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 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 #2 Bacteria 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 #3 Fungi Modus Operandi Similar to bacteria- reproduce rapidly Damage cells directly or indirectly by secreting enzymes Examples: Athlete’s Foot, Pneumocystis carinii (fungal pneumonia)

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

The Immune Response - Overview

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)

Central Role of Helper T Cells

Humoral Immunity B 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

Figure from AccessExcellence.org Clonal Selection

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 Immunity T cell Response Helper T cells (a.k.a. T H or CD-4 T cells) constantly interact with macrophages When T H cell finds a macrophage that is presenting antigen (APC) it becomes activated Activated T H 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