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Immunology
| Question | Answer |
|---|---|
| Acquired IR exhibits 4 immunologic attributes: | specificity, diversity, memory and self/nonself recognition. |
| Natural or Non-specific Immunity or Innate: | A. Antimicrobial Agents B. Phagocytic cells C. Non-phagocytic cells D. Natural killer cells E. Inflammation and Fever |
| Acquired or Adaptive Immunity | A. Lymphocytes T cells, B cells B. Major Histocompatibility complex C. Antibodies |
| Immune system Disorders | Hypersensitivity - Allergies; Autoimmune Disorders; Immunodeficiencies (HIV and AIDS) |
| NATURAL IMMUNITY: | • Present at birth • The two principal types of reactions are inflammation and antiviral defence • First line of defense: Skin + Mucous membrane |
| ACQUIRED IMMUNITY: | • Stimulated by repeated exposure to foreign Ag • Stronger, more rapid, effective response to microbes. • Response specific to individual Antigen (Ag) |
| SELF TOLERANCE: | • Absence of immune response to one’s own tissue Antigens. • Necessary to prevent auto-immune diseases |
| What are the four nonspecific body defenses? | Nonspecific defenses include anatomic barriers, inhibitors, phagocytosis, fever, inflammation, and IFN. |
| Specific defenses: | antibody and cell-mediated immunity |
| What are the barriers of innate immunity? | The mucous membranes of the mouth, respiratory tract & GI tract. Final physical barrier of the innate system is the bronchial cilia. |
| How long does innate immunity last? | 4-7 days |
| Origin of cells of the immune system: | From progenitor cell in bone marrow |
| Progenitor Stem Cells | -Erythroid lineage -Myeloid lineage -Lymphoid lineage |
| Myeloid lineage: | - Monocytes - Macrophages |
| Properties of adaptive immune responses: | Specificity Diversity Memory Clonal expansion Specialization Contraction and homeostasis Nonreactivity to self |
| Clonal Selection of Lymphocytes: | Lymphocytes are made randomly - but each one bears a specific receptor. Antigens select the appropriate lymphocytes which then undergo clonal expansion |
| Activation of antibody producing cells by clonal selection | Proliferation of activated cells is followed by differentiation into plasma cells and memory cells |
| Antigen: | any substance that can specifically bind to an antibody or T cell receptor. |
| Immunogen: | induces an immune response |
| Epitope (Antigenic Determinant): | –Specific site on Ag that is recognized by the immune system, where Ab binds |
| Antibody: | Able to bind to epitopes Consist of 2 light chains and 2 heavy chains |
| Major Histocompatibility Complex (MHC): | Genes that encode proteins that regulate the immune response. Class 1: located on surface of all Nucleated cells and Platelets (HLA–A, HLA-B, HLA-C) Class 11: located on Langerhan cells & activated Macrophages (HLA-DR, HLA-DQ) |
| Cytokines: | Protein mediators secreted by immune cells and act on on other cells to regulate their activity |
| Chemokines/Chemotatic cytokines: | Cytokines that direct migration of cells |
| Steps in antibody production | 1. when antigen delivered intravenously -> antigens enter the spleen 2. if antigen entered subcutaneously, intradermally, topically or intraperitoneally -> antigen enters the lymph nodes |
| Antibodies formed in the lymph nodes differentiate to form: | 1. antibody secreting plasma cells- they secrete IgM 2. memory cells which upon exposure hey convert to plasma cells and produce IgG |
| Humoral response: B-cells | -Stimulated by T-dependent antigens -Helper T become activated, and secrete cytokines that activate B cells -B cells differentiate into effector and memory and produce antibodies |
| 5 immunoglobulins: | Immunoglobulin A IgA Immunoglobulin B IgB Immunoglobulin M IgM Immunoglobulin D IgD Immunoglobulin E IgE |
| Antibody structure: | - 4 polypeptide chains: 2 light & 2 heavy - hypervariable regions at amino cid end - constant regions at carboxyl end - 2 types of light chains: kappa and lamda |
| T cell receptor recognise antigen that... | ....is associated with either class I or class II MHC on the cell surface |
| Idiotype: | areas on the Variable Region responsible for Ag Specificity |
| Isotype: | subclass of Igs that are distinguished by unique constant Regions encoded by Heavy chain gene |
| Allotype: | protein product of an Allele that may be detected as an Ag by another member of the same species |
| Inflammation: | Caused by infection or injury to tissues |
| Humoral response: | -Require Antibodies -Originate from stem cells in bone marrow |
| Cellular immune response: | • Functions of Effector (activated) T cells: – Activate B cells, Cytotoxic T Lymphocytes – Kill Virus infected cells & some Tumor cells |
| Primary antibody response: | After exposure to an antigen, thee is low rise in IgM followed by a slow rise in IgG |
| Secondary antibody response: | Following exposure to previously encountered antigen, there is a rapid rise in IgG an slow or no rise in IgM |
| Immune system consists of: | – Primary (central) Lymphoid Organs – Secondary (peripheral) Lymphoid Organs – Leukocytes in Blood |
| MONOCYTES & MACROPHAGES | • Control infections not overcome by Neutrophils • Associated with chronic infections • Main role in cell-mediated immunity |
| Formation & maturation of monocytes and macrophages: | Formation: Formation and development from stem cells • Stem cell → Monoblast → Promonocyte → circulating Monocyte → tissue Macrophage Mature in the Blood Secrete Inflammatory Mediators & Cytokines |
| Activation of monocytes/macrophages: | • Stimulated by Lymphokines (γ-Interferon) • Kill Microbs + Tumor cells |
| DENTRITIC CELLS | • Present in Blood, Lymph Nodes, Epithelial cells • Digest & process Ag to present to T-cells |
| NEUTROPHILS (PMNs) | • 60% of leukocytes (white blood cells) • First to arrive in acute inflammation, actively killing bacteria Kill microbes by: – Toxic Oxygen molecule – Digestive Enzymes stored within Lysosomal granules |
| EOSIONPHILS | (1 –3% of leukocytes) • Classically seen with: – Atopic allergies – Worm infections – Collagen Vascular diseases – Neoplastic disorders – Skin rash • Granules (histaminase, arylsulfatase) help control allergic reactions |
| BASOPHILS | • Contain much granules with: – RNA Mucopolysaccharide (hypersensitivity mediator) • Have receptors for Fc portion of IgE • IgE binding → degranulation → Histamine →allergic reactions |
| B Lymphocytes: | • Differentiate into Plasma cells → Antibodies • Memory B cells:generated after exposure to Ag |
| T LYMPHOCYTES: | Helper T cells(CD4+) -Stimulate B-Lymphocytes→Plasma cell→Ab -Activation due to recognition of Class 11 MHC -Produce Lymphokines, Differentiation Factors, Inflammatory Cytokines (IL-2) Cytotoxic T cell(CD 8+) –Lyse virus infected cells & tumor cells |
| Natural killer (NK) cells | • Kill Tumor cells • Defend against Viral infections • Recognize Foreign Ag independent of MHC • Activated by Cytokines (γ- Interferon) |
| Primary (central) Lymphoid Organs: | – Bone marrow & Thymus (child & adult) – Hematopoiesis & Lymphopoiesis occur here |
| Secondary (peripheral) Lymphoid Organs: | • Lymph Nodes Spleen • Mucosa-Associated Lymphoid Tissue (MALT) • Gut- Associated Lymphoid Tissue (GALT) • Bronchus-Associated Lymphoid Tissue (BALT) |
| BONE MARROW | • A primary organ • Site for Hematopoiesis + B cell maturation • Site of origin of Stem cell → T-cell production • A secondary organ: site for Plasma cell → Ab • Contains activated T cells |
| HEMATOPOIETIC CELL DIFFERENTIATION | • Pluripotent Stem cell → Myeloid + Lymphoid progenitor cells |
| THYMOSIN | • Lymphokine that stimulate Thymus-dependent zones in Lymphoid tissues • Produced by Thymic Epithelium |
| LYMPH NODES | • Most common site for adaptive immune response • Filters Lymph of Foreign bodies • Facilitates cell-to-cell & Ag-receptor interactions |
| SPLEEN | • White pulp Increases with Antigenic stimulation • Periarteriolar Lymphocyte Sheath (PALS) |
| GUT-ASSOCIATED-LYMPHOID TISSUE | • Non-encapsulated • Located in the Submucosa + Lamina propria • Site of immune responses to ingested Microbs + Food antigens |
| BRONCHUS-ASSOCIATED LYMPHOID TISSUE (BALT) | • Lymphoid tissue beneath Respiratory mucosa • Tonsils |
| IgA: | • Important barrier function on mucosal surfaces • Function in secretory immune response • Secretory IgA (sIgA) found in Tears, Saliva, Colostrum, Breast Milk) • Produced by Plasma cells in GIT & URT |
| Antigens: | substances inducing specific Immune Responses |
| Immunogenicity: | The ability to induce a humoral and/or cell-mediated I.R. |
| immunogen: | Antigen is more appropriately called immunogen |
| Antigenicity | the ability to combine specifically with the final products |
| haptens: | Some small molecules(haptens) possess property of antigenicity but are not capable by themselves to induce specific I.R i.e they lack immunogenicity |
| Factors influencing Immunogenicity | For cell-mediated immunity only proteins serve as immunogens. They are not recognized directly. |
| Immunogenicity | Four properties of the immunogen: i) foreignness ii) molecular size iii)chemical composition and complexity iv) susceptibility to Ag processing and presentation |
| Foreignness | The greater the phylogenetic distance between two species, the greater the genetic/antigenic disparity |
| Molecular size | • Correlation between size of macromolecule and immunogenicity. • Best immunogens have mol.wt. about 100,000 Dalton. Substances ≤ 5-10,000 Da are poor immunogens. • A few substances with ≤ 1000 Da are immunogenic. |
| Chemical composition and heterogeneity | Copolymers of sufficient size containing two or more different AA are immunogenic. |
| Four levels of protein organization: | -1o structure: Linear arrangement of AA -2o : Folding polypeptide parts into regular structure α helices and b sheets -3o: Folding of regions between 2o features -4o: Association of 2 or more polypeptide chains into a single polymeric protein molecule. |
| Susceptibility to Ag processing and presentation: | Development of humoral and cell-mediated I.R’s require interaction of T cells with Ag that have been processed and presented in association with MHC molecules. |
| Generation of B-cell and T-cell Responses | Macromolecules that cannot be degraded and presented with MHC molecules are poor immunogens. |
| Genetic constitution(genotype) | It influences the type of I.R. and the degree of response of individuals. The gene controlling immune responsiveness, was mapped to a subregion of the MHC. |
| Immunogen dosage | There is a dose response curve determined by measuring the I.R. with various doses and administration routes. |
| Tolerance: | Insufficient dose will not stimulate I.R. either because fails to activate enough lymphocytes or excessive high dose can fail because it causes lymphocytes to enter a nonresponsive state. |
| Administration route: | Ag administered intravenously is carried first to the spleen. Ag administered subcutaneously moves first to local lymph nodes |
| Adjuvants: | are substances that when mixed with an Ag and injected with it, enhance immunogenicity. |
| EPITOPES | Epitopes are the immunologically active regions of an immunogen that bind to Ag-specific membrane receptors on lymphocytes or to secreted Abs. |
| The size of the B-cell epitopes: | - those recognized by membrane-bound Ab and free Ab - is determined by the size of an Ab’s Ag-binding site. |
| T-cell epitopes: | - those epitopes recognized by T-cell receptors-generally consist of internal amino acid sequences. |
| B-cell maturation occurs: | -in the bone marrow, involves a sequence of Ig-gene rearrangements and progresses in the absence of Ag.: Ag independent phase of B-cell development. -These naïve B cells circulatein the blood and lymph and are carried to the 2ndary lymphoid organs |
| Ag-dependent phase | • Since B-cell activation and differentiation require Ag, these stages make up the Ag-dependent phase of development. |
| Overview of B-cell development: | • During the Ag-dependent maturation phase, immunocompetent B cells expressing membrane IgM and IgD are generated in the bone marrow. • In the absence of Ag-induced activation, naïve B cells in the periphery die within a few days by apoptosis. |
| B-lineage cell: | • Progenitor B cell (pro-B cell) express a transmembrane tyrosine phosphatase called CD45R. |
| B cell activation and proliferation: | Depending on the nature of the Ag, B-cell activation proceeds by two different routes: one dependent upon TH cells and one independent of TH cells. |
Created by:
elenatz
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