Inflammation and stress Flashcards
Define inflammation
Inflammation is a critical innate defence in the war between microbial invaders and their hosts.
Is inflammation normal?
It is a normal process that serves as the body’s primary method of defence against infection and typically ends when injurious agents are killed or removed from the body.
Bacteria causing inflammation?
Microorganisms trigger inflammation when they are introduced into the body and begin to grow and produce compounds that damage host cells.
Inflammatory diseases
The immune system and the inflammatory response stay “on” by secreting pro-inflammatory cytokines:
Inflammatory Bowel Disease (IBD)- Crohn’s disease
Chronic Obstructive Pulmonary Disease (COPD)
Heart disease / atherosclerosis (inflamed arteries)
Alzheimer’s Disease
Rheumatoid arthritis
Cancer
What are cytokines? What do they do?
Small non-antibody proteins that regulate the immune response
Some diffuse into the vasculature and stimulate endothelial cells to produce selectins thereby recruiting neutrophils in the area of infection
Other cytokines act as mediators of intercellular communication
They induce cell growth, and direct cellular traffic
Name types of cytokines and what secretes them
Monokines: secreted by mononuclear phagocytes
Lymphokines: secreted by activated T cells, especially helper T cells
Interleukins: secreted cytokines mediating signalling between white cells (leukocytes)
Describe how inflammation is regulated
During inflammation immune cells are recruited into a damaged area of the body in a process that involves the release of Pro-inflammatory Cytokines (PIC) from Macrophages which coordinate the inflammatory responses by secreting
Tumor Necrosis Factor (kills tumors)
IL-1, IL-2 which:
Stimulate helper–T cells to differentiate
B-cells to proliferate
Many times, damage due to inflammation is a by-product of effective medical treatments
Define stress
A specific response by the body to a stimulus that disturbs or interferes with normal physiological equilibrium/homeostasis
Give examples of stress
Stressors: can be real, imagined, internal or external Physical/environmental Natural disasters Major life changes (good and bad) Day-to-day aggravations
How does stress affect the immune system?
Hypothalamic- pituitary-adrenal (HPA) axis and cortisol
Stress causes dysregulated cortisol response
Produces too much or too little cortisol
Short term stressor – raises cortisol levels
Long term stresses might result in too low amounts of cortisol produced – no suppression of the inflammation
Depressed patients have blunted cortisol effect – no response to cortisol
relationship between cortisol and WBCs in blood
Effects of cortisol
The levels of cortisol are inversely related to the number of lymphocytes in the blood
Impairs immune function by:
Changing the cytokines secretion mainly decreasing the levels of the tumor necrosis factor
Decreasing IL-2
Inducing death of WBC
Decreasing the inflammatory response
affects of chronic stress
Consistently elevated cortisol and catecholamine levels (Stress response chronically activated)
Diabetes, insomnia, myocardial infarction
Stressful events predispose to disease and immune deregulation – infection, cancer, autoimmune diseases (Multiple Sclerosis)
Depression (resulting from altered immune function)
Impaired learning – atrophy in hippocampus
Adipose tissue in obesity
Adipose tissue can be fractionated into lipid-containing adipocytes and the stromal-vascular fraction, which contains pre-adipocytes, macrophages, other inflammatory cells and endothelial cells. In the obese state, there is an increase in the size and number of adipocytes, and in the inflammatory and endothelial compartments of the stromal-vascular fraction. This change in the composition of the adipose tissue results in the increased secretion of leptin and inflammatory cytokines, and decrease in the secretion of adiponectin. PAI1, plasminogen activator inhibitor 1; TNFα, tumour necrosis factor‑α.
Adipose tissue remodelling
In lean adipose tissue, immune cells and adipocytes interact to maintain homeostasis and regulation of adipocyte lipid handling and storage. The main resident immune cells include NKT cells, Tregs, eosinophils, IgM-producing B cells, and alternatively activated M2 macrophages. IL10 production by NKT, Tregs, and M2 macrophages, and IL4 production by eosinophils is important for maintaining a tolerogenic environment. During adipose expansion in obesity, there is a loss of NKT cells and Tregs, and a phenotypic switch in macrophages from M2 to M1, which accumulate around rupturing adipocytes.
Inflammation and insulin resistance
how liver impacts it
- Hepatic insulin resistance leads to increase hepatic gluconeogenesis and lipogenesis
- accumulation of FFAs in the liver result in hepatic steatosis and contribute to disrupted insulin signalling
- Kuppfer cell activation and additional macrophage infiltration exacerbate the obese hepatic environment
Inflammation and insulin resistance
impact of skeletal muscle
- skeletal muscle is the main target for glucose uptake in the body
- this can be insulin-dependent or independent
- Glycogenesis follows glucose uptake
- defective glycogen synthesis is linked to insulin resistance
- Dysregulation of fatty acid metabolism in skeletal muscle is also associated with defective insulin signalling
Inflammation and insulin resistance
impact of adipose tissue
-White adipose tissue (WAT) is a lipid storage organ that expands with obesity
-composed of adipocytes and a stroma-vascular fraction it also functions as an endocrine organ
-It secretes: leptin, adiponectin, TNFalpha, IL1Beta,
IL-1RA, IL-6, IL-10, MIF
-WAT expansion and immune cell infiltration are crucial events driving insulin resistance
-WAT participates in insulin-stimulated glucose uptake, and releases FFAs following lipolysis
Medicines used to lower cholestrol
Atorvastatin Fluvastatin Lovastatin. Pitavastatin Pravastatin Rosuvastatin Simvastatin
What is immunologic tolerance?
Immunologic tolerance is the specific unresponsiveness to an antigen induced by exposure of lymphocytes to that antigen. All individuals are tolerant of their own (self) antigens. Autoimmune diseases result from the failure of self-tolerance.
Autoimmune diseases
Autoimmune responses resemble normal immune responses to pathogens in that they are specifically activated by antigens in this case self-antigens or autoantigens.
Autoimmune diseases can be divided into organ specific and systemic.
Normally, individuals do not form potentially destructive antibodies to their own cells, but only to foreign antigens. However, in certain diseases, antibodies are produced to our own cells or tissue components. This type of antibody is called an auto-antibody and the diseases they cause autoimmune diseases.
Organ-specific autoimmune disease
Antibodies that react only with specific organs and they do not react with other tissues in the body.
Non-organ specific autoimmune disease
systemic
Serum from patients suffering from this type of auto-immune diseases reacts with many if not all tissues in the body.
Immunosuppressive drugs
Anti-Malarial Drugs DHEA (dehydroepiandrosterone) Immunosuppressive Medications NSAIDs (Non Steroid Anti-Inflammatory Drugs) Steroids
