Cellular and Molecular Immunology from Nptel – Biotechnology

Module 1: Introduction to Cellular and Molecular Immunology

Lecture 1: Introduction to Immunity

The term immunity comes from the Latin word immunitas, means protection from legal prosecution. Immunity refers to protection from disease and other pathogens. The cells and molecules responsible for immunity are called immune system and their efforts in regards to any etiological agent are called immune responses. Normally the immune responses are elicited against the foreign substances but occasionally to the self molecules and are referred as autoimmune responses. Immunology is a branch of life- science which deals with the cellular and molecular events occurring in the body after encounters of micro-organisms and other foreign substances.

The history of immunology is quite old. In ancient China, people often used skin lesions of patients recovered from small pox to cure small pox in young children. The first successful record of vaccination came from the work of Edward Jenner's efficacious vaccination against smallpox. Jenner observed that milkmaid who had recovered from cowpox never showed any symptom of smallpox. Following this observation he inoculated the cowpox pustules into the arm of a young boy who later did not show full progressive smallpox symptoms. Small pox was the first disease that was eradicated worldwide by vaccination.

Recently the science of immunology has grown up by the advent of new molecular biology tools. Our current understanding of the human and animal immune system and its functions has remarkably improved. Advances such as recombinant DNA technology, immunohistochemistry, monoclonal antibody production and x-ray crystallography have changed the immunology to a broader area. The development of techniques to produce transgenic and knockout mice has also played a great role to understand many complex immunological pathways.

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1.1 Innate and Adaptive Immunity

Defense against microbes includes an early response action called innate immunity and a later response called as adaptive immunity. Innate immunity is also called natural or native immunity and provides first line of defense against any microbial infection in human body. It usually involves many cellular and biochemical events that react to microbes and their products in order to clear them from the body. The main components of innate immune system are

1. Barriers - skin and outer epithelial surface.
2. Scavenger cells - neutrophils, macrophages, dendritic cell and natural killer cells.
3. Complement system
4. Cytokines
5. Chemical mediators of inflammation

Microbial agents and pathogens contain some molecules over their surface that act as foreign substance for the body and are collectively called as pathogen associated molecular pattern (PAMP). PAMP's are recognized by specific proteins and biochemical molecules produced by cells of innate immunity and these recognition molecules are called as pattern recognition receptors. The innate immune responses are produced against the specific structures present over the microbes and are common to many of them. Thus, they cannot distinguish the minute differences among microbes.

In contrast, adaptive immunity is stimulated by constant exposure of infectious agents. The most characteristic feature of adaptive immunity is memory against the repetitive exposure of same pathogen. Furthermore, it has a capacity to distinguish between fine differences among microbes and hence also called as specific immunity. As specific immunity is gathered by constant exposure to the foreign agent, it is better termed as acquired immunity. The central components of adaptive immunity are

1. Lymphocytes and their secreted products e.g. antibodies
2. Foreign substances that trigger specific immune responses and are identified by lymphocytes or antibodies are called as antigens.

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Figure 1.1 Graph showing the relation between innate and acquired immunity:

Acquired immunity Innate immunity Level of Protection Physical barrier Minutes Hours Days Weeks Time

Almost all the higher organisms have well developed mechanisms for defending against the microorganisms. Innate and adaptive system work together as they are the components of host integrated system. However there are many microbes that have developed and adapted to resist the innate immunity and hence more robust mechanisms are required for their expulsion. Innate and adaptive immune systems are interlinked; stimulation of anyone against the foreign substances instigates the other and hence functions cooperatively.

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Table 1.1 common features of innate and adaptive immunity:

Features Innate Adaptive Specificity Molecules present in a group of related microbes Microbes and nonmicrobial molecules Memory No Yes Diversity Narrow Wide Reactivity against self No No Part of innate and adaptive system Barrier Skin, epithelial surface Lymphocyte and antibodies Proteins Complements Antibodies Cells Phagocytes Lymphocytes

The mechanism of innate immunity provides an initial defense against the infection. Adaptive immune responses develop later and consist of lymphocytes.

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Figure 1.2 Innate and adaptive immunity:

Microbe 000000000 Epithelial barriers Hours 16 Complement Dendritic cells Phagocytes NK cells 12 Adaptive immunity - 1 B lymphocytes T lymphocytes Days 1 4 - 7 Antibodies Effector T cells 0 Innate immunity Time after infection

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Lecture 2: Properties of Immune System

2.1 Cells of the immune system

Cells of the immune system are present as circulating cells in the blood and lymph. They are distributed to almost every organ and tissue of the animal body. Their distributions upon exposure to an external agent or pathogens are utmost important in the generation of effective immune response. At beginning, the immune system must respond to the entering pathogen followed by an adaptive immune response by specific lymphocyte. Finally, the cells of adaptive immune response destroy the pathogens by the effector cells.

Followings are the major cells of immune system

2.1.1 Macrophages and Phagocytes

They are present in virtually every tissue and organ of the body and respond instantaneously to the entering pathogens. The job of phagocytic cells involves recruitment of cells at the site of infection, ingestion, and destruction of the pathogens.

2.1.2 Neutrophils

These are the granulocytes present in the blood stream and are the first line of the defense in the body. They are the most abundant cells present in the blood stream. They are about 12-15 um in diameter with projection on their surface. The nucleus of neutrophils contains 3-5 lobes (polymorphonuclear cells). The cytoplasm of the neutrophils contains the granules that are filled with enzymes like lysozyme, collagenase, and elastase. They are stained with neutral dyes and produced in the bone marrow. The production of neutrophils is stimulated by granulocyte colony stimulating factors (G-CSF). On an average about 10 cells/day are produced in a normal human individual. Usually neutrophils are recruited at the site of infection immediately following the invasion of the foreign substance, if not they undergo apoptosis and get cleared from the circulation. The other two granulocytes present in the blood are basophils and eosinophils which are stained by basic (hematoxylin) and acidic (eosin) dye, respectively.

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2.1.3 Mononuclear phagocytes

They play a central role in the innate and adaptive immune system. They are formed by precursor hematopoietic cells and are called monocytes. They are about 10-15 um in diameter and have bean shaped nuclei. Once enter into the circulation they are called macrophages. The major function of macrophage includes following

1. To ingest and kill the microbes.
2. To ingest and clear dead cells and unused cells.
3. They secrete cytokines upon activation.
4. They serve as antigen presenting cells to display the antigens to the T lymphocyte.
5. They also help in angiogenesis (formation of blood vessels).

2.1.4 Mast cells

These are derived from bone marrow cells and contain histamine and other chemical mediators of allergic diseases. Mast cells express the receptors for IgE and IgG antibodies. They also provides defense against helminth infection.

2.1.5 Basophils

They are structurally and functionally similar to mast cells and mediate allergic conditions. The granules of basophils contain acidic proteins which bind to basic dyes (hematoxylin)

2.1.6 Eosinophils

They are granulocytes present in the blood and contains the enzyme required to damage the cell wall of the parasite. The granules of the eosinophils contain the basic proteins which bind to acidic dye (eosin).

2.1.7 Dendritic cells

They are the specialized antigen presenting cells which captures the microbes and microbial antigens, and transport them to lymphoid tissues to be recognized by lymphocytes. They activate the naive T cells and form a bridge between innate and adaptive immune response. They are widely distributed into many organs and epithelial surface. Plasmacytoid dendritic cells are the subpopulation of dendritic cells involved in the recognition of the virus infected cells.

2.1.8 Naïve lymphocytes

The lymphocytes that are not previously encountered with antigens are called as Naïve lymphocytes. They trigger the adaptive immune response after encountering with the antigen.

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