Dr Farrokhi Sh., MD, PhDDr Farrokhi Sh., MD, PhD

Immunologist and AllergistImmunologist and Allergist

Email: Email:

Farrokhi_sh@yahoo.comFarrokhi_sh@yahoo.com

Properties and Overview of Immune ResponsesProperties and Overview of Immune Responses

History of Immunology

• Immunity is derived from the Latin word immunitas, which referred to the protection from legal prosecution offered to Roman senators during their tenures in office

• Historically, immunity meant protection from disease and, more specifically, infectious disease

• The cells and molecules responsible for immunity constitute the immune system, and their collective and coordinated response to the introduction of foreign substances is called the immune response

• The physiologic function of the immune system is defense against infectious microbes. However, even noninfectious foreign substances can elicit immune responses

• Under some situations, even self molecules can elicit immune responses (so-called autoimmune responses)

History of Immunology

• Historians often credit Thucydides, in the fifth century BC in Athens, as having first mentioned immunity to an infection that he called plague (but that was probably not the bubonic plague we recognize today)

• Immunology, in its modern form, is an experimental science

• In 1796, Edward Jenner demonstrated that inoculation with cowpox could protect against smallpox that called the procedure vaccination (Latin vaccinus, of or from cows)

• The importance of immunology was the announcement by the World Health Organization (WHO) in 1980 that smallpox was the first disease that had been eradicated worldwide by a program of vaccination

• Since the 1960s, there has been a remarkable transformation in our understanding of the immune system and its functions. Advances in cell culture techniques (including monoclonal antibody production), immunochemistry, recombinant DNA methodology, and x-ray crystallography and the creation of genetically altered animals (especially transgenic and knockout mice) have changed immunology from a largely descriptive science into one in which diverse immune phenomena can be explained in structural and biochemical terms

Clinical Immunology

• Infection Dx (viral, bacterial,…)

• Immunodeficiency (primary and secondary)

• Allergic Dx (AR, Asthma, urticaria, anaphylaxis,…)

• Autoimmunity (RA, SLE, vasculitis,…)

• Lymphoproliferative Dx (leukemia, lymphoma,…)

• Immune manipulation (Immunotherapy, Immunosuppression, mAb,…)

• Transplantation (BMT, organ T.,…)

• Skin Dx (AD, PV,…)

• Eye Dx (conjunctivitis, scleritis,…)

• Lung Dx (infecion, granulomatous Dx,…)

• GI (IBD, liver Dx,…)

• Hematologic Dx (anemia, thrombocytopenia,…)

• Neurologic Dx (MS, MG,…)

• OB and Gyn ( pregnancy, abortion, preeclampcia, …)

Innate Immunity

Innate Immunity

• Defense against microbes is mediated by the early reactions of innate immunity and the later responses of adaptive immunity

• Innate immunity (also called natural or native immunity) provides the early line of defense against microbes

Innate Immunity

• Innate immunity also called natural or native immunity

• Principal components of innate immunity are:

– (1) physical and chemical barriers, such as epithelia and antimicrobial substances produced at epithelial surfaces;

– (2) phagocytic cells (Neutrophils, Macrophages) and Natural Killer (NK) cells;

– (3) blood proteins, including members of the complement system and other mediators of inflammation;

– (4) proteins called cytokines that regulate and coordinate many of the activities of the cells of innate immunity

Innate Immunity

• Mechanisms of innate immunity are specific for structures that are common to groups of related microbes and may not distinguish fine differences between foreign substances

Adaptive Immunity

Adaptive Immunity

• Because adaptive immunity develops as a response to infection and adapts to the infection, it is called

• Defining characteristics specificity for distinct molecules and an ability to remember

• In addition, 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

• It is also sometimes called acquired immunity, to emphasize that potent protective responses are "acquired" by experience

• Main components of adaptive immunity are cells called lymphocytes and their secreted products, such as antibodies afetr recogntion of foreign substances called antigen

Features of Innate and Adaptive Immunity

Types of adaptive immunity

• There are two types of adaptive immune responses, called humoral immunity (B cell) and cell-mediated immunity (T cell)

• Humoral immunity:

– is mediated by molecules in the blood and mucosal secretions, called antibodies

– against extracellular microbes and their toxins

– Antibodies themselves are specialized, (phagocytosis and trigger the release of inflammatory mediators)

• Cell-mediated immunity (CMI), also called cellular immunity, is:

– Mediated by T lymphocytes (also called T cells)

– Intracellular microbes, such as viruses and some bacteria

Types of adaptive immunity

Forms of immunity

– Active immunity• Naïve lymphocyte

– Passive immunity• Transfer of maternal antibodies to the fetus,

Passive Immunity

• Early 1890s, Emil von Behring and Shibasaburo Kitasato discovered the serum of animals immune to diphtheria or tetanus contained a specific 'antitoxic activity‘ or Antibody the award of the first Nobel Prize in Physiology or Medicine

• In the 1880s, Louis Pasteur devised a vaccine against cholera in chickens, and developed a rabies vaccine

• In the early 1900s by Paul Ehrlich, Antibodies (antikörper in German) for the serum proteins that mediate humoral immunity

• The modern definition of antigens includes substances that bind to specific lymphocyte receptors, whether or not they stimulate immune responses

• Substances that stimulate immune responses are called immunogens

• Ehrlich’s concepts are a remarkably prescient model for the function of B cells in humoral immunity (humoral theory of immunity) substances present in body fluids (once called humors)

• The cellular theory of immunity, which stated that host cells are the principal mediators of immunity, was championed initially by Elie Metchnikoff published in 1883

• Ehrlich and Metchnikoff shared the Nobel Prize in 1908,

Specificity, memory, and contraction of adaptive immune responses

CARDINAL FEATURES OF ADAPTIVE IMMUNE RESPONSES

• Specificity and diversity:

– Immune responses are specific for distinct antigens (protein, polysacharide,…)

– Parts of such antigens that are specifically recognized are called determinants or epitopes

– Fine specificity

– Clones of lymphocytes with different specificities are present

– Total number of antigenic specificities of the lymphocytes in an individual, called the lymphocyte repertoire (107-109 distinct antigenic determinants) )

– Lymphocyte repertoire is called diversity

• Memory:

– Responses to second and subsequent exposures to the same antigen, called secondary immune responses, are usually more rapid and larger

– Clone of lymphocytes specific for antigen

• Clonal expansion:

– an increase in the number of cells that express identical receptors for the antigen and thus belong to a clone

• Specialization:

– immune system responds in distinct and special ways to different microbes, maximizing the effectiveness of antimicrobial defense mechanisms (extracellular and intracellular)

• Contraction and homeostasis:

– Returning the immune system to its resting basal state

• Nonreactivity to self:

– Tolerance

– Autoimmune diseases

CELLULAR COMPONENTS OF ADAPTIVE IMMUNE SYSTEM

• Principal cells of the immune system are lymphocytes, antigen-presenting cells (APC), and effector cells

• B lymphocytes diferentiate to Plasma cell

• T lymphocyte– Helper T (Th) 1, 2, 9, 17

– Cytotoxic T lymphocyte (CTL)

– Regulatory T cells (Treg)

• Natural Killer Cells (NKC)

• NKT cell

Classes of Lymphocytes

• Different classes of lymphocytes can be distinguished by the expression of surface proteins that are named "CD molecules" and numbered

• The cells of innate immunity interact with one another and with other host cells during the initiation and effector stages of innate and adaptive immune responses

• Many of these interactions are mediated by secreted proteins called cytokines

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

• called interleukins

• Cytokines are not usually stored as preformed molecules, and their synthesis is initiated by new gene transcription as a result of cellular activation

• Autocrine, paracrine, endocrine

OVERVIEW OF IMMUNE RESPONSES TO MICROBES

The Early Innate Immune Response to Microbes

• Blocks the entry of microbes and eliminates or limits the growth of many microbes that are able to colonize tissues

• The cellular innate immune response to microbes consists of two main types of reactions—inflammation and antiviral defense

• 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

• Antiviral defense consists of a cytokinemediated reaction in which cells acquire resistance to viral infection and killing of virus-infected cells by NK cells

Phases of Adaptive Immune Responses

Antigen Recognition by Lymphocytes

• Clonal selection hypothesis, first suggested by Niels Jerne in 1955, and most clearly enunciated by Macfarlane Burnet in 1957, as a hypothesis to explain how the immune system could respond to a large number and variety of antigens

• Lymphocytes specific for a large number of antigens exist prior to exposure to the antigen, and when an antigen enters, it selects the specific cells and activates them

• Antigen-specific clones of lymphocytes develop before and independent of exposure to antigen

• > 10 1066 different specificities in T and B lymphocytes

Clonal Selection Hypothesis

Reference:

• Cellular and Molecular ImmunologyCellular and Molecular Immunology. Abul K. Abbas, Andrew H. . Abul K. Abbas, Andrew H.

Lichman, S. Pillai , 7Lichman, S. Pillai , 7thth edition 2012 Saunders edition 2012 Saunders