Immunology AND Immunopathology- Henry\'S PDF

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OUTLINE NOTES FROM HENRY'S BOOK BUT A SPECIFIC CHAPTER ONLY...

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IMMUNOLOGY AND IMMUNOPATHOLOGY Friday, 1 January 2021 4:16 PM

CHAPTER 43: OVERVIEW OF THE IMMUNE SYSTEM AND IMMUNOLOGIC DISORDERS 

IMMUNE SYSTEM o Is structured to recognize, respond to, and destroy a wide variety of invading organisms such as:  Bacteria  Fungi  Viruses  Parasites o The immunologic function can be summarized as searching for foreign (or nonself) antigens that do not belong in the body and then destroying them. o also maintains surveillance over the appearance of new or foreign antigens on tumor cells and attempts to destroy them while leaving unharmed the normal (or self) antigens on healthy cells. o Disease states may arise as a result of various aspects of immunologic function going awry:  Hypersensitivity reactions  Autoimmune disease  Immunodeficiency disorders o When functioning properly, the immune system is responsible for rejection of allogeneic organ/tissue transplants and graft-versus-host disease; the quest for tolerance in transplantation continues.

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LYMPHOID CELLS o Reside in:  Lymph nodes  Spleen  Mucosal surfaces  Circulation o They derive from multipotential hematopoietic stem cells, with their production moving progressively from the yolk sac in the embryo to the liver in the fetus, and finally to the bone marrow in the infant through adult ages. o The various lymphoid cells are conveniently identified by the presence of unique protein markers on their surfaces.

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T LYMPHOCYTES o Undergo differentiation in the thymus o After originating in the bone marrow  Prothymocytes pass from the cortex to the medulla of the thymus, during which time they undergo maturation  This process involves a selection process such that self-reactive thymocytes are eliminated, while thymocytes that can recognize antigens

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through interactions with molecules of the major histocompatibility complex (MHC) are retained During maturation, they undergo genetic programming  gene for the T cell antigen receptor (TCR) is rearranged to produce protein receptors that are invariant in their antigen specificity for the life span of that T lymphocyte, as well as for all its descendant cells. Account for about 60%-70% of all lymphocytes in the blood Also found in the paracortical areas of lymph nodes Within periarteriolar lymphoid sheets in the spleen A majority (>95%) of T lymphocytes have antigen receptors made of α- and β-subunits linked with disulfide bonds to form a molecular heterodimer that resides on the outer membrane of the cell in association with the CD3 molecular complex (CD3 is a pan–T cell marker)  Pan-T cell marker is a mouse monoclonal antibody raised against WAG/Ri lymph node cells of rat origin.  α- and β-subunit TCR proteins have  Variable  Joining  Constant regions  Diversity regions (α- )  Encoding regions The CD3 proteins assist transduction of the signal to the interior of the cell when an antigen binds to the TCR on the lymphocyte surface A small percentage of T lymphocytes Have a TCR composed of γ- and δ-subunits that similarly interact with CD3; Generally found in  Mucosal surface of gastrointestinal tract  Respiratory tract T cell proliferation may be characterized as Neoplastic (clonal) Benign (polyclonal)  according to whether their DNA shows predominantly a single form of TCR gene rearrangement or a complete spectrum of such rearrangements Examination of T lymphocytes by flow cytometry focuses on a variety of surface markers. CD4 is found on about 60% of CD3+ cells  these are helper/inducer T cells that direct the functions of other cells of the immune system by secreting cytokines that stimulate various functions.  2 distinct populations:  Th1 cells  secrete interleukin (IL)-2 and interferon (IFN)-γ;  facilitate  macrophage activation  delayed-type hypersensitivity  production of antibodies with opsonizing action  Th2 cells  secrete IL-4 and IL-5

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direct synthesis of other antibodies such as IgE and activate eosinophils. Mechanism of antigen recognition  CD4 molecules bind to the MHC class II molecules on antigenpresenting cells  CD4+ T cells recognize antigens only in the context of MHC class II antigens CD8 is found on about 30% of T cells normal ratio of CD4+ to CD8+ cells in the blood is typically 2:1 exhibit cytotoxicity and suppressor activity in the immune response. Mechanism of antigen recognition  CD8 molecules interact with MHC class I molecules  CD8+ T cells recognize them only through MHC class I antigens. T regular (Treg)cells Subset of T helper cells important for immune tolerance and prevention of autoimmune disorders Have surface markers for CD4 and CD25 (IL-2 receptor) and so are driven by IL-2 transcription factor FOXP3  Plays a role in Treg function  Mutation in foxp3 gene results in  dysregulation of immune tolerance  progression to autoimmune diseases.

B LYMPHOCYTES o make up roughly 10% to 20% of peripheral lymphocytes in the blood o Also found in  Bone marrow  Lymph nodes  Spleen  Other lymphoid tissues o In the spleen and lymph nodes  They aggregate into lymphoid follicles o Differentiation of B lymphocytes occurs in the  Bone marrow  Both positive and negative selection take place  Peripheral locations  Antigenic stimulation of B cells leads to the formation of  Plasma cells  secrete immunoglobulins  the basis of specificity in humoral immunity o The B cell antigen receptor complex uses surface IgM as the antigen-binding component o The antigen specificity of immunoglobulins derives from a rearrangement process in which both heavy and light chain genes are realigned.  Heavy chain  Variable  Diversity

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Joining Constant regions  Light chain  Variable  Joining  Constant regions B cells have on their surfaces receptors for complement and Fc region of immunoglobulins  CD21 - receptor for Epstein-Barr Virus (EBV)  CD19 and CD20 - used for immunologic identification of B cells

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ANTIGEN-PRESENTING CELLS o Macrophages  Function as mononuclear phagocytes in inflammation  Process ingested antigens and present them to immune effector cells in association with MHC molecules on their membranes  secrete cytokines such as IL-1 for modulation of inflammatory processes  directly lyse tumor cells in their role of immunosurveillance  they are effector cells for some types of cell-mediated immunity (e.g. Delayed hypersensitivity) o Dendritic cells  Found in lymphoid tissues and in interstitial regions of other organs o Langerhans cells  Found in epidermis o have extensive dendritic cytoplasmic processes that are rich in MHC class II molecules o very efficient at presenting antigens o considered to be extremely important in that task within the entire immune system

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NATURAL KILLER CELLS o constitute 10% to 15% of lymphocytes in the peripheral blood. o are neither T cells nor B cells and were formerly called null cells. o have the function of lysing other cells without prior sensitization o can attack tumor cells, cells infected with viruses o they form the initial defense against aberrant cells o characterized by the surface markers CD16 and CD56, which are commonly used for their identification  CD16 - is the Fc receptor for IgG  NK cells are able to lyse selectively those cells that are coated with antibodies o also secrete cytokines such as IFN-γ. o NK cells are recognizable on examination of standard stained blood smears as large granular lymphocytes

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NONLYMPHOID CELLS o are not genetically programmed to recognize specific antigens or to interact with lymphoid cells in the induction of an immune response. o they are effectors of immune reactions that are triggered by various factors.

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NEUTROPHILS AND EOSINOPHILS o Neutrophils  are drawn to regions of inflammation by chemoattractants such as IL-8  then release from their granules toxic substances and enzymes that digest cellular structures indiscriminately  also ingest cellular debris, as do eosinophils, and remove it from tissue sites.

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BASOPHILS AND MAST CELLS o Basophils (and their counterparts in tissues, the mast cells)  have on their surfaces high-affinity Fc receptors that bind circulating IgE  Uptake of IgE onto the membranes of basophils apparently is not antigen dependent; instead, it is driven by mass action between the amount of total IgE and the available basophils  When the antigen (or allergen) comes into contact with basophil surface-bound IgE that recognizes it  those basophils become activated and release substances such as histamine, which mediate some hypersensitivity reactions  basophil specificity is directed by the particular IgE that is bound to its surface from the blood...