Lecture 1: Inflammatory Processes Flashcards
cell membrane damage early on; destruction of organelles and leakage of cytoplasm; causes inflammation
necrosis
programmed cell death; does not cause inflammation; cell shrinks and cellular fragments are packaged into pieces of cell membrane and dispersed
apoptosis
area adjacent to the ischemic core where cells undergo apoptosis
ischemic penumbra
evolutionary ancient immune response; immediate activation with inflammation
innate immunity
immune response that targets specific structure via antibodies and cytotoxic T cells; slow
adaptive immunity
cause direct injury at site of infection or release toxins that can cause systemic illness
bacteria
nucleic acids surrounded by protein coat that invade cells to produce copies of themselves
viruses
need to live off a host to complete life cycles
parasites
What are some physical barriers to infection?
- skin
- respiratory tract
- GI tract
- genitourinal system
How does the skin protect from infection?
- keratinized epithelium
- normal cutaneous microbial flora (inhibit colonization of other bacteria)
- normal sebaceous and sweat glands (secretions are acidic, antimicrobial, contain anti-fungal fatty acids, lactic acid, lysosome, and antibodies)
How does the respiratory tract protect from infection?
- cough and sneeze reflexes
- mucociliary escalator
- antibodies
- collectins
- alveolar macrophages
How does the GI tract protect from infection?
- epithelial barrier
- the microbiome
- low gastric pH
- peristaltic movement
- antibodies
If pathogens do make it through the GI tract, whats another method of protection?
they enter the blood which is rerouted to the liver – destroyed by Kuppfer cells (liver macrophages)
How does the genitourinal tract protect from infection?
- physical flushing of urine
- low vaginal pH
- normal vaginal flora
What are the characteristics of inflammation?
- rugor (redness)
- calor (warmth)
- dolor (pain)
- tumor (swelling)
What do neutrophils do?
- first on scene
- release mediators to promote inflammation and vasodilation
- chemotaxis
What are macrophages and what do they do?
- derived from monocytes (enter tissue and change into macrophages)
- phagocytize and destroy foreign cells/particles
What are dentritic cells and what do they do?
- similar to macrophages but not derived from monocytes
- in CNS –> microglia
- clean up debris and maintain other cells
Where is histamine released from and what does it do?
- released from mast cells in tissues
- vasodilation and increased vascular permeability
Where are eicosinoids released from and what do they do?
- produced by virtually all cells
- includes prsotaglandins and leukotrienes (aspirin inhibits these)
Where is neuropeptide released from and what does it do?
- released from sensory C-fiber neurons
- increases sensitivity of noniceptors (increased pain sensation)
Where are cytokines released from and what do they do?
- released from immune cells
- examples: IL-1, IL-6, TNF, interferons
- regulate immune response (activate and inhibit)
- can act locally or systemically
cytokine that is a non-specific blocker of viral replication
interferon
Where are plasma proteins released from and what do they do?
- produced in liver in response to cytokines
- complement – antibody production
- clotting proteins
- C-reactive protein – facilitates phagocytosis
What are some of the effects of an immune response?
- vasodilation
- increase capillary permeability
- chemotaxis
- complement (antibodies)
- phagocytosis
- tissue repair via blood clotting and proliferation of fibroblasts
What are the symptoms of an immune response?
- fever
- decrease plasma iron levels
- lethargy and loss of appetite
- increase production of certain plasma proteins by liver
How can an infection cause damage?
- direct injury from site of infection
- release of toxins
- triggering of a strong host response
- viruses can alter DNA to promote cancer
What immune cells attacks/binds specifically to pathogens making it easier for other immune cells to attack it?
-B cell/antibodies
What cell is able to identify and kill infected host cells?
cytotoxic T cell
What immune cell is responsible for an allergic reaction?
IgE
someone with this is predisposed to allergic responses to allergens (possible explanation: hygiene hypothesis)
atopy
when immune cells do NOT attack molecules associated with the cells of one’s own body
tolerance
What are some ways autoimmune diseases can develop?
- modification of molecule on host cell (via drugs or pathogens)
- molecular mimicry (cloaked pathogens; antibodies attack normal cells by accident)
- exposure of a sequestered antigen (ex. sperm)
- inappropriate activation of lymphocytes
- imbalance of suppressor T cells (inhibit) and helper T cells (activate)
- genetic factors
Examples of causes of chronic inflammation?
- autoimmune disease
- persistent injuries
- persistent infections
- obesity
What is adiponectin and what role does it play in inflammation?
- anti-inflammatory; produced by healthy adipose tissue
- down-regulated by dysfunctional adipocytes
- low in obese patients
- inhibited by cytokines
- decreases risk of diabetes
What is SFRP5 and what role does is play in inflammation?
- anti-inflammatory
- helps maintain normal normal metabolic functioning of fat cells
- inhibited by inflammation and insulin resistance
What is M1 and how does it relate to adipocytes?
- cells found in high levels in DYSFUNCTIONAL adipocytes
- pro-inflammatory
- produces cytokines TNF and IL-6
What is M2 and how does it relate to adipocytes?
- cells found in high levels in HEALTHY adipocytes
- anti-inflammatory
- repairs damaged tissues and promotes resolution of inflammation
How do adipocytes become susceptible to inflammation?
- enlargement increases distance from blood supply
- cells in more interior region become hypoxic and necrotic –> promotes inflammation
- enlarged adipocytes produce more leptin
What is leptin and what is its role in inflammation?
- produced by adipose tissue
- “appetite suppressing hormone”
- leptin resistance when levels are consistently high
- pro-inflammatory; increases TNF and IL-6 and activates immune cells
How does insulin resistance results from obesity?
-damaged adipose tissue is less sensitive to insulin
the “wear and tear” on the body from continually having to deal with stress
allostatic load
What are some responses to acute stress?
- increase HR and contractility
- increased gluconeogenesis
- mobilization of amino acids
- decreased fatigability
- cortisol and ACTH promote learning and memory
- activation of immune system (initially… suppressed long-term)
What are consequences of chronic stress?
- immune suppression (high cortisol levels)
- cognitive impairment
- metabolic changes (increased appetite, weight gain)
- increased risk for CHD (promotes atherosclerosis and hypertension)
- physiological effects - addiction, depression, PTSD
the expected maximal load a structure is able to handle
safety factor