PHA4011E Unit 5 Reading Pack 2023-24 PDF

Fundamentals of Pharmacy Science: PHA4011E Unit 5: Immunology, Microbiology and Pathophysiology...

Fundamentals of Pharmacy Science: PHA4011E Unit 5: Immunology, Microbiology and Pathophysiology Pre-reading Material School of Pharmacy and Medical Sciences Facilitators Required References Unit Lead: Required Dr Sriharsha Kantamneni This reading pack [email protected] Suggested Unit facilitators: (Specific references are given at the end of Dr Keren Bielby-Clarke each section) [email protected] Dr Steven Shnyder [email protected] Dr Stacy-Paul Wilshaw [email protected] Dr Bishwa R Tuladhar [email protected] Learning Objectives The aim of this unit is to introduce you to the role of micro-organism in infections and the immune response of the body which prevents infections. The unit also briefly describes antimicrobial agents and vaccines that are used to supplement our defence against microbial pathogens. Understanding the basic principles of human pathology including cancer and how to apply this knowledge when interacting with patients. By the end of this unit you are expected to be able to 1. Distinguish between innate (nonspecific) and adaptive (specific) defences. 2. Describe the characteristics and functions of the cells and tissues of the immune system. 3. Define cytokines and understand their role in the immune response. 4. Describe the structure and function of antibodies and the consequences of antigen-antibody interactions 5. Discuss the types of T cells and their roles in the immune response, and describe the mechanisms of T cell activation and differentiation. 6. Describe the maturation B cells and discuss the mechanisms of B cell activation and differentiation. 7. Know the distinction between passive and active immunization and different types of vaccine and their use in the prevention of infectious diseases 8. Appreciate the role of micro-organisms in infection Page 1 of 80  9. Describe the general biological characteristics of bacteria, viruses, fungi, protozoa and helminths. 10. Describe the basic structure of the cell wall and its role in enhancing microbial virulence and other microbial virulence factors 11. Understand the role of various extracellular structures 12. Know the modes of action of different classes of antimicrobials. 13. Understand the basic principles of embryology and teratology. 14. Identify and evaluate the different mechanisms regulating cell damage, assess the impact of cell damage in different tissues and its consequences in terms of diseases in the body. 15. Understand cancer hall marks and monoclonal antibody therapy 16. Evaluate and implement strategies acquired during this unit when interacting with real patients. Table of Contents Section 1: Immunity.................................................................................................. 4 Section 2: Microbiology and Prokaryotes............................................................ 23 Section 3: Embryology and teratology................................................................. 47 Section 4: Introduction to disease........................................................................ 52 Section 5: Patient and Public Involvement (PPI) in the Pharmacy course........ 75 Page 2 of 80 Studying this Unit - Please read carefully This pack consists of explanatory notes (including diagrams and videos) and some directed reading, all of which should be covered in preparing for your tests. As you study, keep in mind the learning objectives written above, and be sure to make notes of your own. Some optional reading material – to help you understand tissue structures – is also provided. If you have trouble understanding a concept, please consult these resources before posting a question on the Canvas Discussion board. The required and additional reading is clearly marked and links provided for your easy access. Additional reading is optional but please try to visit all the links. If you are working outside university, some of the eBook links might not work properly in that case please find the eBook from the library website and find the topic in the book. What are we going to do in this unit? Firstly the immune response of the body which prevents infections. Then microbiology and role of micro-organism in infections. Later in the pack, embryology, teratogens, followed by pathological and disease processes including cancer and monoclonal antibody therapy. Finally finishing with aspects of pathology and patient interactions. We aim to consider basic pathology of disease and how this may relate to a patient’s experience and their drug therapy (for example in arthritis). Knowledge of this will then enable you to provide a better and more informed service for the patient. You should read and make suitable notes on the information which follows in this pack, since it will form the basis of the iRAT and Application Exercise tests. Page 3 of 80 Section 1: Immunity Immunity refers to protection from diseases especially infectious diseases. Our immune system achieved this by limiting invasion of the foreign agents and destroying the damaged or infected cells. The immune system is our defence mechanism against potentially harmful invading micro-organisms, such as bacteria, viruses and fungi. The immune system also plays a role in the control of cancer and other diseases. However, our immune system is not perfect and diseases results from both the under or over activity of the immune system. Under or insufficient activity results in infections whereas, inappropriate or over-activity of the immune system is the culprit in the phenomena of allergies, hypersensitivity and the rejection of transplanted organs and many more chronic diseases. In general, the immune response can be involved in many diseases, both infectious and non-infectious chronic diseases, and is responsible for most if not all signs and symptoms of diseases. Immunity is broadly classified into two types 1. Innate immunity (Non-specific defence) o Passive (Physical and chemical barrier to the entry of pathogens) o Active § Humoral (Complements and other blood protein) § Cellular (Phagocytes and NK cells) 2. Acquired or Adaptive immunity (Specific defences) o Humoral (Antibodies) o Cellular (T-cells) It will be helpful to remember that this classification is intended mainly for the ease of understanding the complex system. The two systems work together to limit invasion by non-self and to eliminate altered self. Figure 1 summarises the components of the immune response. The immune system The innate immune system The adaptive immune system Passive Active Humoral Cellular Physical and chemical barriers Antibodies T lymphocytes Humoral Cellular Blood proteins including Phagocytes and NK cells Complement Figure 1: Divisions of the immune response Table 1. The table below summarises the characteristics of innate and adaptive immunity: Page 4 of 80  Innate Immunity Adaptive immunity Inborn Acquired after exposure Much older, in evolutionary Relatively later addition in vertebrates development Non-specific for different pathogens Highly specific for the pathogen responsible for the initial infection Provide an initial defence to prevent Developed if innate system is infection and usually contain the penetrated and usually required for infection until adaptive immunity ultimate clearance of the infective develops agent Rapidly deployed Requires 3-7 days to activate Non-adaptive, do not increase with Highly adaptive, increases with each repeated exposure subsequent exposure Main immune cells: macrophages, Main immune cells: B lymphocytes & neutrophils, eosinophils and NK cells T lymphocytes, macrophages and (a type of lymphocytes) other antigen presenting cells (APCs) The physical and chemical barriers prevent foreign bodies from entering the body. If the barriers are penetrated, the second part of our innate defence is activated. They include phagocytes (monocyte/macrophages and neutrophils) that engulf (phagocytose) and destroy micro-organisms, eosinophils (secrete factors which kill protozoa and worms), Natural Killer cells (NK cells; destroy virus infected cells), complements and acute phase proteins (a system of enzymes and control proteins which helps attract phagocytes and make micro-organisms easily recognisable by phagocytes (opsonisation) and lyses micro-organisms) and various chemicals termed cytokines (cytokines are chemicals messengers of the immune system, both the innate and adaptive). There are many cytokines (released by immunocytes of both the innate and adaptive immunity) and we will briefly describe them later. Cells of the innate immune system are designed to target specifically the conserved molecular signatures on microbial pathogens, referred to commonly as pathogen- associated molecular patterns (PAMP), through many pathogen recognition receptors (PRRs) on their cell surfaces. The PAMPs could be peptidoglycan of G+ve bacteria or lipopolysaccharide (LPS) of G-ve bacteria, sugar mannose or many other features that are present on the surface of a foreign micro-organism but not present in our own cell membrane. There are many know pathogen recognition receptors (PRRs) that include Toll-like receptors (>10 types in human, recognise different microbial component), LPS receptors (recognise LPS), mannose receptors (binds to mannose sugar found on the surface of many bacteria) etc. PRRs help phagocytes to recognise non-self molecules and get activated and remove the Page 5 of 80 foreign material by activating phagocytosis or other mechanisms. If the adaptive immune response involving antibody production is activated later, coating of the foreign substance with antibody molecules further aids in these processes. Innate immunity on its own is usually so effective that it mostly prevents the entry of any micro-organism and eliminate any that gain access crossing our physical and chemical barrier. This is the reason why, although there are so many species of micro-organisms in the environment, only very few of them can cause an infection (are pathogens) in a normal person. The microorganisms which can cause disease/infection are those which have developed some mechanism to evade detection/elimination from the innate immune response. When such a microorganism gains entry in to the body they are able to multiply and then cause disease/infection. In such situations two things happens. First, more of the innate immune response is triggered and second, the innate immune response help body to initiate third line of our defence: the adaptive immune response. This could be antibody-mediated (humoral) or cell mediated (through T cells). Adaptive immunity differs from innate immunity in many ways (see the Table 1 above). Two main differences are 1. it is highly specific and 2. has ability to learn to increase response with each subsequent exposure (has memory). Specificity is achieved because the cells of adaptive immunity (lymphocytes) recognise specific antigens on the invading micro-organism (through antibody molecules in case of B- Cells and T-cell receptors in case of T-cells) rather than general molecular pattern common to whole group/class of that micro-organism recognised by the cells of innate immunity. The second characteristic of the memory is achieved because, with every exposure, the population of lymphocytes that respond to that specific antigen increases as some of the activated cells remain in the body for long time as memory cells (see activation of T and B cells later). There are probably billions of type of antigens to which body can respond (through B and T lymphocytes) to try to eliminate it. Only a very very small portion of this will actually be encountered in the whole life. So it would be an absolute waste of resource if we keep a sufficient number (army) of each of these B or T cells so that antigens would be removed straight away as is done by the cells of the innate immune response (e.g. neutrophils to remove most bacteria). Instead, our body keeps very small numbers of all these B and T cells which respond to each antigen and if any of the foreign body with these antigen manage to cross both of our initial defences (i.e. physical and chemical barrier and innate immunity) the cells of innate immunity (acting as antigen presenting cells and causing inflammation by releasing cytokines) helps find the right B or T cells which respond to the antigens on the invading foreign bodies and selectively activate them. Finding right B or T cells of the adaptive immunity from all other B or T cells, however, does take some time and that is the reason for another characteristic of the adaptive immune response, a lag period that is seen before the adaptive immune response develops (see Figure 2). Page 6 of 80 Figure 2: Characteristics of adaptive Immunity With all above discussion, you should understand that although most people take innate immunity for granted and usually implies adaptive immunity when they loosely talk of “immunity”, innate immunity is the most important component of our defence. Whole lower species of animals lacking in adaptive immunity are able to survive and prosper but no human can survive even without phagocytes (one important component, among many other, of innate immunity). Cells and tissue of the immune system White blood cells (WBCs) or leukocytes are the main cells involved in the immune response. The classifications of WBC based on their staining characteristics (using Giemsa or Wright stain), morphology and their relative abundance in the blood are shown in the Figure 3. Leukocytes or WBCs in the blood Polymorphonuclear cells Monocytes Lymphocytes or 2-8 % 20-30 % Granulocytes Neutrophils Eosinophils Basophils Small Large 50-70 % 2-4 %