INFECTIOUS DISEASES A

1 EJC H2 Biology T2W8 Infectious Diseases Part I Extension Topic A: Infectious Diseases (Part 1) 1. Introduction Immunology is the study of the body’s defence against infection at cellular and molecular levels. The following are the questions we would address in this topic: How does the body prevent pathogens from entering the body? When infection occurs, how does the body eliminate the pathogen? How does the body develop long -lasting immunity to many infectious diseases we encountered once before? 2. Learning Outcomes a. Describe the specific (adaptive) and non -specific (innate) immune systems including active and passive, natural and acquired immunity. b. Outline the roles of B lymphocytes, T lymphocytes, antigen -presenting cells and memory cells in specific primary and secondary immune responses. c. Explain the relationship of the molecular structure of antibodies to their functions, using IgG as an example. d. Explain how genetic recombination during development results in millions of different antibody molecules (including somatic recombination, hyper-mutation and class switching). 3. References Judith Owen, Jenni Punt, Sharon Stranford. Kuby Immunology, 7th Edition. Murphy KM, P Travers, M Walport (Eds.) Janeway’s Immunobiology. 8 th Edition. Pommerville, Jeffrey C. Alcamo’s Fundamentals of Microbiology: Body Systems.

2 EJC H2 Biology T2W8 Infectious Diseases Part I Contents 1. Introduction ............................................................................................................... 1 2. Learning Outcomes.................................................................................................... 1 3. References ................................................................................................................. 1 4. Pathogens, Antigens and Epitopes ............................................................................ 3 5. Overview of the Components of the Immune System .............................................. 3 6. Immune Response - Innate Immunity ...................................................................... 5 7. Antigen Presentation ................................................................................................. 8 8. Immune Response - Adaptive Immunity ................................................................. 10 a. Activation of T Cells & Role of T Cells in Adaptive Immunity ................................ 10 b. Activation of B Cells & Role of B cells in Adaptive Immunity ................................ 13 c. Antibodies (or Immunoglobulins) ................................ ................................ ........ 17 9. Mechanisms to Generate Huge Variety of Antibodies ............................................ 20 a. Somatic Recombination / V(D)J Recombination ................................ .................. 20 b. Somatic Hypermutation ................................ ................................ ....................... 24 c. Class Switching ................................ ................................ ................................ ..... 25 10. Immunological Memory ...................................................................................... 26

3 EJC H2 Biology T2W8 Infectious Diseases Part I 4. Pathogens, Antigens and Epitopes Infection is the process where a pathogen invades and multiplies in its host . There are 5 classes of pathogens that invade the body to cause diseases : viruses, bacteria, fungi, protozoa and worms. A pathogen has many different components that can be recognised by cells of the immune system i.e. many different antigens. Antigens are substances that induce an immune response as they are recognised by cells of the immune system and antibodies. An antigen can be a foreign protein, carbohydrate, lipid or nucleic acid . e.g. a bacterium’s antigens can be found on its cell wall and flagellum, a virus’s antigens can be found on its viral glycoprotein. Cells of the immune system and antibodies usually do not bind to the entire antigen molecule. Epitopes are the parts on a single antigen that contact the antigen-binding site of an antib ody or T cell receptor. An epitope is also known as an antigenic determinant. (Fig. 1) Fig. 1 : Diagram showing an antigen with ep itopes (antigenic determinants); an antigen has many epitopes. Two attached antibodies are also shown. 5. Overview of the Components of the Immune System The immune system is typically divided into two categories , the non -specific innate immune system and the adaptive immune system: Notes to self

4 EJC H2 Biology T2W8 Infectious Diseases Part I The innate immune system has anatomical features that function as barriers to infection. “Humoral” comes from the term, humour, which means body fluid. Thus, “humoral” refers to molecules found in extracellular fluid such as secreted antibodies. Most cells of the immune system are derived from hematopoietic stem cell s and develop through the process of differentiation into functionally mature blood cells of different lineages. Fig. 2 : Haematopoietic stem cell differentiates to either myelo id progenitor cell or lymphoid progenitor cell. Progenitor cells cannot self -renew and are committed to a particular cell lineage. (Source: Kuby Immunology 7th Edition) Cellular components of innate immunity e.g. phagocytes such as macrophages, dendritic cells and neutrophils . Neutrophils are found in the bloodstream while macrophages and dendritic cells mostly reside in tissues of the body. Cells involved in adaptive immunity e.g. lymphocytes such as T lymphocytes (or T cells) and B lymphocytes (or B cells). Notes to self

5 EJC H2 Biology T2W8 Infectious Diseases Part I Fig. 3 : Summary of components of the non -specific innate immune system and specific adaptive immune system. Although the innate and adaptive immune systems have distinct characteristics, there is interplay between these two systems. Components of innate immune system influence the adaptive immune system and vice versa. Fig. 4: Overview of Immune Response 6. Immune Response - Innate Immunity The non -specific innate immune system is the first l ine of defenc e upon exposure to a pathogen. Any pathogen that breaches the anatomical barrier (e.g. skin is the first line of defence of innate immunity) will be gre eted by cells of innate immunity (e.g. macrophage is the second line of defenc e of innate immunity). Macrophages are always present under the skin and other tissues to function as “guards” against any pathogen that has penetrated the anatomical barrier. Innate immunity is not specific to any pathogen and has no memory (i.e. no improved response on repeated exposures to same pathogen). Notes to self

6 EJC H2 Biology T2W8 Infectious Diseases Part I This response to an encounter with a pathogen occurs rapidly. The first line of host defence is immediate as it consists of mechanisms that are ready to kill and resist an invader at any time. First line of defence of innate immunity (anatomical barriers to infection):  Epithelial cell layers such as skin, mucous membranes lining the respiratory tract and gastrointestinal tract are barriers that prevent penetration of microorganisms.  Secretions such as saliva and tears wash away potential invading microorganisms to prevent their attachment.  These secretions also contain antimicrobial s ubstances to kill these microorganisms. e.g. lysozyme is an antibacterial protein that cleaves glycosidic bonds of peptidoglycans in cell walls of bacteria, leading to lysis.  Other chemical barriers include acidic pH. Some pathogens may have evolved strat egies to penetrate the epithelial cell barrier, or wounds may have disrupted the epithelial layer to allow pathogens to enter the body. The second l