 Immune System Topics in Human Pathophysiology Fall 2011 Gilead Drug Safety and Public Health

Outline  Lymphatic and Immune System  Lymphatic System  White Blood Cells  Innate Defenses  First Line Defenses  Second Line Defenses  Adaptive Defenses (Third Line Defenses)  Pathophysiology of Immune System

Figure 9.3a

Lymphatic System  Functions:  Drains excess tissue fluid (interstitial fluid)  Transports fats and fat-soluble vitamins absorbed from digestive system  Defends against infection

Figure 9.3b Pathway of Fluid

White Blood Cells

First Line of Defense  Skin – barrier, sloughs, acidic pH  Tears- Lubricate and wash eye, contain lysozyme  Saliva - Lubricates and rinses teeth, contains lysozyme  Earwax – waterproof, prevents water (and bacteria) entry  Digestive acids – kills pathogens that enter stomach

First Line of Defense  Mucus – traps pathogens for WBCs to kill, cilia sweeps  Vomiting – removes toxins and pathogens from stomach  Urination – slightly acidic, cleanses urinary tract  Defecation – removes bacteria from GI tract  Resident bacteria – outcompete harmful organisms

Second Line of Defense (Nonspecific)  Phagocytosis  Inflammatory response  Interferons  Natural killer cells  Fever

Phagocytosis and antigen presentation Figure 9.6a

Figure 9.7 Inflammation Link

Figure 21.5 Interferon

Third Line of Defense (Specific Immunity)  B cells and T cells  B lymphocytes (B cells)  Mature in bone marrow, responsible for antibody mediated immunity  When they recognize a pathogen (antigen) and are activated, develop into plasma cells and memory cells  Plasma cells produce 1000s of antibodies (immunoglobulins) per second

B lymphocytes Recognition Activation Attack (cloning and antibody production)

Figure Antibody functions

Third Line of Defense (Specific Immunity)  T lymphocytes  3 types: helper T cells, cytotoxic T cells, suppressor T cells  When recognize a pathogen and are activated, these attack the pathogen and create a cadre of memory cells

Figure 9.13

Figure Helper T cells are presented with antigen by specialized WBCs When activated these helper T cells clone themselves into memory cells and active cells

Cytotoxic T cells  AKA killer T cells  Recognize pathogen (antigens) in virally infected cell or cancer cells  Activated by cytokines from helper T cells  “Clone” themselves into attack cells and memory cells  Attack by producing proteins that open holes in infected cells

Figure 21.19

Immunologic Memory  Memory cells circulate, sometimes for a lifetime, scanning for that pathogen they recognize  A second infection by the same pathogen will yield a stronger, faster immune response that prevents illness

Figure 9.15

Immune System Pathophysiology  Allergies  Autoimmune disorders  Immunodeficiencies

HIV Pathophysiology  A retrovirus that infects host cells macrophages and helper T cells  Its RNA is reverse transcribed into DNA, then inserted into host chromosomes and lays dormant, sometimes for years  Some trigger will cause the viral genome to be expressed and new virus is made  New virus erupts from WBCs, killing them and infecting other WBCs until the levels are dangerously low

Time Course of HIV infection and disease link

Gilead therapies against infectious agents

 Figure 9.19

 Figure 9.20 Reverse transcriptase required Protease required

Figure 9.20 Reverse transcriptase Inhibitors work here Protease inhibitors work here