IIT 4: Granulomatous Inflammation, Macrophage and Lymphocyte Responses, Delayed Type Hypersensitivty Flashcards
Define granulomatous inflammation
A type of chronic inflammation dominated by activated (epithelioid) macrophages and also usually involves lymphocytes. The macrophages have been activated to form epitheloid or giant cells.
Define epitheloid cells
Macrophages that have become activated or stimulated and thus contain abundant cytoplasm and cling together.
Define giant cells
Large macrophages that contain multiple nuclei.
Define granuloma
A nodular mass of activated macrophages usually surrounded by a rim of lymphocytes and/or fibrous tissue.
-a discrete nodule of granulomatous inflammation
Are macrophages present in types of inflammation other than granulomatous inflammation?
Yes, the neutrophils quickly invade sites of bacterial infection, but macrophages join the neutrophils by 12-24 hours after the time of infection
-monocytes need time to differentiate into macrophages
What is the gross appearance of granulomatous inflammation?
- may not be grossly visible
- may cause diffuse thickening and pallor of affected tissue
- can cause focal nodules (raised white, tan, red)
- homogeneous or central necrosis
- often resembles a neoplasm
- the centre of a granuloma doesn’t usually contain liquid pus
What is the difference between granulation tissue and granulomatous inflammation?
Granulation tissue represents immature fibrosis and new blood vessel formation in healing tissues.
What are the four main causes of granulomatous inflammation?
- foreign bodies
- mycobacteria
- fungi
- delayed type hypersensitivity reactions
All are persistent stimuli
What does granulomatous inflammation often represent?
A cell-mediated immune response to a persistent antigen.
What kind of foreign bodies elicit a neutrophilic vs granulomatous inflammation?
Foreign material with bacteria is likely to have a neutrophilic response. Sterile foreign bodies elicit granulomatous inflammation.
Define pyogranulomatous
Lots of macrophages and neutrophils. Bacteria survives in macrophage.?
What is the duration of granulomatous inflammation
Always chronic, gives time for macrophages to come in.
Is mycobacterium the same as mycoplasma?
No, they are different bacteria
What is the pathogenesis of granulomatous inflammation?
- response to inert foreign material
- Immune response stimulated by T helper cells
What is the sequelae of granulomatous inflammation?
- space occupying lesions (lesion gradually takes up more space)
- cachexia
- Impinge on a vital structure (especially if forming mass, eg can constrict bile duct)
Define cachexia
Wasting of tissue due to chronic granulomatous inflammation
____ drive granulomatous inflammation and macrophage activation
Helper T lymphocytes
Ideally, macrophages respond to fungi, mycobacteria, or some protozoal agents by secreting ___-
Interleukin 12
- this cytokine encourages T lymphocytes and natural killer cells to secrete interferon Y, which activates macrophages
- macrophages activated by IFN Y are better equipped to kill intracellular pathogens
Why are activated macrophages big?
- they have more cytoplasm
- more lysosomal enzymes
- produce more oxygen radicals during an oxidative burst
- better able to phagocytose and kill pathogens
How is the macrophage response in inflammation similar to that of neutrophils?
- inflammatory mediators stimulate endothelial cells and monocytes
- rolling adhesion
- firm adhesion
- diapedesis
- chemotaxis
- effector functions: phagocytosis, killing of bacteria
What are neutrophils and macrophages called in blood and tissue?
Neutrophils are called neutrophils in blood and tissue.
Macrophages are only macrophages in tissue, when in blood they are monocytes.
What is the difference between the response in inflammation between macrophages and neutrophils?
- resident populations of macrophages, and recruitment of monocytes from blood is poised for rapid responses
- coordination of Immuno inflammatory responses
What is the main significance of granulomatous inflammation to an animal?
- physically impairing organ function
- Infiltrating macrophages take up space in an organ, or displace the resident cells, and interfere with organ function by their physical presence
- may impinge on or compress viral structures as space occupying mass
- granulomas slowly erode through blood vessels
- cytokines release by macrophages alter tissue function, cachexia
What is the role of macrophages?
- recognize, ingest, kill bacteria
- secrete chemical mediators that initiate and modify inflammatory responses, immune responses, tissue repair, thrombosis
- facilitate tissue repair by removing debris from areas of necrosis, using proteolytic enzymes and phagocytosis
Abscess vs granuloma?
- both are attempt of body to localize infection or other irritant that cannot be eliminated and cause clinical signs as result of physical size and location
- abscesses contain liquefying neutrophils and eventually rupture to hopefully drain and eliminate infection
- granulomas contain activated macrophages and do not form draining lesions
What are the four main functions of macrophages?
- removal of necrotic debris
- killing of bacteria and fungi
- secretion of cytokines
- antigen presentation
When macrophages remove necrotic debris, what does this enable?
tissue repair
When macrophages kill bacteria and fungi, what does this enable?
host defence
When macrophages secrete cytokines, what does this enable?
tissue repair, host defence, inflammation, immune response
When macrophages present antigens, what does this enable?
immune response
What do macrophages regulate?
- granulomatous inflammation
- Inflammation, tissue repair, immune responses
How do macrophages recognize pathogens?
Similar mechanisms of neutrophils.
-recognize particles that are opsonized with immunoglobulins (IgG or IgM), complement (C3b) or mannose binding proteins
What is delayed type hypersensitivity?
Also called contact hypersensitivity.
-DTH is a type IV hypersensitivity and is a cellular immune response involving CD4+ T helper lymphocytes and macrophages, and manifests as granulomatous or lymphocytic inflammation.
What are examples of things that may cause DTH?
- plants (grasses, trees, poison ivy)
- topical medications, shampoos, disinfectants
- textile fibres, dyes, cleansers
- rubber, latex and plastics: collars, food dishes
- metal: collars, jewellery
What are the phases of the DTH reaction?
-sensitization phase where the first exposures result in formation of memory T lymphocytes that recognize antigens
-elicitation phase occurs months or years later
-
What is the elicitation phase of the DTH reaction?
- antigen presentation to antigen specific memory Th1 lymphocytes
- Th1 lymphocytes secrete: cytokines that induce an inflammatory response, IFN Y that activates macrophages
- occurs when sensitized animal is re-exposed to the antigen
- macrophages or dendritic cells present antigen to CD4+ t helper 1 memory lymphocytes, and secretion of chemokine by these T lymphocytes draws in additional lymphocytes and macrophages, resulting in congestion, edema and damage to tissues in the area of inflammation, and clinical signs of swelling, reddening and pruritus of the affected tissue
How many hours do DTH reactions take?
24-74 hours delayed
-APC have to find antigen, turn on genetic machinery presentation, memory T cell has to find, activate and produce cytokines which lead to cardinal signs of inflammation
What happens in mycobacterial infection?
- mycobacteria infect macrophages
- macrophages secrete chemokine that recruit macrophages and T lymphocytes, leading to granulomatous inflammation
- lymphocytes lead to cell mediated immunity - th1 cells secrete IFY y, which activates macrophages, more effective killing of mycobacteria
What is defined as immune mediated disease?
Granulomatous inflammation from an unidentified and innocuous cause
What is the difference in pathogenesis of a harmful pathogen and a harmless antigen?
Harmful pathogen -> immune response -> protective immunity
Harmless antigen -> minimal response in most animals
in some animals, harmless antigen -> immune response -> hypersensitivity reaction
What is hypersensitivity?
- an unusually severe Immuno inflammatory reaction to an innocuous antigen
- causes disease in a minority of individuals
- eliminating the Immuno inflammatory response eliminates the disease
