Transcript Slide 1

Dr Farrokhi Sh., MD, PhD
Immunologist and Allergist
Email:
[email protected]
Properties 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 (socalled 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
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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:
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(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 MEDIATORS
OF 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
• > 106 different specificities in T and B lymphocytes
Clonal Selection Hypothesis
Reference:
• Cellular and Molecular Immunology. Abul K. Abbas, Andrew H.
Lichman, S. Pillai , 7th edition 2012 Saunders