An overview of Immune system- Adaptive immunity

1. An overview of Immune system- Adaptive immunity

2. Common terms… • Individuals and lymphocytes that have not encountered a particular antigen are said to be naive, implying that they are immunologically inexperienced • Individuals who have responded to a microbial antigen and are protected from subsequent exposures to that microbe are said to be immune

3. Adaptive immunity • Immune responses that are stimulated by exposure to infectious agents, adapts to the infection and increase in magnitude and defensive capabilities with each successive exposure to a particular microbe is called adaptive immunity • Because this form of immunity develops as a response to infection, it has an extraordinary capacity to distinguish between different, even closely related, microbes and molecules, and for this reason it is also called specific immunity

4. CELLULAR COMPONENTS OF THE ADAPTIVEIMMUNE SYSTEM • The principal cells of the immune system are • lymphocytes • effector cells • antigen-presenting cells • Lymphocytes-recognition is based on certain cell surface expressed molecules termed as CD • B lymphocytes are the only cells capable of producing antibodies. • They recognize extracellular (including cell surface) antigens and differentiate into antibody-secreting plasma cells, thus functioning as the mediators of humoral immunity • T lymphocytes, the cells of cell-mediated immunity, recognize the antigens of intracellular microbes and either help phagocytes to destroy these microbes or directly kill the infected cells. • There are different types of T cells • Helper T cells • Cytotoxic killer T cells • Treg cells • NKT cells Ig TCR

6. CELLULAR COMPONENTS OF THE ADAPTIVEIMMUNE SYSTEM • The principal cells of the immune system are • lymphocytes • effector cells • The activation of lymphocytes by antigen leads to the generation of numerous mechanisms that function to eliminate the antigen • Antigen elimination often requires the participation of cells that are called effector cells because they mediate the final effect of the immune response, which is to get rid of the microbes • Activated T lymphocytes • mononuclear phagocytes • other leukocytes function as effector cells in different immune responses

7. B cells may recognize microbial antigens in their native conformation but the T cells cannot!!! • T cells can recognize processed antigens presented through MHC molecules

8. The principal cells of the immune system are • lymphocytes • effector cells • Antigen presenting cells • The initiation and development of adaptive immune responses require that antigens be captured and displayed to specific lymphocytes The cells that serve this role are called antigen-presenting cells (APCs) • APCs deliver the antigens to specific lymphocytes • The most specialized APCs are dendritic cells, which capture microbial antigens that enter from the external environment, transport these antigens to lymphoid organs, and present the antigens to naive T lymphocytes to initiate immune responses

9. Antigen presenting cells • Dendritic cells are the APCs that display microbial peptides to naive CD4+ and CD8+ T lymphocytes and initiate adaptive immune responses to protein antigens • Dendritic cells located in epithelia and connective tissues • capture microbes, • digest their proteins into peptides, • and express on their surface peptides bound to MHC molecules, the specialized peptide display molecules of the adaptive immune system • Dendritic cells carry their antigenic cargo to draining lymph nodes and take up residence in the same regions of the nodes through which naive T lymphocytes continuously recirculate • Thus, the chance of a lymphocyte with receptors for an antigen finding that antigen is greatly increased by concentrating the antigen in recognizable form in the correct anatomic location

10. Types of Adaptive Immune responses • Humoral immunity is mediated by molecules in the blood and mucosal secretions, called antibodies, which are produced by cells called B lymphocytes (also called B cells) • Humoral immunity is the principal defense mechanism against extracellular microbes and their toxins • The first experimental demonstration of humoral immunity was provided by Emil von Behring and ShibasaburoKitasatoin 1890 • They showed that ifserum from animals that had recovered from diphtheria infection was transferred to naive animals, the recipients became specifically resistant to diphtheria infection. • The active components of the serum were called antitoxins because they neutralized the pathologic effects of the diphtheria toxin • Antibodies themselves are specialized and may activate different effector mechanisms. • Antibodies recognize microbial antigens, neutralize the infectivity of the microbes, and target microbes for elimination by various effectormechanisms • different types of antibodies promote the ingestion of microbes by host cells (phagocytosis) through the process of opsonization • are actively transported into the lumens of mucosal organs to provide defense against ingested and inhaled microbes • through the placenta to provide immunity to the newborn

11. Cellular arm of adaptive immunity is especially designed to counteract the intracellular bacterial and viral infection Some viruses and bacteria survive and proliferate inside phagocytes and other host cells, where they are inaccessible to circulating antibodies It is mainly mediated by T lymphocytes cell-mediated immunity was defined as the form of immunity that can be transferred to naive animals with cells (T lymphocytes) from immunized animals but not with plasma or serum

12. Types of Adaptive Immune responses

13. Cardinal features of adaptive immunity • Specificity and diversity: • Immune responses are specific for distinct antigens • The parts of such antigens that are specifically recognized by individual lymphocytes are called determinants or epitopes • The total number of antigenic specificities of the lymphocytes in an individual, called the lymphocyte repertoire, is extremely large • It is estimated that the immune system of an individual can discriminate 107 to 109 distinct antigenic determinants • Diversity is essential if the immune system is to defend individuals against the many potential pathogens in the environment

14. The number of naive lymphocytes specific for any antigen is very small (on the order of 1 in 105 or 106 lymphocytes) and the quantity of the available antigen is also small therefore what mechanisms are in place to increase the possible chances of interaction of lymphocytes specific for an antigen?

15. Lymphocytes and APCs are concentrated in anatomically discrete lymphoid organs, where they interact with one another to initiate immune responses • Lymphocytes are also present in the blood; from the blood, they can recirculate through lymphoid tissues and home to peripheral tissue sites of antigen exposure to eliminate the antigen

16. Cardinal features of adaptive immunity • Specialization • the immune system responds in distinct and special ways to different microbes, maximizing the effectiveness of antimicrobial defense mechanisms • Thus, humoral immunity and cell-mediated immunity are elicited by different microbes or at different stages of infection (extracellular and intracellular) • and each type of immune response protects different classes of microbes or stages of microbe • Even within humoral or cell-mediated immune responses, the nature of the antibodies or T lymphocytes that are generated may vary from one class of microbe to another.

17. Cardinal features of adaptive immunity • Memory: • secondary immune responses, are usually more rapid, larger, and often qualitatively different from the first, or primary, • memory cells have special characteristics that make them more efficient at responding to and eliminating the antigen than are naive lymphocytes that have not previously been exposed to the antigen • B lymphocytes produce antibodies that bind antigens with higher affinities than do antibodies produced in primary immune responses • and memory T cells react much more rapidly and vigorously to antigen challenge than do naive T cells

18. Cardinal features of adaptive immunity • Clonal expansion: • Lymphocytes specific for an antigen undergo considerable proliferation after exposure to that antigen • The term clonal expansion refers to an increase in the number of cells that express identical receptors for the antigen and thus belong to a clone • This increase in antigen-specific cells enables the adaptive immune response to keep pace with rapidly dividing infectious pathogens

20. Specificity and memory enable the immune system to mount heightened responses to persistent or recurring exposure to the same antigen and thus to combat infections that are prolonged or occur repeatedly

21. Cardinal features of adaptive immunity • Contraction and homeostasis: • All normal immune responses wane with time after antigen stimulation, thus returning the immune system to its resting basal state, a state that is called homeostasis • This contraction of immune responses occurs largely because responses that are triggered by antigens function to eliminate the antigens, thus eliminating an essential stimulus for lymphocyte survival and activation • Lymphocytes, other than memory cells, that are deprived of these stimuli die by apoptosis

22. Cardinal features of adaptive immunity • Nonreactivity to self: • One of the most remarkable properties of every normal individual’s immune system is its ability to recognize, respond to, and eliminate many foreign (non-self) antigens while not reacting harmfully to that individual’s own (self) antigenic substances • Immunologic unresponsiveness is also called tolerance • Tolerance to self antigens, or self-tolerance is maintained by several mechanisms • These include • eliminating lymphocytes that express receptors specific for some self antigens • inactivating self-reactive lymphocytes, or suppressing these cells by the actions of other (regulatory) cells • Abnormalities in the induction or maintenance of self-tolerance lead to immune responses against self (autologous) antigens, which may result in disorders called autoimmune diseases.

23. Cardinal features of adaptive immunity • All humoral and cell-mediated immune responses to foreign antigens have a number of fundamental properties that reflect the properties of the lymphocytes that mediate these responses

24. Regulatory mechanisms • Immune responses are regulated by a system of positive feedback loops that amplify the reaction and by control mechanisms that prevent inappropriate or pathologic reactions • Positive feed back helps small number of lymphocytes to eradicate an infection • However, many control mechanisms become active to prevent excessive activation of lymphocytes, which may cause collateral damage to normal tissues, and to avoid responses against self antigens.

25. CYTOKINES, SOLUBLE MEDIATORSOF THE IMMUNE SYSTEM • Cytokines, a large and heterogeneous group of secreted proteins produced by many different cell types, mediate and regulate all aspects of innate and adaptive immunity. • The human genome contains about 180 genes that may encode proteins with the structural characteristics of cytokines. • many cytokines arbitrarily named on the basis of one of the biologic activities they were discovered to have • interleukins, with a number suffix because cytokines were thought to be made by and to act on leukocytes. • Cytokine synthesis involves new gene transcription as a result of cellular activation • Such transcriptional activation is transient, and the messenger RNAs encoding most cytokines are unstable and often rapidly degraded, so cytokine synthesis is also transient • Various features displayed by cytokines are: • pleiotropism • redundant • antagonize one another or produce additive or synergistic effects. • Endocrine, autocrine and paracrine effect

26. OVERVIEW OF IMMUNE RESPONSES TO MICROBES • The common interfaces between microbes and body i.e. skin and gastrointestinal and respiratory tracts— are lined by continuous epithelia, which serve as barriers to prevent the entry of microbes from the external environment • cellular innate immune response to microbes consists of two main types of reactions— • Inflammation: Inflammation is the process of recruitment of leukocytes and plasma proteins from the blood, their accumulation in tissues, and their activation to destroy the microbes • The major leukocytes that are recruited in inflammation are the phagocytes, neutrophilsand monocytes • On engagement of these receptors, the phagocytes produce reactive oxygen and nitrogen species and lysosomal enzymes, which destroy the microbes that have been ingested • antiviral defense: Antiviral defense consists of a cytokine mediated reaction in which cells acquire resistance to viral infection and killing of virus-infected cells by NK cells • Microbes that are able to withstand these defense reactions in the tissues may enter the blood, where they are recognized by the circulating proteins of innate immunity i.e. complement proteins • The reactions of innate immunity are effective at controlling and even eradicating infections • However many pathogens have evolved mechanisms to evade the innate immunity

27. OVERVIEW OF IMMUNE RESPONSES TO MICROBES • The adaptive immune system uses one or more of these three main strategies to combat most microbes located at various anatomic locations in the body • Secreted antibodies bind to extracellular microbes, block their ability to infect host cells, and promote their ingestion and subsequent destruction by phagocytes • Phagocytes ingest microbes and kill them, and helper T cells enhance the microbicidal abilities of the phagocytes • Cytotoxic T lymphocytes (CTLs) destroy cells infected by microbes that are inaccessible to antibodies and phagocytic destruction