Immunology Lectures Mini-Course

By Harris Goldstein, M.D., director, Einstein-Montefiore Center for AIDS Research, professor of pediatrics and microbiology & immunology and the Charles Michael Chair in Autoimmune Diseases, delivers a mini-course that provides a comprehensive overview in basic immunology for graduate and medical students and for anyone interested in understanding how the immune system works.

This mini-course was organized by the KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH) at the Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa to provide Sub-Saharan students, research trainees and HIV and TB investigators with a comprehensive course in immunology. (January 2010).

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Immunology
MRSA, Ingestion by Neutrophil.jpg
A bacterium (MRSA, yellow) being ingested by an immune cell (Neutrophil, purple).
System Immune
Subdivisions
  • Cellular
  • Clinical
Genetic (Immunogenetics)
  • Humoral
  • Molecular
Significant diseases
  • Autoimmune disease
  • Hypersensitivity
  • Immune disorder
  • Immunodeficiency
Significant tests
  • Agglutination
  • Immunoassay
  • Immunoprecipitation
  • Serology
Specialist Immunologist

Immunology is a branch of biomedical science that covers the study of all aspects of the immune system in all organisms.[1] It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders (autoimmune diseases, hypersensitivities, immune deficiency, transplant rejection); the physical, chemical and physiological characteristics of the components of the immune system in vitro, in situ and in vivo. Immunology has applications in several disciplines of science, and as such is further divided.

Even before the concept of immunity (from immunis, Latin for "exempt") was developed, numerous early physicians characterized organs that would later prove to be part of the immune system. The key primary lymphoid organs of the immune system are the thymus and bone marrow, and secondary lymphatic tissues such as spleen, tonsils, lymph vessels, lymph nodes, adenoids, and skin and liver. When health conditions warrant, immune system organs including the thymus, spleen, portions of bone marrow, lymph nodes and secondary lymphatic tissues can be surgically excised for examination while patients are still alive.

Many components of the immune system are actually cellular in nature and not associated with any specific organ but rather are embedded or circulating in various tissues located throughout the body.

Contents

  • 1 Classical immunology
  • 2 Clinical immunology
  • 3 Developmental immunology
  • 4 Immunotherapy
  • 5 Diagnostic immunology
  • 6 Cancer immunology
  • 7 Reproductive immunology
  • 8 Theoretical immunology
  • 9 Immunologist
    • 9.1 Career in immunology
  • 10 See also
  • 11 Notes and references
  • 12 External links

Classical immunology

Classical immunology ties in with the fields of epidemiology and medicine. It studies the relationship between the body systems, pathogens, and immunity. The earliest written mention of immunity can be traced back to the plague of Athens in 430 BCE. Thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time. Many other ancient societies have references to this phenomenon, but it was not until the 19th and 20th centuries before the concept developed into scientific theory.

The study of the molecular and cellular components that comprise the immune system, including their function and interaction, is the central science of immunology. The immune system has been divided into a more primitive innate immune system and, in vertebrates, an acquired or adaptive immune system. The latter is further divided into humoral (or antibody) and cell-mediated components.

The humoral (antibody) response is defined as the interaction between antibodies and antigens. Antibodies are specific proteins released from a certain class of immune cells known as B lymphocytes, while antigens are defined as anything that elicits the generation of antibodies ("anti"body "gen"erators). Immunology rests on an understanding of the properties of these two biological entities and the cellular response to both.

Immunological research continues to become more specialized, pursuing non-classical models of immunity and functions of cells, organs and systems not previously associated with the immune system (Yemeserach 2010).

Clinical immunology

Clinical immunology is the study of diseases caused by disorders of the immune system (failure, aberrant action, and malignant growth of the cellular elements of the system). It also involves diseases of other systems, where immune reactions play a part in the pathology and clinical features.

The diseases caused by disorders of the immune system fall into two broad categories:

  • immunodeficiency, in which parts of the immune system fail to provide an adequate response (examples include chronic granulomatous disease and primary immune diseases);
  • autoimmunity, in which the immune system attacks its own host's body (examples include systemic lupus erythematosus, rheumatoid arthritis, Hashimoto's disease and myasthenia gravis).

Other immune system disorders include various hypersensitivities (such as in asthma and other allergies) that respond inappropriately to otherwise harmless compounds.

The most well-known disease that affects the immune system itself is AIDS, an immunodeficiency characterized by the suppression of CD4+ ("helper") T cells, dendritic cells and macrophages by the Human Immunodeficiency Virus (HIV).

Clinical immunologists also study ways to prevent the immune system's attempts to destroy allografts (transplant rejection).

Developmental immunology

The body’s capability to react to antigen depends on a person's age, antigen type, maternal factors and the area where the antigen is presented.[2] Neonates are said to be in a state of physiological immunodeficiency, because both their innate and adaptive immunological responses are greatly suppressed. Once born, a child’s immune system responds favorably to protein antigens while not as well to glycoproteins and polysaccharides. In fact, many of the infections acquired by neonates are caused by low virulence organisms like Staphylococcus and Pseudomonas. In neonates, opsonic activity and the ability to activate the complement cascade is very limited. For example, the mean level of C3 in a newborn is approximately 65% of that found in the adult. Phagocytic activity is also greatly impaired in newborns. This is due to lower opsonic activity, as well as diminished up-regulation of integrin and selectin receptors, which limit the ability of neutrophils to interact with adhesion molecules in the endothelium. Their monocytes are slow and have a reduced ATP production, which also limits the newborn's phagocytic activity. Although, the number of total lymphocytes is significantly higher than in adults, the cellular and humoral immunity is also impaired. Antigen-presenting cells in newborns have a reduced capability to activate T cells. Also, T cells of a newborn proliferate poorly and produce very small amounts of cytokines like IL-2, IL-4, IL-5, IL-12, and IFN-g which limits their capacity to activate the humoral response as well as the phagocitic activity of macrophage. B cells develop early during gestation but are not fully active.[3]

Artist's impression of monocytes.

Maternal factors also play a role in the body’s immune response. At birth, most of the immunoglobulin present is maternal IgG. Because IgM, IgD, IgE and IgA don’t cross the placenta, they are almost undetectable at birth. Some IgA is provided by breast milk. These passively-acquired antibodies can protect the newborn for up to 18 months, but their response is usually short-lived and of low affinity.[3] These antibodies can also produce a negative response. If a child is exposed to the antibody for a particular antigen before being exposed to the antigen itself then the child will produce a dampened response. Passively acquired maternal antibodies can suppress the antibody response to active immunization. Similarly the response of T-cells to vaccination differs in children compared to adults, and vaccines that induce Th1 responses in adults do not readily elicit these same responses in neonates.[3] Between six to nine months after birth, a child’s immune system begins to respond more strongly to glycoproteins, but there is usually no marked improvement in their response to polysaccharides until they are at least one year old. This can be the reason for distinct time frames found in vaccination schedules.[4][5]

During adolescence, the human body undergoes various physical, physiological and immunological changes triggered and mediated by hormones, of which the most significant in females is 17-β-oestradiol (an oestrogen) and, in males, is testosterone. Oestradiol usually begins to act around the age of 10 and testosterone some months later.[6] There is evidence that these steroids act directly not only on the primary and secondary sexual characteristics but also have an effect on the development and regulation of the immune system,[7] including an increased risk in developing pubescent and post-pubescent autoimmunity.[8] There is also some evidence that cell surface receptors on B cells and macrophages may detect sex hormones in the system.[9]

The female sex hormone 17-β-oestradiol has been shown to regulate the level of immunological response,[10] while some male androgens such as testosterone seem to suppress the stress response to infection. Other androgens, however, such as DHEA, increase immune response.[11] As in females, the male sex hormones seem to have more control of the immune system during puberty and post-puberty than during the rest of a male's adult life.

Physical changes during puberty such as thymic involution also affect immunological response.[12]

Immunotherapy

Main article: Immunotherapy

The use of immune system components to treat a disease or disorder is known as immunotherapy. Immunotherapy is most commonly used in the context of the treatment of cancers together with chemotherapy (drugs) and radiotherapy (radiation). However, immunotherapy is also often used in the immunosuppressed (such as HIV patients) and people suffering from other immune deficiencies or autoimmune diseases.

Diagnostic immunology

Main article: Diagnostic immunology

The specificity of the bond between antibody and antigen has made it an excellent tool in the detection of substances in a variety of diagnostic techniques. Antibodies specific for a desired antigen can be conjugated with an isotopic (radio) or fluorescent label or with a color-forming enzyme in order to detect it. However, the similarity between some antigens can lead to false positives and other errors in such tests by antibodies cross-reacting with antigens that aren't exact matches.[13]

Cancer immunology

Main article: Cancer immunology

The study of the interaction of the immune system with cancer cells can lead to diagnostic tests and therapies with which to find and fight cancer.

Reproductive immunology

Main article: Reproductive immunology

This area of the immunology is devoted to the study of immunological aspects of the reproductive process including fetus acceptance. The term has also been used by fertility clinics to address fertility problems, recurrent miscarriages, premature deliveries and dangerous complications such as pre-eclampsia.

Theoretical immunology

Immunology is strongly experimental in everyday practice but is also characterized by an ongoing theoretical attitude. Many theories have been suggested in immunology from the end of the nineteenth century up to the present time. The end of the 19th century and the beginning of the 20th century saw a battle between "cellular" and "humoral" theories of immunity. According to the cellular theory of immunity, represented in particular by Elie Metchnikoff, it was cells – more precisely, phagocytes – that were responsible for immune responses. In contrast, the humoral theory of immunity, held, among others, by Robert Koch and Emil von Behring, stated that the active immune agents were soluble components (molecules) found in the organism’s “humors” rather than its cells.[14][15][16]

In the mid-1950s, Frank Burnet, inspired by a suggestion made by Niels Jerne,[17] formulated the clonal selection theory (CST) of immunity.[18] On the basis of CST, Burnet developed a theory of how an immune response is triggered according to the self/nonself distinction: "self" constituents (constituents of the body) do not trigger destructive immune responses, while "nonself" entities (pathogens, an allograft) trigger a destructive immune response.[19] The theory was later modified to reflect new discoveries regarding histocompatibility or the complex "two-signal" activation of T cells.[20] The self/nonself theory of immunity and the self/nonself vocabulary have been criticized,[16][21][22] but remain very influential.[23][24]

More recently, several theoretical frameworks have been suggested in immunology, including "autopoietic" views,[25] "cognitive immune" views,[26] the "danger model" (or "danger theory",[21] and the "discontinuity" theory.[27][28] The danger model, suggested by Polly Matzinger and colleagues, has been very influential, arousing many comments and discussions.[29][30][31][32]

Immunologist

Immunologist
Occupation
Occupation type
Profession / Specialty
Activity sectors
  • Medicine
  • Physiology
  • Science
  • Laboratorial
Description
Education required
  • MD
  • PhD
  • DO
Related jobs
  • Physician
  • Research scientist

According to the American Academy of Allergy, Asthma, and Immunology (AAAAI), "an immunologist is a research scientist who investigates the immune system of vertebrates (including the human immune system). Immunologists include research scientists (PhDs) who work in laboratories. Immunologists also include physicians who, for example, treat patients with immune system disorders. Some immunologists are physician-scientists who combine laboratory research with patient care."[33]

Career in immunology

Bioscience is the overall major in which undergraduate students who are interested in general well-being take in college. Immunology is a branch of bioscience for undergraduate programs but the major gets specified as students move on for graduate program in immunology. The aim of immunology is to study the health of humans and animals through effective yet consistent research, (AAAAI, 2013).[34] The most important thing about being immunologists is the research because it is the biggest portion of their jobs.[35]

Most graduate immunology schools follow the AAI courses immunology which are offered throughout numerous schools in the U.S.[36] For example, in New York State, there are several universities that offer the AAI courses immunology: Albany Medical College, Cornell University, Icahn School of Medicine at Mount Sinai, New York University Langone Medical Center, University at Albany (SUNY), University at Buffalo (SUNY), University of Rochester Medical Center and Upstate Medical University (SUNY). The AAI immunology courses include an Introductory Course and an Advance Course.[37] The Introductory Course is a course that gives students an overview of the basics of immunology.

In addition, this Introductory Course gives students more information to complement general biology or science training. It also has two different parts: Part I is an introduction to the basic principles of immunology and Part II is a clinically-oriented lecture series. On the other hand, the Advanced Course is another course for those who are willing to expand or update their understanding of immunology. It is advised for students who want to attend the Advanced Course to have a background of the principles of immunology.[38] Most schools require students to take electives in other to complete their degrees. A Master’s degree requires two years of study following the attainment of a Bachelor’s degree. For a Doctoral or Ph.D. program it is required to take two additional years of study. [39]

The expectation of occupational growth in immunology is an increase of 36 percent from 2010 to 2020.[40] The median annual wage was $76,700 in May 2010. However, the lowest 10 percent of immunologists earned less than $41,560, and the top 10 percent earned more than $142,800, (Bureau of Labor Statistics, 2013). The practice of immunology itself is not specified by the U.S. Department of Labor but it belongs to the practice of life science in general.[41]

See also

  • History of immunology
  • Immunomics
  • International Reviews of Immunology
  • List of immunologists
  • Osteoimmunology
  • Outline of immunology

Notes and references

  1. ^ Janeway's Immunobiology textbook Searchable free online version at the National Center for Biotechnology Information
  2. ^ Goldsby RA, Kindt TK, Osborne BA and Kuby J (2003). Immunology (5th ed.). San Francisco: W.H. Freeman. ISBN 0-7167-4947-5. 
  3. ^ a b c Jaspan HB, Lawn SD, Safrit JT, Bekker LG (February 2006). "The maturing immune system: implications for development and testing HIV-1 vaccines for children and adolescents". AIDS 20 (4): 483–94. doi:10.1097/01.aids.0000210602.40267.60. PMID 16470112. 
  4. ^ Glezen WP (December 2001). "Maternal vaccines". Prim. Care 28 (4): 791–806, vi–vii. doi:10.1016/S0095-4543(05)70041-5. PMID 11739030. 
  5. ^ Holt PG, Macaubas C, Cooper D, Nelson DJ, McWilliam AS (1997). "Th-1/Th-2 switch regulation in immune responses to inhaled antigens. Role of dendritic cells in the aetiology of allergic respiratory disease". Adv. Exp. Med. Biol. Advances in Experimental Medicine and Biology 417: 301–6. doi:10.1007/978-1-4757-9966-8_49. ISBN 978-1-4757-9968-2. PMID 9286377. 
  6. ^ Sizonenko PC, Paunier L (November 1975). "Hormonal changes in puberty III: Correlation of plasma dehydroepiandrosterone, testosterone, FSH, and LH with stages of puberty and bone age in normal boys and girls and in patients with Addison's disease or hypogonadism or with premature or late adrenarche". J. Clin. Endocrinol. Metab. 41 (5): 894–904. doi:10.1210/jcem-41-5-894. PMID 127002. 
  7. ^ Verthelyi D (June 2001). "Sex hormones as immunomodulators in health and disease". Int. Immunopharmacol. 1 (6): 983–93. doi:10.1016/S1567-5769(01)00044-3. PMID 11407317. 
  8. ^ Stimson WH (September 1988). "Oestrogen and human T lymphocytes: presence of specific receptors in the T-suppressor/cytotoxic subset". Scand. J. Immunol. 28 (3): 345–50. doi:10.1111/j.1365-3083.1988.tb01459.x. PMID 2973658. 
  9. ^ Benten WP, Stephan C, Wunderlich F (June 2002). "B cells express intracellular but not surface receptors for testosterone and estradiol". Steroids 67 (7): 647–54. doi:10.1016/S0039-128X(02)00013-2. PMID 11996938. 
  10. ^ Beagley KW, Gockel CM (August 2003). "Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone". FEMS Immunol. Med. Microbiol. 38 (1): 13–22. doi:10.1016/S0928-8244(03)00202-5. PMID 12900050. 
  11. ^ Kanda N, Tamaki K (February 1999). "Estrogen enhances immunoglobulin production by human PBMCs". J. Allergy Clin. Immunol. 103 (2 Pt 1): 282–8. doi:10.1016/S0091-6749(99)70503-8. PMID 9949320. 
  12. ^ McFarland RD, Douek DC, Koup RA, Picker LJ (April 2000). "Identification of a human recent thymic emigrant phenotype". Proc. Natl. Acad. Sci. U.S.A. 97 (8): 4215–20. doi:10.1073/pnas.070061597. PMC 18202. PMID 10737767. 
  13. ^ Miller JJ, Valdes R (February 1991). "Approaches to minimizing interference by cross-reacting molecules in immunoassays". Clin. Chem. 37 (2): 144–53. PMID 1993317. 
  14. ^ Silverstein A (1989). A History of Immunology. New York: Academic Press. 
  15. ^ Tauber AI and Chernyak L (1991). Metchnikoff and the Origins of Immunology. New York: Oxford University Press. 
  16. ^ a b Tauber AI (1994). The Immune Self: Theory or Metaphor?. Cambridge: Cambridge University Press. 
  17. ^ Jerne NK (1955). "The natural selection theory of antibody formation". Proceedings of the National Academy of Sciences USA 41: 849–57. doi:10.1073/pnas.41.11.849. PMC 534292. PMID 16589759. 
  18. ^ Burnet FM (1959). The Clonal Selection Theory of Acquired Immunity. Cambridge: Cambridge University Press. 
  19. ^ Burnet FM (1969). Cellular Immunology: Self and Notself. Cambridge: Cambridge University Press. 
  20. ^ Bretscher P, Cohn M (1970). "A theory of self-nonself discrimination". Science 169 (3950): 1042–49. doi:10.1126/science.169.3950.1042. 
  21. ^ a b Matzinger P (2002). "The danger model: A renewed sense of self". Science 296 (5566): 301–5. doi:10.1126/science.1071059. PMID 11951032. 
  22. ^ Pradeu (2012). The Limits of the Self: Immunology and Biological Identity. New York: Oxford University Press. 
  23. ^ Langman RE, Cohn M (2000). "A minimal model for the self-nonself discrimination: a return to the basics". Seminars in Immunology 12: 189–195. doi:10.1006/smim.2000.0231. 
  24. ^ Clark WR (2008). In Defense of Self: How the Immune System Really Works. New York: Oxford University Press. 
  25. ^ Coutinho A et al (1984). "From an antigen-centered, clonal perspective of immune responses to an organism-centered network perspective of autonomous reactivity of self-referential immune systems". Immunological Reviews 79: 151–168. doi:10.1111/j.1600-065x.1984.tb00492.x. 
  26. ^ Irun C (2000). Tending Adam’s garden: Evolving the cognitive immune self. San Diego: Academic Press. 
  27. ^ Pradeu T, Carosella ED (2006). "On the definition of a criterion of immunogenicity". Proc Natl Acad Sci U S A. 103(47): 17858–17861. doi:10.1073/pnas.0608683103. 
  28. ^ Pradeu T, Jaeger S, Vivier E (2013). "The speed of change: towards a discontinuity theory of immunity?". Nature Reviews Immunology. 13(10): 764–769. doi:10.1038/nri3521. 
  29. ^ Janeway CA Jr, Goodnow CC, Medzhitov R (1996). "Immunological tolerance: Danger - pathogen on the premises!". Current Biology 6(5): 519–522. doi:10.1016/S0960-9822(02)00531-6. 
  30. ^ Vance RE (2000). "Cutting edge commentary: a Copernican revolution? Doubts about the danger theory". Journal of Immunology. 165(4): 1725–1728. doi:10.4049/jimmunol.165.4.1725. 
  31. ^ Matzinger P (2012). "The evolution of the danger theory. Interview by Lauren Constable". Expert Rev Clin Immunol. 8(4) (4): 311–317. doi:10.1586/eci.12.21. PMID 22607177. 
  32. ^ Pradeu T, Cooper EL (2012). "The danger theory: 20 years later". Frontiers in Immunology 3: 287. doi:10.3389/fimmu.2012.00287. 
  33. ^ "Office of Science Education - LifeWorks - Immunologist". Retrieved 2009-09-10. 
  34. ^ http://www.aaaai.org/about-the-aaaai/allergist---immunologists--specialized-skills.aspx.
  35. ^ [1] North Carolina Association for Biomedical Research, 2013.
  36. ^ [2] American Association of Immunology, n.d.
  37. ^ http://www.aai.org/Careers/Graduate_Programs.html.
  38. ^ [3] The American Association of Immunologists, n.d.
  39. ^ [4] Stanford School of Medicine.
  40. ^ http://www.bls.gov/bls/confidentiality.htm Bureau of Labor Statistics, 2013, May 02.
  41. ^ http://www.bls.gov/bls/confidentiality.htm Bureau of Labor Statistics, 2013.

External links

  • The Immunology Link
  • American Academy of Allergy, Asthma & Immunology
  • British Society for Immunology
  • Annual Review of Immunology journal
  • BMC: Immunology at BioMed Central, an open-access journal publishing original peer-reviewed research articles.
  • Nature reviews: Immunology
  • The Immunology Database and Analysis Portal, a NIAID-funded database resource.
  • Immunology group at researchgate.net.
  • Federation of Clinical Immunology Societies
  • Immunology Simplified—from AIDS to ZZZZZZ (PowerPoint file).