7. Immunity (Microbiology)

Immunity for B.Sc. Nursing

1. Introduction Immunology is the science that is concerned with the immune response to foreign challenges. Immunity (derived from Latin term immunis , meaning exempt ) , is the ability of an organism to resist infections by pathogens or state of protection against foreign organisms or substances. The array of cells, tissues and organs which carry out this activity constitute the immune system.

2. Refers to the resistance exhibited by the host towards injury caused by microorganism and their products; Protection against infectious diseases Distinguishes self from non-self Eliminate potentially destructive foreign substances from body Immunity to microorganism is usually indicated by the presence of antibody to that organism. Immunity is generally specific to a single organism or group of closely related organism. There are two basic mechanism for acquiring immunity, they are active and passive immunity.

3. Active immunity is protection that is produced by the persons own immune system. This type of immunity is usually permanent. Passive immunity is protection by products produced by an animal or human transferred to human, usually by injection. Passive immunity often provides effective protection, but this disappears with time, usually within weeks or months.

4. Immunity is classified into two types: Innate immunity Species Racial Individual Acquired immunity Active Natural Artificial Passive Natural Artificial

5. Innate immunity (natural/native) is present since birth and consists of many factors that are relatively nonspecific that is, it operates against almost any foreign molecules and pathogens . It provides first line defense against pathogens. It is non specific to any one pathogen but rather acts against all foreign molecules and pathogens. It also does not rely on previous exposure to a pathogen and response is functional since birth and has no memory.

6. Physical barriers are the first line of defence against microbes. It includes skin, mucous and mucous membrane. Most organisms and foreign substance cannot penetrate intact skin but can enter the body if the skin is damaged. Secondly, the acidic pH of sweat and sebaceous secretions and the presence of various fatty acids and hydrolytic enzymes like lysozyme inhibit growth of most microorganism. Similarly, respiratory and gastrointestinal tracts are line by mucous membranes. Mucus membranes entraps foreign microbes. The respiratory tracts is also covered by cilia, which are hair like projections of the epithelial-cell membranes. The synchronous movement of cilia propels mucus-entrapped microorganism out of these tracts.

7. Similarly, conjunctiva is a specialized mucus-secreting epithelial membrane that lines the interior surface of the each eyelid. It keep moist by the continuous flushing action of tears (lacrimal fluid). Tears contain lysozyme, lactoferrin, IgA and thus provide chemical as well as physical protection. In case of innate immune response several antimicrobial chemicals and phagocytic cells provide protection against pathogens.

8. Chemical mediator, variety of chemical mediate protection against microbes during the period before adaptive immunity develops. The molecules of the innate system include complement proteins, cytokines, pattern recognition molecules, acute-phase proteins, cationic peptides, enzyme like lysozymes and many others.

9. Complement proteins are soluble proteins/ glycoproteins that are synthesized by liver and circulate in the blood and extracellular fluids. They were originally identified by their ability to amplify and complement the action of antibodies; hence the name complement. It also bridge innate and adaptive immunity and removes immune complexes. The complement system is composed of over 30 serum proteins. Activation of complement proteins in response to certain microorganism results in a controlled enzymatic cascade, which target membrane of pathogenic organism and leads to their destruction.

10. Cytokines term is a generic term for any low molecular weight soluble protein or glycoprotein released by one cell population which act as an intercellular mediator. It includes monokines , lymphokines, interleukins, inerferons and others. Cytokines are required for immunoregulation of both innate as well as adaptive immune responses. Interferons are cytokines made by cells in response to virus infection, which essentially induce a generalized antiviral state in surrounding cells. Chemokines are small, positively charged secreted proteins that have a central role in guiding the migrations of various type of WBC.

11. Pattern recognition molecules, many molecules involved in innate immunity have the ability to recognize Pathogen-Associated Molecular Pattern (PAMP) for the initial detection of microbes. PAMPs are micro-specific molecular signatures. PAMPs are recognized by Pattern-Recognition Receptors (PRRs). Mammals have several classes of PRRs including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), Nod-like receptors (NLRs), AIM2-like receptors (ALRs) and C-type lectin receptors (CLRs). TLRs were the first to be identified, and are the best characterized.

12. Cellular defenses, many specialized cell type like neutrophils, macrophages, monocytes, natural killer cells (NK cells) participate in innate host defense mechanisms. Once pathogen evades physical and chemical barriers, these specialized cells play important role in protection. Phagocytosis is a fundamental protective mechanism carried out by these cell types, neutrophils, macrophages, monocytes and dendritic cells. In vertebrates, macrophages reside in tissues throughout the body. Macrophages are long lived cells, which patrol the tissues of the body.

13. The second major type of phagocytic cells in vertebrates, the neutrophils, are short lived cells which are abundant in blood but are not present in normal healthy tissues. Phagocytosis is the ingestion of invading foreign particles, such as bacteria by individual cell. Phagocytosis may enhanced by a variety of factors collectively referred to as Opsonins (Greek word meaning ‘prepared food for’) which consists of antibodies and various serum components of complement. The process by which particle more susceptible to phagocytosis is called opsonization. After ingestion it forms phagosome, which fuses with lysosomes forming the phagolysosome.

14. Inflammatory barriers is an important nonspecific defense reaction to cell injury. The hallmark signs of inflammatory are pain, redness (erythema), swelling (edema) and heat. Each of these result of specific changes in the local blood vessels. Erythema is caused by increased vascular diameter, which leads to increased blood flow, thereby causing heat and redness in the area. The blood vessels become permeable to fluid and proteins, leading to local swelling and an accumulation of blood proteins that aid in defense.

15. Antigen specificity: It is the ability to discriminate among different epitopes/antigens. Immunologic memory: It is the ability to recall previous contract with a foreign molecule and response to it in a learned manner-that is, with a more rapid and larger response. Diversity: The ability to respond to different epitopes even if the individual has not previously encountered them. Self/non-self recognition: It is the ability to recognize and respond to molecules that are foreign and to avoid making a response to those molecules that are self (self tolerance).

16. Immune response of adaptive immunity There are two arms (branches) of acquired immunity, which have different sets of participants and different purposes but one common aim: to eliminate antigen. Of this two arms of the acquired immune response, one is mediated mainly by B-cells and circulating antibodies, a form of immunity which is referred to as humoral immunity ( the word humors was formerly used to define body fluids).

17. The other is mediated by T-cells, which, do not synthesize antibody but instead synthesize and release various cytokines that affect other cells. Hence, this arm of the acquired immune response is termed cellular or cell-mediated immunity.

18. Innate and adaptive immunity are not independent The innate and adaptive immunity operate in cooperative and interdependent ways. They cooperate in many ways;

19. The cells responsible for both non-specific and specific immunity are the leukocytes or white blood cells. All leukocytes arise from a type of cell called the hematopoietic stem cell. A hematopoietic stem cell is multipotent cell. During hematopoiesis, hematopoietic stem cell differentiates along one of the two pathways Lymphoid progenitor cell Myeloid progenitor cell Cells of immune system

20. Responsible for adaptive immune response Lymphocytes are mononuclear leukocytes (20-40% of total WBC) Occurs in large number in lymph and in lymphoid organs such as the thymus, lymph nodes, spleen and appendix. Up to 99% of lymphocytes cell in lymph. Three main types; B-lymphocytes (B-cells) T-lymphocytes (T-cells) Natural Killer (NK cells) cells Lymphoid progenitor

21. Matures in the bone marrow in mammalian species Expresses membrane bound antibody After interacting, it differentiates into antibody secreting plasma cells and memory cells Only cell type capable of producing antibody molecules Central cellular component of humoral immune responses Serves as Antigen Presenting Cells (APCs) B-lymphocytes (B-cells)

22. Arise in bone marrow Maturation in thymus gland T-cells do not make antibodies Performs various effectors function when APC bring antigen into secondary lymphoid organ Helps in eliminating APCs, cancer cells, virus-infected cells or grafts which have altered self-cells Helper T-cells are crucial for defense against both extracellular and intracellular pathogens T-lymphocytes

23. Properties B-cells T-cells Origin Bone marrow Bone marrow Maturation Bone marrow Thymus Expression of Ag receptors Bone marrow Thymus Differentiation In lymphoid tissue Lymphoid tissue Surface Ig Present Absent Immunity Humoral Cell mediated Secretory product Antibodies and Cytokines Cytokines Receptos Present TCR on membrane

24. NK cells are neither T-cells nor B-cells Plays role in destroying cells infected with intracellular pathogens 5-10% of total lymphocyte population NK cells destroys target cell not by phagocytosis but by releasing biologically potent molecules Natural killer cells (NK cells)

25. Bone marrow derived cells Rises from both the myeloid and lymphoid D endritic cells are classified into; Langerhans cells Intestinal dendritic cells Myeloid dendritic cells Lymphoid dendritic cells Dendritic cells

26. Cells arises from a common myeloid progenitor includes RBC (erythroid cells) as well as various types of WBC (myeloid cells such as granulocytes, monocytes, macrophages and some dendritic cells). Myeloid progenitor

27. Irregular shaped nuclei Also called polymorphonuclear neutrophils or PMNs Multilobed nucleus Granular cytoplasm (stains with both acidic and basic dyes) 50-70% of the circulating white blood cells Produced in bone marrow Neutrophils

28. Bilobed nucleus Stains with acidic dyes (eosin) 2-5% of WBC Motile phagocytic cells Can migrate from blood into tissue space Role is important in the defense against protozoan and helminth parasites Eosinophils

29. Lobed nucleus Stains with basic dye (methylene blue) Less than 1% of WBC Non-phagocytic, release substances that cause an allergic responses Includes histamine, prostaglandins, serotonin and leukotrienes Posses high affinity receptors for one type of antibody, known as IgE . Basophils

30. Mast cell precursors are formed in bone marrow and released into the blood in an undifferentiated state , until they reach the tissues L arge number of cytoplasmic granules containing histamine M ast cell and Basophils play role in allergic responses Mast cells

31. Phagocytes derived from blood monocytes Monocytes migrates into tissue to response to infection can differentiate into specific tissue macrophages Monocytes is small, spherical cell with few projections, abundant cytoplasm and many granules Migration of monocytes from blood to various tissues, which undergo differentiation and all will play role of phagocytosis, including; Kupffer cells, in liver Alveolar macrophages, in the lungs Splenic macrophages, in the white pulp Peritoneal macrophages, free-floating in peritoneal fluid Osteoclast, in bone Mesangial cells, in kidney , and Microglial cells, in the CNT Macrophages

32. Primary lymphoid organs Bone marrow Thymus Secondary lymphoid organs/tissues Spleen Lymph nodes Mucosa associated lymph tissue (MALT) Organs involved in the adaptive immune system

33. Adaptive immune response arise as a result of exposure of foreign compounds. The compounds that evokes the response is referred to as antigen. An antigen is any agent capable of binding specifically to T-cell receptors (TCR) or an antibody molecules (membrane bound or soluble). An ability of a compound to bind with an antibody or a TCR is referred to as antigenicity. Functional distinction between the term antigen and immunogen An immunogen is any agent capable of inducing an immune response and is therefore immunogenic. All immunogens are antigens, but not all antigens are immunogens. Antigen

34. Foreignness Size Chemical complexity ( Eg. Homopolymer of poly-gamma-D-glutamic acid) Dosage and route of administration Requirement for immunogenicity

35. Antigen-Antibody interactions

36. Ag-Ab interaction is highly specific and occurs in a similar way as biomolecular association of an enzyme-substrate. The binding between antigens and immune components involves weak non-covalent interactions. The binding forces are weak and reversible and consists mainly of; Van der waals forces Hydrogen bond Electrostatic forces (Ionic bond) Hydrophobic forces

37. The smallest unit of antigen that is capable of binding with antibodies is called an antigenic determinant (or epitope) The corresponding area on the Ab molecule combining with the epitope is called paratope The number of epitopes on the surface of an antigen is its valence The valence determines the number of antibody molecules that can bind with the antigen at one time. Monovalent and Polyvalent

38. The intrinsic association constant that characterizes the noncovalent interaction between single antigen binding site of an antibody (paratope) with an epitope is termed as affinity. Avidity is used to denote the overall binding between antibodies and the multivalent antigen. So, when complex Ag having multiple repeating epitopes, are mixed with Ab having multiple binding sites the interaction of such type between multivalent Ab and Ag is called, the Avidity. Affinity and Avidity

39. Although Ag-Ab reaction is very specific, sometimes antibodies elicited by one antigen can cross-react with an unrelated antigen. An immunologic reaction in which a particular antibody or T-cell receptors react with two or more antigens that posses a common epitope is called a cross-reaction. Another form of cross-reaction is seen when antibodies or cells with specificity to one epitope bind, usually more quickly, to another epitope that is not quite identical but has a structural resemblance to the first epitope. Cross-reactivity

40. Affinity: Higher the affinity of the Ab for the Ag, the more stable will be the interaction Avidity: Reaction between multivalent antigens and multivalent antibodies are more stable Antigen to antibody ratio: The ratio between Ag and Ab influences the detection of Ag-Ab complexes because the size of complexes formed is related to the concentration of the antigen and antibody. Physical form of the antigen: When the Ag is particulate, the reaction of an antibody with the Ag can be detected by agglutination of antigen. Factors affecting Ag-Ab interaction

41. Immunization for various disease