Immunology Ch 1 1-22
Introduction to the Immune System
-Immunity is resistance to disease through the use of the immune system, which carries out the
immune response (immunology is study of immune system)
-most important function of immune system is to prevent infections and eradicate infections
Innate and Adaptive Immunity – Host defense consists of innate immunity (immediate
response against infections), and adaptive immunity which develops slowly and is specialized
-Innate immunity is always present in healthy people and blocks entry of microbes and
eliminates microbes
-Adaptive immunity requires expansion and differentiation of lymphocytes
-first line of defense against microbes in innate immunity are epithelial barriers; if microbes
breach this, they are attacked by phagocytes, lymphocytes called natural killer cells and
complement which recognize and react against these agents
-defense against microbes pathogenic to humans requires adaptive immune responses, which
includes lymphocytes and their products, such as antibodies
-adaptive immune cells express receptors for a wide variety of antigens
-adaptive cells often use molecules of innate immunity to eliminate microbes, and adaptive cells
function to enhance these responses
Types of Adaptive Immunity – two types of adaptive immunity are humoral and cell-mediated
Humoral Immunity – mediated by antibodies produced by B cells and secreted into circulation
-most important function of Ab is to eliminate toxins at mucosal surfaces and blood
-antibodies cannot gain access to microbes living INSIDE cells,
Cell-mediated Immunity – mediated by T lymphocytes, which activate phagocytes to ingest
microbes for destruction. Other T cells kill cells harboring infection themselves
-Therefore, antibodies  extracellular, T cells  protein antigens
-Immunity may be induced by infection OR vaccination or conferred by transfer of Ab or
lymphocytes from immunized individual
-Active Immunity – exposure to antigen mounts immune response and develops resistance to
later infection. Passive Immunity – person receives Ab or cells from someone already immune
Properties of Adaptive Immune Responses –
1. Specificity and Diversity – specificity is ability to distinguish between many antigens, totality
is called lymphocyte repertoire is diverse; lymphocytes express clonally distributed
receptors
a. Clonal Selection Hypothesis – clones of lymphocytes develop B4 antigen encounter
b. Diversity – very few immature cells are specific for any one antigen, which can
proliferate and expand for any antigen exposure through positive feedback loops
2. Memory – primary immune response – response to first exposure to antigen and is
mediated by naïve lymphocytes seeing antigen for first time. Secondary responses occur
after second+ encounter with antigen; it is more rapid, larger, and better able to eliminate;
result from activation of memory lymphocytes (long-lived cells). Reason why vaccine works
-clonal expansion is when lymphocytes proliferate in response to an antigen to rapidly increase
numbers of cells specific for that antigen
-Immunological Tolerance – unresponsiveness to self-antigens
Cells of the Immune System – consist of lymphocytes, effector cells, APCs
Lymphocytes – cells produce receptors specific for diverse antigens, mediate adaptive immunity
-distinguished by different surface markers Clusters of Differentiation
-B cells capable of producing antibodies and mediate humoral immunity; express membrane
forms of antibodies, to which antigens bind and initiate B cell activation to secrete same Ab
-T cells are responsible for cell-mediated immunity using antigen receptors that recognize
protein fragments bound to major histocompatibility complexes on antigen presenting cells
-CD4+ T cells are helper T cells which help B cells produce antibodies and help
phagocytes ingest microbes (some belong to T regulatory cells to limit response)
-CD8+ T cells are cytotoxic T cells because they kill cells with intracellular microbes
-Natural Killer (NK) cells – kill host cells but do not express clonal receptors and are
components of innate immunity
-All lymphocytes arise in bone marrow; B cells mature in marrow, T cells mature in thymus
-sites where mature lymphocytes are produced are called generative lymphoid organs, mature
lymphocytes enter circulation and enter peripheral lymphoid organs, where they meet antigen
-Naïve lymphocytes recognize microbial antigens and receive additional signals induced by
microbes and antigen-specific lymphocytes proliferate and differentiate into effector cells and
memory cells
-Naïve Lymphocytes express antigen receptors but do not function to eliminate them. If they
do not find antigen, they die after a while and replaced by new cells. If recognized by antigen,
naïve lymphocytes proliferate and differentiate into effector cells and memory cells
-Effector Cells – ability to produce molecules to eliminate antibodies; B cell  Plasma cell in
response to antigen in peripheral lymphoid organs where they secrete antibodies: plasmablasts
-also present in the blood or migrate to bone marrow
-Effector CD4 T cells produce cytokines to activate B cells, macrophages, and other cell types
-Effector CD8 cells can kill host cells
Memory Cells – also generated from antigen-stimulated lymphocytes and survive long time
-memory cells are functionally inactive unless stimulated by same antigen from earlier infection,
and these cells proliferate rapidly to initiate secondary immune responses
Antigen Presenting Cells – APCs capture antigens, transport them to peripheral lymphoid organs
and present them to lymphocytes
-Dendritic Cells – have long processes that capture microbes and move them to lymph nodes
where they display protein fragments to T cells (**most effective APCs for T cell responses)
-Macrophages can phagocytize microbes in tissues and present antigens to lymphocytes
-Cells presenting antigen respond to microbes by producing surface and secreted proteins to
activate naïve T cells to differentiate into effector cells
-Follicular Dendritic Cell – resides in germinal centers of lymphoid follicles and present to B cells
Effector Cells – eliminate microbes and consist of lymphocytes, granulocytes, and macrophages
Tissues of the Immune System – generative lymphoid organs where T and B cells mature, and
peripheral lymphoid organs, in which adaptive immune responses to microbes are initiated
Peripheral Lymphoid Organs – lymph nodes, spleen, mucosal and cutaneous immune system,
APCs, and lymphocytes; T and B cells must locate microbes that enter at any body site
Lymph Nodes are encapsulated nodular aggregates of lymphoid tissues along lymph channels
throughout body; fluid leaks out of blood vessels in all epithelia and CT and parenchymal organs.
This fluid, called lymph is drained into lymph vessels  nodes and back into circulation
-APCs in lymph nodes sample the antigens of microbes that enter, and dendritic cells pick up
antigens from epithelia and microbes and transport them to lymph nodes
Spleen – vascularized organ collecting blood through network of sinusoid channels; blood borne
antigens are trapped and concentrated by dendritic cells and macrophages, which destroy blood
microbes
Cutaneous/Mucosal Immune System – APCs and effectors in epithelium of skin and
GI/respiratory tracts are diffusely scattered, but some are organized.
-Pharyngeal tonsils and Peyer’s patches in intestine are defined mucosal lymph tissue
-1/4 of body lymphocytes are in these mucosal tissues and skin, many are memory cells
-in peripheral lymph organs, T and B cells are organized into different anatomic compartments
-in lymph nodes, B cells are in follicles around the periphery which may contain a
staining region known as a germinal center which produces antibodies. Follicles contain
follicular dendritic cells for activation of B cells
-T cells are concentrated outside, but adjacent to follicles in the paracortex,
containing dendritic cells for T cell presentation
-Chemokines keep B cells retained in follicles; specific chemokine secreted by FDCs binds to B
cell receptor CXCR5 which attracts B cells from blood into follicles of lymphoid organs
-T cells express receptor CCR7 that recognizes chemokines produced in paracortex of
lymph nodes and spleen to recruit T cells from blood into parafollicular cortex region of
lymph nodes and periarteriolar region of lymphoid sheaths of spleen
-when B and T cells activated, new chemokines are expressed that make them migrate toward
each other and meet at edge of follicles; they differentiate into antibody producing cells
-activated lymphocytes, particularly T cells, exit node from efferent lymphatic vessels and leave
spleen through veins
Lymphocyte Recirculation and Migration into Tissues – naïve lymphocytes recirculate between
blood and peripheral organs where they are activated by antigens, and migrate from organs to
sites of infection, where microbes are eliminated
-most relevant to T cells since effector T cells have to locate and eliminate microbes
-plasma cells do not need to migrate to secrete antibodies
-naïve T cells matured in thymus enter lymph nodes through special post-capillary venules (high
endothelial venules) and find antigen
-chemokines produced in T cell zones bind to CCR7 and attract T cells to bind tightly to
high endothelial venules and then migrate into T cell zone where antigens displayed by
dendritic cells
-B cells also enter lymphoid tissues into follicles following CXCR5 binding to chemokine
Some Summary Information – two reactions of innate immunity are inflammation to bring
leukocytes and plasma cells to site of infection, and antiviral defense mediated by type I
interferons and NK cells
-Adaptive immune response uses these strategies: antibodies bind microbes and block their
infectious ability, promote ingestion and destruction; phagocytes ingest microbes with help of
Th cells; Th cells recruit leukocytes to destroy microbes; T cytotoxic cells destroy cells
-cells in epithelia capture microbes (dendritic cells) and transport them to lymph nodes to
present them to T cells on MHC molecules
-polysaccharides and non-protein antigens are recognized by B cells
-innate immune response to some pathogens is complement activation to enhanve B cell
proliferation/differentiation
-B cell immunity involves antibody secretion from plasma cells
-polysaccharides and lipids induce IgM antibody secretion
-Protein antigens stimulate helper T cells, which stimulate IgG, IgA and IgE antibody production
-production of different antibody classes with same specificity is called heavy-chain/isotype
switching to increase defensive capability of antibody response
Affinity Maturation – Helper T cells stimulate production of antibodies with higher and higher
affinity for antigen to improve quality of humoral response
-antibodies bind microbe and prevent infection, antibodies opsonize microbes for phagocytosis,
antibodies activate complement system to promote phagocytosis and destruction