Neutrophil engulfing anthrax bacterium

INNATEADAPTIVE Vertebrate Immune System Fast acting, non specific Does not confer long lasting protection Slower response, but highly specific Leaves memory cells cellularhumoralcellularhumoral B-cell T-cell 1. Helper T cell Th0 Th1 Th2 1.Natural Killer Cells 2.Basophils 3.Eosinophils 4.Phagocytes a)Macrophges b)Neutrophils c)Dendritic cells complement antitoxins bacteriolysins B-cell Producing antibodies 2.Cytotoxic T cell Mark pathogens for destruction and clearance Inflammation Kill specific pathogens Inflammation Kill and clear any non-self

Cytotoxic T cell CD8+ Helper T cell Presenting antigen T cell CD4+ Macrophage Interleukin 2 Interferon γ Interleukin 4 Helper Th1 IFN γ Helper Th2 Il4 Th1 memory Macrophage Activate more macrophages IFN γ Tumor Necrosis Factor Il4 Il5 Il6 Il10 Il13 B cell unactivated B cell ACTIVATED T cell CD8+ Macrophage B cell memory Cytotoxic T cell CD8+ Perforin granulysin cytotoxins

STRESS Sympathetic Nervous System (Epinephrine and Norepinephrine): – Increases inflammation—increases adhesion molecules from macrophages—allowing all cells to stick into tissues better – Increase inflammation—Th1 cells have receptors for Epinephrine and Norepinephrine Glucocorticoids: Acute Glucocorticoids: Chronic

Effect of stress on T cell response ACUTE

STRESS Sympathetic Nervous System (Epinephrine and Norepinephrine): – Increases inflammation—increases adhesion molecules from macrophages—allowing all cells to stick into tissues better – Increase inflammation—Th1 cells have receptors for Epinephrine and Norepinephrine Glucocorticoids: Acute – Enhances IFNγ action on Th1 Glucocorticoids: Chronic

Effect of stress on T cell response ACUTE CHRONIC

STRESS Sympathetic Nervous System (Epinephrine and Norepinephrine): – Increases inflammation—increases adhesion molecules from macrophages—allowing all cells to stick into tissues better – Increase inflammation—Th1 cells have receptors for Epinephrine and Norepinephrine Glucocorticoids: Acute – Enhances IFNγ action on Th1 Glucocorticoids: Chronic – Reduce numbers of lymphocytes (T>B), basophils, eosinophils, macrophages

Duration of stressor Habitat modification Invasive species Pollution Aggressive interaction Parasite detection Predation Minutes-hours Inclement weather Social status change Infection Injury Hours-daysDays-weeks Weeks-months Immune function Fig. 1. Juxtaposition of typical stressors for wild animals and known effects of stressors on immune function in domesticated rodents basal immune function Immune enhancement Immune suppression Scope of baseline shift (or GC insensitivity) contingent on experience (#, timing or intensity of prior stressors) Protective up-regulation Protective down-regulationAllostatic overload Food restriction

INNATEADAPTIVE Vertebrate Immune System Fast acting, non specific Does not confer long lasting protection Slower response, but highly specific Leaves memory cells cellularhumoralcellularhumoral B-cell T-cell 1. Helper T cell Th0 Th1 Th2 1.Natural Killer Cells 2.Basophils 3.Eosinophils 4.Phagocytes a)Macrophges b)Neutrophils c)Dendritic cells complement antitoxins bacteriolysins B-cell Producing antibodies 2.Cytotoxic T cell Mark pathogens for destruction and clearance Inflammation Kill specific pathogens Inflammation Kill and clear any non-self acute chronic

Definitions Adaptive arm—humoral: responsible for extracellular pathogen control through generation of antibodies (B cells) specific to particular components of pathogens (antigens) Adaptive arm—cell mediated: responsible for intracellular pathogen control (cytotoxic T cells), and upregulating both cell mediated (Th1) and humoral (Th2) adaptive immune Innate arm—cell mediated: cells that destroy non-self Innate arm—humoral—proteins, acellular components identify and destroy non-self Leukocytes—all white blood cells Lymphocytes—specific leukocytes, two sizes – Large, granular: natural killer cells – Small: T and B cells MHC—recognition of self

Cytotoxic T cell CD8+ Helper T cell Presenting antigen T cell CD4+ Macrophage Interleukin 2 Interferon γ Interleukin 4 Helper Th1 IFN γ Helper Th2 Il4 Th1 memory Macrophage Activate more macrophages IFN γ Tumor Necrosis Factor Il4 Il5 Il6 Il10 Il13 B cell unactivated B cell ACTIVATED T cell CD8+ Macrophage B cell memory Cytotoxic T cell CD8+ Perforin granulysin cytotoxins