Basic Principles of Specific Immunity and Immunization

Important words and concepts from Chapter 17, Black, 1999 (3/28/2003):

by Stephen T. Abedon (abedon.1@osu.edu) for Micro 509 at the Ohio State University

Course-external links are in brackets

Click [index] to access site index

Click here to access text’s website

Vocabulary words are found below

(1) Chapter title: Basic Principles of Specific Immunity and Immunization

(a) [basic principles of specific immunity and immunization (Google Search)] [index]

(2) Immunology

(a) Immunology is the study of specific immunity and the body's immune system that effects (i.e., causes) this specific immunity

(b) [immunology (Google Search)] [index]

(3) Specific immunity

(a) Specific immunity is that aspect of your body's defenses against pathogens (and other foreign material) that acts against specific molecules, usually requiring that your immune system "learn" the properties of specific molecules over a number of days or weeks before mounting an effective response against the foreign material

(b) Typically a specific immune response against one pathogen will be ineffective against a different pathogen, sometimes even a closely related but still different pathogen

(c) Specific immunity is that aspect of immunity that is primed when individuals are vaccinated against, for example, pathogens or their toxins

(d) Specific immunity includes humoral immunity and cell-mediated immunity

(e) A number of body organs, tissues, and cell types are involved in effecting each of these forms of specific immunity

(f) We can additionally describe specific immunity as being

(i) Naturally acquired versus artificially acquired

(ii) Actively acquired versus passively acquired

(g) [specific immunity (Google Search)] [index]

(4) Antigen

(a) Another way of defining specific immunity is that it is a means by which a body defends itself against the presence of specific antigens associated with, for example, pathogens

(b) Antigens are the protein or polysaccharide components of pathogens

(c) The reason that specific immunity is specific to specific pathogens (and their molecules) is because these molecules (antigens) are somewhat unique going from pathogen to pathogen (e.g., proteins with different amino acid sequences and therefore different structures, or polysaccharides made up of different sugars in different orders)

(d) For example, antibodies work by interacting with (binding to) specific structures found on specific antigens

(e) [antigen (Google Search)] [index]

(5) Nonspecific immunity

(a) Nonspecific immunity includes those defenses against pathogens, etc., that are not specific to each pathogen including such things as physical barriers, chemical barriers, some cellular defenses, inflammation, fever, and molecular defenses

(b) [nonspecific immunity (Google Search)] [nonspecific host defenses and host systems (MicroDude)] [index]

(6) Innate immunity (genetic immunity, species immunity)

(a) While specific immunity must be learned (i.e., may be acquired), innate immunity (a.k.a., genetic immunity) is present prior to the exposure to a pathogen

(b) This is because innate immunity refers simply to the inability of many organisms that have not evolved to be, for example, human pathogens, to cause disease in (again, for example) humans because of the absence of mechanisms necessary to be invasive in humans

(c) Thus, you are immune to the majority of pathogens associated with the majority of host species simply because those pathogens are adapted to causing disease in a different host setting (a.k.a., species immunity)

(d) [innate immunity, genetic immunity, species immunity (Google Search)] [index]

(7) Acquired immunity(use as target for "immune"?)

(a) Acquired immunity contrasts with innate immunity because it requires previous exposure to a pathogen (or its product) before immunity is acquired by the host

(b) Acquired (specific) immunity is the immunity that is responsible for subsequent exposures to the same pathogens causing less or no disease (i.e., your becoming "immune")

(d) See Figure 17.1, The various types of immunity

(e) [acquired immunity (Google Search)] [index]

(8) Naturally acquired immunity (colostrum)

(a) Naturally acquired immunity is that immunity acquired upon exposure to a specific pathogen particularly in the course of an infection/disease

(b) Additionally, naturally acquired immunity occurs when an infant obtains colostrum from mom

(c) "Colostrum is the first fluid secreted by the mammary glands after childbirth. Although deficient in many nutrients found in milk, colostrum contains large quantities of antibodies that cross the intestinal mucosa and enter the infant's blood."

(d) The infant is thus naturally immune against many or all of the diseases that the mother is immune to especially as a consequence of the mother possessing antibodies (a form of specific immunity) against the associated pathogens

(e) See Figure 17.1, The various types of immunity

(f) [naturally acquired immunity, colostrum (Google Search)] [index]

(9) Artificially acquired immunity (antiserum, antitoxin)

(a) Specific immunity may also be acquired artificially

(b) Artificially acquired specific immunity basically constitutes the various means by which humans enhance, via technology, the specific immunity of individuals

(c) Artificially acquired immunity specifically refers to vaccination (which is an artificial exposure to a pathogen's antigens, i.e., without infection or, at least, without disease) and to the transfusion of antibodies from one individual into another (antiserum or antitoxin, etc.)

(d) See Figure 17.1, The various types of immunity

(e) [artificially acquired immunity, antiserum, antitoxin (Google Search)] [index]

(10) Active immunity

(a) Active immunity occurs when an individual's own immune system is induced to produce a specific immune response against an antigen/pathogen

(b) Active immunity can occur either upon infection or disease (naturally acquired active immunity), or artificially upon vaccination (artificially acquired active immunity); note that there is some ambiguity in the definitions I've used since vaccines can cause infections so the distinction between artificially and naturally acquired immunity is really one between how the antigens were acquired, by natural versus by artificial means

(c) Active immunity can last as long as the immune system cells, that mediate this immunity, survive within an individual; this can be for weeks, months, or years

(d) See Figure 17.1, The various types of immunity

(e) [active immunity (Google Search)] [index]

(11) Passive immunity

(a) Passive immunity results when antibodies are produced by one individual and then acquired by another

(b) The acquisition of the antibodies in colostrum by an infant is an example of (naturally acquired) passive immunity; the crossing of the placenta by maternal antibodies is another example of naturally acquired passive immunity

(c) Passive immunity may also be artificially acquired, particularly when antiserum or antibodies produced by one individual are transfused into a second individual

(d) In all cases, passive immunity represents the passive acquisition of an immune response that was actively acquired by another individual

(e) However, because passive immunity involves the transfusion of molecules rather than the transfusion of immune system cells, passive immunity can last for at most months since antibodies have a finite life span within the body

(f) On the other hand, passive immunity is functional immediately upon reception, whereas active immunity (ironically) requires time (days, weeks) before a functional immune response develops

(g) See Figure 17.1, The various types of immunity

(h) [passive immunity (Google Search)] [index]

(12) Immunogen

(a) Synonymous with antigen, an immunogen/antigen is "a substance the body identifies as foreign and toward which it mounts an immune response… Most antigens are large protein molecules with complex structures and molecular weights greater than 10,000 [Daltons]. Some antigens are polysaccharides, and a few are glycoproteins (carbohydrate and protein)… Proteins usually have greater antigenic (immunogenic) strength because they have a more complex structure than polysaccharides." That is, proteins possess many more potential epitopes than do carbohydrates

(b) "Antigens are found on the surface of viruses and all cells, including bacteria, other microorganisms, and human cells. The exact chemical structure of each of a cell's antigens is determined by genetic information in its DNA. Bacteria can have antigens on capsules, cell walls, and even flagella. Many microorganisms have several different antigens somewhere on their surface. Determining how the human body responds to these different antigenic determinants is important in making effective vaccines. …antigens on the surfaces of red blood cells determine blood types, and antigens on other cells determine whether a tissue transplanted from another person will be rejected."

(13) Epitope (antigenic determinant)

(a) Complex antigens such as proteins produce more robust immune responses because each structure/complexity on an antigen can serve as the site of binding of a different immune system molecule (e.g., an antibody)

(b) Each of these separate binding areas/structures is called an epitope (a.k.a., antigenic determinant)

(c) Complex antigens possess numerous epitopes and the binding of immune system molecules (e.g., antibodies) to epitopes can have different effects depending on the epitope

(d) [epitope (Google Search)] [index]

(14) Hapten

(a) Haptens are small molecules that can serve as antigens (i.e., display immunologically recognized epitopes) upon binding to a larger molecule (e.g., a protein)

(b) Allergies to penicillin occur because penicillin can serve as a hapten upon binding to certain body proteins

(15) Antibody (titer)

(a) One of the immune system molecules that bind to the epitopes on antigens is the antibody

(b) Antibodies are secreted proteins that are found as soluble proteins in body fluids (for more on antibodies, see immunoglobulin, below)

(d) See Figure 17.2, A typical antigen-antibody reaction

(e) [antibody defenses, antibody titer (Google Search)] [index]

(16) Lymphocytes (white blood cells)

(a) Lymphocytes are one category of white blood cells

(b) Lymphocytes mediate specific immunity

(c) We can differentiate lymphocytes into a variety of types including, particularly, the B lymphocytes (B cells) and the T lymphocytes (T cells)

(d) [lymphocytes, white blood cells (Google Search)] [index]

(17) B lymphocytes (B cells)

(a) B lymphocytes are the producers of antibodies; that is, they mediate humoral immunity

(b) B cells are not matured in the thymus

(18) T lymphocytes (T cells)

(a) T cells mediate cell-mediated immunity

(b) T cells come in a variety of types which possess different antigens (proteins) on their surfaces and which have different roles in the immune response

(d) ["T lymphocytes" and immunity -HIV -AIDS (Google Search)] [index]

(19) Clonal selection hypothesis (self, nonself, tolerance)

(a) The immune system possesses the ability to recognize antigens/epitopes to which it has never been exposed (nonself)

(b) In addition, the immune system possesses the ability to not recognize (i.e., not bind to) antigens/epitopes associated with normal body tissues (self)

(c) The means by which both of these mechanisms occur includes the selective amplification of those immune system components that recognize foreign antigens and the selective deletion of those immune system components that recognize normal body tissues

(d) Together these mechanisms constitute the clonal selection hypothesis

(e) "According to this hypothesis, embryos contain many different lymphocytes, each genetically programmed to recognize a particular antigen and make antibodies to destroy it. If a lymphocyte encounters and recognizes that antigen after development is complete, it divides repeatedly to produce a clone, a group of identical progeny cells that make the same antibody. If, during embryonic development, it encounters its programmed antigen as part of a normal host substance (self), the lymphocyte is somehow destroyed or inactivated. This mechanism removes lymphocytes that can destroy host tissues and thereby creates tolerance for self. It also selects for survival [of] lymphocytes that will protect the host from foreign antigens."

(f) See Figure 17.5, Clonal selection hypothesis

(g) See Figure 17.6, Clonal deletion

(h) [clonal selection hypothesis, tolerance and clonal selection hypothesis, self and clonal selection hypothesis, non-self and clonal selection hypothesis, nonself and clonal selection hypothesis (Google Search)] [B cell maturation, activation of B cell with thymus-independent antigen, B cell selection (shockwave movies of complex molecular process) (Immunology Bio307)] [index]

(20) Specificity

(a) The hallmark of specific immunity is the specificity of the immune response

(b) This means that an immune response to specific epitopes will not be effective against a pathogen lacking these epitopes, even if the second pathogen is otherwise closely related to the first

(c) Specificity is not necessarily perfect thus allowing, using the above example, partial immunity against the second pathogen because the second pathogen shares some, but not all epitopes with the first pathogen

(d) [specificity and immunity (Google Search)] [index]

(21) Memory

(a) Actively acquired specific immunity possesses memory

(b) This is another way of saying that an immune response may be primed by exposure to an antigen, and thereafter with subsequent exposure to the same antigen the immune response against that antigen occurs much more rapidly

(c) This memory is a function of the circulation of the lymphocytes which either mediate the specific immune response or can give rise to cells (i.e., by dividing) that differentiate into immune-response-mediating cells

(d) Subsequent exposure to an antigen, in sufficient quantity, will also serve to strengthen subsequent immune responses

(e) [memory and immunity (Google Search)] [index]

(22) Humoral immunity [memory cells, plasma cells]

(a) That aspect of specific immunity that is mediated by antibodies is termed humoral immunity

(b) Humoral immunity is particularly effective against toxins (exotoxins), whole bacteria, and free viruses (i.e., viruses not currently infecting cells)

(c) "Humoral immunity depends first on the ability of B lymphocytes to recognize specific antigens and second on their ability to initiate responses that protect the body against foreign agents. The most common response is the production of antibodies that will inactivate an antigen and lead to destruction of infectious organisms."

(d) B cells, which mediate humoral immunity, each produce only a single kind of antibody (i.e., one structure with the ability to bind to only a single type/structure of epitope)

(e) These antibodies are displayed on the surface of B cells

(f) The binding of an antigen to one of these surface B cells induces those cells either to start producing antibody or to differentiate into cells that produce antibody

(g) These antigens may be soluble, found on the surface of pathogens, or displayed by other immune system cells such as macrophages

(h) Plasma cells are those B cells that can immediately produce (and secrete) antibody molecules

(i) Memory cells are those more long-term-stable B cells that can differentiate into plasma cells

(j) [humoral immunity, memory cells, "plasma cells" and humoral (Google Search)] [index]

(23) Immunoglobulin (Ig)

(a) Another name for antibody is immunoglobulin

(b) See Figure 17.7, Antibody structure

(c) Note that antibodies come in a variety of classes (i.e., IgG, IgM, IgA, IgE, and IgD) possessing variations on the basic antibody structure

(d) These different classes are made by different body tissues and vary in their properties and uses

(e) By far the most commonly studied is IgG which is the common blood antibody

(f) See Table 17.4, Properties of antibodies

(g) See Figure 17.8, The structures of different classes of antibodies

(h) Antibodies function by binding to antigens and

(i) Directly inactivating them (viruses and toxins)

(ii) Stimulating the attachment of complement (bacteria)

(iii) Directly stimulating lysis (via membrane attack complexes)

(iv) Stimulating phagocytosis (opsonization)

(v) Stimulating killer T cells (ADCC)

(i) See Figure 17.10, Antibodies produced by humoral immune responses eliminate foreign agents

(j) [immunoglobulins (Google Search)] [index]

(24) Multivalence (agglutination)

(a) Note that an antibody is multivalent meaning that a single antibody molecule can bind to two epitopes (e.g., the upper tips of the "Y" shape of the antibody molecule)

(b) Note that each half (left and right) of the molecule are essentially identical; the two epitopes that a given antibody may bind therefore must be structurally identical (i.e., a given IgG molecule can bind two otherwise identical epitopes)

(c) This multivalent nature of antibodies allows antibodies (especially the highly multivalent IgM) to bind together antigens in a clumping known as agglutination, which can aid in pathogen phagocytosis

(d) [antibody agglutination (Google Search)] [index]

(25) Primary response

(a) Upon initial exposure to an antigen that a body has never been exposed to, there is a 10 to 17 day lag before the peak in antibody (particularly IgG) concentration

(b) ["primary immune response" -HIV (Google Search)] [index]

(26) Secondary response

(a) The second (or later) time an antibody is exposed to an antigen there is only a 2 to 7 day lag before the peak in antibody (particularly IgG) concentration

(b) This is why your body is able to rapidly defeat many of the pathogens to which you have been previously exposed

(d) See Figure 17.9, Primary and secondary responses to an antigen

(e) ["secondary immune response" -HIV (Google Search)] [index]

(27) Cell-mediated immunity

(a) Cell-mediated immunity, not surprisingly, is mediated by cells rather than via secreted proteins (i.e., not by antibodies)

(b) Cell-mediated immunity is particularly active against virus-infected cells, though also can function against other foreign or otherwise renegade (e.g., cancer) eukaryotic cells

(d) [cell-mediated immunity (Google Search)] [index]

(28) Cytotoxic T cells (killer T cells)

(a) Cytotoxic T cells act by first recognizing that other body cells are virally infected, and then killing those cells, thus destroying the viral infection (of a cell) while destroying the cell

(b) This cell killing by the host immune system is one means by which virus infections damage hosts and thus cause disease

(i) Body cells degrade internal cellular proteins on a regular basis, whether because the protein deteriorates, because the protein was incorrectly folded, or simply in the course of normal cell metabolism

(ii) Some of these degraded cells are broken up into short peptides which are then presented on the surface of normal body cells in association with MHC class I proteins

(iii) If a virus or some other pathogen is infecting a cell, then the pathogen, too, will produce proteins, and these nonself proteins will also eventually be presented on the surface of cells in association with MHC class I proteins

(iv) It is the MHC-presented peptide antigens, from intracellularly infecting pathogens, that cytotoxic T cells recognize; self antigens are not recognized by T cells because T cells that recognize self antigens are deleted during T cell maturation

(d) The MHC class I-associated presentation of the antigens essentially serves as a means of allowing the immune system to "look" inside of cells, e.g., serving as a window onto a cell's metabolism

(e) See Figure 17.3, The reactions in cell-mediated immunity [though note that this figure does not do a very good job of describing how it is that antigens are processed intracellularly and then presented on the cell surface]

(f) [cytotoxic T cells, killer t cells (Google Search)] [index]

(29) Vaccination

(a) Vaccination is artificially acquired active immunity

(b) The goal of vaccination is to prime humoral and cellular immune responses against pathogens (or their toxins) without simultaneously causing disease

(c) Typically vaccines are most easily developed against either toxins or against pathogens that, upon infection, induce lifetime immunity (i.e., naturally acquired active immunity) in their hosts

(d) Pathogens for which even infection accompanied by disease does not result in immunity (particularly diseases that cause gastrointestinal distress) are not easy to prevent by the application of vaccination (note that the polio vaccines are seemingly exceptions but instead do not prevent the gastrointestinal ailment so much as systemic infection by the virus)

(e) Note that most vaccines do not prevent infection (i.e., growth of the pathogen) so much as the disease that results from infection; this is accomplished either by blocking the effects of pathogen toxins or by priming the immune system against the pathogen such that infection is brought under control much more quickly, before full-blown disease results

(f) Vaccines do not necessarily confer life-long immunity; the duration of immunity typically is dependent on to what degree the vaccination mimics a natural infection plus to what degree subsequent natural infections are capable of boosting the immunization

(g) Categories of vaccine types include

(i) Live vaccines

(ii) Whole-killed vaccines

(iii) Toxoid vaccines

(iv) Recombinant vaccines

(v) (subunit vaccines and DNA vaccines are additional varieties that we won’t discuss)

(h) Typically vaccines are employed to prevent disease though not as a means of treating existing infections; exceptional is the rabies vaccines which is employed, in humans, to prevent the development of disease given infection

(i) [vaccination (Google Search)] [index]

(30) Live vaccine (live-attenuated vaccine)

(a) Live vaccines result in infection but not disease, and confer the most long-lasting immunity

(b) Live vaccines typically are attenuated so that while they can still cause infection, they have a reduced propensity to cause disease

(31) Whole-killed vaccine (“dead” vaccine)

(a) One alternative to a live vaccine is a vaccine consisting of an inactivated whole pathogen, i.e., a whole-killed vaccine

(b) An advantage to employing a whole-killed vaccine over a live vaccine is that the former can be safer

(c) However, these “dead” vaccines do not result in infection and therefore do not produce as robust an immune response as live vaccines (particularly lacking is cytotoxic T cell-mediated immunity against intracellular pathogens), but if boosted by subsequent natural infection by the same pathogen can produce long-lasting immunity

(d) [whole-killed vaccines (Google Search)] [index]

(32) Toxoid vaccine

(a) Toxoid vaccines, against toxins (exotoxins), are not boosted by subsequent infections (since the amount of toxin produced by natural infections is not great) and require a sufficient standing antibody titer; declines in this titer necessitates boosting

(b) [toxoid vaccines (Google Search)] [index]

(33) Recombinant vaccine

(a) In contrast to a whole vaccine (i.e., either live-attenuated or whole-killed vaccines), a recombinant vaccine contains only part of a microorganism (i.e., the vaccine is not whole).

(b) Such vaccines are typically safer than whole vaccines because they (ideally) contain only those parts that induce a good immune response and not those parts that can lead to complications or side effects

(c) However, recombinant vaccines are also typically less effective than whole vaccines, especially live-attenuated vaccines, since at best recombinant vaccines induce an incomplete immune response against a pathogen (i.e., an immune response against only part of the pathogen and then, except in the case of DNA vaccines, only inducing humoral immunity)

(d) [recombinant vaccines (Google Search)] [index]

(34) Booster

(a) Boosting a vaccine involves revaccination by the same vaccine (or, at least, against the same organism)

(b) Booster vaccines are employed for a number of reasons

(i) To assure that the immune response induced by an at least partially successful vaccination is boosted to a sufficiently large immune response to be effective in protecting against disease

(ii) To assure that all recipients of the vaccination display at least some immune response (e.g., oral polio vaccine does not always lead to infection, but if given three times over a relatively long period, at least one of the vaccinations is likely to result in infection and therefore potentially successful vaccination)

(iii) To replenish the immune response after a long period (e.g., 10 years as is the case for tetanus vaccine)

(35) Routinely administered vaccines (DPT vaccine, MMR vaccine, poliomyelitis vaccines, hepatitis B vaccine)

(a) Vaccines that are routinely administered in this country include

(i) DPT vaccine = Diphtheria toxoid, killed Pertussis (whooping cough) bacteria (previously typically whole-killed but more recently an acellular has been introduced which is much less than whole), Tetanus toxoid

· [DPT vaccine (Google Search)] [index]

(ii) MMR vaccine = Measles (rubeola), Mumps, and German measles (Rubella), all live-attenuated viruses

· [MMR vaccine (Google Search)] [index]

(iii) Poliomyelitis vaccines; Sabin vaccine = oral trivalent (three virus strains), live-attenuated virus vaccine; Salk vaccine = same except a whole-killed virus that is injected intramuscularly

· [poliomyelitis vaccine (Google Search)] [index]