Antigen Presenting Cells



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Dr. Fadwah Al-Ghalib Basic Immunology 2nd Year2009

Antigen Presenting Cells

Routes of Microbes to enter the body, they are mainly through:



Skin (contact) gastrointestinal tract Respiratory tract

(ingestion) (inhalation)

Blood Stream

( insect-born microbes)

An antigen-presenting cell (APC): is a cell that displays foreign antigen complexed with MHC on its surface

APCs fall into two categories: professional or non-professional. There are three main types of professional antigen-presenting cells:


Professional APC:


Non professional Antigen presenting Cells

  • Dendritic cells

  • Macrophages

  • B-cells




  • Fibroblasats (skin)

  • Thymic epithelial cells

  • Thyroid epithelial cells

  • Glial cells (brain)

  • Pancreatic beta cells

  • Vascular endothelial cells

Dendritic Cells:

  1. in the skin and mucosal epithelium,they are referred to as Langerhan's cells

  2. When DCs interact with T cells they are termed interdigitating cells

  3. Follicular DCs are found in the primary & secondary follicles of the B cell areas of lymph node, Spleen and MALT and Present Ag to B cell

  4. The germinal center dendritic cells (GCDC)

Interdigitating cells:



  1. rich in MHC II molecules

  2. Present Ag to Th cells, found in the thymus

FDC (follicular dendritic cells)

  1. Present Ag to B cell

  2. Are not migratory cells

  3. They lack Class II MHC ,but bind Ag by complement receptors (CD21 & CD35)

  4. Express Fc receptors

GCDC (germinal center dendritic cells)

  1. Migrating cells

Professional: - refers to the ability of the cells to both :-

      1. display Ags (antigens) for T cells

      2. Provide the additional signals needed to activate naïve T- cells

Naïve Lymphocytes: B-lymphocytes or T-lymphocytes that have not yet reacted with an epitope of an antigen

They differentiate into ( when they recognize an antigen)

effector cells Memory cell

( Th1, Th2)

Effector Cells : Are lymphocytes that have encountered an antigen, proliferated, and matured into a form capable of actively carrying out immune defenses.

Effector cells :are short-lived, and die when antigen (Ag) is eliminated

What is the most potent APC?

Dendretic cells are most potent and to a lesser extent the macrophage.



Dendritic in different tissues:

  1. DC in lymphoid organs are called interdigitating cells.Are prevelant in T cell areas.

  2. DC in Skin are known epidermal Langerhans Cells.

  3. DC in the Heart are known as interstitial dendritic cells.

  4. DC in Blood and Lymph are known as Veiled Cells


Dendretic cells: (properties)

  1. They express high levels of MHC II molecules. they can present antigen via MHC I.

  2. They retain MHC-peptide Antigen complexes on their surface for periods of time

  3. Activated DCs are especially potent TH cell activators

  4. they express Toll-like receptors (TLRs)

  5. they express co-stimulatory molecules such as (CD80, B7)

  6. are mostly found in the skin and mucosal epithelium, where they are referred to as Langerhan's cells

  7. Upon recognition of infectious particles, these cells migrate through the lymphatics to the nearest lymph node

  8. In the follicles of the lymph node they come into close contact with naive T cells. 

  9. Unlike macrophages however, Dendritic cells can also recognize viral particles as non-self.  In addition,

  10. they can activate both CD8 and CD4 T cells, directly. Once the T cells are activated, they will leave the lymph nodes and travel to the sites of inflammation.

  11. Dendritic cells are also very numerous in the thymus, where they act in positive and negative selection

** Capture steps of protein Antigen by Antigen presenting cells (APC) dendritic cells :

The epithelia is the physical barrier to prevent infection.



  1. The epithelia contain professional APC such as dendritic cells [DC]( called langerhans cells in skin) , these DCs, are found also in T cell-rich areas of secondary lymphoid organs.

  2. Ag binds to Toll-like receptors on DC epithelial cells and M

  3. Will result in production of inflammatory cytokines (TNF & IL-1)

  4. combination of Cytokines and TLR will activate dendritic cells

  5. result in losing their adhesiveness for epithelial and start in expressing specific surface receptors for chemoattracing cytokines(chemokines) which produced in T cell zone of lymph node

  6. These chemokines direct the dendritic cells to the lymph node.

  7. DCs mature to APC during migration to the lymph node, be able to stimulate T cell

  8. maturation means expressing MHC molecules and co-stimulators

  9. Display Ag to T- cells

See figure 1.0



Fig: 1.0
Macrophages Cells (properties):



    1. Are the mature forms of circulating monocytes that have left the blood and taken up residence in the tissues.

    2. They are prevalent in the connective tissues, the lining of the gastrointestinal and respiratory tracts, the alveoli of the lungs and in the liver, where they are known as Kupffer cells.

    3. Macrophages are long lived cells.

    4. Macrophage when activated , release a variety of cytokines that have important function in natural immunity.

    5. they do not contain any specific receptors

    6. posses certain types of receptors that recognize differential carbohydrate patterns on foreign cells.

    7. have receptors for specific bacterial products such as lipopolysaccharide (LPS)

B cells (properties):

  1. the least efficient antigen presenting cells

  2. they possess specific antigen receptors, surface immunoglobulins.

  3. B cells ingest soluble proteins by pinocytosis

  4. recognize wide variety of Ags: proteins, polysaccharides, lipids & small chemicals

  5. present antigen via MHC-II.

  6. To express co-stimulatory molecules they need to be activated by Th cells

B cells Recognition to microbes is either

Recognize Ags of microbes Ags are delivered to them by other

cells in lymphoid organs
Function of the Professional APCs:

    1. They are very efficient at internalizing antigen, either by phagocytosis or by endocytosis,

    2. They display a fragment of the antigen, bound to a class II MHC molecule, on their membrane.

    3. The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen presenting cell.

    4. A co-stimulatory signal is then produced by the antigen presenting cell, leading to activation of the T cell.



The differences between the three APCs:





Macrophage

Dendritic Cell

B cell

MHC-II Expression

Low levels.
Induced by Bacteria and/or Cytokines

Always Expressed.

Always Expressed.
Inducible upon Activation

Antigen type and
presentation by MHC

Extracellular Antigens:
presentation via MHC-II

Intracellular &
Extracellular Antigens:
presentation via MHC-I & II

Extracellular Antigen binds
to specific Ig receptors:
presentation via MHC-II

Co-Stimulation
(B7 expression)

Low levels.
Induced by Bacteria and/or Cytokines

Always expressed
at high Levels

Low levels.
Inducible upon Activation

Location

Lymphoid tissue
Connective tissue
Body Cavities

Lymphoid tissue
Connective tissue
Epithelium

Lymphoid tissues.
Blood







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