Immune System Basics  Immunity: The capacity to resist infectious pathogens.  Pathogens: Disease-causing organisms  Self vs. Non-self recognition  Major Histocompatibility Complex (MHC 1)  Antigen- a particle or piece of pathogen an immune system recognizes as foreign. MHC 1 Antigens

1st Defense: Non-specific Immune System  Reacts immediately after infection- does not need to ID pathogen. 1.Barrier Defenses: Skin and Mucous membranes 2.Inflammatory Defenses:  Histamine is released at the sign of damage  Blood vessels leak fluid and WBC’s 3.Cellular and Molecular Defenses : 1.Macrophages: Use pocket transport (phagocytosis) to destroy foreign particles. 2.Natural Killer Cells (NK): Release hydrolytic enzymes onto target cells to rupture/destroy them. 3.Interferon 4.Complement  Reacts immediately after infection- does not need to ID pathogen. 1.Barrier Defenses: Skin and Mucous membranes 2.Inflammatory Defenses:  Histamine is released at the sign of damage  Blood vessels leak fluid and WBC’s 3.Cellular and Molecular Defenses : 1.Macrophages: Use pocket transport (phagocytosis) to destroy foreign particles. 2.Natural Killer Cells (NK): Release hydrolytic enzymes onto target cells to rupture/destroy them. 3.Interferon 4.Complement

Final Defense: Specific Immune System Recognizes pathogens and develops a sustained immune response. Comprised of two parts: 1.Cell- Mediated Response 2.Humoral Response White blood cells characters (lymphocytes): Helper T cells (T h ) Killer T cells (T c ) B cells Macrophage Recognizes pathogens and develops a sustained immune response. Comprised of two parts: 1.Cell- Mediated Response 2.Humoral Response White blood cells characters (lymphocytes): Helper T cells (T h ) Killer T cells (T c ) B cells Macrophage

Specific Immunity- The Battle Begins!  Macrophages search body tissues for pathogens.  Consume pathogens with phagocytosis, kill it with lysosomes, and save the antigens.  Antigens placed into MHC 2 receptors and displayed on macrophage’s membrane.  The macrophage is now considered an antigen-presenting cell (APC).  Macrophages search body tissues for pathogens.  Consume pathogens with phagocytosis, kill it with lysosomes, and save the antigens.  Antigens placed into MHC 2 receptors and displayed on macrophage’s membrane.  The macrophage is now considered an antigen-presenting cell (APC).

Specific Immunity Cont.  Macrophage chemically signals Helper T to attach to it.  Helper T attaches to MHC 2 receptor (with foreign antigen stuck in it) with a CD4 receptor.  Helper T cells have incredible variety of receptors that act like a “lock and key” in regards to the displayed antigen.  If the Helper T’s “key” fits the displayed antigen’s “lock”, the Helper T is activated.  Activation results in Helper T releasing cytokines (ex. Interleukin)- chemicals that cause lymphocytes to start mitosis.  Macrophage chemically signals Helper T to attach to it.  Helper T attaches to MHC 2 receptor (with foreign antigen stuck in it) with a CD4 receptor.  Helper T cells have incredible variety of receptors that act like a “lock and key” in regards to the displayed antigen.  If the Helper T’s “key” fits the displayed antigen’s “lock”, the Helper T is activated.  Activation results in Helper T releasing cytokines (ex. Interleukin)- chemicals that cause lymphocytes to start mitosis.

Fig Antigen- presenting cell Peptide antigen Cell-mediated immunity (attack on infected cells) Class II MHC molecule CD4 TCR (T cell receptor) Helper T cell Humoral immunity (secretion of antibodies by plasma cells) Cytotoxic T cell Cytokines B cell Bacterium

Cell-Mediated Response Seek and Destroy  Body cells can be infected by viruses that will hide inside the cell.  As the virus reproduces inside cells, pieces of it fall off and are put into new MHC 1 receptors that the cell puts on its own membrane.  Killer T cells can bind to MHC 1 receptors with their CD8 receptors.  If Killer T binds to MHC 1 receptors with antigen attached, it releases a chemical called perforin.  Perforin ruptures the infected cells membrane and exposes the virus to other immune cells.  Body cells can be infected by viruses that will hide inside the cell.  As the virus reproduces inside cells, pieces of it fall off and are put into new MHC 1 receptors that the cell puts on its own membrane.  Killer T cells can bind to MHC 1 receptors with their CD8 receptors.  If Killer T binds to MHC 1 receptors with antigen attached, it releases a chemical called perforin.  Perforin ruptures the infected cells membrane and exposes the virus to other immune cells.

Fig Antigen Top view: binding surface exposed to antigen receptors Plasma membrane of infected cell Antigen Class I MHC molecule

Fig Cytotoxic T cell Perforin Granzymes TCR CD8 Class I MHC molecule Target cell Peptide antigen Pore Released cytotoxic T cell Dying target cell

Fig Infected cell Antigen fragment Class I MHC molecule T cell receptor (a) Antigen associates with MHC molecule T cell recognizes combination Cytotoxic T cell(b)Helper T cell T cell receptor Class II MHC molecule Antigen fragment Antigen- presenting cell Microbe

Humoral System Bring in the artillery!  B cells have receptors called antibodies (100,000/cell).  Different B cells have uniquely shaped antibodies that match specific antigens.  If a B cell’s antibody is able to bind with a specific antigen (lock and key effect), the B cell receives a message from Helper T’s to become activated.  Activated B cells divide into Plasma B and Memory B cells.  B cells have receptors called antibodies (100,000/cell).  Different B cells have uniquely shaped antibodies that match specific antigens.  If a B cell’s antibody is able to bind with a specific antigen (lock and key effect), the B cell receives a message from Helper T’s to become activated.  Activated B cells divide into Plasma B and Memory B cells.

Humoral System Cont.  Plasma B cells produce and secrete 10,000 “keyed” antibodies per hour.  Due to their shape, each can bind to several antigens at once.  Antigen/Antibody binding has three effects.  Neutralization  Macrophage signaling  Complement pore formation  Plasma B cells produce and secrete 10,000 “keyed” antibodies per hour.  Due to their shape, each can bind to several antigens at once.  Antigen/Antibody binding has three effects.  Neutralization  Macrophage signaling  Complement pore formation

Fig Viral neutralization Virus Opsonization Bacterium Macrophage Activation of complement system and pore formation Complement proteins Formation of membrane attack complex Flow of water and ions Pore Foreign cell

Memory B cells  These cells do not actively produce antibodies  Instead, they remain in the bloodstream and maintain their cell life cycle independently from T h commands.  If the same pathogen/antigen complex presents itself in the future, these cells are already activated and ready to produce antibodies.  There are also Memory versions of T h and T c cells that serve a similar function.  These cells do not actively produce antibodies  Instead, they remain in the bloodstream and maintain their cell life cycle independently from T h commands.  If the same pathogen/antigen complex presents itself in the future, these cells are already activated and ready to produce antibodies.  There are also Memory versions of T h and T c cells that serve a similar function.