Inflammation and Immunity Flashcards
Understand the purpose of inflammation and components of the inflammatory response. Differentiate between innate and adaptive immunity and understand the factors involved in immune response.
What is involved in the body’s first line of defense?
- Skin
- Epithelial cells ( which lines all organs and secretes antimicrobial enzymes to help fight off pathogens)
- Mucous membranes
- Cilia (“moving”, they filter, found in our trachea, bronchi, so basically lungs, ears and respiratory tract)
What is your body’s second line of defense?
Innate inflammation; it’s also non-specific
What is your body’s third line of defense?
Adaptive immune system response (T and B cells); it is a specific response
What is inflammation?
An innate, non-specific , rapid automatic response to cell injury
What is the purpose of inflammation?
To create a response that:
- Neutralizes harmful agents
- Is vascular (move through the bloodstream)
- Depends on cellular and chemical mediators
- Removes damaged and dead tissue and generates new tissue
What are the cells involved in inflammation?
- Endothelial cells (-line inner walls of blood vessels, -regulate vessel patency by secreting heparin to dissolve clots and -prevent them from forming, -allows permeability, -vasodilation, -adhesion and repair)
- Platelets/Thrombocytes (clotting)
- Granulocytes (Neutrophils, Eosinophils, Basophils, Mast cells)
- Agranulocytes ( Macrophages, dendritic cells)
- Lymphocytes (NK cells)
What are neutrophils?
- First responders of inflammation
- most common WBC in our blood
- small phagocytes (they engulf bacteria)
- short lifespan, 24-48 hours
- they release chemical mediators
- they create pus cells (these are dead neutrophils that have phagocytized the pathogen)
What are mast cells?
-most important activator in inflammatory response
What do mast cells secrete?
- Histamine
- Chemokines
- Other Cytokines (Interleukin, TNF)
What is histamine?
A biochemical mediator that releases vasoactive amines.
It Causes:
–Vasodilation (this leads to redness, swelling, or heat)
–Increased vascular permeability
–Bronchoconstriction ( *which is a parasympathetic NS response b/c vasodilation=parasympathetic NS)
What are chemokines?
-They are small protein molecules that attract a specific type of WBC (neutrophils, eosinophils) to inflammation site
What do mast cells synthesize?
- Leukotrienes
- Eicosanoids-Prostaglandins
- PAF (Platelet Activating Factor)
What are Leukotrienes and their functions?
They are inflammatory mediators that:
-Increase vascular permeability
-Cause smooth muscle contraction (bronchoconstriction-parasympathetic)
-Cause neutrophil and eosinophil chemotaxis (these are chemical signals that summon WBC)
-Act later/last longer than histamine in response
( this means your secondary response to allergen is much stronger)
What are Prostaglandins and their functions?
They are mediators that cause:
– Increase vascular permeability
– Vasodilation
– Smooth muscle contraction (bronchoconstriction)
– Induce pain
–Cause neutrophil chemotaxis
[ASA & NSAIDS block inflammatory prostaglandin synthesis-inhibit inflammation & pain]
What are Platelet Activating Factors (PAF) and their functions?
They are mediators that:
- Induce platelet aggregation, clotting
- Stimulate WBC aggregation and migration, endothelial cells
- Vascular permeability
What are Basophils?
Granulocytes that are:
–prominent in allergic reactions
–phagocytic
–release histamine and vasoactive agents
–activated to release granules w/ allergic immune reactions (IgE)
(1% of WBCs)
What are Eosinophils?
-Arrive at injury site 2-3 hours after neutrophils
-phagocytic
-Important in allergic reactions, parasitic infections (by secreting toxins), chronic inflammation
-Long lifespan
(2-3% of WBCs)
What are Monocytes/Macrophages?
- Monocytes mature to macrophages in tissues
- Produced by bone marrow
- Located in lymph nodes, spleen, lymph tissue, and lungs (lymph filters out toxins, pathogens and excess fluid)
- Largest of the leukocytes
- Lifespan is 3-4 times longer than any leukocytes
What are the functions of Macrophages?
- Phagocytosis
- Scavenger cells
- Secretion of cytokines to cause inflammation ( TNF, interleukins, interferons, CSF, fibroblast GF)
- direct recognition of pathogens
- Antigen-presenting cells { they display a part of the pathogen to the helper T cells) } (making them a bridge to adaptive immunity)
- Produce cytokines and co-stimulators to stimulate innate and adaptive immune response
- –activate T cells, B cells, innate immune cells
What are cytokines?
They are inflammatory mediators that:
- have a short half life
- low molecular weight proteins
- brief, self-limiting, mediate cell reactions
- pleotrophic and redundant ( meaning they act on many different kind of cells and cause calls to have similar functions—this happens b/c we want the inflammatory response to be big enough to contain what’s going on; makes the response more powerful)
What are the types of cytokines?
- Tumor necrosis factor (TNF)
- Interleukins (IL)
- Interferons (IFN)
- Colony Stimulating Factor (CSF)–RBCs, WBCs, Platelets
- Chemokines (recruit/direct migration of inflammatory/immune cells)
Describe Interleukins (IL) and their role.
- Produced mainly by macrophages
- Calls lymphocytes and WBCs into action
- Immunotherapy ( IL treatment b/c patients whom has gone through chemo have become immunocompromised, this helps get their WBCs and lymphocyte counts up)
- Induces fever ( which is a systemic response)
Describe Interferons (INF) and their role.
- Produced by host cells invaded by viruses or cancer to prevent disease from invading healthy cells
- Interferes with DNA replication
- Inhibits cancer proliferation and viral binding
- Activates macrophages, NK cells in innate immunity
- Activate lymphocytes in adaptive immunity
- DOES NOT save cells already infected by virus
Describe Tumor Necrosis Factor and their role.
-Produced mainly by macrophages and T cells
-Can cause cancer cell death
-Responds to gram-negative bacteria ( E.coli, Chlamydia), virus-infected cells, cancer cells
- Induces fever
Very high doses can be lethal
What are Dendritic Cells?
- Phagocytic cells of the innate immune response
- found under epithelial tissue-skin, lungs, nose, go (b/c its easy access to pathogens)
- They capture dead cells and pathogens
- Activated by pathogens
- secrete cytokines
- migrate to regional lymph nodes ( when they come into contact with the pathogen)
- Antigen-presenting cells- activate Helper T cells
What are Natural Killer Cells?
- They are the only lymphocytes to take part in the innate immune response
- They don’t have T cell or B cell receptors
- Primary defense against tumor cells, abnormal body cells, cells infected with pathogens
- They destroy cells that are diseases but doesn’t kill the pathogen itself.
- They have vesicles filled with perforin which when released punches holes in/kills the cells/.
Eosinophils are predominant in ______and______.
allergic reactions and parasitic infections
What are the 3 key plasma protein systems?
- Complement system ( proteins produced by the liver)
- Coagulation cascade
- Kinin system (proteins produced by liver)
Describe pathogen recognition by the immune system.
???
Describe the function of the complement system.
- Recruit phagocytes, activates mast cells, and destroys pathogens
- Used in innate and humoral (antibody) response
- Activation of C3 and C5 proteins by pathogens or antibody-antigen complex
- –C3b=Opsonins (which marks/coats pathogen and neutralizes it)
- –C3a,C5a=Chemokines
- –C55-C9=membrane attack complexes (makes a pore in the pathogen thus killing it)
Describe the function of the Coagulation (clotting) System.
- Platelet Activation Factor (PAF)-aggregates platelets
- -released by most inflammatory cells
- -Has an intrinsic (blood vessel) and extrinsic factor (tissue injury)
- Fibrin (insoluble, polymerized protein) forms meshwork at the injured or inflamed site
- –This helps prevents the spread of infection, localizes the microorganisms and foreign bodies, forms a clot that stops bleeding, provides framework for repair and healing.
Describe the function of the Kinin System and most important type of kinin.
- Blood proteins activated by the coagulation system (factor xii); clots off area, stops bleeding. Bradykinin: -Dilation of blood vessels -Induces pain -Causes smooth muscle contraction -Increases vascular permeability
State the five cardinal signs of acute inflammation and the describe the physiological mechanisms associated.
- Rubor (redness)–increase blood flow to area
- Tumor (swelling)–increase capillary permeability
- Calor (Heat)-Increase blood flow to area
- Dolor (Pain)-stretching of nerves by swelling
- Loss of function-?
What are the systemic changes inflammation?
-Fever
-Leukocytosis
-Increase in circulating plasma proteins
Could lead to septic shock
Compare the vascular and cellular stages of inflammatory response.
Vascular Phase:
-Vasodilation [increased blood flow to injured area, redness and warmth result]
-Capillary permeability [mediators allow exudate to escape into tissues resulting in edema, swelling pain, and impaired function result]
Cellular Phase
-White blood cells travel to injured tissue[1. Margination( accumalation) 2. Tethering( adhesion) 3.Transmigration ( through blood vessels out to tissue) 4. Chemotaxis ( attracted to site of injury)
-Phagocytosis [phagocytes move in to remove microbes; Opsonization, engulfment, phagosome)
What are exudates? What are the types of exudates that form with acute inflammatory response?
Exudates are fluid, proteins, RBCs, leukocytes, cell debris that form following phagocytosis. Include: -Serous (clear) -Fibrinous (thick & sticky; fibrin) -Purulent (pus) -Hemorrhagic/sanguineous (blood)
Acute Phase Response
- An innate body defense seen during acute illnesses and involves increased production of certain blood proteins called acute phase proteins.
- occurs hours-days from onset.
- Inflammatory mediators cause increased WBC production, elevation of fibrinogen, C-reactive proteins and SAA proteins.
- symptoms=Increased HR, anorexia, somnolence and malaise
What is the role of CRP during the acute phase response?
Binds to pathogen, marking it for phagocytosis. It functions as an opsonin sticking microorganisms top phagocytes .