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Immunology And Serology SBD2023

CHAPTER ONE: INTRODUCTION TO IMMUNOLOGY 1.1 INTRODUCTION Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with, among other things, the physiological functioning of the immune system in states of both health and disease; malfunctions of the immune system in immunological disorders (autoimmune diseases, hypersensitivities, immune deficiency, transplant rejection); the physical, chemical and physiological characteristics of the components of the immune system in vitro, in situ, and in vivo.

1.2 HISTORY Earliest recognition of innate immune response can be found on document from ancient Egypt where inflammation was described. Celsus, a Roman physician in the first century described the four cardinal signs of inflamation: rubor (redness), tumor (swelling), calor (heat) and dolor (pain). Smallpox in China and Turkey in the fifteenth century led to the first recorded attempt to intentionally induced and immune response through the use of vaccination with infectious material through cut in the skin or variolation.

1.3 CLASSIFICATION There are two major divisions in immune system: innate immunity and adaptive immunity The innate immune system, which is sometimes called nonspecific immunity or natural immunity that includes physical, chemical and other non-specific mechanical barriers. Innate immunity serves as the first line of defense against microorganism and other invaders. If the first line of defense is broken and the invading organism are able to initiate an infection, the adaptive immune system, also called specific or acquired immunity, becomes activated to produces specific responses to infectious agent The adaptive immune system is able to remember the infectious agent and try to prevent it from causing a similar infection in the future

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Immunology And Serology SBD2023

TABLE 1.1 Summary of differences between innate and adaptive immunity Innate Adaptive Type of response Timing of response Antigen-independent Immediate-maximal response Antigen-dependent Lag time between exposure and maximal response Antigen-specific

Specificity response

of Not antigen-specific

Post exposure result Organism

No immunologic memory

Immunologic memory in jawed

Found nearly in all organism Found only vetebrates

1.2.1 Innate Immunity Nonspecific form of defense inherent to the host Nonspecific immunity consist of o Physical and chemical barriers such as the skin and mucous membrane that line the respiratory tract, gastrointestinal tract and urogenital tract o Secretions such as tears, sweat, saliva and mucus o Plasma protein such as compliment and acute phase proteins that mediate the destruction of microorganism o Cellular components such as polymorphonuclear neutrophils (PMNs), other leukocytes and macrophages that are capable of phagocytosis Innate immunity serve as the first line of defense Although its ability to defense the host is limited it does not require previous exposure to the foreign invader in order to stimulate an effective response

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Immunology And Serology SBD2023

Figure 1.1: Innate Immune Defense: Physical and Chemical Barriers The Physical Barriers Skin and mucosa-Intact skin and mucosa provide a physical barrier to prevent entry of organism. Cilia- The respiratory tract is lined with little hair like structure functioning in propel particles towards the throat where they can be expelling by coughing or swallowing. Mucus- Mucus secreted by epithelial cells of the gut, respiratory tract and genitor-urinary tract. It has unusual properties of being sticky and slimy and the same time and is able to entrap microorganism so they can be expelled. In the respiratory tract, cilia and mucus combined to provide an effective way of trapping and eliminating microbes.

The Chemical and Biochemical Defense Acids- Hydrochloric acids secreted by stomach is lethal to many bacteria (but not all). Commensal bacteria in the vagina produce lactic and proprionic acids resulting in low pH, which is inhibitory to the division of many bacteria. Fatty acids- Sebaceous gland in the skin produces fatty acids that have antimicrobial properties.

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Immunology And Serology SBD2023

Lysozyme- This is present in sweat, tears and many other secretions. It breakdown peptidoglicans in bacterial cell walls, thus damaging and killing bacteria. Defensins- Defensins are antimicrobial peptides that are found in the secretion of mucosa and skin. Cathelicidins- The antibacterial peptides were originally discovered as insect defense peptide. Other members of cathelicidins family have been found in mucosal secretions. Collectins- Collectins are protein that can bind sugars of microbial surface and promote the elimination of microbs. Protein that bind sugars is known as lectins, because collectin bind sugars in a calcium dependent manner known as C-type lectins. The A and D lung surfactants are collectin that provide protection at the lung surface. Other collectins, such as mannosebinding protein are found in serum. Interferon This is a family of proteins produce rapidly by many cells in the body in response to any viral infection. It interferes with viral replication.

Humoral Factor Include immunological substances present in the bodily fluid such as lysozyme and lactoferrin

TABLE 1. ANTIMICROBIAL SUBSTANCES OF HOST ORIGIN PRESENT IN BODY FLUIDS AND ORGANIZED TISSUES

Substance Lysozyme Complement

Common Sources Serum, saliva, sweat, tears Serum

Chemical Composition Protein Proteincarbohydrate lipoprotein complex Proteins or basic peptides

Activity Bacterial cell lysis Cell death or lysis of bacteria; participates in inflammation Disruption of bacterial plasma membrane

Basic proteins and polypeptides (histones, -lysins and other cationic proteins, tissue polypeptides) Lactoferrin and transferring Peroxidase

Serum or organized tissues

Body secretions, serum, organized tissue spaces Saliva, tissues, cells (neutrophils)

Glycoprotein

Inhibit microbial growth by binding (withholding ) iron Act with peroxide to cause lethal oxidations of cells

Protein

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Immunology And Serology SBD2023

Fibronectin

Serum and mucosal surfaces Virus-infected cells, lymphocytes Macrophages, lymphocytes

Glycoprotein

Clearance of bacteria (opsonization) Resistance to virus infections Cause fever; promote activation of immune system

Interferons

Protein

Interleukins

Protein

Resident Flora Non phatogenic bacteria in the intestine, vagina, nasopharynx and etc Prevent colonization of new microorganism

Cellular Component Phagocytes-Macrophages and polymorphonuclear (PMN) leucocytes are most active phagocytic cells which are present in blood and other tissues. Majority of foreign material in tissue as well as bacteria are phagocytes and eliminated by phagocytes. Macrophages - Macrophages have three main function: 1. Phagocytosis. Macrophages ingest the bacteria, virus and other foreign. After the ingestion the phagosome containing the microb fuses with lysosome. The microb is killed within this phagolysosome by reactive oxygen and reactive nitrogen compound by lysosomal enzymes. 2. Antigen presenting cell (APC): Foreign material is ingested and degraded, and fragment of antigent are presented on the macrophage cell surface (by class II MHC protein) for interaction with T4 cells. 3. Cytokine production: Macrophages produce several cytokine that play role in the activation of helper T cell. Dendritic cells- Dendritic cells is the third cell function as APC (macrophages and B cells are other two). They express class II MHC proteins and present antigen to T4 cells. The name dendritic describes their many long, narrow processes (that resembles neuronal dendrites) which make them very efficient in making contact with foreign material. Primarily located under skin. Natural Killer Cells- In the peripheral blood, 10% of lymphocytes lack of T and B cells markers. Due to the absent of these two surface, these lymphocytes are called Null cells. These large granular lymphocytes mediate rapid lysis of virus infected cell, tumor cell and foreign graft T cells and also called natural killer cells. Eosinophils Eosinophils are polymorphic nuclear leucocytes. They contain large protein granules which have a high affinity for acids dyes such as eosin. They constitute about 2-6 percent of peripheral blood. Eosinophils are

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Immunology And Serology SBD2023

phagocytic cells whose primary function is to ingest and destroy foreign particles. The eosinophils are more suited to extracellular destruction of large parasites than to phagocytes of small particles. They release the content of their granules into the surrounding to reach the parasitic worms. Mast cell and basophils Mast cell are large, round cell distributed in the connective tissue through out the body. Basophils are similar to mast cell but are present in peripheral blood. They constitute about 0.5% of blood leucocytes. Both mast cell and basophil have reseptor for IgE and when the IgE bind the antigen or allergen it will trigger the release the content of cytoplasmic granules. These granules contain vasoactive amines which cause capillary dilatation and increase vascular permeability.

Table 1.2 Cells that involved in innate immunity Cells Function Phagocytes Engulf and destroy foreign substances or microorganism Natural Killer cells Eliminate cells that are infected with virus Eosinophils Destruction of helminthes Antigen Presenting cells Mast cells and basophils Process antigen Release substance into local microenvironment to facilitate recruitment of immune cells to the site of infection

1.2.2 Adaptive Immunity Acquired or adaptive immunity enhances and compliment innate immunity in protecting the host Adaptive immunity occurs after exposure to an agent, improves upon repeated exposure and is specific. It is mediated by antibody produced by B lymphocytes and by T cells. The cells responsible for acquired immunity have long-term memory for a specific antigen. Acquired immunity can be active or passive. a. Active immunity Acquired by direct exposure to antigen which stimulates individuals own immune system. The exposure to the antigen may be natural, for example through infection or artificial such as in vaccination. The disadvantage of this type of immunity is that it take sometime after the exposure to develop. However one produced it last for a long time because of the memory. b. Passive immunity Transferred passively from an immune individual to a non-immune individual. The transfer can be effective without the induction of any immune response in the recipient. It occurs through soluble mediators of immunity such as antibodies or cytokines. Passive transfer immunity naturally occurs from mother to fetus in form of IgG which can pass through placenta r IgA through breast milk. It also can be transferred artificially by administration of known antibody against an infectious agent (eg:anti-tetanus).
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Immunology And Serology SBD2023

TABLE 1.3 Host defenses in adaptive immunity Cells B cells Plasma cells T cytotoxic cells T helper cell Antibodies Cytokines

Humoral Factors

Cellular Adaptive Immunity Lymphocytes are the adaptive cell: B cells & T cells. Matured lymphocytes in peripheral blood are round in shape, measuring approximately 6-15m in diameter. The nucleus is large in size giving a high nucleus to cytoplasm ratio. Lymphocytes comprised off 20-50% of WBC in normal adult. When stain with Giemsa or Leishman Stain, the nucleus of lymphocytes stain intense purple with coarse masses of chromatin. The cytoplasm appears pale blue without any granules or may contain a few fine granules. B-Lymphocytes B-cells forms about 20-25% of the small lymphocytes in peripheral blood. They have a short life span, only a few days or weeks. Although they originally develop in bone marrow, when activated by antigenic stimulus they undergo differentiation in secondary lymphoid organs. Matured B-cells have a large number of immunoglobulin molecules (105 molecules per cell) on their surface. When activated by antigen, B cells undergo transformation, enlarge and become lymphoblast. The lymphoblasts proliferate and quickly increase in number. Some of this lymphoblast further differentiates into plasma cells. Plasma cells are oval shape cells, 7-5m in diameter with round, eccentrically placed nucleus. Plasma cell is the cell that secrete antibody instead of expressing them on the cell surface Some lymphoblast revert to a resting stage and form memory cells specific for the antigen which induced it transformation. When reexposed to the same or related antigen, these memory cells generate a rapid and more intense secondary response. T-Lymphocytes T-Lymphocytes constitute approximately 65-80% of circulating small lymphocytes in the peripheral blood. They have a long life span extending up to a few month even years. T cell requires an intact thymus for their functional maturation. Unlike B-cells, T cells do not have immunoglobulin molecules on their surface and cannot synthesis antibodies when stimulate by antigen. T-cells have many surface receptor called as CD (cluster of differentiation) markers. One markers may bind with several monoclonal antibodies. CD 2 is present on all T-cells; CD 4 is expressed primarily by T helper cell.
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Immunology And Serology SBD2023

i.

T-helper cells (Th/T4). These T cells are responsible for producing lymphokines and help B-cells in the process of antibody production. Most of T4 have CD4 marker on the cell surface.

ii. T-cytotoxic T cells (Tc). Some T cells are cytotoxic or lethal to a cell that carry certain antigen on their surface such as virus infected cells, tumor cells or transplanted cells. A large number of Tc have a CD8 surface marker. Humoral Adaptive Immunity Humoral adaptive immunity are proteins secreted by adaptive immune cells. Antibody- Serum immunoglobulin produced by plasma cell in response to antigenic stimulus. Cytokines- small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis secreted by various cell.

REFERENCES 1. ESSENTIAL IMMUNOLGY PUBLISHED BY BLACKWELL SCIENCE Year 2000 2. IMMUNOLOGY A SHORT COURSE PUBLSHED BY WILLEY-LISS Year 2003 3. CLINICAL LABORATORY IMUNOLOGY PUBLISHED BY PEARSON Year 2006

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