IIT 4: Granulomatous Inflammation, Macrophage and Lymphocyte Responses, Delayed Type Hypersensitivty

Question 1

Define granulomatous inflammation

Answer 1

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.

Question 2

Define epitheloid cells

Answer 2

Macrophages that have become activated or stimulated and thus contain abundant cytoplasm and cling together.

Question 3

Define giant cells

Answer 3

Large macrophages that contain multiple nuclei.

Question 4

Define granuloma

Answer 4

A nodular mass of activated macrophages usually surrounded by a rim of lymphocytes and/or fibrous tissue.
-a discrete nodule of granulomatous inflammation

Question 5

Are macrophages present in types of inflammation other than granulomatous inflammation?

Answer 5

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

Question 6

What is the gross appearance of granulomatous inflammation?

Answer 6

• 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

Question 7

What is the difference between granulation tissue and granulomatous inflammation?

Answer 7

Granulation tissue represents immature fibrosis and new blood vessel formation in healing tissues.

Question 8

What are the four main causes of granulomatous inflammation?

Answer 8

• foreign bodies
• mycobacteria
• fungi
• delayed type hypersensitivity reactions

All are persistent stimuli

Question 9

What does granulomatous inflammation often represent?

Answer 9

A cell-mediated immune response to a persistent antigen.

Question 10

What kind of foreign bodies elicit a neutrophilic vs granulomatous inflammation?

Answer 10

Foreign material with bacteria is likely to have a neutrophilic response. Sterile foreign bodies elicit granulomatous inflammation.

Question 11

Define pyogranulomatous

Answer 11

Lots of macrophages and neutrophils. Bacteria survives in macrophage.?

Question 12

What is the duration of granulomatous inflammation

Answer 12

Always chronic, gives time for macrophages to come in.

Question 13

Is mycobacterium the same as mycoplasma?

Answer 13

No, they are different bacteria

Question 14

What is the pathogenesis of granulomatous inflammation?

Answer 14

• response to inert foreign material

- Immune response stimulated by T helper cells

Question 15

What is the sequelae of granulomatous inflammation?

Answer 15

• space occupying lesions (lesion gradually takes up more space)
• cachexia
• Impinge on a vital structure (especially if forming mass, eg can constrict bile duct)

Question 16

Define cachexia

Answer 16

Wasting of tissue due to chronic granulomatous inflammation

Question 17

____ drive granulomatous inflammation and macrophage activation

Answer 17

Helper T lymphocytes

Question 18

Ideally, macrophages respond to fungi, mycobacteria, or some protozoal agents by secreting ___-

Answer 18

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

Question 19

Why are activated macrophages big?

Answer 19

• they have more cytoplasm
• more lysosomal enzymes
• produce more oxygen radicals during an oxidative burst
• better able to phagocytose and kill pathogens

Question 20

How is the macrophage response in inflammation similar to that of neutrophils?

Answer 20

• inflammatory mediators stimulate endothelial cells and monocytes
• rolling adhesion
• firm adhesion
• diapedesis
• chemotaxis
• effector functions: phagocytosis, killing of bacteria

Question 21

What are neutrophils and macrophages called in blood and tissue?

Answer 21

Neutrophils are called neutrophils in blood and tissue.

Macrophages are only macrophages in tissue, when in blood they are monocytes.

Question 22

What is the difference between the response in inflammation between macrophages and neutrophils?

Answer 22

• resident populations of macrophages, and recruitment of monocytes from blood is poised for rapid responses
• coordination of Immuno inflammatory responses

Question 23

What is the main significance of granulomatous inflammation to an animal?

Answer 23

• 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

Question 24

What is the role of macrophages?

Answer 24

• 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

Question 25

Abscess vs granuloma?

Answer 25

• 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

Question 26

What are the four main functions of macrophages?

Answer 26

• removal of necrotic debris
• killing of bacteria and fungi
• secretion of cytokines
• antigen presentation

Question 27

When macrophages remove necrotic debris, what does this enable?

Answer 27

tissue repair

Question 28

When macrophages kill bacteria and fungi, what does this enable?

Answer 28

host defence

Question 29

When macrophages secrete cytokines, what does this enable?

Answer 29

tissue repair, host defence, inflammation, immune response

Question 30

When macrophages present antigens, what does this enable?

Answer 30

immune response

Question 31

What do macrophages regulate?

Answer 31

• granulomatous inflammation

- Inflammation, tissue repair, immune responses

Question 32

How do macrophages recognize pathogens?

Answer 32

Similar mechanisms of neutrophils.

-recognize particles that are opsonized with immunoglobulins (IgG or IgM), complement (C3b) or mannose binding proteins

Question 33

What is delayed type hypersensitivity?

Answer 33

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.

Question 34

What are examples of things that may cause DTH?

Answer 34

• plants (grasses, trees, poison ivy)
• topical medications, shampoos, disinfectants
• textile fibres, dyes, cleansers
• rubber, latex and plastics: collars, food dishes
• metal: collars, jewellery

Question 35

What are the phases of the DTH reaction?

Answer 35

-sensitization phase where the first exposures result in formation of memory T lymphocytes that recognize antigens
-elicitation phase occurs months or years later
-

Question 36

What is the elicitation phase of the DTH reaction?

Answer 36

• 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

Question 37

How many hours do DTH reactions take?

Answer 37

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

Question 38

What happens in mycobacterial infection?

Answer 38

• 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

Question 39

What is defined as immune mediated disease?

Answer 39

Granulomatous inflammation from an unidentified and innocuous cause

Question 40

What is the difference in pathogenesis of a harmful pathogen and a harmless antigen?

Answer 40

Harmful pathogen -> immune response -> protective immunity
Harmless antigen -> minimal response in most animals
in some animals, harmless antigen -> immune response -> hypersensitivity reaction

Question 41

What is hypersensitivity?

Answer 41

• 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