Encyclopedia: Immune System

Innate Immune System

Innate immunity provides the first line of defense against infection. Most of its components are present before infection and represent a set of disease-resistance mechanisms that are not specific to particular threats.

 

The skin provides a mechanical barrier of entry of microbes, while its low pH (3-5) slows microbial growth. Mucous membranes are covered with normal flora that competes with pathogens, while mucus traps organisms and cilia propel them from the body. Temperature and various soluble and cell-surface molecules contribute to innate immunity by impeding the growth of certain pathogens.

 

Inflammation is a key innate response to invasion. The systemic, or acute phase response, includes fever and release of serum proteins to increase host immunity.

 

Phagocytic cells are responsible for ingesting pathogens and debris.

• neutrophils: the first line of defence against pathogens
• macrophages/monocytes: other phagocytic cells, responsible for ongoing clearing of pathogens and debris.

Other important cells of the innate immune system include:

• mast cells
• eosinophils

 

Many of the molecules involved in innate immunity use pattern recognition to detect classes of molecules found on pathogens, such as lipopolysaccharides.

• complement
• cytokines and chemokines

Opsonization refers to the binding of molecules such as immunglobulins or complement fragments (ie C3b) to microbes, enhancing their phagocytosis.

 

 

 

Mast Cells

Mast cells are important mediators of the allergic response.

They release vasoactive mediators, such as histamine and cytokines.

They also release growth factors such as PDGF and proteases, triggering smooth muscle proliferation. This is important in asthma airway remodeling.

 

 

Eosinophils

All content about these cells should go here initially..

Adaptive immune system

Adaptive immunity is responsible for the selective recognition and elimination of pathogens and molecules the body has previously seen. It is characterized by antigen specificity, diversity, immunologic memory, and self/non-self recognition.

 

An effective response involves two cell types - lymphocytes and antigen presenting cells.

Antigen-presenting cells include:

• dendritic cells

 

Lymphocytes are responsible for developed immunity. Lymphocytes continually circulate throughout the blood, lymph, and lymphoid organs, making a complete circuit as much as 1-2 times daily.

Lymphocytes spend approximately 30 minutes in the bloodstream and end up in either the spleen or various peripheral lymph nodes, where they remain for 5-10 hours.

About 10% of lymphocytes leave the circulation through venules and migrate to extralymphoid tissues that are in contact with the external environment, such as the skin, various mucosal surfaces, and the pulmonary and urogenital tracts.

Continual lymphocyte recirculation maximizes the chances that antigenically committed lymphocytes will encounter antigen.

 

Leukocyte Trafficking

Different subsets of lymphocytes migrate differentially into different tissues in a process called trafficking, or homing. This is mediated by unique combinations of CAMs, chemokines, and receptors. Trafficking patterns of effector and memory lymphocytes are different from those of naive cells due to the former's expression of LFA-1.

 

Lymphocyte Extravasation

Lymphocytes continually circulate and home to various tissues. Extravasation occurs at sites of inflammation and into lymphoid organs, with patterns differing by cell type. Naive lymphcytes circulate indiscriminately to secondary lymphoid tissue, assisting in antigen encounter.

Some regions of lymphoid organ venules have a cuboidal cell morphology, leading to the name high-endothelial venules (HEVs). A high proportion of lymphocytes flowing through these regions adhere to HEVs, and it has been estimated that perhaps 10⁴ lymphocytes extravasate through HEVs per second per lymph node.

HEV extravasation is mediated by antigenic induction of cytokine expression.

Naive lymphocytes bind to HEV GlyCAM-1 or Cd34 using L-selectin.

 

 

Naive lymphocytes

Naive lymphcytes circulate indiscriminately to secondary lymphoid tissue and bind to HEVs GlyCAM-1 or Cd34 using L-selectin. This constant trafficking assists in antigen encounter.

Encounter with antigen in secondary lymphoid tissue leads to activation, a process taking approximately 48 h.

Effector Lymphocytes

Effector cells tend to home to regions of infection by recognizing activated endothelium and chemoattractant signals.

Memory Lymphocytes

Memory lymphocytes home selectively to the type of tissue in which they first encountered antigen.

 

B lymphocytes/plasma cells: produce immunoglobulins (antibodies).

 

 

T cells arise in the bone marrow and mature in the thymus gland. During maturation they express a unique antigen-binding molecule, the T Cell Receptor (TCR).

• CD 4+ cells: help orchestrate the adaptive immune system
• CD 8+ cells: important effectors, especially against viruses and cancers

Double Negative T Lymphocytes

Double negative T lymphocytes are involved in the recognition of non-peptide antigen, including lipids and polysaccharides.

They do not recognize MHC class I or II molecules.

DN T cells are present in mucosal sites, such as the gut.

 

Natural Killer Cells

Natural Killer (NK) Cells are T lymphocytes that kill.

Activation

NK cells are activated by IL-2 expression from CD4+ cells