immune with stress

Neutrophil engulfing anthrax bacterium

Vertebrate Immune System INNATE humoral complement antitoxins bacteriolysins

cellular 1. 2. 3. 4.

Inflammation Kill and clear any non-self

Natural Killer Cells Basophils Eosinophils Phagocytes a) Macrophges b) Neutrophils c) Dendritic cells

Fast acting, non specific Does not confer long lasting protection

ADAPTIVE cellular

humoral

T-cell

B-cell

1. Helper T cell Th0 Th1

Th2

2. Cytotoxic T cell Inflammation Kill specific pathogens

B-cell

Producing antibodies Mark pathogens for destruction and clearance

Slower response, but highly specific Leaves memory cells

Macrophage

cytotoxins

Cytotoxic Cytotoxic Cytotoxic Cytotoxic Cytotoxic Cytotoxic T Tcell Tcell Tcell Tcell Tcell cell CD8+ CD8+ CD8+ CD8+ CD8+ CD8+

T cell CD8+

Perforin granulysin

Presenting antigen Interleukin 2

Macrophage

T cell Helper T CD4+ Helper T cell Helper T cell Helper T cell Helper T cell Helper T cell Helper T cell cell IFN γ Helper Th1

Th1 memory

Interleukin 2 Interleukin 4 Interferon γ

Il4

Helper Th2

Il4 Il5 Il6

Il10 Il13

B cell memory

IFN γ Tumor Necrosis Factor

Activate more macrophages

Macrophage

B cell unactivated

B cell ACTIVATED

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

Fig. 1. Juxtaposition of typical stressors for wild animals and known effects of stressors on immune function in domesticated rodents

Immune function

Habitat modification Invasive species Pollution

Immune enhancement

basal immune function

Inclement weather Social status change

Scope of baseline shift (or GC insensitivity) contingent on experience (#, timing or intensity of prior stressors)

Infection Injury

Aggressive interaction Parasite detection Predation

Minutes-hours

Immune suppression

Food restriction

Hours-days

Days-weeks

Weeks-months

Duration of stressor Protective up-regulation

Protective down-regulation

Allostatic overload

Vertebrate Immune System INNATE humoral complement antitoxins bacteriolysins

acute

cellular 1. 2. 3. 4.

Inflammation Kill and clear any non-self

Natural Killer Cells Basophils Eosinophils Phagocytes a) Macrophges b) Neutrophils c) Dendritic cells

Fast acting, non specific Does not confer long lasting protection

chronic

ADAPTIVE

cellular

humoral

T-cell

B-cell

1. Helper T cell Th0 Th1

Th2

2. Cytotoxic T cell Inflammation Kill specific pathogens

B-cell

Producing antibodies Mark pathogens for destruction and clearance

Slower response, but highly specific Leaves memory cells

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

Macrophage

cytotoxins

Cytotoxic Cytotoxic Cytotoxic Cytotoxic Cytotoxic Cytotoxic T Tcell Tcell Tcell Tcell Tcell cell CD8+ CD8+ CD8+ CD8+ CD8+ CD8+

T cell CD8+

Perforin granulysin

Presenting antigen Interleukin 2

Macrophage

T cell Helper T CD4+ Helper T cell Helper T cell Helper T cell Helper T cell Helper T cell Helper T cell cell IFN γ Helper Th1

Th1 memory

Interleukin 2 Interleukin 4 Interferon γ

Il4

Helper Th2

Il4 Il5 Il6

Il10 Il13

B cell memory

IFN γ Tumor Necrosis Factor

Activate more macrophages

Macrophage

B cell unactivated

B cell ACTIVATED