2. Outline
▪ The Normal Immune Response
▪ Cells and Tissues of the Immune System
▪ Overview of Lymphocyte Activation and Adaptive Immune
Response
▪ References
3. Immune System
▪ Immunity refers to protection against infections.
▪ The immune system is the collection of cells and molecules that are
responsible for defending the body against the countless pathogens that
individuals encounter.
▪ Immunodeficiency Diseases; Defects in the immune system render
individuals easy prey to infections
▪ Hypersensitivity Disorders; when the immune system is itself capable of
causing tissue injury and disease.
4. Normal Immune Response
▪ Defense against pathogens consists of two types of reactions
▪ Innate immunity (Natural or Native immunity) is mediated by cells and
proteins that are always present poised to react against infectious
pathogens.
▪ Called into action immediately in response to infection
▪ Provide the first line of defense.
▪ Some of these mechanisms also are involved in clearing damaged
cells and tissues.
▪ A major reaction of innate immunity is inflammation
5. Normal Immune Response
▪ Many pathogens have evolved to resist innate immunity,
▪ Adaptive Immunity (Acquired/ Specific); More specialized and
powerful mechanisms of protection against these infections
▪ Adaptive immunity is normally silent and responds (or adapts) to
the presence of infectious agents by generating potent
mechanisms for neutralizing and eliminating the pathogens.
▪ The terms immune system and immune response generally refer
to adaptive immunity.
6.
7. Innate Immunity
▪ The major components of innate immunity are:
▪ Epithelial barriers that block the entry of microbes.
▪ Phagocytic cells (mainly neutrophils and macrophages)
▪ Dendritic cells (DCs)
▪ Natural killer (NK) cells
▪ Other innate lymphoid cells, and several plasma proteins, including the
proteins of the complement system
8. Innate Immunity
▪ Phagocytes, dendritic cells and many other cells express receptors that
sense the presence of infectious agents and substances released from dead
cells.
▪ The microbial structures recognized by these receptors are called pathogen-
associated molecular patterns;
▪ They are shared among microbes of the same type, and they are essential
for the survival and infectivity of the microbes
▪ The substances released from injured and necrotic cells are called damage-
associated molecular patterns.
▪ The cellular receptors that recognize these molecules are often called
pattern recognition receptors.
▪ It is estimated that innate immunity uses about 100 different receptors to
recognize 1000 molecular patterns.
9.
10. Reactions of Innate Immunity
▪ The innate immune system provides host defense by the following
two main reactions:
▪ Inflammation. Cytokines and products of complement activation,
are produced during innate immune reactions and trigger the
vascular and cellular components of inflammation.
▪ Anti-viral defense. Type I interferons produced in response to
viruses act on infected and uninfected cells and activate enzymes
that degrade viral nucleic acids and inhibit viral replication.
11. Adaptive Immunity
▪ The adaptive immune system consists of lymphocytes and their products,
including antibodies.
▪ The adaptive immune system can recognize a vast array of foreign
substances.
▪ Humoral immunity, mediated by soluble proteins called antibodies that
are produced by B lymphocytes
▪ Cell-mediated (or cellular) immunity, mediated by T lymphocytes
▪ Cytotoxic T Lymphocytes; directly killing infected cells
▪ Helper T Cells; activating phagocytes to kill ingested microbes, via the
production of soluble protein mediators called cytokines
12. Cells and Tissues of the Immune System
▪ The cells of the immune system consist of lymphocytes, most of which
have specific receptors for antigens and mount adaptive immune
responses.
▪ Specialized APCs, which capture and display microbial and other
antigens to the lymphocytes.
▪ Various effector cells, whose function is to eliminate microbes and
other antigens.
13. Lymphocytes
▪ Present in the circulation and in various lymphoid organs.
▪ Although all lymphocytes are morphologically similar, they actually
consist of several functionally and phenotypically distinct populations
▪ Lymphocytes develop from precursors in the generative (primary)
lymphoid organs;
▪ T lymphocytes mature in the thymus, whereas B lymphocytes mature in
the bone marrow.
▪ Each T or B lymphocyte and its progeny, which constitute a clone,
express a single antigen receptor
▪ The total population of lymphocytes (numbering about 1012 in
humans) can recognize tens or hundreds of millions of antigens.
14. Lymphocytes
▪ All mature lymphocytes go through distinct phases during their lives
▪ Naïve lymphocytes; express antigen receptors but have not responded to
antigens and do not serve any functions.
▪ Effector lymphocytes are induced by lymphocyte activation and perform the
functions that eliminate microbes.
▪ Memory lymphocytes induced during activation survive in a functionally silent
state even after the antigen is eliminated and respond rapidly upon
subsequent encounters with the antigen.
15. T Lymphocytes
▪ Thymus-derived T lymphocytes develop into the effector cells of
cellular immunity and “help” B cells to produce antibodies against
protein antigens.
▪ T cells constitute 60% to 70% of the lymphocytes in peripheral
blood and are the major lymphocyte population in splenic peri-
arteriolar sheaths and lymph node inter-follicular zones.
▪ T cells cannot recognize free or circulating antigens;
▪ The vast majority (>95%) of T cells sense only peptide fragments
of proteins displayed by molecules of the major histocompatibility
complex (MHC).
16.
17. B Lymphocytes
▪ B (bone marrow–derived) lymphocytes are the cells that produce
antibodies, the mediators of humoral immunity.
▪ B cells make up 10% to 20% of the circulating peripheral lymphocyte
population.
▪ They also are present in bone marrow and in the follicles of peripheral
(secondary) lymphoid organs.
▪ After stimulation, B cells differentiate into plasma cells.
▪ Which secrete large amounts of antibodies.
▪ There are five classes, or isotypes, of immunoglobulins: IgG, IgM, and IgA
constitute more than 95% of circulating antibodies.
▪ IgA is the major isotype in mucosal secretions.
18. B Lymphocytes
▪ IgE is present in the circulation at very low concentrations
▪ Also is found attached to the surfaces of tissue mast cells
▪ IgD is expressed on the surfaces of B cells but is secreted at very
low levels.
19. Natural Killer Cells
▪ NK cells are innate immune cells, as they are functional without prior
activation and do not express highly variable and clonally distributed
receptors for antigens.
▪ NK cells have two types of receptors; inhibitory and activating.
▪ Inhibitory receptors recognize self class I MHC molecules, which are
expressed on all healthy cells
▪ Activating receptors recognize molecules that are expressed or
upregulated on stressed or infected cells
▪ Innate lymphoid cells (ILCs) are populations of lymphocytes that lack
TCRs but produce cytokines similar to those that are made by T cells.
20. Dendritic Cells
▪ Dendritic cells (DCs) are the most important antigen presenting cells for
initiating T-cell responses against protein antigens. Plasmacytoid
▪ They have numerous fine cytoplasmic processes that resemble dendrites.
▪ These cells are located at the right place to capture antigens—under epithelia,
the common site of entry of microbes and foreign antigens, and in the
interstitia of all tissues, where antigens may be produced. DCs within the
epidermis are called Langerhans cells.
▪ DCs express many receptors for capturing and responding to microbes (and
other antigens), including TLRs and C-type lectin receptors.
▪ In response to microbes, DCs are recruited to the T-cell zones of lymphoid
organs, where they are ideally positioned to present antigens to T cells.
▪ DCs express high levels of MHC and other molecules needed for antigen
presentation and activation of T cells.
21.
22. Lymphoid Tissues
▪ The tissues of the immune system consist of the generative
(primary, or central) lymphoid organs.
▪ In which T lymphocytes and B lymphocytes mature and become
competent to respond to antigens.
▪ The peripheral (or secondary) lymphoid organs, in which adaptive
immune responses to microbes are initiated.
▪ The principal generative lymphoid organs are the thymus, where T
cells develop.
▪ The bone marrow, the site of production of all blood cells and
where B lymphocytes mature.
23. Lymph Nodes
▪ Encapsulated, highly organized collections of lymphoid cells and innate
immune cells that are located along lymphatic channels throughout the
body.
▪ As lymph passes through lymph nodes, resident APCs are able to
sample antigens that are carried to the node in lymph derived from the
interstitial fluids of tissues.
▪ DCs transport antigens from nearby epithelial surfaces and tissues by
migrating through lymphatic vessels to the lymph nodes.
▪ Thus, antigens become concentrated in draining lymph nodes
24. Adaptive Immune Response Steps
1. Antigen recognition;
2. Activation, proliferation and differentiation of specific
lymphocytes into effector and memory cells
3. Elimination of the antigen.
4. Decline of the response, with memory cells being the long-lived
survivors
