Introduction To Immunology PDF

INTRODUCTION TO IMMUNOLOGY  Immunology Study of molecules, cells, or organs and systems responsible for the: Recognition and disposal of foreign material How body components respond and interact Desirable and undesirable consequences of immune interactions Ways in which the i...

INTRODUCTION TO IMMUNOLOGY  Immunology Study of molecules, cells, or organs and systems responsible for the: Recognition and disposal of foreign material How body components respond and interact Desirable and undesirable consequences of immune interactions Ways in which the immune system can be advantageously manipulated to protect against or treat disease  IMMUNE SYSTEM The collection of cells, tissues and molecules that mediate resistance to infections. Physiologic functions: 1. Defense against infections 2. Defense against tumors 3. It recognizes and responds to tissue grafts and newly introduced molecules. 4. It can injure cells and induce pathogenic inflammation. COMPONENTS OF IMMUNITY NATURAL/INNATE/NONSPECIFIC ACQUIRED/ ADAPTIVE/SPECIFIC Provides protection against MANY Provides protection against SPECIFIC pathogen DIFFERENT pathogen PRESENT at birth NOT Present at birth Standardized response for all pathogens Diverse response to each antigen Lacks memory (unable to remember prior With memory exposure) General response does not improve upon Specific response improves upon repeated repeated exposure exposure Recognizes foreign molecules via TOLL- Recognizes foreign molecules via SPECIFIC LIKE receptors (pattern-recognition receptors which interacts with corresponding receptors) which interacts with Pathogen- epitopes Associated Molecular Patterns (PAMP’s) NATURAL IMMUNITY  First Line of Defense 1. Physical/ Mechanical A. Intact skin ▪ Physical barrier to pathogens ▪ Normal skin flora B. Mucous membranes ▪ Line open body cavities ▪ Secretion of mucous C. Cilia ▪ Line the respiratory tract ▪ Traps and propels harmful air particulates and airborne pathogen out of the body First Line of Defense D. LACRIMAL APPARATUS: Continual washing and blinking prevents microbes from settling on the eye surface. E. SALIVA: Washes microbes from teeth and mouth mucous membranes. F. MUCUS: Thick secretion that traps many microbes. G. COUGHING AND SNEEZING: Expel foreign objects. H. EPIGLOTTIS: Covers larynx during swallowing. I. URINATION: Cleanses urethra. J. VAGINAL SECRETIONS: Remove microbes from genital tract. First Line of Defense 2. Biological/ Chemical A. Lysozyme (muramidase) ▪ Abundant in secretion like tears, saliva. Human milk and mucus ▪ Damage bacterial cell walls B. pH C. Sebum Contains unsaturated fatty acids which inhibit growth of certain pathogenic bacteria and fungi. D. Perspiration ▪ Produced by sweat glands. Contains lysozyme and acids. ▪ Traps and propels harmful air particulates and airborne pathogen out of the body  Second Line of Defense CELLULAR FACTORS A. Phagocytes- neutrophils, macrophages, monocytes, eosinophils B. NK cells C. Basophils and Mast Cells  Second Line of Defense MAST CELLS Included in granulocytes The enzyme content of the granules helps to distinguish them from basophils, as they contain acid phosphatase, alkaline phosphatase, and protease MONOCYTES Generally classified as “agranulocyte” Phagocyte in blood Largest blood cell A. Monocytes (in the blood) B. Tissue Macrophages A. Liver → Kupffer cells B. Lungs → Alveolar macrophages/ Dust cells C. Kidney → D.CNS → Microglial cells E. Lymph nodes → Dendritic cells F. Skin → G.Spleen → Splenic/ Littoral macrophages H.Connective tissue → I. Bone → Osteoclast J. Peyer’s patches K. Tonsils  Second Line of Defense Predominant WBC in the blood Presents approximately 50 to 70 percent of the total peripheral white blood cells WBC are divided into two: 1. Granulocytes – contain granules on their cytoplasm 2. Agranulocytes – absence of the granules A. Primary granules contain enzymes such as myeloperoxidase; elastase; proteinase 3; lysozyme; cathepsin G; and defensins B. Secondary granules: collagenase, lactoferrin, lysozyme, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase C. Tertiary granules contain gelatinase and plasminogen activator Second Line of Defense EOSINOPHILS Increased in the presence of allergens and parasitic infections Included in granulocytes Primary granules contain acid phosphatase and arylsulfatase Eosinophil-specific granules contain several different proteins: major basic protein, eosinophil cationic protein, eosinophil peroxidase, and eosinophil derived neurotoxin Second Line of Defense BASOPHILS Included in granulocytes Increased if you have allergy Granules are histamine, a small amount of heparin Function of Phagocytosis To kill invading microorganisms To dispose damaged or dying cells To remove aging erythrocytes from the spleen To remove tissue debris from repairing wounds To remove debris as embryonic tissues replace one another To remove cancer cells Steps in phagocyte extravasation STEPS IN PHAGOCYTOSIS 1. Chemotaxis 2. Adherence 3. Engulfment 4. Phagosome formation 5. Fusion 6. Digestion and Killing  Second Line of Defense Natural Killer Cells Forms an initial defense against aberrant cells (tumors and virally-infected cells) Comprise 10-15% of circulating lymphocytes Identified by the presence of ______and _______ surface markers Known as LYMPHOKINE-ACTIVATED KILLER CELL when exposed to IL-2 and IFN gamma Antibody Dependent Cellular Cytotoxicity (ADCC)- needs IgG molecule  ADCC Final mechanism of cellular cytotoxicity Cytotoxic potential: NK cells, Neutrophils, Macrophages and Eosinophils Mechanism of target cell killing may involve Lytic enzymes Tumor necrosis factor Perforin and Granzymes  Second Line of Defense HUMORAL A. TRANSFERRINS: Iron-binding proteins in blood which inhibit bacterial growth by reducing available iron B. Complement System: Groups of more than 30 circulating glycoproteins which function as: Anaphylatoxin, Chemotaxin, Opsonin and Lysis C. Fever Generalized response of the body against infection characterized by elevation of body temperature above the basal level (36.5-37.5 C) Stimulus: Pyrogens Augments host defenses D. Acute Phase reactants: plasma proteins which increase in concentration during chronic or intensive inflammation Second Line of Defense E. Cytokines: : Chemicals released by many cell types of the body that serves as messengers that enable cells within the immune system to communicate with each other.  Second Line of Defense 1. INTERFERONS: A family of glycoproteins that exerts a virus-nonspecific but host specific-antiviral activity Type I Interferons: NONIMMUNE; produced as an initial response to viral infection Interferon alpha: produced by leukocytes Interferon beta: produced by fibroblast Type II Interferons: IMMUNE; produced primarily as a component of the specific immune response to viral and other pathogens Interferon gamma: produced by immunologically stimulate T-cells  Second Line of Defense 2. Tissue Necrosis Factor Tumor necrosis factor-alpha (TNFa): Produced by macrophages, lymphocytes, and NK cells when encountering bacteria, viruses, tumor cells, toxins, and complement protein C5a TNF-beta : Produced by CD4 and CDS positive cells after exposure to specific antigen 3. Interleukin IL-1 activates T helper cells, increases number of B cells, activates vascular endothelium, causes fever and acute-phase protein synthesis, and induces T cells to produce lymphokines. IL-2 causes proliferation of activated T and B cells. IL-3 increases the number of mast cells in skin, spleen, and liver. IL-4 induces proliferation of T cells and class switching from IgM to IgG and IgE. Second Line of Defense F. Inflammation: local response of the body to repair tissue damages. Series of biochemical and cellular changes that leads to the elimination of the irritant and repair of damaged tissue  Cardinal Signs of Inflammation 1. Rubor : redness of the area where the infection occurred 2. Calor : generation of heat due to the increased blood flow in the area 3. Tumor : swelling 4. Dolor : patient suffers from pain 5. Functio laesa : loss of function in the inflamed part prior to the exposure of foreign material ADAPTIVE IMMUNITY Components of the Adaptive Immune System: Cellular T lymphocytes B lymphocytes Plasma cells Humoral Antibodies Cytokines LYMPHOCYTES Included in agranulocytes Key cells involved in the immune response 7 - 10 μm in diameter and has a large rounded nucleus that may be somewhat indented Primary lymphoid organs in humans: bone marrow (B lymphocytes) and the thymus (T lymphocytes) Secondary organs: spleen, lymph nodes, appendix, tonsils, and other mucosal-associated lymphoid tissue PRIMARY LYMPHOID TISSUE a.k.a Central Lymphoid Organs a. Thymus: b. Bone marrow: PRIMARY LYMPHOID TISSUE Bone Marrow -Bursa of Fabricius -origin of all the hematopoietic cells -plays a role into differentiation of progenitor B cells into mature B cells B lymphocyte Effector cells of humoral-mediated immunity Derived from progenitor cells through an Ag-independent maturation process occurring in the bone marrow and GALT Differentiates into plasma cells upon antigenic stimulation STAGES OF B CELL DEVELOPMENT Pro-B cell ▪ Rearrangement of genes on chromosome 14 coding for heavy chains Pre-B cell ▪ Presence of mu chains in the cytoplasm ▪ May have some surface immunoglobulin consisting of heavy chains with surrogate light chains Immature B cell ▪ Expression of IgM on the surface CD19, CD21, CD35, CD40, CD45 Mature B cell IgD in expression to IgM on the surface and increased density of IgM Cells are released from the marrow and seed in peripheral organs  STAGES OF B CELL DEVELOPMENT Activated B cell ▪ When activated by antigen CD25 appears, which is a receptor for Interleukin-2 Plasma Cell End stage of B-cell differentiation Results from antigenic stimulation and transformation of activate B cells Distinguished by the presence of abundant cytoplasmic immunoglobulin, which is excreted into the bloodstream PRIMARY LYMPHOID TISSUE Thymus ▪ Site of maturation of T cells ▪ The human thymus has two parts: CORTEX and MEDULLA Cortex: “nursery area”; immature T cells Medulla: mature cells T-cells ▪ Responsible for cellular immune response ▪ Expression of T-cell antigen depends on maturation stage and stage of activation ▪ It has the ability to bind with sheep’s RBC forming rosette. ▪ Chief lymphocytes in blood and lymph ▪ Longer life span compared to B – cells  SUBSET OF T CELLS SUBTYPE FUNCTION T-helper cells (Th) T-cytotoxic cells (Tc) T-suppressor cells (Ts) Suppress B cell not to produce antibodies Limit immune reactions T-delayed type hypersensitivity Involved in some delayed allergic (Tdth) reactions T cell maturation  Phases of T cell responses Naïve T cell with no prior exposure to Antigen recognizes Ag in the secondary lymphoid organs. So once they recognize antigen presented by APC. They will be stimulated and proliferate to clones and differentiated to become effector cells and production of memory cells. Lymphocytes activated with Ag it will produce effector cells at the same time it will also produce memory cell. The differentiated effector cell will enter again the circulation where they will encounter same ag presented to them and perform effector function. T cell relapses cytokines. Helper T cell CD4  T LYMPHOCYTES B LYMPHOCYTES Effector cells of cellular-mediated immunity Effector cells of humoral-mediated immunity Recognize antigens only in the context of MHC Able to recognize antigens in their native form molecules Differentiate and develop in THYMUS Differentiate and develop in the BONE MARROW Identified by rosette formation with sheep Identified by surface Immunoglobulins RBCs Located in the PARACORTICAL region of lymph Located in the CORTICAL region of lymph nodes nodes  CELLULAR-MEDIATED IMMUNITY HUMORAL-MEDIATED IMMUNITY Antigens include CD2, CD3, CD4 and CD8 Antigens include CD19, CD20, CD21 and CD2: classic T cell marker; CD40, MHC Class II CD19: CD3: part of TCR complex CD4: CD20: Ion channel CD21: EBV receptor; receptor for C3d CD8: CD40: B cell isotype switching and memory formation End products of activation: ____________ End products of activation: _____________ 60-80% of total circulating lymphocyte 20-35% of total circulating lymphocyte Longer life span (4-10 years) Shorter life span (3-5 days)  SECONDARY LYMPHOID ORGANS Privileged sites where mature T and B cells are stored until they encounter an antigen or any stimulus Spleen, Lymph nodes, Tonsils, Peyer’s patches FUNCTIONS 1. Standby areas of T cells, B cells and macrophages 2. Trapping sites of captured infectious agents 3. Antibody production 4. Production of immunocompetent T cells  SECONDARY LYMPHOID ORGANS Lymph node Lymphoid filters in the lymphatic system Respond to antigens introduced distally and routed to them by afferent lymphatics AREAS: 1. Cortex - B cells 2. Paracortex - T cells 3. Medulla- mixed cells SECONDARY LYMPHOID ORGANS Spleen The largest secondary lymphoid organ Lymphatic filter within the blood vascular tree >sequesters “senescent” RBCs (graveyard of RBCs): culling >removal of inclusion bodies: pitting Major site of Ab synthesis Respond to antigens introduced intravenously  SECONDARY LYMPHOID ORGANS MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT) A. Gut-Associated Lymphoid Tissue (GALT) ▪ Includes the Peyer’s patches of the ileum and liver ▪ Site of immunoglobulin A production B. Bronchus-Associated Lymphoid Tissue (BALT) ▪ Includes lymphoid tissues of the lower respiratory tract and hilar lymph nodes ANTIGENS Any molecular structure that when introduced is capable of antibody production Parts of antigen ▪ Epitope- ▪ Carrier portion-responsible for the molecular weight of antigen Antibodies Specific glycoproteins produced by B lymphocytes or Plasma Cells in response to antigenic stimulation Immunoglobulins or Gamma Globulins 20% of proteins in the blood plasma Part of the adaptive immune response (humoral immunity) Functions of the Immunoglobulins Bind Antigens Fix complement Facilitate Phagocytosis Neutralize toxins  Virus small amount of genetic material surrounded by a protein envelope. They cannot reproduce independently Viruses are very small particles composed of nucleic acid and protein. The entire virus particle is called the virion. At the center of the virion is the nucleic acid. Surrounding this is the capsid, which is a protein coat. The combination of the nucleic acid and the capsid is called the nucleocapsid. Many other viruses, including HIV, have a membrane envelope surrounding the nucleocapsid. Many viruses also have protein spikes that help them attach to their host cell. Life Cycle of Virus HIV and AIDS  HUMAN IMMUNODEFICIENCY VIRUS Aka: HTLV – III, ARC, LAV Types of HIV: HIV 1 (GLOBAL) and HIV – 2 (AFRICA) Family: RETROVIRIDAE Subfamily: LENTIVIRIDAE Has a marked preference for T – HELPER/INDUCER LYMPHOCYTES (CD4+) which serves as the receptor site for the virus Discovered by LUC MONTAGNIER (1983) 1st Retrovirus discovered by ROBERT GALLO (1981)  HIV GENOME Gene Viral Gene Products Functions gag p24, p18, p15 Codes for CORE STRUCTURAL CHON pol - Reverse Transcriptase - Transcribes RNA into DNA (polymerase) - RNAse - Degrades RNA - Protease - Makes HIV particles into complete and functional HIV virus - Integrase - Inserts viral DNA into host DNA env gp120 Binds to CD4 receptors (envelope) Knoblike structure attached to Gp41 gp41 Required fro viral fusion of the cell Protein that traverses the membrane  Mode of Transmission 1. SEXUAL CONTACT 2. Blood Transfusion 3. Parenteral injection 4. Transplacental 5. Breastfeeding 6. Passage through infected birth canal  CLINICAL MANIFESTATION 1. PRIMARY STAGE Patient is either asymptomatic or may show lymphadenopathy 2. INTERMEDIATE STAGE ARC → AIDS RELATED COMPLEX Quantitative T – cell deficiencies with inverted CD4:CD8 ratio When HIV replication occurs, the CD4 cell is killed → Severe depletion of Helper – Inducer T lymphocytes Normal CD4:CD8 ratio → 2:1 AIDS patients → 0.5:1  CLINICAL MANIFESTATION 3. FINAL STAGE 2 – 10 years after initial infection A syndrome of CD4 depletion resulting in opportunistic infections Infections and cancers suggestive of cell – mediated immunity defects THANK YOU FOR LISTENING!