B or T cell B or T cells have antigen receptors specific for parts of that pathogen – so they can recognize specific antigens Antigen receptors Mature B cell Mature T cell

Recognizing antigens

The specificity of the T & B receptors (and antibodies) is a result of shuffling and recombining several gene segments to produce the protein There are more than 1 million different B cells and 10 million different T cells Due to random arrangment, some receptors are specific for epitopes on organism’s own molecules, so B & T cells must be tested for self- reactivity.

http://www.youtube.com/watch?v=JiOwZsTO02w

B cells: Mature in bone marrow Produce antibodies Receptors bind to intact antigens T cells: Mature in thymus Do not produce antibodies Receptors bind to antigens displayed by antigen-presenting cells (APCs) on their MHCs Both: Activated by cytokines, from helper T cells

MHC – major histocompatability complex – cell surface glycoproteins that differ among individuals - aid in recognition of “self” - Class I – found on nearly all body cells - can present fragments of proteins made by infecting microbes to cytotoxic T cells - Class II – made by some cells of immune system - macrophages & B cells - molecules collect remnants of microbes and present them to helper T cells

Clonal selection Activation occurs when antigen binds to B or T cell. Clones formed in clonal selection – two types produced: Effector cells – fight the antigen Memory cells – have receptors for same antigen, so allow quick response to subsequent infection http://www.youtube.com/watch?v=HUSDvSknIgI

Responses Primary response- when body first exposed to antigen and lymphocyte is activated Secondary response – when same antigen is encountered later, faster more efficient response due to memory cells

Antibody concentration (arbitrary units) Primary immune response to antigen A produces antibodies to A. Secondary immune response to antigen A produces antibodies to A; primary immune response to antigen B produces antibodies to B. Exposure to antigen A Exposure to antigens A and B Time (days) Antibody concentration (arbitrary units) 104 103 102 101 100 7 14 21 28 35 42 49 56 Antibodies to A Antibodies to B

Cell- mediated immunity Activation & clonal selection of cytotoxic T- cells Macrophages engulf antigens, process them internally, then display parts of them on their surface together with some of their own proteins. This sensitizes the T cells to recognize these antigens.

T-cells are trained in thymus T- cells are chosen that have correct receptors to recognize MHC molecules T- cells that can recognize MHC molecules complexed with foreign peptide are allowed to pass out of thymus

Cytotoxic T cells (Killer T cells) bind to class 1 MHC molecules, display fragments on surface of body cells. Destroy infected cells. Helper T-cells: secrete cytokines in response to interaction with class 2 MHC molecules – stimulate & activate both cytotoxic T cells & B cells Memory T cells – recognize & respond to antigen once it has already been encountered. http://www.youtube.com/watch?v=1tBOmG0QMbA

Humoral response Activation & clonal selection of effector B cells Fight pathogens in body fluids Activated B cells produce plasma & memory cells Plasma cells –(effector cells) produce antibodies Memory cells – for secondary response

Antibodies destroy antigens through: Antibodies – soluble proteins secreted by B cells during an immune response Antibodies destroy antigens through: Neutralization: bind & block activity of antigen Lysis: caused by activation of complement system- form a hole in membrane of pathogen Agglutination: clumping of bacteria or viruses Opsonization: results in increased phagocytosis of antigen (attracts macrophages)

Humoral response: http://www.youtube.com/watch?v=hQmaPwP0KRI&list=UUDwoLF9pXx4RgB7BgmsnY0w&index=7 Specific immunity http://www.dnatube.com/video/194/Specific-Adaptive-immunity-humoral-and-cell-mediated

Active immunity – when body is exposed directly to pathogen, body responds (infection, vaccination) Passive immunity – when an individual receives antibodies (to fetus from mother across placenta)

What can go wrong- Over reaction of immune system – allergies Reaction against self – autoimmune disease Defects or problems with immune system - immunodeficiency

Allergy reaction animation http://www.youtube.com/watch?v=IGDXNHMwcVs Our immune system/ autoimmune diseases http://www.youtube.com/watch?v=MI-BLaj5nFk