Immune System Chapter 35

Immune System Functions Protection from pathogens and cancer Viruses Bacteria Parasites Toxins Innate Immunity – nonspecific defenses 1st line of defense 2nd line of defense Acquired immunity – specific defenses 3rd line of defense Humoral immune response B-cell response Cell mediated immune response T-cell response

broad range of microbes INNATE IMMUNITY Rapid responses to a broad range of microbes ACQUIRED IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Mucous membranes Secretions Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Invading microbes (pathogens)

Immune System Structures Skin Mucous Membranes Bone Marrow WBC’s - leukocytes Neutrophils – attack pathogens in the blood and tissues Monocytes  macrophages – in body tissues Eosinophils – attack parasites Basophils – allergies and parasites Dendritic cells  Lymphocytes B-cells T-cells Lymph nodes Spleen Lymph vessels Thymus

Innate Immunity – Non Specific Defense 1st lines of defense Skin Barrier to pathogens Sebaceous (oil) and sweat glands secrete lysozyme which destroys bacteria pH of 3-5 – acidic Mucous Membranes Line the respiratory, digestive, and urinary tracts Mucus and cilia trap and expel pathogens Secretions Stomach – gastric juice – pH 2 Saliva, tears, and mucous all contain lysozyme proteins

Innate Immunity – Non Specific Defenses 2nd lines of defense Only activated if the 1st line fails Phagocytes – Phagocytic WBC’s Attach to microbes (pathogens)  ingest them  lysosome destroys them Nitric oxide and lysozyme in lysosomes Tuberculosis is resistant to lysosome destruction Neutrophils Engulf pathogens traveling in the blood and self destruct  killing the pathogen Macrophages (monocytes) Reside in tissues and organs and attack pathogens that enter or begin to infect Eosinophils Attack parasites Dendritic cells Attack like macrophages and stimulate acquired immunity (3rd line of defense) lymphocytes

Innate Immunity – Non Specific Defenses Antimicrobial proteins – impede pathogen reproduction Complement system Lyses microbes and triggers inflammation (inflammatory response) Interferon Inhibit viral reproduction Natural Killer Cells Attack virus infected body cells and cancer cells  apoptosis Programmed cell death Fever Stimulate WBC production and tissue repair

Inflammatory Response Pathogen Pin Macrophage Chemical signals Capillary Phagocytic cells Red blood cell Blood clotting elements Blood clot Phagocytosis Fluid, antimicrobial proteins, and clotting elements move from the blood to the site. Clotting begins. 2 Chemical signals released by activated macrophages and mast cells at the injury site cause nearby capillaries to widen and become more permeable. 1 Chemokines released by various kinds of cells attract more phagocytic cells from the blood to the injury site. 3 Neutrophils and macrophages phagocytose pathogens and cell debris at the site, and the tissue heals. 4

Innate Immunity – Non Specific Defenses Inflammatory Response 1. Skin is punctured and pathogens enter 2. Mast cells in connective tissue release histamine increasing permeability and dilation of capillaries to injured site 3. WBC’s and blood clotting factors move from the blood to the infection 4. Clot forms a scab 5. Neutrophils and macrophages attack pathogens 6. WBC’s release chemokines which attract more phagocytes to attack the pathogen Positive feedback 7. Redness, swelling, and soreness are side effects

Acquired Immunity – Specific Defense 3rd line of defense Lymphocytes Humoral Immune Response B-Cells  Antibodies Made and matured in bone marrow Cell Mediated Immune Response T- Cells  attack infected body cells Made in bone marrow and matured in the thymus Bone marrow Lymphoid stem cell B cell Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others) T cell Thymus

Triggering a lymphocyte response Antigen Presentation - Dendritic cells engulf and display antigens activating Helper T-Cells Antigen displayed on class II MHC MHC = Major Histocompatability Complex Helper T-Cells activate B-Cells AND secrete cytokines which activate Cytotoxic T-Cells Cell-mediated immunity (attack on infected cells) Humoral (secretion of antibodies by plasma cells) Dendritic cell Bacterium Peptide antigen Class II MHC molecule TCR CD4 Helper T cell Cytokines Cytotoxic T cell B cell 1 2 3

Triggering a lymphocyte response Humoral Response – B-Cell Cell Mediated Response – T-Cell B-Cells are also activated by intact antigens on pathogens B-Cells give rise to Plasma cells and Memory Cells Plasma Cells make antibodies to trap pathogens and mark them for destruction Memory cells “remember” antigens so antibodies can be made quickly upon second exposure. 43_18CytotoxicTCells_A.swf Cytotoxic T-Cells are also activated by antigens displayed on infected body cells Antigen displayed in Class I MHC Cytotoxic T-Cells give rise to Active Cytotoxic T-Cells and Memory Cytotoxic T-Cells Active Cytotoxic T-Cells kill infected body cells, cancer cells, and transplant tissues Memory Cytotoxoic T-Cell “remember” the antigen so infected cells can be killed quickly upon second exposure.

Humoral immune response Cell-mediated immune response First exposure to antigen Intact antigens Antigens engulfed and displayed by dendritic cells Antigens displayed by infected cells Activate Gives rise to B cell Helper T cell Cytotoxic T cell Plasma cells Memory B cells Active and memory helper T cells Memory cytotoxic T cells Active cytotoxic T cells Secrete antibodies that defend against pathogens and toxins in extracellular fluid Defend against infected cells, cancer cells, and transplanted tissues Secreted cytokines activate

Antigen Recognition Memory B-Cells and T-Cells recognize antigens by antigen specific receptors Both have constant and variable regions Variable regions have antigen binding sites and vary from cell to cell for specificity B-Cell Receptors – recognize intact antigens Y shaped 2 identical heavy chains 2 identical light chains Linked by disulfide bridges T-Cell Receptors – recognize fragments of antigens presented by infected body cells or macrophages or dendritic cells 2 non identical chains Alpha and beta 43_09bTCellReceptors_VT.swf

V C Antigen- Binding site b chain Disulfide bridge a chain T cell Light chain Heavy chains Cytoplasm of B cell V A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges. (a) Variable regions Constant Transmembrane region Plasma membrane B cell C Antigen- Binding site b chain Disulfide bridge a chain T cell A T cell receptor consists of one chain and one b chain linked by a disulfide bridge. (b) Variable regions Constant Transmembrane region Plasma membrane Cytoplasm of T cell

43_21Antibodies_A.swf Antigen- binding sites Epitopes (antigenic Antibody A Antigen Antibody B Antibody C Epitopes (antigenic determinants)

Antigen Presentation Class I MHC Class II MHC Found on all nucleated body cells Identify self from non-self Display antigens from pathogens by becoming infected Display antigens to Cytotoxic T-Cells which contain a CD8 protein which recognizes and binds Class I MHC Found on antigen presenting cells - dendritic cells, macrophages and B-cells Bind antigens that have been ingested through phagocytosis Display antigens to Helper T-Cells which contain a CD4 surface protein which recognizes and binds the Class II MHC

Antigen Presentation Antigen- Microbe Infected cell presenting cell 1 fragment Class I MHC molecule T cell receptor (a) Cytotoxic T cell 1 Microbe Antigen- presenting cell Antigen fragment Class II MHC molecule T cell receptor Helper T cell (b)

Active vs. Passive Immunity Active Immunity Passive Immunity Lasts a lifetime Exposure to an infectious agent (pathogen) 3rd line of defense Specific immune response Immunizations – vaccines Inactive pathogen that stimulates the immune response producing memory cells Lasts a few weeks Antibodies are transferred from one person to another Pregnant women  fetus placenta Mother  baby breast milk

Primary vs. Secondary Response 1st exposure to antigen Takes 10-14 days to produce antibodies Slow 2nd or more exposure to the same antigen Memory cells produce antibodies Quick

Antibody concentration (arbitrary units) 104 103 102 101 100 7 14 21 28 35 42 49 56 Time (days) Antibodies to A to B Primary response to antigen A produces anti- bodies to A 2 Day 1: First exposure to 1 Day 28: Second exposure to antigen A; first antigen B 3 Secondary response to anti- gen A produces antibodies to A; primary response to anti- gen B produces antibodies to B 4

Blood Groups Blood Type Antigen(s) Antibodies Produced Can Receive A B A antigens B antigens A and B antigens NONE Anti - B Anti - A NONE Anti – A and Anti - B A and O Blood B and O Blood A, B, AB, and O Blood Universal recipient O only Universal donor

Rhesus Factor and Blood Rh factor – blood antigen Can be problematic in pregnancy if the mom is Rh- (lacks the antigen) and the baby is Rh+ (has the antigen) If blood mixes during delivery mom will produce antibodies for the Rh antigen If mom has a 2nd child that is Rh+ her antibodies will attack the fetus during late pregnancy and child birth Mom is injected with anti-Rh antibodies to prevent this

Transplants No two people except identical twins have identical MHC molecules % matches are made in a transplant to minimize rejection Transplant recipients take medicine to suppress the immune response to the transplant Leaves the recipient susceptible to other infections Bone Marrow Transplant Graft vs. Host Graft is bone marrow – unless matched carefully could cause the new blood cells produced in the bone marrow to reject the host, most hosts reject because they’re immune system is working well. Use anti-rejection medications

Autoimmune Diseases Immune system does not recognize body cells as self and creates antibodies against them Lupus – attack histones and DNA Arthritis – attack cartilage and joints Insulin dependent Diabetes – attack beta cells of the pancreas which secretes insulin Multiple Sclerosis – attacks myelin sheath on neurons

AIDS People with AIDS are susceptible to opportunistic infections that the immune system cannot fight off. HIV (RNA Virus)  AIDS Retrovirus – uses the enzyme reverse transcriptase HIV invades and destroys Helper T-Cells impairing both the Humoral and Cell Mediated Responses

Systems Approach to Vaccine Development Old Method: Use a control group and an experimental group Give control group a placebo Give experimental group an experimental drug Monitor to determine effectiveness of the vaccine Systems Method: Give experimental subject a vaccine Measure protein levels, DNA activity, cellular components The vaccine that produces a result closest to “normal” will be the most effective http://www.nature.com/scientificamerican/journal/v304/n5/images/scientificamerican0511-66-I4.jpg