Macrophage

22/09/2009 1

By : Anthony (1-4206-003) Retty (1-4206-020)

Macrophage Definition• A type of cell derived from white blood cells that ingests (takes in) foreign material.

22/09/2009 2

• is a kind of swallowing cell, which means it functions by literally swallowing up other particles or smaller cells

• So what are the types of white blood cell??

Type pictureDiameter

(μm) Main targets Lifetime

Neutrophil 10–12• bacteria

• fungi

6 hours–few days(days in spleen and other tissue)

Eosinophil 10–12• parasites

• in allergic reactions

8–12 days (circulate for 4–5 hours)

Basophil 12–15 • in allergic reactions  ?

Lymphocyte 7–8

•B cells: various pathogens•T cells:

•Inflammatory T cell•Helper T cell

•Natural killer cells: virus -infected and tumor cells.

weeks to years

Types of white blood cell

Type of white blood cellType picture

Diameter (μm)

Main targets Lifetime

Monocyte 14–17Monocytes migrate from the bloodstream to other tissues and differentiate into tissue resident macrophages or dendritic cells.

hours to days

21 (human)

Phagocytosis (engulfment and digestion) of cellular debris and pathogens, and stimulation of lymphocytes and other immune cells that respond to the pathogen.

activated: daysimmature: months to years

Dendritic cellsMain function is as an antigen-presenting cell (APC) that activates T lymphocytes.

similar to macrophages

Macrophage

Macrophage Definition• Taken from Greek Words (Greek: big eaters, from makros

"large" + phagein "eat"; abbr. MΦ). • Human macrophages are about 21 micrometres

(0.00083 in) in diameter.• Monocytes and macrophages are phagocytes, acting in

both non-specific defense (or innate immunity) as well as to help initiate specific defense mechanisms (or adaptive immunity) of vertebrate animals.

• They move by action of Amoeboid movement.• Life time depends on the type of tissue, viability ranges

between 6 and 16 days.22/09/2009 5

Formation of Macrophage• Development in bone marrow and passes through the

following steps:stem cell committed stem cell monoblast promonocyte monocyte (bone marrow) – monocyte (peripheral blood) macrophage (tissues)

• Monocyte differention in the bone marrow proceeds rapidly (1.5 to 3 days).

• During differentation, granules are formed in monocyte cytoplasma and these can be divided as in neutrophils.

22/09/2009 6

Formation of Macrophage• The blood monocytes are young cells (immature

macrophage) that already possess migratory, chemotactic, pinocytic and phagocytic activities.

• Under migration into tissues, monocytes undergo further differentiation (at least one day) to become multifunctional tissue macrophages.

22/09/2009 7

Monocyte

Neutrophil

Exhibit 3 main functions in body:

1. Destroy bacteria by phagocytosis

2. Activate other immune function

3. Phagocytose apoptotic cells

22/09/2009 8

Function of Macrophage

1. Phagocytosis

22/09/2009 9

Function of Macrophage

• Once it leaves blood vessel and migrated to tissue, the next job is to EAT the pathogen. This human macrophage, like neutrophil, is a professional "phagocyte" or eating cell (phago = "eating", cyte = "cell").

• Furthermore, the pathogen will be digested by using enzyme from macrophage, in the end resulting antigen and waste material.

• Steps of phagocytosis;1. A phagosome is formed to ingest the pathogen2. Lysosome + phagosome phagolysosome3. Pathogen is digested by using enzyme

and toxic (such as superoxide anion or nitric oxide)

4. Secreting waste material

22/09/2009 10

Function of Macrophage

Function of Macrophage2. Perform Specific Immune Function• After digesting a pathogen,present antigen

(identification)• Churn out powerful chemical substances (monokines)

including enzymes and complement proteins.• The presentation is done by integrating it into the cell

membrane, indicating to other white blood cells that the macrophage is not a pathogen, despite having antigens on its surface.

• Antigen presentation results in the production of antibodies that attach to the antigens of pathogens, making them easier for macrophages to adhere to with their cell membrane and phagocytose

22/09/2009 11

• Secrete hormones cytokines To attract system immune cells to the site

and activate cells involved in tissue repair To send signaling path to injury site.

22/09/2009 12

Function of Macrophage

Function of Macrophage3. Phagocytose apoptotic cells

• reduces the potential for an inflammatory response by ensuring that the dying cells are cleared before their intracellular contents are released.

22/09/2009 13

The Macrophage Work

22/09/2009 14

Types of Macrophage• Normal macrophageo connective tissue (histiocytes)o liver (Kupffer's cells)o lung (alveolar macrophages)o lymph nodes (free and fixed macrophages)o spleen (free and fixed macrophages)o bone marrow (fixed macrophages)o serous fluids (pleural and peritoneal macrophages)o skin (histiocytes, Langerhans's cell) and in other tissues

• Inflammatory macrophages o present in various exudates (developmental stage and not the functional

state)o Derived exclusively from monocytes, thus similar properties

22/09/2009 15

Maintenance of Macrophage Population 3 mechanisms: • Intake of monocytes from the circulating blood, • local proliferation and • biological turnover

Under normal steady-state conditions, the renewal of tissue macrophages occurs through local proliferation of progenitor cells and not via monocyte influx.

22/09/2009 16

Mechanism of Inflammation

22/09/2009 17

• Is "dynamic response of vascularized tissues to injury“• It is a complex multi step process of tissue response to

injury• Purposes: to defend against injurious agent Start healing & repair of injured tissue (bring defence forces

such as WBC, antibodies, more nutrients and healing factors to the site of injury)

Localizes infection and prevents spread

22/09/2009 18

22/09/2009 19

• Chemical mediators : Chemical substances synthesised or released which mediate the changes in inflammation.

Histamine by mast cells - vasodilatation.Prostaglandins – Cause pain & fever.Bradykinin - Causes pain.

22/09/2009 21

Mechanism of Inflammation

Mechanism of Inflammation• Clinical signs of inflammation (due to vascular permeabi

lity which allows for phagocytic chemotaxis)

Lewis triple response Flush (redline) : capillary dilatation Flare (red zone) : arteriolar dilatation Weal (edema) : exudation

Classic five signs Rubor(redness) Tumor(swelling) Calor(Heat) Dolor (pain) Loss of function22/09/2009 22

Heat Redness Swelling Pain Loss Of Function

The 5 Cardinal Signs of

22/09/2009 24