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Cell & tissue of Immune System

various types of Cells & Tissues involved in Immune response

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Dr Alok Tripathi
Department of Biotechnology,
Saaii College of Medical Science & Technology, Kanpur
aquaimmuno@yahoo.co.in
09451662231
LYMPHOID ORGANS
Definition: organs participate in
conducting immune operations are
highly localized microenvironments.
are structural basis of
immune response
3 functional
environments
PRIMARY
lymphoid organs
– mature but
naïve lymphocyte
production
SECONDARY –
mechanism of co-
localizing
antigens and
lymphocytes
TERTIARY – sites of infection
must be able to survey for it
and also regulate the influx of
effector cells
Cell & tissue of Immune System
PRIMARY LYMPHOID TISSUE
– bone marrow and thymus
antigen recognition
development
positive/negative selection
signaling apparatus in response
to antigenic stimulation
capacity to home to proper
microenvironment
BONE MARROW – for B Cells
contains no lymphatic channels but is vascularized
hematopoetic stem cells are nestled next to osteoblasts and receive
survival signals from them
• very inefficient process (frameshift
recombination)
• pro-thymocyte also is made from
hematopoetic stem cell
• stromal cells: support
development/maturation of lymphocytes in
marrow
• secrete cytokines (IL-7)
antigen independent maturation
of B-cells
• cell-cell contact w/ stromal cells also directs
lymphopoesis
C-KIT and stem cell factor
interact on B-cell surface for
lymphopoesis
Cell & tissue of Immune System

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Cell & tissue of Immune System

  • 1. Dr Alok Tripathi Department of Biotechnology, Saaii College of Medical Science & Technology, Kanpur aquaimmuno@yahoo.co.in 09451662231
  • 2. LYMPHOID ORGANS Definition: organs participate in conducting immune operations are highly localized microenvironments. are structural basis of immune response 3 functional environments PRIMARY lymphoid organs – mature but naïve lymphocyte production SECONDARY – mechanism of co- localizing antigens and lymphocytes TERTIARY – sites of infection must be able to survey for it and also regulate the influx of effector cells
  • 4. PRIMARY LYMPHOID TISSUE – bone marrow and thymus antigen recognition development positive/negative selection signaling apparatus in response to antigenic stimulation capacity to home to proper microenvironment
  • 5. BONE MARROW – for B Cells contains no lymphatic channels but is vascularized hematopoetic stem cells are nestled next to osteoblasts and receive survival signals from them • very inefficient process (frameshift recombination) • pro-thymocyte also is made from hematopoetic stem cell • stromal cells: support development/maturation of lymphocytes in marrow • secrete cytokines (IL-7) antigen independent maturation of B-cells • cell-cell contact w/ stromal cells also directs lymphopoesis C-KIT and stem cell factor interact on B-cell surface for lymphopoesis
  • 7. THYMUS – many epithelial-derived cells CORTEX: CAPSULE = lining; invaginates to form lobes lined w/ early T-cell progenitors Cortical Epithelial Cells – dendridic cells, stimulate T- cell maturation Macrophages – clearance of unproductive rearrangements Interdigitating Cells – boundary between cortex and medulla also called “thymic dendridic cells” bone-marrow derived MHCI/MHCII presentation
  • 8. The thymus is enclosed by a thin connective tissue capsule from which numerous septa extend into the thymus subdividing the two lobes into numerous lobules (about 0.5 - 2 mm in diameter). Blood vessels enter and leave the thymus via the connective tissue septa. Each lobulus is divided into a darker peripheral zone, the cortex, and a lighter, central zone, the medulla. Medullary tissue is continuous from lobule to lobule throughout each lobe.
  • 10. Cells in Thymus Reticular cells Reticular cells sheathe the cortical capillaries • are quite abundant. • cytoplasm eosinophilic, with large, ovoid and light nuclei may contain 1 or 2 nucleoli. • cells branched, and their slender processes are connected with the processes of other reticular cells to form a cellular reticulum • This cellular network (reticular fibres are scant in the thymus) provides support for other cells of the thymus. • form an epitheloid layer which delimits the cortical tissue from the connective tissue • and secrete substances important for thymic function. • → create and maintain the microenvironment necessary for the development of T- lymphocytes in the cortex.
  • 12. Macrophages occur in both cortex and medulla. They are difficult to distinguish from the reticular cells in H&E stained sections. Lymphocytes are present in both cortex and medulla, • more numerous (denser) in the cortex. • sizes are variable (5 - 15 µm) in the cortex but generally small in the medulla. • The vast majority of them will be developing T-lymphocytes. • They are also called thymic lymphocytes or thymocytes.
  • 13. Function of the Thymus necessary for the development of the recirculating pool of small, long-lived lymphocytes, the T-lymphocytes. T cells mainly responsible for the cell-mediated immune response. Stem cells invade the cortical regions of the thymus, where they divide to form lymphocytes. Only a small fraction (10-30%) of the cells generated in the cortex leave the thymus. They migrate via the medulla into the blood stream to populate the T-lymphocyte areas of other lymphoid tissues and organs. Cells which do not express the necessary receptors to recognize AP to them or which react incorrectly towards "self-antigens" die and are removed by cortical macrophages. Since the function of the thymus is to produce lymphocytes for the other lymphoid tissues it is a primary lymphoid organ.
  • 14. SECONDARY LYMPHOID TISSUES – lymph nodes (true and musocal), spleen mechanisms for APC or antigen to access necessary microenvironment from site of infection • - specialized vascularization (lymphatics and high endothelial venules) to recruit lymphocytes and send them back out (effect lymphatics) • - distinct regions for B (follicles) and T cell priming (between follicles)
  • 15. FOLLICLES primary follicles – B cells have not yet encountered antigen secondary follicles – rapid growth of B cells after antigenic exposure germinal center and marginal zone Lymphocyte compartmentalization is a directed process chemokine secretion by HEV to recruit lymphocytes out of blood activated effector cells no longer express chemokine receptors
  • 16. FOLLICULAR dendridic cells - not bone marrow derived; NOT APC’s make chemokines (BLC) and organize follicles HEV and Stromal cells secrete SLC/ELC  attracts T cells Epithelial Dendridic Cells (APC’s) also respond to SLC ensures Dendridic cells and T- cells COLOCALIZE HEL/OVA experiment demonstrated that T cells move to follicular areas upon antigen exposure, causing B cell proliferation
  • 17. NAÏVE  EFFECTOR TRANSITION: occurs in lymph nodes T cells: decreased activation threshold (no costimulation) • effector function activity (helper or killer) • homing capacity (directed to tertiary, not secondary tissues) B cells: memory and effector (plasma) cells • affinity maturation • class switching  antibody secretion
  • 18. OVERVIEW no antigen  B and T cells come in from high endothelial venule migrate to follicle/dendridic cell So they LEAVE via the efferent lympathics antigen present  B cell enters and remains in follicle (binds soluble antigen) antigen on DC causes CD4 TH2 differentiation CD4 proliferates and releases cytokines (IL4/5/6) CD4 follows SLC and moves to follicular margin for T/B interaction •CD40L----CD40 •TCR/CD4 -----MHC: peptide •CD28 ----B7 (stim) •CTLA4 --- B7 (inhib) migration occurs in the absence of CCR7 receptors **localization is very important**
  • 19. B cell proliferation and class switching CD40L is not constitutively expressed by all T cells, but CD40 is by B cells • requires that TCR crosslinking first takes place CD40 binds CD40L  • survival advantage (upregulates anti-apopotitic proteins) • proliferation • upregulation of costimulatory molecules for T cells
  • 20. GERMINAL CENTER PROLIFERATION clonal expansion occurs in presence of antigen/CD40L DARK ZONE (centroblasts) during this point that hypermutation is taking place centroblasts move to light zone  now are CENTROCYTES interact with follicular dendridic cells  differentiate into memory or plasma cells if they bind more antigen than dendridic cells
  • 21. Phagocyte: Macrophage (MФ) & Neutrophils (PMN) A phagocyte is a cell that ingests (and destroys) foreign matter, such as microorganisms or debris via a process known as phagocytosis, • in which these cells ingest and kill offending cells by cellular digestion. These phagocytes are extremely useful as an initial immune system response to tissue damage.
  • 22. Blood Cells Granulocytes Cells with various types of granules Agranulocytes Cells without granules Eosinophils Stain with acidic dyes Lymphocytes Basophils Satin with basic dyes Monocytes Neutrophils Stain with neutral dyes
  • 23. MФ Macrophages adapted specially for sustained battles against foreign agents. In addition, they help to clean up and remove damaged tissues. Immature macrophages which are circulating in the bloodstream are called monocytes. These macrophages cannot react immediately, but once they have developed, they are often referred to as 'killing machines' they act by phagocytizing and destroying anything that isn't recognized as belonging to the body.
  • 24. A number of cell types are closely related to MФ - Dendritic cells (including Langerhans cells) Microglia Kupffer cells Osteoclasts
  • 25. Neutrophil • express receptors for immunoglobulin and complement and are involved in the acute inflammatory response. Morphology • Large mononuclear cells with granular cytoplasm • Smaller cells with multi-lobed nucleus and neutral cytoplasmic granules Location • Often resident in tissues (remove routine cell debris) • Blood – requires recruitment to site of infection
  • 26. Killing ability After killing Antigen presentation • Require activation by bacterial molecules ±IFNg • Activated during recruitment, then able to kill internalised bacteria automatically • Migrate to local lymph nodes • Die at site by apoptosis (then taken up by macrophages) • Can present antigen (Class II upregulated by IFNg) • Cannot present antigen (don't normally express Class II) Neutrophil
  • 27. Eosinophil granulocyte Eosinophil granulocytes, commonly referred to as eosinophils (or less commonly as acidophils), are white blood cells that are responsible for combating infection by parasites in the body. Transparent in vivo, these cells appear brick-red when stained with eosin using the Romanowsky method (and are thus, 'eosin (or acid)-loving' cells, hence the name). The red color is visible as small granules within the cellular cytoplasm. These granules contain histamine and proteins such as eosinophil peroxidase, RNase, DNases, lipase, plasminogen, and Major Basic Protein that are toxic to both parasites and the host's tissues. Eosinophils make up about 2.3% of the all white blood cells, and are about 10-12 micrometres in size. A key mediator in eosinophil activation is interleukin 5.
  • 28. Functions of eosinophils • Eosinophils play a role in fighting viral infections which is evident from the abundance of RNAses they contain within their granules. • Eosinophils also play a role in the allergic response, and in fibrin removal in inflammation. • Eosinophils are considered the main effector cells in asthma pathogenesis and are associated with disease severity. • Eosinophils fight helminth (worm) colonization.
  • 29. Basophil granulocyte  least common of the granulocytes, representing about 1% of circulating leukocytes.  They contain large cytoplasmic granules which obscure the cell nucleus under the microscope.  when unstained, the nucleus is visible and it usually has 2 lobes.  A cell in tissues, the mast cell, has many similar characteristics.  For example, both cell types store histamine, a chemical that is secreted by the cells when stimulated in certain ways (histamine causes some of the symptoms of an allergic reaction).  Like all circulating granulocytes, basophils can be recruited out of the blood into a tissue when needed.
  • 30. Function Basophils tend to appear in specific kinds of inflammatory reactions, particularly those that cause allergic symptoms. While the exact purpose of basophils has never been proven, they appear often in tissues where parasites are found. They can be found in unusually high numbers at sites of exoparasite infection, e.g., ticks. also appear in tissues where allergic reactions are occurring and probably contribute to the severity of these reactions. Basophils have protein receptors on their cell surface that bind IgE antibody very tightly. It is the bound IgE antibody that confers a selective response of these cells to environmental substances, for example, pollen proteins.
  • 31. Secretions When activated, basophils secrete histamine, several proteoglycans, lipid mediators like leukotrienes, and several cytokines. Histamine and proteoglycans are pre-stored in the cell's granules while the other secreted substances are newly generated. Each of these substances contributes to inflammation. Recent evidence suggests that basophils are an important source of the cytokine, IL-4, perhaps more important than T cells. Interleukin-4 is considered one of the critical cytokines in the development of allergies and the production of IgE antibody by the immune system. other substances that can activate basophils to secrete which suggests that these cells have other roles in inflammation.
  • 32. Lymphocyte A lymphocyte is a type of white blood cell involved in the human body's immune system. There are two broad categories of lymphocytes, namely T cells and B cells. Lymphocytes play an important and integral part of the body's defenses. T cells are chiefly responsible for cell- mediated immunity whereas B cells are primarily responsible for humoral immunity (relating to antibodies). T cells are named such because these lymphocytes mature in the thymus; B cells, named for the bursa of Fabricius in which they mature in bird species, are thought to mature in the bone marrow in humans. In the presence of an antigen, B cells can become much more metabolically active and differentiate into plasma cells, which secrete large quantities of antibodies.
  • 33. Microscopically, in a Wright's stained peripheral blood smear, a normal lymphocyte has a large, dark-staining nucleus with little to no basophilic cytoplasm. In normal situations, the coarse, dense nucleus of a lymphocyte is approximately the size of a red blood cell (about 7 micrometres in diameter). Some lymphocytes show a clear perinuclear zone (or halo) around the nucleus or could exhibit a small clear zone to one side of the nucleus. It is impossible to distinguish between T cells and B cells in a peripheral blood smear. Normally, flow cytometry testing is used for specific lymphocyte population counts. When one must specifically determine the percentage of lymphocytes that produce a particular secretion (say, a specific antibody or cytokine), the ELISPOT or secretion assay techniques can be used instead.
  • 34. The HIV hijacks and destroys T cells (specifically, CD4+ lymphocytes). Without this key defense, the body is susceptible to opportunistic diseases that otherwise would not kill healthy people. A lymphocyte count is part of a peripheral complete blood cell count and is expressed as percentage of lymphocytes to total WBC counted. An increase in lymphocytes is usually a sign of a viral infection A general increase in the number of lymphocytes is known as lymphocytosis whereas a decrease is lymphocytopenia.
  • 35. Monocyte A monocyte is a leukocyte, part of the human body's immune system that protect against blood-borne pathogens and move quickly to sites of infection in the tissues. It is one of the five major types of white blood cell, based on the appearance of white blood cells in stained smears as viewed under a light microscope. Microscopic anatomy • Monocytes are 13 to 25 μm in diameter. On a Wright's stained peripheral blood smear they appear larger than red blood cells and have a bluish-grey cytoplasm with a large cytoplasm to nucleus ratio. Monocytes are typically identified by flow cytometry by surface expression of the protein CD14, a receptor for bacterial endotoxin that gives rise to septicaemia.
  • 36. Physiology Monocytes are produced by the bone marrow from haematopoietic stem cell precursors, circulate in the blood stream for about one to three days and then typically move into tissues throughout the body. In the tissues monocytes mature into different types of macrophages at different anatomical locations. Monocytes are responsible for phagocytosis Monocytes can perform phagocytosis using intermediary (opsonising) proteins such as antibodies or complement. Monocytes are also capable of killing infected host cells via antibody, termed antibody- mediated cellular cytotoxicity. Vacuolization may be present in a cell that has recently phagocytized foreign matter. Monocytes which migrate from the blood stream to other tissues are called macrophages. Macrophages are responsible for protecting tissues from foreign substances but are also the predominant cells involved in atherosclerosis.
  • 37.  Diagnostic use  A monocyte count is part of a complete blood count and is expressed either as a ratio of monocytes to the total number of white blood cells counted, or by absolute numbers. Both may be useful. Monocytosis is the state of excess monocytes in the peripheral blood. It may be indicative of various disease states.