Psycho neuro immunology

Psychoneuroimmunology : 

Psychoneuroimmunology

Psycho-neuro-immunology (PNI) : 

Psycho-neuro-immunology (PNI) “Study of the interactions between psychological, neuroendocrine and immune processes” (Whitesman and Booth 2004). Mind-brain-immune interactions Term introduced by Dr.Robert Ader in 1975 conditioned immunosuppression in animals

PNI : 

PNI Psychological Neuroendocrine Immunological

Neuroendocrine : 

Neuroendocrine Interaction between the nervous system and hormones released by the endocrine glands Fight or flight response HPA axis

Introduction to Immunology : 

Introduction to Immunology -Recognition of self vs. non-self components (Antigens/Pathogens) “State of protection from infectious disease”

Innate vs. Adaptive Response : 

Innate vs. Adaptive Response Non-specific vs. Specific Non-specific Response: Anatomical barriers: skin Physiological barriers: body temperature Phagocytic barriers: neutrophils, macrophages Inflammation Specific Response: Specific recognition and elimination of pathogens Immune cells, Antibodies

Cells of the Immune System : 

Cells of the Immune System Lymphocytes : B , T cells Antigen Presenting Cells: Macrophages, Dendritic cells and B cells Other cells: Neutrophils, Eosinophils etc, Natural Killer (NK) cells Graphic courtesy of: http://www.mansfield.edu/~mcb/images/macrophage.gif

Antibody-Antigen Interaction : 

Antibody-Antigen Interaction

Immunoglobulin Structure : 

Immunoglobulin Structure Antibody (Ab) or Immunoglobulin (Ig)

Isotypes : 

Isotypes

Elimination of non-self components: : 

Elimination of non-self components: Respond (Effector) Recognize 14 days Remember (Memory) 8-10 days Basis for design of vaccinations Image courtesy of : http://www.jenniferharp.com/cells.htm

B cells : 

B cells -Mature in Bone marrow (self-reactive cells get eliminated) -Perform 3 main functions: Plasma cells: make antibody/Ig (bound or free) Effector cells: help recognize and eliminate antigens Memory cells: maintains an arsenal of memory cells, with increased affinity for antigen

B cell Response: : 

B cell Response: CLONAL PROLIFERATION

T cells : 

T cells Mature in the Thymus (self-reactive cells get eliminated) T helper (CD4+) & Cytotoxic T cells (CD8+) T cell Receptor (TCR) Graphic courtesy of: http://www.adarc.org/content/HIV_and_Cell/wbc.gif.

T cell Response : 

T cell Response

Immunoglobulin Gene Rearrangements (VDJC/VJC Joining) : 

Immunoglobulin Gene Rearrangements (VDJC/VJC Joining) Graphic Courtesy of: http://depts.washington.edu/labweb/Divisions/MolDiag/MolDiagHema/pcrfig1.gif.

Humoral vs. Cell-mediated Immunity : 

Humoral vs. Cell-mediated Immunity Humoral Immunity: Mediated by secreted Ab’s Gives protection against extracellular pathogens (bacteria) encountered in bodily liquids such as blood Pathogens eliminated via neutralization, complement activation or opsonization Graphic courtesy of: http://www.cs.indiana.edu/~ccheah/ck.html.

Cell-Mediated Immunity : 

Cell-Mediated Immunity Does not involve Antibody Direct contact with T cells T cells help destroy intracellular pathogens ex. virus-infected cells by triggering apoptosis or recruiting macrophages Image courtesy of : http://www.jenniferharp.com/cells.htm

Cytokines : 

Cytokines Chemical Messengers Mediators of immune system Small proteins Ex. Interleukin-2 (IL-2) Graphic Courtesy of: http://www.life.umd.edu/CBMG/faculty/mosser/cytokines/cytokines.gif

The History of Mind-Body Medicine : 

The History of Mind-Body Medicine The traditional view held by scientists is based on the germ theory Autonomy of the Immune system Humoral Medicine: Hippocratic Chinese medicine Ayurveda of India Focus on individual and not just not bodily processes

Evidence for Mind-Body Connection : 

Evidence for Mind-Body Connection Presence of multiple neuropeptides and their receptors in cells of the immune system Many immunopeptides are produced in the brain Earliest evidence demonstrated through classical conditioning – conditioned immunosuppressive response Extensive research in humans showing correlations linking stress and/or emotions to immune response

The Placebo Puzzle : 

The Placebo Puzzle An interesting piece of evidence for mind-body connection Placebo effect : patient makes genuine recovery from a sugar pill May explain efficacy of faith healings and alternative medicines More research needed to explain underlying mechanisms

Stress : 

Stress “A particular relationship between an individual and his/her environment that is appraised by the individual as taxing/exceeding his/her resources and endangering one’s well-being” (Lazarus and Folkman,1984) Stress manifested in physiological ways ex. cortisol Cortisol helps restore homeostasis by increasing blood pressure, sugar levels, and enhances metabolism while suppressing immune system Chronic stress inhibits feedback inhibition of cortisol

HPA Axis : 

HPA Axis Graphic courtesy of: http://cti.itc.virginia.edu/~psyc220/kalat/JK367.fig12.6.HPA_axis.jpg.

Current Research in PNI : 

Current Research in PNI Burns et al. 2003 study on correlations between chronic stress and the antibody response to influenza vaccination in a young healthy adult population Chronic stress measured using perceived stress scale and life events scale 4 fold increase in antibody levels necessary for protection Unprotected participants (low antibody levels) reported significantly more life event exposure and perceived stress than those who were protected Concluding that psychological stress is detrimental to long-term maintenance of antibody levels following vaccination

Current Research in PNI Contd….. : 

Current Research in PNI Contd….. Edwards et al. 2005 study on the effect of acute stress exposure prior to influenza vaccination Acute stress induced via acute exercise mental stress task, see themselves in a mirror, brief loud bursts of sound every 10 trials In both exercise and mental stress tasks women showed higher antibody titers, men had similar levels for both treatments First study demonstrating effect of acute stress in humans, thereby concluding that further study is needed

Acute vs. Chronic Stressors : 

Acute vs. Chronic Stressors Acute stress : ↑ Immune system (immunoenhancing) improved response to vaccination possibly reduced likelihood of acquiring disease Chronic stress: ↓ Immune system (immunosuppressive) increased risk for acquiring disease

Potential mechanisms of interaction between stress & immunity : 

Potential mechanisms of interaction between stress & immunity Direct Mechanisms: HPA axis: chronic stress-increased cortisol secretion - immunosuppression Sympathetic nervous system activation: fight/flight response Indirect Mechanisms: Stress causes changes in health behaviors such as smoking, alcohol intake, diet etc.

Co-morbidity of mental and physical disorders : 

Co-morbidity of mental and physical disorders Cardiovascular disease : hostile personality, type A behavior, low socioeconomic status, depression PTSD : Patients likely to have more medical conditions such as arthritis, anemia, diabetes, kidney disease, ulcers etc. GAD : Associated with increased risk for ulcer disease Panic attacks : Association with asthma, chronic bronchitis Depression : Poor physical health in children, increases likelihood for depression and vice versa Elevated cortisol levels

Correlation ≠ Causality : 

Correlation ≠ Causality PNI research focuses on finding correlations between factors such as stress and immunity not causation Causation is challenging to establish Most research provides only correlational data i.e. gather support for a certain hypothesis Stress ≠ Disease

Depression as a risk factor for Neoplasia? : 

Depression as a risk factor for Neoplasia? Psychosocial factors may have an impact on the incidence and progression of certain types of cancers (those associated with immune system ex. virus) Natural killer cells (NK) play a role tumor surveillance and in resisting metastasis of tumors once they have developed NK cell population down regulated by stress Ex. During final examinations Interferon alpha ( regulates NK cell activity) levels fell from 2000 micro/ml to 80micro/ml Depression often coupled with elevated cortisol levels, indicating chronic stress

Depression as a risk factor for Neoplasia? Contd……. : 

Depression as a risk factor for Neoplasia? Contd……. Suppressed immune system, leads to: faulty DNA repair of damaged cells (carcinogens), leading to increased incidence of abnormal cells Studies done in non-medicated depressed patients, exposed to X-radiation showed significantly poorer repair of damaged cells than less depressed patients Additionally stress also seen to affect apoptosis (programmed cell death) Behavioral interventions such as relaxation training, social support may help improve immune function

Depression & HIV : 

Depression & HIV Depression common in patients with HIV HIV attacks immune cell population, with death occurring from secondary, opportunistic infections Depression may serve to accelerate the lymphocyte cell population decline

Limitations & Scope of Future Research in PNI : 

Limitations & Scope of Future Research in PNI Relatively new area of research established in 1975 Paucity of researchers with interdisciplinary training: psychology, immunology and endocrinology Short term: Collaboration Long term: Training in both biology & psychology could equally benefit both fields Use of animal models not feasible for all aspects of research in PNI Paradigm shifts usually faced with initial resistance

References : 

References Burns, V.E., Douglas, C., Drayson, M., Whitham, M. and Ring, C. 2003. Life events, perceived stress and antibody response to influenza vaccination in young, healthy adults. J. of Psycosom. Res. 55: 569-572. Burns, V.E., Carroll, D., Ring, C. and Drayson, M. Antibody response to vaccination and psychosocial stress in humans: relationships and mechanisms. 2003. Vaccine 21: 2523-2534. Croyle, R.T. 1998. Depression as a risk factor for Cancer: Renewing a debate on the psychobiology of disease. J of the National Cancer Institute. 90 (24). Edwards, K.E, Burns, V.E, Reynolds, T., Carroll, D., Drayson, M. and Ring, C. 2005. Acute stress exposure prior to influenza vaccination enhances antibody response in women. Brain Behav. Immun. Article in Press. Kiecolt-Glaser, J. et al. 2002. Psychoneuroimmunology and Psychosomatic Medicine: Back to the Future. Psychosomatic Medicine 64: 15-28. Kiecolt-Glaser, J. et al. 2002. Psycho-oncology and cancer: psychoneuroimmunology and cancer. European society for Med Oncology. Kumar, N. 2004. The relationship between physical & mental health: Co-occurring mental & physical disorders. Indian J Med Res. 120: 434-436. Milan, S, Ickovics, J. et al. 2005. Interpersonal predictors of Depression Trajectories in women with HIV. J of Consul & Clin Psyc. 75 (4): 678-688. Phillips, A.C., Burns, V.E., Carroll, D., Ring, C. and Drayson, M. 2005. The association between life events, social support, and antibody status following thymus-dependent and thymus- independent vaccinations in healthy adults. Brain Behav. Immun. 19: 325-333. Segerstrom, S.C and Miler, G. 2004. Psychological stress and the Human Immune system: A Meta-Analytic Study of 30 years of Inquiry. Psychological Bulletin 130 (4):601-630. Stewart-Williams, S. 2004. The Placebo Puzzle: Putting together the Pieces. Health Psychology. 23 (2): 198-206. Whitesman, S and Booth, R. 2004. Psychoneuroimmunology---mind-brain-immune interactions. SAMJ Forum 94 (4).