Download Lecture outline: Role of neutrophils Form an essential part of the

Lecture outline:
Role of neutrophils
 Form an essential part of the innate immune system.
 Are recruited to the site of injury within minutes following trauma and are the hallmark
of acute inflammation.
 Undergo a process called chemotaxis, which allows them to migrate toward sites of
infection or inflammation. Cell surface receptors allow neutrophils to detect chemical
gradients of molecules such as interleukin-8 (IL-8), interferon gamma (IFN-gamma),
and C5a, which these cells use to direct the path of their migration.
 Being highly motile, neutrophils quickly congregate at a focus of infection, attracted by
cytokines expressed by activated endothelium, mast cells, and macrophages.
 Neutrophils express and release cytokines, which in turn amplify inflammatory
reactions by several other cell types.
 Have three strategies for directly attacking micro-organisms :
1.Phagocytosis (ingestion)
2.Release of soluble anti-microbials (including granule proteins)
3.Generation of neutrophil extracellular traps (NETs)
Phagocytosis:
 Internalize and kill many microbes, each phagocytic event resulting in the formation of
a phagosome into which reactive oxygen species and hydrolytic enzymes are secreted
 The consumption of oxygen during the generation of reactive oxygen species has been
termed the "respiratory burst”
Degranulation
 Neutrophils also release an assortment of proteins in three types of granules by a
process called degranulation
 Have three types of granules:
1. Specific granules (or "secondary granules") contains Lactoferrin and Cathelicidin
2. Azurophilic granules (or "primary granules") contains myeloperoxidase,
bactericidal/permeability increasing protein (BPI), Defensins and the serine proteases
neutrophil elastase and cathepsin G
3. Tertiary granules contains cathepsin and gelatinase
Neutrophil extracellular traps NETs
 Activation of neutrophils causes the release of web-like structures of DNA !
 This represents a third mechanisms for killing bacteria.These neutrophil extracellular
traps (NETs) comprise a web of fibers composed of chromatin and serine proteases that
trap and kill microbes extracellularly
 Recently discovered mechanism of neutrophil killing
Role of Basophils
 Basophils appear in many specific kinds of inflammatory reactions, particularly those
that cause allergic symptoms
 Basophils contain anticoagulant heparin, which prevents blood from clotting too
quickly.
 They also contain the vasodilator histamine, which promotes blood flow to tissues.
 They can be found in unusually high numbers at sites of ectoparasite infection, e.g.,
ticks.
 Like eosinophils, basophils play a role in both parasitic infections and allergies
 Basophils have protein receptors on their cell surface that bind IgE, an immunoglobulin
involved in macroparasite defense and allergy
Role of Eosinophils
Following activation, eosinophils effector functions include production of:
 cationic granule proteins and their release by degranulation
 Reactive oxygen species such as superoxide, peroxide, and hypobromite (hypobromous
acid, which is preferentially produced by eosinophil peroxidase)
 Lipid mediators like the eicosanoids from the leukotriene (e.g., LTC4, LTD4, LTE4)
and prostaglandin (e.g., PGE2) families. enzymes, such as elastase.
 Growth factors such as TGF beta, VEGF, and PDGF
 Cytokines such as IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-13, and TNF alpha
Role of monocytes
 Monocytes have two main functions in the immune system:
(1) Replenish resident macrophages and dendritic cells under normal states
(2) In response to inflammation signals, monocytes can move quickly (approx. 8-12 hours) to
sites of infection in the tissues and divide/differentiate into macrophages and dendritic cells to
elicit an immune response.
Half of them are stored in the spleen
Role of Macrophages
 Three important roles :
1.Phagocytosis
2.Antigen presentation
3.Muscle regeneration
Reticuloendothelial system
 Also called as Mononuclear phagocytic system and lympho reticular system
 The total combination of monocytes, mobile
macrophages, fixed tissue macrophages, and a few specialized endothelial cells in the bone
marrow, spleen, and lymph nodes is called the reticuloendothelial system
Components of RES
 Basically it is formed by two different types of tissues:
1. Primary Lymphoid organs
2. Secondary Lymphoid organs
Primary lymphoid organs
 Include all those organs where the cells of RES are formed and get matured
 Includes :
1. Bone Marrow
2. Thymus
Secondary lymphoid organs
 Includes the sites where the cells of RES function
 Includes :
1. Lymph nodes
2. Tonsils
3. Spleen
4. MALT (mucosa associated lymphoid tissue)
5. Others ( kupfer cells , Microglia etc.)
MALT
 MALT is further divided in two types
1. BALT (Bronchus associated Lymphoid tissue)
2. GALT (Gut associated lymphoid tissue)
3. NALT (nose-associated lymphoid tissue)
4. LALT (larynx-associated lymphoid tissue)
5. SALT (skin-associated lymphoid tissue)
6. VALT (vascular-associated lymphoid tissue. A newly recognized entity that exists
inside arteries; its role in the immune response is unknown.)
7. CALT (conjunctiva-associated lymphoid tissue in the human eye)
Macrophages in lymph nodes
 Can be regarded as CHECK POSTS of the body
 All the particles including microorganisms after invasion of tissues donot enter directly
in the blood
 Instead they enter the lymph and are then trapped in the nodes in the sinusoids lined by
the tissue macrophages
Macrophages in spleen and bone marrow
 If the organism has been successful in passing through the lymph nodes , then its enters
the blood !
 But it has another obstacle to encounter THE SPLEEN
 The spleen is similar to the lymph nodes, except that blood, instead of lymph, flows
through the tissue spaces of the spleen.
 The red pulp and the venous sinuses in the spleen are lined by macrophages where they
are active in removing the invading organism as well as unwanted debris in the blood,
like old and distorted RBCs
Macrophages in tonsils
 Four groups of tonsils in the pharyngeal region provides effective defense mechanism
against the intruders trying to enter the body via nose and mouth
 They all form Waldeyer's tonsillar ring.
 Have got the same function as that of lymph nodes as they too have the macrophages
lining their interior.
MALT
 MALT is populated by lymphocytes such as T cells & B cells, as well as plasma cells
and macrophages, each of which is well situated to encounter antigens passing through
the mucosal epithelium
 In the case of intestinal MALT, M cells are also present, which sample antigen from
the lumen and deliver it to the lymphoid tissue.
GALT (Gut associated lymphoid tissue)
 Immune system of GIT
 Comprises of 70% of the body’s immune system
 The GALT is made up of several types of lymphoid tissue that store immune cells, such
as T and B lymphocytes, that carry out attacks and defend against pathogens
 Payer’s patches ,found in the small intestine , mostly in the ileum ,are a part of GALT
 New research indicates that GALT may continue to be a major site of HIV activity,
even if drug treatment has reduced HIV count in the peripheral blood
Macrophages in tissues and subcutaneous tissues
 Also called as HISTIOCYTES
 Are derived form the circulating monocytes that have become lodged in the tissues and
the subcutaneous
 Provide the first line of defense if the skin gets interupted because of some damage to
epithelium
Macrophages in Lungs
 Alveolar Macrophages
 Sometimes the entering organism of the material is too small to be captured by the
waldeyer’s ring and thus it is able to get all the way to the lungs and into the alveoli
 Large numbers of tissue macrophages are present as integral components of the
alveolar walls
 Two fates of the entering organism:
1. If the particles are digestible, the macrophages can also digest them and release the
digestive products into the lymph
2. If the particle is not digestible, the macrophages often form a “giant cell” capsule
around the particle until such time—if ever—that it can be slowly dissolved.
Macrophages in liver sinusoids
 Also called as KUPPFER cells
 If the organism entering through GIT has been able to enter the GALT in the
submucosa of the intestinal tract , then it is carried all the way through the portal
circulation to the sinusoids of the liver where the tissue macrophages are present
 Effectively remove ALL the invading organisms ,thus none of them is able to enter the
blood stream
Macrophages in brain
 The Microglia of the Central Nervous System (CNS) can be considered a part of the
reticuloendoethelial system.
 They are scavenger cells that proliferate in response to CNS injury
Learning Objectives:
Role of Neutrophils , basophils , eosinophils , monocytes and macrophages
Reticulo endothelial system
Components of Reticulo endothelial system
Mucosa associated lymphoid tissue and its types
Gut associated lymphoid tissue
Role of macrophages in different entry points in the body