Immunology Handouts PDF

IMMUNOLOGY Prepared by: Laodicea A. Sy, RMT Immunology – can be defined as the study of a host’s reactions when foreign substances are introduced into the body. A foreign substance that induces such an...

IMMUNOLOGY Prepared by: Laodicea A. Sy, RMT Immunology – can be defined as the study of a host’s reactions when foreign substances are introduced into the body. A foreign substance that induces such an immune response is called an antigen. Immunology as a science has its roots in the study of immunity. Immunity – the condition of being resistant to infection Facts in Immunology and Serology: ▪ Emil von Behring - 1901 - Serum antitoxins ▪ Robert Koch - 1905 - Cellular immunity ▪ Elie Metchnikoff - 1908 - Phagocytosis ▪ Paul Ehrlich - 1908 - Immunity - ▪ Charles Richet - - Anaphylaxis - - 1913 - ▪ Jules Bordet - - 1919 - Complement ▪ Karl Landsteiner - - 1930 - Human blood group antigens ▪ Macfarlane Burnet, Peter Medawar - 1960 - Discovery of tolerance ▪ Gerald Edelman, Rodney Porter - 1972 - Structure of antibodies ▪ Rosalyn Yalow - 1977 - Radioimmunoassay ▪ George Snell, Jean Dausset & Baruj Benacerraf - 1980 - Major histocompatibility complex ▪ Niels Jerne - 1984 - Immunoregulation - ▪ George Koehler, Cesar Milstein - Major histocompatibility complex ▪ Susumu Tonegawa - 1987 - Antibody diversity ▪ E. Donnall Thomas, Joseph Murray - 1991 - Transplantation ▪ Rolf Zinkernage - 1996 - Specificity of the cell mediated immune defense “dual recognition ▪ Peter Doherty - 1996 - Novel Prize Winner in Immunology - Specificity of the cell mediated immune defense “dual recognition” ▪ Stanley Prusiner - 1997 - Novel Prize Winner in Immunology - Prions (a new biological principle of infection) ▪ Guntel Blobel - 1999 - Novel Prize Winner in Immunology - Signal transduction DIVISION OF IMMUNOLOGY DEFINITIONS Immune system = cells, tissues, and molecules that mediate resistance to infections Immunology = study of structure and function of the immune system Immunity = resistance of a host to pathogens and their toxic effects Immune response = collective and coordinated response to the introduction of foreign substances in an individual mediated by the cells and molecules of the immune system. IMMUNITY NATURAL ACQUIRED *Physical Barriers *Humoral Immunity *Susceptibility vs. - B cells, plasma cells, Nonsusceptibility memory cells *Inflammation - Antibodies *Phagocytosis *Cell-mediated Immunity - chemotaxis vs opsonization - T cells, NK, LAK, *Nonspecific Plasma Proteins K cells - Lymphokines Lymphoid Organs 1. Primary BM Thymus 2. Secondary Spleen Lymph nodes Tonsils Appendix Peyer’s Patches Mucosal-associated lymphoid tissues (MALT)  Branches of Immunity Natural/innate - present from birth - non-adaptive/ non-specific Acquired/adaptive/specific - produces anamnestic response Natural Immunity A. First line of defense: Anatomical Barriers: 1. skin and mucous membrane – skin pH 2. Ciliary action (respiratory tract) Humoral Factors: 1. Lysozyme – antibacterial; cleaves in cell wall of class of bacteria 2. Stomach acidity 3. Pepsin – digest bacterial surface proteins 4. Lactoferrin – comes from Neutrophil - binds iron which is essential for microbial growth B. Second line of defense: Cellular Factors What are the cells involve in the Second line of Defense in Natural Immunity? Cells involve in Natural Immunity i. Neutrophils (PMN) – responds to bacterial infections - Phagocytosis and killing of foreign material of infectious agents. iv. APC – Antigen Presenting Cells 1. Dendritic cells – phagocytose antigen and present it to T-helper 2. B cells 3. Macrophages –tissue monocyte * Monocyte and Macrophage are predominant in Chronic inflammation  Alveolar Macrophages Histiocytes Kupffer cells Macrophages according to tissue location Microglial cells v. Eosinophil – increases in an allergic reaction or in response to many parasitic infections. - has MBP (Major basic protein) for role in allergic reactions by lessening hypersensitivity rxn. through release of an amine oxidase, which neutralizes histamine. vi. Basophil – responds to allergic or hypersensitivity reactions - histamine mediates in some hypersensitivity rxn. *Mast cell – is tissue based Basophil BRANCHES OF IMMUNITY ▪ May be NATURAL or ACQUIRED (the ability to resist infection) ▪ Resistance to disease or poison ▪ Protection I. NATURAL/INNATE/ INHERENT/NONSPECIFIC IMMUNITY - non-specific; limited to its response. A. Physical Barriers - Such as skin and mucous membrane. - coughing, sneezing and vomiting are physiologic responses of nonspecific immunity. - B. Genetically controlled SUSCEPTIBILITY and NONSUSCEPTIBILITY to certain diseases. - Ex. Type A – susceptible to have Pernicious Anemia - C. INFLAMMATION - - A nonspecific exaggerated physiologic response which involves a vascular and a cellular response by phagocytic cells to infection/ injury 2 Phases of Inflammation: 1. Vascular Response a. Localized dilation of blood vessels to increase blood flow in the area of injury (Hyperemia) b. Plasma leaks between the spaces of endothelial cells into the tissue (Exudate Formation)  2. Cellular Response a. Pavementation of the epithelium (wbcs line walls of blood vessels) b. Diapedesis - Migration of cells into tissues from the circulation - Squeezing out of wbcs from endothelial spaces c. Emigration - In the initial stage, Neutrophils predominate - 4 hrs. after, Monocytes migrate to the site of injury d. Repair and Resolution D. PHAGOCYTOSIS - Engulfment of cells or particulate matter of Leukocytes (WBC). - Neutrophil, Eosinophil, Macrophages Steps in Phagocytosis: 1. Initiation – initiated through tissue damage 2. Chemotaxis – cell movement in a certain direction under the stimulation of chemical substance. 2 Kinds of Chemotaxis: 1. Positive – movement toward the stimulus 2. Negative – movement away from the stimulus Ex. Of Chemotaxins – C5a, C5b, C6,C7 ▪ Opsonization – coating of antibody or complement to facilitate phagocytosis. Ex. C3b, C4b, C5b, fibronectin, Leukotrienes, Immunoglobulins 3. Engulfment - Achieved through amoeboid motion. - Final structure is called Vacuole or Phagosome. 4. Degranulation and Digestion E. NONSPECIFIC PLASMA PROTEINS 1. Natural Antibodies - Antibodies present in a host without prior contact with stimulating agents 2. Lysozyme - Enzyme found in many types of cells. - Can also be found in tears, saliva and other secretions. 3. Properdin - Serum protein that exerts bactericidal and viricidal effects in the presence of C3 and Mg. 4. Betalysin - Heat-stable cationic substance with antibacterial activity found in Serum - It is released by Platelets during coagulation 5. Complement - Nonspecific Serum Proteins that enhance the effect of antibody.  - It is activated by Ag – Ab interaction. 6. C-Reactive Protein - Acute Phase Plasma Protein which increases in response to inflammation and tissue necrosis. 7. Cytokines - Protein molecules that transmit messages between the cells - Means of communication between different cells a. Interferons – glycoproteins that have virus-nonspecific antiviral activity 3 groups of Interferons (IFN): Alpha IFN – aka Leukocyte IFN Beta IFN – aka Epithelial IFN, Fibroblast IFN, Fibroepithelial IFN, B-cell Stimulating Factor produced 2. Gamma IFN – aka Immune IFN - Produced by immunologically stimulated Lymphocytes - Immune regulation (main function) - Enhance Natural Killer Cells Ex. Lymphokine b. Tumor Necrosis Factor (TNF) - Produced mainly by Macrophages/Monocytes (Monokine) - Mediator of host response to Gram negative bacteria c. Interleukins - Means of communication between Leukocytes only. 1. Interleukin 1 (IL1) - Lymphocyte Activating Factor 2. Interleukin 2 (IL2) - T-Cell Growth Factor - Activates Cytotoxic cells, NK cells, LAK cells. 3. Interleukin 3 (IL3) - Multicolony Stimulating Factor - Stimulates hematopoietic cells 4. Interleukin 4 (IL4) - Produced by activated T cells to stimulate proliferation of B cells 5. Interleukin 5 (IL5) - B cell Growth Factor 2 - Shares functions with IL4 6. Interleukin 6 (IL6) - IFN beta 2 - Induces secretion of Ig and other plasma proteins 7. Interleukin 7 (IL7)  - Lymphopoietin 1 - Stimulates maturation of early B and T cells 8. Interleukin 8 (IL8) - Monocyte-Derived Neutrophil Chemotactic Factor - Principal inflammatory Cytokine 9. Interleukin 9 (IL9) - Stimulates proliferation of T cell and Mast cells 10. Interleukin 10 (IL10) - Inhibits Cytokine synthesis 11. Interleukin 11 (IL11) - Regulates Hematopiesis 12. Interleukin 12 (IL12) - NK Cell Stimulating Factor - Enhances activity of Cytotoxic Effector T cells II. ACQUIRED/ADAPTIVE/SPECIFIC IMMUNITY Based upon resistance acquired during life Relies on genetic events and cellular growth Responds more slowly, over few days Is specific –each cell responds to a single epitope on an antigen Has anamnestic memory –repeated exposure leads to faster, stronger response Complex, involves a network of cells: cytokines, B cells, T cells, antibodies Types of Acquired Immunity: 1. Active – result of actual infection or inoculation that causes production of antibodies a. Artificial Active _______________________________ b. Natural Active_____________________________ 2. Passive – result of transmission of Antibodies a. Artificial Passive __________________________ b. Natural Passive______________________________ Types of Immunologic Reactions: 1. Humoral (HIR) – Involves synthesis and release of Abs by B cells. - Mediated by Abs - eliminate extra-cellular microbes and their toxins 2. Cell-Mediated (CMIR) – Involves the production of sensitized T lymphocytes. - eliminate intracellular microbes that survive within phagocytes or other infected cells  ANTIGEN DEFINITIONS A. Immunogen - A substance that induces a specific immune response. B. Antigen (Ag) - A substance that reacts with the products of a specific immune response. C. Hapten - A substance that is non-immunogenic but which can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule. D. Epitope or Antigenic Determinant - That portion of an antigen that combines with the products of a specific immune response. E. Antibody (Ab) - A specific protein which is produced in response to an immunogen and which reacts with an antigen. F. Allergen – a special class of immunogen that induces hypersensitivity reactions G. Adjuvants – substances added to an immunogen to enhance immune response; stimulate the influx; increases the effectiveness size of immunogen; stimulate the influx of Macrophage and /or Lymphocytes. H. Affinity – refers to the strength of a single Antibody-Antigen interaction I. Avidity – is the strength of interactions between many different Abs in a serum against a particular Ag. ANTIGEN - Any molecular structure that when introduced is capable of antibody production. Parts of Antigen: 1. Carrier portion –responsible for the molecular weight of antigen 2. Epitope/Determinant – determines specificity of Antigen; dictates the identity of antigen; antigenic determinant 2 Properties of Antigen: 1. Immunogenicity – induction of immune response Factors that affect Immunogenicity: a. FOREIGNESS Types of Antigen as to Foreigness: i. Autologous - Found on the same individual Ex. Skin graft from an individual’s thigh to his own back ii. Isologous/Syngeneic - Found in identical twins iii. Homologous/ Allogeneic - Found within the same species but different individual Ex. BM transplant from father to son iv. Heterologous/Xenogeneic - Found between different species Ex. Kidney of Monkey transplanted to man v. Sequestered Ex. Brain and Corneal Ags which are not accessible to the ab. (if these organs are expose to Ab, immune response will occur) vi. Tissue Specific Antigens - Ag common and unique in some organs Ex. Thyroglobulin (Thyroid specific) b. SIZE c. CHEMICAL COMPLEXITY i. Proteins iv. Polypeptide ii. Polysaccharides v. Nucleic Acids and Lipids iii. Glycoproteins 2. Antigenicity/Specificity - The ability to react specifically with the Ab or cell that caused it to be produced. 2 Origins of Antigen: 1. Exogenous Ag – from outside - enter the body by inhalation, ingestion or injection. - these are taken by the APCs and degraded into small peptides. APCs then present them to helper T cells by using MHC type II molecules. 2. Endogenous Ag – generated within the cell as a: - result of normal cell metabolism, or - because of viral or intracellular pathogenic infection. - The fragments are presented along with MHC type I molecules to cytotoxic T cells. ANTIBODIES - Are glycoproteins produced by B cells - Immunoglobulins IMMUNOGLOBULIN Structure of Immunoglobulin 1. Basic Ig unit is composed of 4 polypeptide chains: 2 Identical Light chains 2 Identical Heavy chains 2. Both light and heavy chains are held together by COVALENT DISULFIDE BONDS 3. Heavy chains are interconnected by DISULFIDE LIKAGES in the HINGE region. 4. Ig has 2 terminal regions: a. Carboxyl Terminal – with constant amino acid sequence (constant region) b. Amino Terminal – with varying Ab specificity (variable region) 5. Treatment with Papain will produce 3 fragments: a. One Fc fragment – fragment crystalline;  involves in the Ig biologic function. - involves in Complement Fixation, placental transfer of Ig and serve as the binding site for cell. b. Two Fab fragments – capable of Ag binding even without the Fc but cannot agglutinate or precipitate. 6. Treatment with Pepsin results in digestion of Fc fragments, leaving 2 Fab fragments. The two Fab fragments have two Ag combining sites (Bivalent), therefore, it is capable of Ag binding, precipitation and agglutination. Domains of Immunoglobulins Variable Region – responsible for specificity; Ag binding site CH2 – binds with complement (specially C1q and initiates Complement Fixation) CH3 – responsible for cytotropic reactions involving Macrophages and Monocytes, Mast cells, Cytotoxic Killer cells and B cells. C1q – Complement activation CL – responsible for the light chain type: either Kappa or Lambda (constant light chain). Immunoglobulin Variations: 1. Isotype – variants present in all members of specie Ex. Ig class and subclass 2. Allotype – present primarily in constant region and not all variants occur in all members of a species. 3. Idiotype – variations happen at variable region an dis specific for Ab molecule. - refers to the unique antigenic determinants or AA sequences in the variable region associated with Ag binding capacity.  RIST (Radioimmunosorbent Test) - measures total IgE RAST/FAST (Radio allegro sorbent Test) - Measures the allergen specific IgE Humoral factors: 1. Immunoglobulins 2. Complement 3. Cytokines 2 Types of Adaptive Immune Response: 1. Humoral Immunity/Antibody Mediated Immunity (AMI) 2. Cell Mediated Immunity (CMI) Humoral Immunity/ Antibody Mediated Immunity (AMI) - Defense against 1. most extracellular bacterial pathogens 2. viruses that infect through the respiratory or intestinal tracts - Prevents recurrence of viral infections. - Takes part in the pathogenesis of Immediate (Types 1, 2 & 3) hypersensitivity & certain autoimmune disorders. - Acquired Immunity HUMORAL IMMUNITY B Lymphocytes - Mature B lymphocytes secrete immunoglobulins - Comprise 5-15% of lymphocytes - Possess MHC Class II molecule - Identified by CD19, CD20, CD21 (CD marker) - Developed in BM in adults and later localized in spleen and lymph nodes. Lymphocyte capping – accumulation of surface Ig into distinct foci that further blend into one agglomerate. Plasma cells – terminally differentiated B cells; can be a memory cells. Mitogen – subs. that stimulate the differentiation of B cells to plasma cells. Memory cells – recognize antigen on reexposure (function) Ab production follows a characteristic pattern consisting of : 1. Lag Phase – immediate stage following antigenic stimulus during which Ab is not detectable in the circulation. 2. Log Phase – steady rise in the titre of Abs. 3. Plateau or Steady Phase – equilibrium between Ab synthesis & its catabolism. 4. Decline Phase – catabolism exceeds production, fall in Ab titre. Cell Mediated Immunity Refers to the specific immune responses that do not involve antibodies. CMI response 1st described by Jenner in 1798. 1890 - Koch described the exaggerated cutaneous reaction of tuberculous guinea pigs to the I.D. injection of tubercle bacillus – Delayed hypersensitivity (DH). DH- skin lesions appear 48-72 hrs after administration of the Ag. T lymphocytes - They are responsible for cell-mediated immune reponses. - About 80% of total lymphocytes - This subset of lymphocyes migrate to the thymus. T cell subsets: 1. T helper/Inducer cells (TH) -MHC class II - Present glycoprotein are CD2, CD3 and CD4 - Collaborate with B cells to induced humoral immune response - Recognibze ag in association with MHC class II molecule - CD4+ 2. T suppressor cells (TS) - Present glycoproteins are CD2, CD3 and CD8 - 25-40% of peripheral T cells - CD8+ - Control and inhibit ab production by suppressing T cells or turning off B cells - Recognized ag in association with MHC class I molecule 3. T cytotoxic cells (Tc) - Express either CD4 or CD8 but most are Cd8 positive - Destroy target cells upon contact - Limited power 4. T delayed type hypersensitivity cells (TDTH) - Peripheralized lymphocytic cells and responsible for delayed type hypersensitivity reactions. - They secrete macrophage chemotaxin and macrophage migration inhibition factor (MIF). - CD4+ Non – T , Non – B lymphocytes: 1. Natural Killer cells - Kiss of death - Have the ability to destroy virally infected cells of tumor cells without prior sensitization - Are not MHC class restricted (unlike cytotoxic T cells) 2. Killer cells - Lyse target cells by an antibody-dependent cell mediated cytolysis (ADCC) ADCC - Cytotoxic response is mediated by cells in the presence of Ab. Ex. Eosinophils are very efficient mediators of ADCC against parasitic worms. 3. Lymphokine-Activated Killer (LAK) cells - Stimulated by IL2 to help lyse tumor cells Monocyte and Macrophages: 2 Main Functions: 1. Removal of particulate antigen through phagocytosis (non-specific) 2. Presentation of antigens to the lymphocytes (specific) Monocytes can also be a phagocytes Monocytes and Macrophages are also known as Antigen Presenting Cells (APC). METHODS USED TO SEPARATE MONONUCLEAR CELLS AND PMNs IN PERIPHERAL BLOOD: 1. Ficoll-Hypaque Density Gradient – most common technique for separating lymphocyte Separation is achieved by centrifugation in a special density adjusted medium. 2. FLOW CYTOMETRY – a fluorescent immunoassay FITC – dye conjugated to specific antibody and used for the analysis of cells in flow cytometry 3. Dextran sedimentation  COMPLEMENT SYSTEM - complement is a complex series of more than 30 soluble and cell-bound proteins that interact in a very specific way to enhance host defense mechanisms against foreign cells. - functions of Complement System: Activation of the immune system, Opsonization and Cell lysis. - A set of proteins that play a role in cytolytic destruction of cellular antigen by specific antibody. - A group of circulating proteins that promote inflammation and host defense. - Reaction is non-specific to the target cell - Destroyed at 56◦C for 30 minutes - Portions of the system contribute to chemotaxis, opsonization, immune adherence, anaphylatoxin formation and virus neutralization. Complement: - Chemotaxins – C5a, C5b, C6, C7 - For immune adherence – C3b - Kinin activator – C2b - Anaphylatoxins – C3a, C4a, C5a - Opsonins – C3b, C4b, C5b - For virus neutralization – C4b 3 Pathways of Activation 1. CLASSICAL PATHWAY a. C1 – RECOGNITION UNIT - trimolecular complex (C1q, C1r, c1s) held together by ca++ ions - C1q attaches to at least two Fc regions (CH2) of Igs adjacent to one another - C1s activates C4 b. C4 – FIRST ACTIVATION UNIT - cleaved into C4a and C4b (C4a – anaphylatoxin; C4b – attaches to the cell membrane - C1s interaction with C4 activates C2 c. C2 – SECOND ACTIVATION UNIT - COMBINES WITH c4 TO FORM C4b2a complex (C3 convertase) d. C3 – THIRD ACTIVATION UNIT/AMPLIFICATION PHASE UNIT - C3b combines with c4b2a to form C4b2a3b (C5 convertase) e. C5, C6, C7, C8, C9 – MEMBRANE ATTACK PHASE UNITS - C8 and C9 are acted on by C5bC6C7 complex and insert themselves into the cell membrane resulting in cell lysis 2. ALTERNATIVE/PROPERDIN PATHWAY a. Factor B – activated into its active form Bb with the participation of C3 - Bb will cleave C3 into C3a and C3b and will combine with C3b to form C3bBb b. Factor D – cleaves Factor B into Bb in the presence of C3 and Mg++ ions Therefore, Factor B + Factor D + C3 + Mg++ → C3bBb (C3 convertase) c. Properdin (Factor P) – binds to C3bBb to prevent spontaneous decay of the complex d. C5, C6, C7, C8, C9 – MEMBRANE ATTACK PHASE UNIT - Cell lysis 3. LECTIN PATHWAY - New pathway Activating factors: Mannose group of carbohydrate in microbial cell Effectors: MBP/MBL – Mannan Binding Protein/Lectin MASP – MBP-Associated Serine Protease MEASUREMENT OF COMPLEMENT COMPONENTS CH50 Hemolytic Assay - Assesses the hemolytic activity of the complement system - Uses antibody-coated sheep rbc which is incubated with patient serum - The degree of hemolysis is proportional to the hemolytic activity of the complement Elevated complement components – have little clin. significance Decreased complement components – clin. Importance Causes: Complement has been consumed/genetic defects C1 esterase inhibitor deficiency – congenital def. which results in a clin. Syndrome called hereditary angioedema. C2 deficiency – most common of the human complement deficiencies; pyrogenic infection; bacterial infections COMPLEMENT DEFICIENCIES IMMUNE RESPONSE THE GENETIC CONTROL OF THE IMMUNE RESPONSE Major Histocompatibility Complex (MHC) 1) Originally identified in mice as blood cell antigens by R.A. Gorer and G.D. Snell in 1930s, and defined on the basis of tissue graft rejection - 1980 Nobel prize awarded to Snell. 2) Work by Rolf Zinkernagel and Peter Doherty in the 1970s revealed that it is the complex of MHC molecule plus antigen that is recognized by T cells (MHC restriction of T cell responses) - 1996 Nobel Prize 3) Two classes of MHC molecule: Class I (single MHC a chain + b2-microglobulin) and Class II (a chain plus b chain) - more Ig-superfamily members (Ig-C domains) Major Histocompatibility Complex - A group of genes that code for cell-surface Histocompatibility antigens and are the principal determinants of tissue type and transplant compatibility. They are the most diverse genes in humans and are used to determine if a sample of DNA comes from a specific person. - Located at the short arm of chromosome 6 - The Major Histocompatibility Complex (MHC) is a set of molecules displayed on cell surfaces that are responsible for lymphocyte recognition and "antigen presentation". The MHC molecules control the immune response through recognition of "self" and "non-self" and, consequently, serve as targets in transplantation rejection. Importance: 1. Organ transplant 2. Bone marrow transplant 3. Paternity testing 4. HLA disease associated 5. Immunoregulation 1. MHC Class I - Present in nucleated cells and some remnants have been found in red cells - Process cytoplasmically derived antigens and presented to CD8 positive cells  - Includes HLA-A, HLA-B, HLA-C, B2-Microglobulin, HLA-E - Described as serologically-defined antigens - Defined by Complement-dependent cytotoxic test/Microlymphocytotoxicity test 2. MHC Class II - Restricted to immunocompetent cells of the immune system - Present in restricted immunocompetent cells (B cells, Macrophages, Dendritic cells) - Processed extracellularly derived antigens and presented to CD4 positive cells - Important in ag presention and interaction between immunocompetent cells - Includes HLA, DP, DR, DQ - Determined by Mixed Lymphocyte Culture (MLC) Mixed Lymphocyte Culture – used to determine class II compatibility between donor and recipient 3. MHC Class III - Minor MHC antigen; involves complement components C2, C4 and Factor B. MHC CLASS 2 TEST: MHC RELATED DISEASES  IMMUNE DISORDERS HYPERSENSITIVITY REACTIONS - adaptive response which occurs in an exaggerated or inappropriate manner causing tissue damage TYPE I. IMMEDIATE OR ANAPHYLACTIC HYPERSENSITIVITY - Antibody involved: IgE - effector cells : tissue mast cells and circulating basophils - mediators: histamine, Eosinophil Chemotactic Factor (ECF) - Clinical States: Hay fever, asthma, eczema, anaphylactic shock, helminthic infxn TYPE II. CYTOTOXIC HYPERSENSITIVITY - Antibody involved: IgG and IgM - Reactions involved antibodies directed to antigen on surface of specific cells or tissues resulting to cytolysis - Clinical states: HTR, HDN, rxns to plt. transfusions, Goodpasture’s syndrome, Myasthenia gravis TYPE III. IMMUNE COMPLEX HYPERSENSITIVITY - Antibody involved: IgG and IgM - Affects organs where antigen-antibody reactions are deposited - Clinical states: Arthus reaction, Rheumatoid arthritis, SLE, glomerulonephritis, serum sickness TYPE IV. CELL-MEDIATED/DELAYED-TYPED HYPERSENSITIVITY - Reaction involves sensitized T cells and release of its lymphokines as mediators and amplifiers - Mediated by cells rather than antibodies - Clinical states: Contact dermatitis, GVHD reactions, Transplant rejection, PPD (Tuberculin Test for MTB) SUMMARY OF HYPERSENSITIVITY MANTOUX TEST IMMUNO PROLIFERATIVE PLASMA CELL DYSCRASIAS: 1. Multiple Myeloma ________________________________________ 2. Waldenstrom’s Macroglobulinemia ______________________________________ IMMUNO DEFICIENCIES B Lymphocyte Immunodeficiencies: 1. X – linked Bruton’s agammaglobulinemia – _______________________________ 2. Common variable Hypogammaglobulinemia –____________________________________ 3. Selective IgA deficiency – _______________________________________ 4. Neonatal hypogammaglobulinemia – __________________________________ T lymphocyte Immunodeficiencies: 1. DiGeorge syndrome – ______________________________ 2. Nezelof syndrome – _______________________________ Combined B and T lymphocyte Immunodeficiencies: 1. Severe combined Immunodeficiency Disease (SCID) – ______________________________ 2. Wiskott Aldrich Syndrome (WAS) – ____________________________________ 3. Bare-lymphocyte Syndromes – _________________________________________ Phagocytic cell Deficiencies: 1. Chediak Higashi Syndrome – ________________________________________ 2. Chronic Granulomatous Disease – _____________________________________ 3. CR3 Deficiency – _____________________________________ 4. G6PD Deficiency –______________________________________ 5. MPO Deficiency – __________________________________ 6. Specific Granule Deficiency – _________________________________ Lazy Leukocyte Syndrome: 1. Actin Dysfunction – _____________________________________ 2. Job Syndrome – _________________________________________ 3. Tuftsin Deficiency – ________________________________________ -END OF IMMUNOLOGY-