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Defense against Disease. Non-specific and specific strategies. Inherent Challenges. Constant surveillance and vigilance Unpredictable invaders. The Enemy. Pathogens: microorganisms that are capable of causing disease Viruses Bacteria Fungi. Public Enemy #1 The Viruses. Modus Operandi
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Defense against Disease Non-specific and specific strategies
Inherent Challenges • Constant surveillance and vigilance • Unpredictable invaders
The Enemy • Pathogens: microorganisms that are capable of causing disease • Viruses • Bacteria • Fungi
Public Enemy #1The Viruses • Modus Operandi • Dock with receptors on target cell surface • Insert viral DNA or RNA into host cell • Use host cell machinery to replicate new viruses • Lyse host cell and spread to nearby cells • Lytic vs. Lysogenic life cycles • Examples: smallpox, chickenpox, polio, HIV
Public Enemy #2Bacteria • Modus operandi • Set up shop in tissues but remain EXTERNAL to cells • Reproduce rapidly • Secrete exotoxins or contain endotoxins as part of cell wall • Examples: Escherichia coli, Clostridium botulinum, Salmonella Figure from Holt Biosources
Public Enemy #3Fungi • Modus Operandi • Similar to bacteria- • reproduce rapidly • Damage cells directly or indirectly • by secreting enzymes • Examples: Athlete’s Foot, • Pneumocystis carinii (fungal pneumonia) http://www.ces.ncsu.edu/depts/pp/bluemold/
So what’s a body to do? • First line defenses: Nonspecific anatomical barriers and secretions that prevent entry, such as skin, saliva, tears (lysozyme), mucus, stomach acid, fever • Second line defenses: Inflammation A nonspecific response triggered by histamine secreted by basophils when tissue is damaged
If all else fails…The Immune Response • A highly specific, long lasting response tailored to combat pathogens • Vocabulary: Antigen- a molecule (usually carried on the surface of a pathogen) that is capable of eliciting an immune response B-Lymphocytes- white blood cells that produce and secrete antibodies T-Lymphocytes- white blood cells that serve as part of the cell-mediated immune response
Self- Nonself Recognition • Critical to appropriate immune system function • Tcells “learn” to distinguish self from non self as they mature in the thymus • All nucleated self cells display unique Human Leukocyte Antigens (HLA) on their Major Histocompatibility Complex (MHC) receptors • As T cells mature, they randomly produce and display a variety of receptors • Any T cell with receptors that bind to self MHC-HLA complexes will commit apoptosis • Only T cells that do NOT bind to self cells should emerge from the thymus and enter circulation
Immune Response- Step by Step 1. Pathogen (carrying foreign antigens)enters and survives the inflammatory response 2. Some pathogens remain exposed in tissues where their antigens may be recognized by circulating B cells OR 3. Macrophages engulf pathogens and display their antigens on MHC (major histocompatibility complex) receptors. Macrophage has now become an Antigen Presenting Cell (APC)
Humoral ImmunityB cell response • If a circulating B cell’s receptors bind to foreign antigens, the B cell becomes activated • Activated B cells divide into Memory B cells and Plasma B cells • Plasma B cells rapidly produce and secrete antibodies (immunoglobulins) • Clonal selection amplifies the production of cells that produce effective antibodies
Clonal Selection Figure from AccessExcellence.org
Mechanism of Antibody Function • Antibodies bind to antigens and aggregate pathogens for removal by macrophages • Antibodies disrupt function of pathogen’s surface proteins • Antibody-antigen complexes trigger the Complement system, a a series of enzymes carried in the bloodstream that lyse invaders Figure from AccessExcellence.org
Cell-Mediated ImmunityT cell Response • Helper T cells (a.k.a. TH or CD-4 T cells) constantly interact with macrophages • When TH cell finds a macrophage that is presenting antigen (APC) it becomes activated • Activated TH cells secrete cytokines, chemicals that stimulate both T and B cells • Stimulated cytotoxic T cells (a.k.a. killer or CD-8 T cells) divide rapidly, bind directly to pathogen infected cells and secrete enzymes that lyse infected cells