SYS-P-05.01-DISEASES-OF-IMMUNE SYSTEM.pdf

P.05.01 DISEASES OF IMMUNE SYSTEM Capable of recognizing microbial and nonmicrobial substances Develops later, after exposure to microbes and other foreign Arlene L. Qu...

P.05.01 DISEASES OF IMMUNE SYSTEM Capable of recognizing microbial and nonmicrobial substances Develops later, after exposure to microbes and other foreign Arlene L. Quitasol, MD, FPSP | September 12, 2024 substances OUTLINE More powerful than innate immunity in combating infections I. NORMAL IMMUNE D. TISSUES OF THE RESPONSE IMMUNE SYSTEM II. INNATE IMMUNITY A. IMMUNITY E. MAJOR A. COMPONENTS OF INNATE IMMUNITY II. INNATE IMMUNITY HISTOCOMPATIBILITY Epithelial barriers that block entry of microbes A. COMPONENTS OF (MHC) MOLECULES: THE Phagocytic cells (mainly neutrophils and macrophages) INNATE IMMUNITY PEPTIDE DISPLAY Dendritic cells, natural killer (NK) cells Several plasma proteins, including the proteins of the complement B. CELLULAR RECEPTORS SYSTEM OF ADAPTIVE system FOR MICROBES, IMMUNITY PRODUCES OF IV. HYPERSENSITIVITY: A.1 Epithelia of the skin and gastrointestinal and DAMAGED CELLS, AND IMMUNOLOGICALLY respiratory tracts FOREIGN SUBSTANCES MEDIATED TISSUE INJURY Mechanical barriers to the entry of microbes from the external C. CLASSES OF PATTERN A. HYPERSENSITIVITY environment OF RECOGNITION B. IMPORTANT GENERAL Also, profuce antimicrobial molecules such as defensins, and III. ADAPTIVE IMMUNITY FEATURES OF lymphocytes located in the epithelia combat microbes at these sites A. HUMORAL IMMUNITY HYPERSENSITIVITY A.2 Monocytes and neutrophils B. CELLS OF THE IMMUNE DISORDERS SYSTEM C. CLASSIFICATIONS OF Phagocytes in the blood that can rapidly be recruited to any site of infection C. LYMPHOCYTE DISEASES Macrophages: monocytes that enter the tissues and mature DIVERSITY A.3 Dendritic cells I. NORMAL IMMUNE RESPONSE Specialized cell population present in epithelia, lymphoid organs, A. IMMUNITY and most tissues Protection from infectious pathogens Antigen presenting function – capture protein antigens and display Mechanisms of defesnse against microbes fall into two broad peptides for recognition by T lymphocytes categories Endowed with a rich collection of receptors that sense microbes and cell damage and stimulate the secretion of cytokines, mediators that play critical roles in inflammation and anti-viral defense A.4 Natural killer cells Provide early protection against many viruses and intracellular bacteria A.5 Mast cells Capable of producing many mediators of inflammation A.6 Soluble proteins Figure 1. The principal mechanisms of innate immunity and adaptive Complement system immunity. Lifted from lecturer ppt Plasma proteins that are activated by microbes using the alternative and lectin pathways in innate immune responses A.1 Innate Immunity In adaptive immunity activated by antibodies using the classical Also called NATURAL, or NATIVE IMMUNITY pathway Mechanisms that are ready to react to infections even before they Mannose-binding lectin and C-reactive protein occur Both of which coat microbes and promote phagocytosis Evolved to specifically recognize and combat microbes Lung surfactant First line of defense Provides protection against inhaled microbes Mediated by cells and molecules that recognize products of microbes and dead cells and induce rapid protective host reactions B. CELLULAR RECEPTORS FOR MICROBES, PRODUCES OF Always present, ready to provide defense against microbes and to DAMAGED CELLS, AND FOREIGN SUBSTANCES eliminate damaged cells B.1 Pathogen-Associated Molecular Patterns Receptors and components have evolved to serve these purposes Microbial components that are shared among related microbes and Function in stages are often essential for infectivity Recognition of microbes and damaged cells Cannot be mutated to allow the microbes to evade the defense Activation of various mechanisms mechanisms Elimination of the unwanted substances B.2 Damage-Associated Molecular Patterns A.2 Adaptive Immunity Molecules released by injured and necrotic cells Also called AQUIRED, or SPECIFIC IMMUNITY Consists of mechanisms that are stimulated by (“adapt to”) microbes NOTE TAKERS: CALA MED202 SEM1 Page 1 of 9 Last date edited: 07/00/2024 | Editor / QC: Nichole Euki ｡ﾟ ┈୨♡୧┈ ﾟ｡  B.3 Pattern Recognition Receptors Mediated by B (bone marrow-derived) lymphocytes and their Cellular receptors that recognize these molecules secreted products, ANTIBODIES (also called Located in all the cellular compartments where microbes may be IMMUNOGLOBULINS, Ig) present: Both classes of lymphocytes express highly specific receptors for a Plasma membrane recetors – detect extracellular microbes wide variety of substances, which are called ANTIGENS Endosomal receptors – detect ingested microbes Cystolic receptors – detect microbes in the cytoplasm B. CELLS OF THE IMMUNE SYSTEM B.1 T and B Lymphocytes C. CLASSES OF PATTERN RECOGNITION RECEPTORS Heterogeneous and specialized in molecular properties and C.1 Toll-Like Receptors functions Best known of the pattern recognition receptors Not fixed in particular tissues but constantly circulate among Present in the plasme membrane and endosomal vesicles lymphoid and other tissues cia the blood and the lymphatic Signal by a common pathway that cultimates in the activation of two circulation sets of transcription factors: This feature promotes IMMUNE SURVEILLANCE by allowing NF-kB lymphocytes to home to any site of infection o Stimulates the synthesis and secretion of cytokines and the expression of adhesion molecules, both of which are critical for B.2 Naïve (Immunologically inexperienced) the recruitment and activation of leukocytes Mature lymphocytes that have not encountered the antigen for INTERFERON REGULATORY FACTORS (IRFs) which they are specific o Stimulates the production of the antiviral cytokines, type I interferons B.3 Effector cells Lymphocytes after are activated by recognication of antigens and C.2 NOD-Like Receptors and Inflammasomes other signals NOD-Like Receptors Perform the function of eliminating microbes Cystolic receptors Recognize a wide variety of substances, including products of B.4 Memory cells necrotic cells (e.g., uric acid and released ATP), ion disturbances Live in a state of heightened awareness and are able to react rapidly (e.g., loss of K+), and some microbial products and strongly to combat the microbe in case it returns Inflammasomes Cystolic multiprotein complex in which NOD-like receptors signal C. LYMPHOCYTE DIVERSITY Activates an enzyme (caspase-1) that cleaves a precursor form of Clonal Selection the cytokine interleukin-1 (IL-1) to generate the biologically active Lymphocytes express specific receptors for antigens and mature form into functionally competent cells before exposure to antigen Autoinflammatory Syndromes Lymphocytes of the same specificity are said to constitute a o Gain-of-function mutations in one of the NLRs result in periodic CLONE; one clone express identical antigen receptors fever syndromes Antigen receptor diversity is generated by somatic recombination of o Respond very well to treatment with IL-1 antagonists the genes that encode the receptor proteins Enzyme in developing lymphocytes that mediates recombination of C.3 Other Receptors for Microbial Products these gene segments is the product of RAG-1 and RAG-2 C-Type Lectine Receptors (CLRs) (recombination activating genes); inherited defects in RAG proteins Expressed on the plasma membrane of macrophages and result in failure to generate mature lymphocytes dendritic cells Germline antigen receptor genes are present in all cells in the body, Detect fungal glycans and elicit inflammatory reactions to fungi but only T and B cells contain recombined (also called rearranged) RIG-Like Lectine Receptors (RLRs) antigen receptors genes (the T-cell receptor [TCR]) in T cells and Located in the cytosol of most cell types immunoglobulin [Ig] in B cells Detect nucleic acids of viruses that replicate in the cytoplasm of Presence of recombined TCR or Ig genes, demostrated by molecular infected cells analysis, is a marker of T- or B-lineage cells Stimulate the production of antiviral cytokines Each T or B cell and its clonal progeny have a unique DNA G Protein-Coupled Receptors rearrangement, it is possible to distinguish polyclonal Found in neutrophils, macrophages, and most other types of (nonneoplastic) lymphocyte proliferations from monoclonal leukocytes (neoplastic) lymphoid tumor Recognize short bacterial peptides containing N-formulmethionyl Analysis of antigen receptor gene rearrangements is a valuable residues assay for detecting tumors derived from lymphocytes Enables neutrophils to detect bacterial proteins and stimular chemotactic responses of the cells C.1 T Lymphocytes Mannose Receptors Three major populations of T cells, which serve distinct functios Recognize microbial subtances HELPER T LYMPHOCYTES Induce phagocytosis of the microbes o Stimulates B lymphocytes to make antibodies and activate other leukocytes (e.g., phagocytes) to destroy microbes III. ADAPTIVE IMMUNITY CYTOTOXIC T LYMPHOCYTES (CTLs) Consists of lymphocytes and their products, including antibodies o Kill infected cells Two types of adaptive immunity: REGULATORY T LYMPHOCYTES o Limit immune responses and prevent reactions against self A. HUMORAL IMMUNITY antigens Protects against extracellular microbes and their toxins NOTE TAKERS: CALA MED202 SEM1 Page 2 of 9 Last date edited: 07/00/2024 | Editor / QC: Nichole Euki ｡ﾟ ┈୨♡୧┈ ﾟ｡  Develop in the thymus from precursors that arise from T cells express several other proteins that assist the TCR complex in hematopoietic stem cells functional responses Mature T Lymphocytes CD4 Found in the blood, constitute 60% to 70% of lymphocytes, and CD8 in T-cell zones of peripheral lymphoid organs CD28 Each T cell recognizes a specific cell0bound antigen by means of an Integrins antigen-specific TCR Aprroximately 60% of mature T cells are CD4+ and about 30% are Approximately 95% of T cells, the TCR consists of a disulfide- CD8+ linkedheterodimer made up an alpha and beta polypeptide chain, Most CD4+ T cells function as cytokine-secreting helper cells that each having a variable (antigen-binding) region and a constant assist macrophages and B lymphocytes to combat infections region Most CD8+ cells function as cytotoxic (killer) T lymphocytes (CTLs) Alpha beta TCR recognized peptide antigens that are presented by to destroy host cells harboring microbes major histocompatibility complex (MHC) molecules on the surfaces During antigen recognition, CD4 molecules bind to class II MHC of antigen-presenting cells molecules that are displaying antigen and CD8 molecules bind to By limiting the specificity of T cells for peptides displayed by cell class I MHC molecules surface MHC molecules, called MHC RESTRICTION, the immune system ensures that T cells see only cell-associated antigens (e.g., C.2 B Lymphocytes those derived from microbes in cells or from proteins ingested by Only cells in the body that is capable of producing antibody cells) molecules, mediators of humoral immunity Each TCR is noncovalently linked to six polypeptide chains, which Develop from precursors in the bone marrow form the CD3 complex and the zeta chain dimer Mature B cells constitute 10% to 20% of the circulating peripheral CD3 and zeta proteins lymphocyte population and are also present in peripheral lymphoid Invariant (i.e., identical) in all T cells tissues Involved in the transduction of signals into the T cell that are Recognize antigen via the B-cell antigen receptor complex triggered by binding of antigen to the TCR Membrane-bound antibodies of the IgM and IgD isotypes, present Together with the TCR, these proteins form the TCR complex on the surface of all mature, naïve B cells, are the antigen-binding component of the B-cell receptor complex After stimulation by antigen and other signals, B cells develop into PLASMA CELLS, protein factories for antibodies PLASMABLAST Antibody-secreting cells detected in human peripheral blood B-cell antigen receptor complex contains a heterodimer of two invariant proteins called IgA and IgB Similar to the CD3 and zeta proteins of the TCR complex, IgA (CD79a) and IgB (CD79b) are essential for signal transduction via the antigen receptor Also express several other molecules that are essential for their responses TYPE 2 COMPLEMENT RECEPTOR (CR2, or CD21) o Recognizes complement products generated during innate immune responses to microbes o Also used by the Epstein-Barr virus (EBV) as a receptor to enter and infect B cells CD40, which receives signals from helper T cells C.3 Dendritic cells Interdigitating dendritic cells Most important antigen-presenting cells for initiating T-cell responses against protein antigens Cells have numerous fine cytoplasmic processes that resemble Figure 2. The T-cell receptor (TCR) complex and other molecules dendrites, from which they derive their name involved in T-cell activation. Lifted from lecturer ppt Several features of dendritic cells account for their key role in antigen presentation The TCR heterodimer, consisting of an alpha and a beta chain, recognizes antigen (in the form of peptide-MHC complexes expressed on antigen-presenting cells, or APCs), and the linked CD3 Located at the right place to capture antigens— under epithelia and complex and zeta chains initiate activating signals. CD4 and CD28 are also involved in T-cell in the interstitia of all tissues, where antigens may be produced activation. (Not that some T cells express CD8 and not CD; these molecules serve analogous LANGERHANS CELLS roles). The sizes of the molecules are not drawn to scale. MHC, Major histocompatibility complex. Immature dendritic cells within the epidermis Express many receptors for capturing and responding to microbes A small population of mature T cells expresses another type of TCR Recreuited to the T-cell zones of lymphoid organs, where they are composed of gamma and delta polypeptide chains ideally located to present antigen to T0cells Gamma-delta TCR recognizes peptides, lipid, and small molecules, Express high levels of MHC and other molecules needed for without a requirement for display MHC proteins presenting antigens to and activating T cells Gamma-delta T cells tend to aggregate at apithelial surfaces, such FOLLICULAR DENDRITIC CELL as the skin and mucosa of the gastrointestinal and urogenital tracts, Second type of cell with dendritic morphology suggesting that these cells are sentinels that protect against Present in the germinal centers of lymphoid follicles in the spleen microbes that try to enter through epithelia and lymph nodes NOTE TAKERS: CALA MED202 SEM1 Page 3 of 9 Last date edited: 07/00/2024 | Editor / QC: Nichole Euki ｡ﾟ ┈୨♡୧┈ ﾟ｡  Bear Fc receptors for IgG and receptors for C3b and can trap If the B cells in a follicle have recently responded to an antigen, antigen bound to antibodies or complement proteins this follicle may contain a central region called the GERMINAL Play a role in humoral immune responses by presenting antigens CENTER to B cells and selecting the B cells that have the highest affinity T lymphocytes are concentrated in the paracortex, adjacent to the for the antigen, thus improving the quality of the antibody follicles produced Follicles contain the follicular dendritic cells that are involved in the activation of B cells, and the paracortex contains the dendritic C.4 Macrophages cells that present antigens to T lymphocytes Part of the mononuclear phagocyte system Spleen Function as antigen-presenting cells in T-cell activation Abdominal organ that serves the role in immune responses to Key effector cells in certain forms of cell-mediated immunity, the bloodborne antigen reaction that serves to eliminate intracellular microbe Blood entering the spleen flows through a network of sinusoids In this type of response, T-cells activate macrophages and Bloodborne antigens are trapped by dendritic cells and enhance their ability to kill ingested microbes macrophages in spleen Participate in the effector phase of humoral immunity T lymphocytes are concentrated in periarteriolar lymphoid sheaths surrounding small arterioles C.5 Natural Killer Cells B cells reside in the follicles Cutaneous and Mucosal Lymphoid Systems Function is to destroy irreversibly stressed and abnormal cells, such Located under the epithelia of the skin and the gastrointestinal as virus-infected cells and tumor cells and respiratory tracts Make up approximately 5% to 10% of peripheral blood lymphocytes Responds to antigens that enter through breaches in the Do not express TCRs or Ig epithelium Morphologically Pharyngeal tonsils and Peyer’s patches of the intestine are two Somewhat larger than small lymphocytes anatomically defined mucosal lymphoid tissues Contain abundant azurophilic granules Endowed with the ability to kill a variety of virus-infected cells and E. MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) tumor cells, without prior exposure to or activation by these microbes or tumors MOLECULES: THE PEPTIDE DISPLAY SYSTEM OF ADAPTIVE Two cell surface molecules, CD16 and CD56, are commonly used to IMMUNITY identify NK cells Function: display peptide fragments of protein antigens for CD16 recognition by antigen specific T cells o Fc receptor for IgG In humans the MHC molecules are called HUMAN LEUKOCYTE o Confers on NK cells the ability to lyse IgG-coated target cells ANTIGENS (HLA) because they were initially detected on ▪ This phenomenon is known as ANTIBODY-DEPENDENT leukocytes by the binding of antibodies CELL-MEDIATED CYTOTOXICITY (ADCC) Genes clustered on a small segment of chromosome 6 NKG2D FAMILY o Activating receptor o Receptors recognize surface molecules that are induced by various kinds of stress, such as infection and DNA damage NK cell inhibitory receptors recognize self clas I MHC molecules, which are expressed on all healthy cells NK cells secrete cytokines such as interferon-y (IFN-y), which activates macrophages to destroy ingested microbes, and thus NK cells provide early defense against intracellular microbial infections D. TISSUES OF THE IMMUNE SYSTEM D.1 Generative Lymphoid Organs AKA PRIMARY, or CENTRAL LYMPHOID ORGANS T and B lymphocytes mature and become competent to respond to antigens Thymus – where T cells develop Bone marrow – site of production of all blood cells and where B lymphocytes mature D.2 Peripheral Lymphoid Organs Figure 3. Major Histocompatibility Complex (MHC) Molecules. Lifted AKA SECONDARY LYMPHOID ORGANS from lecturer ppt Within the peripheral lymphoid organs, T lymphocytes and B lymphocytes are segregated into different regions E.1 Class I MHC Molecules Lymph nodes Expressed on all nucleated cells and platelets Nodular aggregates of lymphod tissues located along lymphatic Heterodimers consisting of a polymorphic alpha, or heacy, chain channels throughout the body (44-kD) linked non covalently to a smaller (12-kD) nonpolymorphic Antigens of microbes that enter through epithelia or colonize protein called B2-MACROGLOBULIN tissues become concentrated in draining lymph nodes Alpha chains are encoded by three genes, designated HLA-A, HLA- B cells are concentrated in disccrete structures, called B, and HLA-C, that lie close to one another in the MHC locus FOLLICLES, located around the periphery, or CORTEX, of each node NOTE TAKERS: CALA MED202 SEM1 Page 4 of 9 Last date edited: 07/00/2024 | Editor / QC: Nichole Euki ｡ﾟ ┈୨♡୧┈ ﾟ｡  Display peptides that are derived from proteins, such as viral and Rapid immunologic reactions occuring in a previously sensitized tumor antigens, that are located in the cytoplasm and usually individual that is triggered by the binding of an antigen to IgE produced in the cell antibody on the surface of mast cells Class I-associated peptides are recognized by CD8+ T lymphocutes Reactions are often called ALLERGY, and the antigens that elicit CD8+ T cells are said to be class I MHC-restricted them are ALLERGENS Because one of the important functions of CD8+ CTLs is to eliminate Systemic disorder or as a local reaction ciruses, which may infect any nucleated cell, and tumors, which may Local reactions are diverse and vary depending on the portal of entry arise from any nucleated cell, it makes good sense that all nucleated of the allergen cells express class I HLA molecules and can be surveyed CD8+ T Form of localized cutaneous rash or blisters (skin allergy, hives) cells Nasal and conjunctival discharge (allergic rhinitis and conjunctivitis) E.2 Class II MHC Molecules Hay fever Encoded in a region called HLA-D, which has three subregions: Bronchial asthma HLA-DP, HLA-DQ, and HLA-DR Allergic gastroenteritis (food allergy) Heterodimer consisting of a noncovalently associated alpha and beta Two well-defined phases chain, both polymorphic IMMEDIATE REACTION Present antigens that are internalized into vesicles, and are typically o Characterized by vasodilation, vascular leakage, and depending derived from extracellular microbes and soluble proteins on the location, smooth muscle spasm or glandular secretions Class II beta 2 dkmain has a binding site for CD4, and therefore, the o Usually become evident within minutes after exposure to an class II-peptide complex is recognized by CD4+ T cells, which allergen and tend to subside in a few hours function as helper cells LATE-PHASE REACTION Because CD4+ T cells can recognize antigens only in the context of o 2 or 24 hours later without additional exposure to antigen and self class II molecules, they are referred to as class II MHC restricted may last for several days Mainly expressed on cells that present ingested antigens o Characterized by infiltration of tissues with eosinophils, (macrophages, B lymphocytes, and dendritic cells) neutrophils, basophils, monocytes, and CD4+ T cells, as well as tissue destruction, typically in the form of mucosal epithelial cell IV. HYPERSENSITIVITY: IMMUNOLOGICALLY MEDIATED damage TISSUE INJURY They are induced by environmental antigens (allergens) that stimulate strong TH2 responses and IgE production in genetically A. HYPERSENSITIVITY susceptible individuals Injurious immune reactions IgE coats mast cells by binding to FCℇ receptors; reexposure to the Term arose from the idea that individuals who have been previously allergen leads to cross-linking of the IgE and FCℇRI, activation of exposed to an antigen manifest detectable reaction to that antigen mast cells, and release of mediators and therefore said to be SENSITIZED Principal mediators are histamine, proteases, and other granule Excessive or harmful reaction to antigen contents, prostaglandines and leukotrienes, and cytokines Mediators are responsible for the immediate vascular and smooth B. IMPORTANT GENERAL FEATURES OF HYPERSENSITIVITY muscle reactions and the late-phase reaction (inflammation) DISORDERS Clinical manifestations may be local or systemic, and range from Hypersensitivity reactions can be elicited by exogenous mildly annoying rhinitis to fatal anaphylaxis environmental antigens (microbial and nonmicrobial) or endogenous self antigens Some of the most common reactions to environmental antigens cause the group of diseases known as ALLERGY Immune responses against self, or autologous antigens, result in AUTOIMMUNE DISEASES Hypersensitivity usually results from an imbalance between the effector mechanism of immune responses and the control mechanisms that serve to normally limit such responses Development of hypersensitivity diseases (both allergic and autoimmune (is often associated with theinheritance of particular susceptibility genes Mechanisms of tissue injury in hypersensitivity reactions are the same as the effector mechanisms of defense against infectious Table 1. Examples of Disorders Caused by Immediate pathogens Hypersensitivitiy. Lifted from lecturer ppt C. CLASSIFICATIONS OF DISEASES C.2 Antibody-Mediated (Type II) Hypersensitivity Classified on the basis of the immunologic mechanism that mediates Secreted IgG and IgM antibodies injure cells by promoting their the disease phagocytosis or lysis and injure tissues by inducing inflammation Antibodies may also interfere with cellular functions and cause C.1 Immediate (Type I) Hypersensitivity disease without tissue injury Injury caused by TH2 cells, IgE antibodies, and mast cells and other Antibodies that react with antigens present on cell surfaces or in the leukocytes extracellular matric cause disease by destroyingthese cells, Mast cells release mediators that act on vessels and smooth muscle triggering inflammation, or interfering with normal functions and proinflammatory cytokines that recruit inflammatory cells Antibodies may be specific for normal cell or tissue antigens (autoantibodies) or for exogenous antigens, such as chemical or microbial proteins, that bind to a cell surface or tissue matrix NOTE TAKERS: CALA MED202 SEM1 Page 5 of 9 Last date edited: 07/00/2024 | Editor / QC: Nichole Euki ｡ﾟ ┈୨♡୧┈ ﾟ｡  Table 3. Examples of Immune Complex-Mediated Diseases. Lifted from lecturer ppt Morphology: Principal morphologic manifestation of immune complex injury is acute vasculitis, associated with necrosis of the vessel wall and intense neutrophilic infiltration Necrotic tissue and deposits of immune complexes, complement, and plasma protein appear as smudgy eosinophilic area of tissue destruction, an appearance termed fibrinoid necrosis When deposited in the kidney, the complexes can be seen on immunofluorescence microscopy as glandular lumpy deposits of immunoglobulin and complement and on electron microscopy as electron-dense deposits along the glomerular basement membrane C.4 Cell-Mediated Immune Disorders (Type IV Figure 4. Mechanisms of antibody-mediated Injury. Lifted from Hypersensitivity) lecturer ppt Sensitized T lymphocytes (TH1 and TH17 cells and CTLs) are the A. Opsonization of cells by antibodies and complement components and ingestion by cause of the tissue injury phagocytes. B. Inflammation induced by antibody binding to FC receptors of leukocytes and by TH2 cells infuce lesions that are part of immediate hypersensitivity complement breakdown products. C. Antireceptor antibodies disturb the normal function of reactions and are not considered a form of type IV hypersensitivity receptors. Antibodies to the acetylcholine (Ach) receptor impair neuromuscular transmission in myasthenia gravis, and antibodies against the thyroid-stimulating hormone (TSH) receptor Caused by inflammation resulting from cytokines produced by CD4+ activate thyroid cells in Graves disease. T cells and cells killing by CD8+ T cells CD4+ T cell-mediated hypersensitivityinduced by environmental and self antigens is the cause of many chronic inflammatory diseases, including autoimmune diseases CD8+ cells may also be involved in some of these autoimmune diseases and may be the dominant effector cells in certain reactions, especially those that follow viral infection Table 2. Examples of Antibody-Mediated Diseases (Type II Hypersensitivity). Lifted from lecturer ppt Table 4. Examples of Cell-Mediated Diseases. Lifted from lecturer ppt C.3 Immune Complex-Mediated Disorder (Type III Hypersensitivity) IgG and IgM antibodies bind antigens usually in the circulation, and the antigen-antibody complexes deposit in tissues and induce inflammation Leukocytes that are recruited (neutrophils and monocytes) produce tissue damage by release of lysosomal enzymes and generation of toxic free radicals Antigen-antibody complexes produce tissue damage mainly by eliciting inflammation at the sites of deposition Table 5. Mechanisms of Hypersensitivity Reactions. Lifted from Pathologic reactions are usually initiated when antigen combines lecturer ppt with antibody in the circulation, creating immune complexes that typically deposit in vessel walls Complexes may be formed at sites where antigen has been “planted” previously (called in situ immune complexes) Immune complex-mediated diseases tend be systemic, but often preferentially involve the kidney (glomerulonephritis), joints (arthritis), and small blood vessels (vasculitis), all of which are common sites of immune complex deposition NOTE TAKERS: CALA MED202 SEM1 Page 6 of 9 Last date edited: 07/00/2024 | Editor / QC: Nichole Euki ｡ﾟ ┈୨♡୧┈ ﾟ｡  RECALL CHECK POINT! 1. These are the most important antigen-presenting cells for initiating T-cell responses against protein antigens A. Mast Cells B. Dendritic Cells C. Macrophages D. NK Cells 2. Two leukocytes that are recruited produce tissue damage by release of lysosomal enzymes and generation of toxic References: free radicals Dr. Quitasol’s ppt presentation A. Eosinophils and Mast Cells B. Neutrophils and Eosinophils Legend: C. Neutrophils and Monocytes D. Monocytes and Mast Cells COLOR SCHEME CODES 3. T/F: Type II Hypersensitivity: HLA-D Black Exactly from lecture presented #262626 Type I Hypersensitivity: HLA-A, HLA-B, HLA-C (PowerPoint slide) 4. Matching Type: Red Important concepts #C00000 A. Type I 1. Antibody Mediated Pink Clinical correlations or significance #CF6E8A Hypersesitivity Blue Explanation of doctor not found in slide #0070C0 B. Type II 2. Immune Complex- Hypersesitivity Mediated Disorder Green From old transes but not presented in #549E39 class C. Type III 3. Cell-Mediated Hypersesitivity Immune Violet Additional info from book #7030A0 D. Type IV 4. Immediate Orange Reading assignment answers #E36C0A Hypersesitivity 5. This protein receives signals from helper T cells A. Integrin B. CD 8 C. CD 40 D. CD 28 E. CD 4 6. Enumerate: Three major populations of T cells ______________________________________ ______________________________________ ______________________________________ 7. Identification: Term arose from the idea that individuals who have been previously exposed to an antigen manifest detectable reaction to that antigen. ____________________________ 8. Peripheral Lymphoid Organs are also known as: A. Primary Lymphoid Organs B. Tertiary Lymphoid Organs C. Secondary Lymphoid Organs D. Central Lymphoid Organs 9. A phase in Type I Hypersensitivity reactions that is characterized by vasodilation, vascular leakage, and depending on the location, smooth muscle spasm or glandular secretions A. Immediate Phase B. Primary Phase C. Late-Phase D. Secondary Phase 10. Enumerate: (2) Primary Lymphoid Organs ________________________ ________________________ NOTE TAKERS: CALA MED202 SEM1 Page 7 of 9 Last date edited: 07/00/2024 | Editor / QC: Nichole Euki ｡ﾟ ┈୨♡୧┈ ﾟ｡  NOTE TAKERS: CALA MED202 SEM1 Page 8 of 9 Last date edited: 07/00/2024 | Editor / QC: Nichole Euki ｡ﾟ ┈୨♡୧┈ ﾟ｡  NOTE TAKERS: CALA MED202 SEM1 Page 9 of 9 Last date edited: 07/00/2024 | Editor / QC: Nichole Euki ｡ﾟ ┈୨♡୧┈ ﾟ｡