1. Foundations in Microbiology Sixth Edition
Lecture PowerPoint to accompany
Foundations in Microbiology Sixth Edition
Talaro
Chapter 15
Adaptive, Specific Immunity and Immunization
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2. Specific Immunity – Adaptive Line of Defense
Third line of defense – acquired
Production of specific antibodies by dual system of B and T lymphocytes in response to an encounter with a foreign molecule, called an antigen
Two features that characterize specific immunity:
specificity – antibodies produced, function only against the antigen that they were produced in response to
memory – lymphocytes are programmed to “recall” their first encounter with an antigen and respond rapidly to subsequent encounters

3. Classifying Immunities
Active immunity – results when a person is challenged with antigen that stimulates production of antibodies; creates memory, takes time and is lasting
Passive immunity – preformed antibodies are donated to an individual; does not create memory, acts immediately, and is short term.
Natural immunity – acquired as part of normal life experiences
Artificial immunity - acquired through a medical procedure such as a vaccine

4. Natural active immunity – acquired upon infection and recovery
Natural passive immunity – acquired by a child through placenta and breast milk
Artificial active immunity – acquired through inoculation with a selected Ag
Artificial passive immunity – administration of immune serum or globulin

6. Overview of Specific Immune Responses
Separate but related activities of the specific immune response:
Development and differentiation of the immune system
Lymphocytes and antigens
The challenge of B and T lymphocytes by antigens
B lymphocytes and the production and activities of antibodies
T lymphocyte responses

8. Development of the Immune Response System
Cell receptors or markers confer specificity and identity of a cell.
Major functions of receptors are:
To perceive and attach to nonself or foreign molecules
To promote the recognition of self molecules
To receive and transmit chemical messages among other cells of the system
To aid in cellular development

9. Major Histocompatibility Complex (MHC)
Receptors found on all cells except RBCs
Also known as human leukocyte antigen (HLA)
Plays a role in recognition of self by the immune system and in rejection of foreign tissue

10. Functions of MHC Genes for MHC clustered in a multigene complex:
Class I – markers that display unique characteristics of self molecules and regulation of immune reactions
required for T lymphocytes
Class II – receptors that recognize and react with foreign antigens; located primarily on macrophages and B cells
involved in presenting antigen to T-cells

11. Lymphocyte Receptors
Lymphocyte’s role in surveillance and recognition is a function of their receptors.
B-cell receptors – bind free antigens
T-cell receptors – bind processed antigens

12. Clonal Selection Theory
Lymphocytes use 500 genes to produce a tremendous variety of specific receptors.
Undifferentiated lymphocytes undergo genetic mutations and recombinations while they proliferate in the embryo.
Form a billion different clones with the ability to react with a tremendous variety of antigens

13. In the bone marrow, lymphocytic stem cells differentiate into either T or B cells.
B cells stay in the bone marrow.
T cells migrate to the thymus.
Both T and B cells migrate to secondary lymphoid tissue.

15. Lymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen has ever entered the system.
Each genetically different type of lymphocyte expresses a single specificity.
First introduction of each type of antigen into the immune system selects a genetically distinct lymphocyte.
Causes it to expand into a clone of cells that can react to that antigen

17. Specific B-Cell Receptor: Immunoglobulin
Receptor genes of B cells govern immunoglobulin (Ig) synthesis.
Large glycoproteins that serve as specific receptors of B cells
Composed of 4 polypeptide chains:
2 identical heavy chains (H)
2 identical light chains (L)
Y shaped arrangement – ends of the forks formed by light and heavy chains contain a wide range of variable antigen binding sites
Variable regions
Constant regions

19. Development of Receptors
Immunoglobulin genes lie on 3 different chromosomes
Undifferentiated lymphocyte has 150 different genes for the variable region of light chains and 250 for the variable region and diversity region of the heavy chain
During development, recombination causes only the selected V and D genes to be active in the mature cell.
Once synthesized, immunoglobulin is transported to cell membrane and inserted there to act as a receptor.

21. T-Cell Receptors for Antigen
Formed by genetic recombination, with variable and constant regions
2 parallel polypeptide chains
small, without humoral functions

23. B-cell Maturation
Directed by bone marrow sites that harbor stromal cells, which nurture the lymphocyte stem cells and provide hormonal signals
Millions of distinct B cells develop and “home” to specific sites in the lymph nodes, spleen, and GALT
Come into contact with antigens throughout life

24. T-Cell Maturation
Maturation is directed by the thymus gland and its hormones.
7 classes of T-cell receptors termed CD - cluster of differentiation
Mature T cells migrate to lymphoid organs and occupy specific sites.

25. Entrance and Processing of Antigens and Clonal Selection
Antigen (Ag) is a substance that provokes an immune response in specific lymphocytes.
Also called an immunogen
Property of behaving as an antigen is antigenicity

26. Characteristics of Antigens
Perceived as foreign, not a normal constituent of the body
Foreign cells and large complex molecules over 10,000 MW are most antigenic.
Antigenic determinant, epitope – small molecular group that is recognized by lymphocytes
Antigen has many antigenic determinants.

28. Foreign molecules less than 1,000 MW, called haptens
Not antigenic unless attached to a larger carrier

30. Special Categories of Antigens
Alloantigens – cell surface markers of one individual that are antigens to another of that same species
Superantigens – potent T cell stimulators; provoke an overwhelming response
Allergen – antigen that provokes allergy
Autoantigens – molecules on self tissues for which tolerance is inadequate

31. Antigen Processing and Presentation to Lymphocytes
T-cell dependent antigens must be processed by phagocytes called antigen presenting cells (APC).
APCs modify the antigen so it is more immunogenic and recognizable; then the Ag is moved to the APC surface and bound to MHC receptor.
Antigen presentation involves a direct collaboration among an APC, a T helper cell and an antigen-specific B or T cell.
Interleukin-1 is secreted by APC to activate TH cells.
Interleukin-2 is produced by TH to activate B and other T cells.

33. B-cell Activation and Antibody Production
Once B cells process the Ag, interact with TH cells and are stimulated by growth and differentiation factors, they enter the cell cycle in preparation for mitosis and clonal expansion.
Divisions give rise to plasma cells that secrete antibodies and memory cells that can react to the same antigen later.

35. Antibody Structure and Functions
Immunoglobulins
Large Y-shaped protein
Consist of 4 polypeptide chains
Contains 2 identical fragments (Fab) with ends that bind to specific antigen
Fc binds to various cells and molecules of the immune system.

37. Antibody-Antigen Interactions
Principle antibody activity is to unite with the Ag to call attention to, or neutralize the Ag for which it was formed.
Opsonization – process of coating microorganisms or other particles with specific antibodies so they are more readily recognized by phagocytes
Agglutination – Ab aggregation; cross-linking cells or particles into large clumps
Neutralization – Abs fill the surface receptors on a virus or the active site on a microbial enzyme to prevent it from attaching
Antitoxins are a special type of Ab that neutralize a bacterial exotoxin.

39. Functions of the Fc Fragment
Fc fragment binds to cells – macrophages, neutrophils, eosinophils, mast cells, basophils, and lymphocytes.

41. Classes of Immunoglobulins
5 classes of immunoglobulins (Ig):
IgG
IgA
IgM
IgD
IgE

43. Antibodies in Serum
If separated by electrophoresis, globulin separates into 4 bands:
Alpha-1 (α-1), alpha-2 (α-2), beta (β), and gamma (γ)
Most are antibodies.
γ is composed primarily of IgG; β and α-2 are a mixture of IgG, IgA, and IgM.

45. Primary and Secondary Responses to Antigens
Primary response – after first exposure to an Ag immune system produces IgM and a gradual increase in Ab titer (concentration of antibodies) with the production of IgG
Secondary response –after second contact with the same Ag, immune system produces a more rapid, stronger response due to memory cells – anamnestic response

47. Monoclonal Antibodies
Pure preparation of antibody
Single specificity antibodies formed by fusing a mouse B cell with a cancer cell.
Used in diagnosis of disease, identification of microbes and therapy

49. T Cells & Cell Mediated Immunity
Cell mediated immunity requires the direct involvement of T lymphocytes.
T cells act directly against Ag and foreign cells when presented in association with an MHC carrier.
T cells secrete cytokines that act on other cells.
Sensitized T cells proliferate into long-lasting memory T cells.

50. Types of T cells
T helper cells (CD4 or TH) most prevalent type of T cell; regulate immune reaction to antigens, including other T and B cells; also involved in activating macrophages and improving opsonization; differentiate into T helper 1 (TH1) cells or T helper 2 (TH2) cells
Cytotoxic T cells (CD8 or TC) destroy foreign or abnormal cells by secreting perforins that lyse cells.
Natural killer cells – lack specificity; circulate through the spleen, blood, and lungs

52. Immunization: Manipulating Immunity
Passive immunity – immune serum globulin (ISG), gamma globulin, contains immunoglobulin extracted from pooled blood; immunotherapy
Treatment of choice in preventing measles and hepatitis A and in replacing antibodies in immunodeficient patients
Sera produced in horses are available for diphtheria, botulism, and spider and snake bites.
Acts immediately; protection lasts 2-3 months

53. Vaccination
Artificial active immunity – deliberately exposing a person to material that is antigenic but not pathogenic
Principle is to stimulate a primary and secondary anamnestic response to prepare the immune system for future exposure to a virulent pathogen
Response to a future exposure will be immediate, powerful, and sustained.

54. Vaccine Preparation Most vaccines are prepared from:
Killed whole cells or inactivated viruses
Live, attenuated cells or viruses
Antigenic molecules derived from bacterial cells or viruses
Genetically engineered microbes or microbial agents

56. Killed or Inactivated Vaccines
Cultivate the desired strain, treat it with formalin or some other agent that kills the agent but does not destroy its antigenicity.
Often require a larger dose and more boosters to be effective

57. Live Attenuated Cells or Viruses
Process that substantially lessens or negates the virulence of viruses or bacteria – eliminates virulence factors
Advantages of live preparations are:
organisms can multiply and produce infection (but not disease) like the natural organism
They confer long-lasting protection.
usually require fewer doses and boosters
Disadvantages include:
require special storage, can be transmitted to other people, can conceivably mutate back to virulent strain

58. Antigenic Molecules
Acellular or subcellular vaccines (subunit – if a virus)
Exact antigenic determinants can be used when known:
capsules – pneumococcus, meningococcus
surface protein – anthrax, hepatitis B
exotoxins – diphtheria, tetanus
Antigen can be taken from cultures, produced by genetic engineering, or synthesized.

59. Genetically Engineered Vaccines
Insert genes for pathogen’s antigen into plasmid vector, and clone them in an appropriate host.
stimulated the clone host to synthesize and secrete a protein product (antigen), harvest and purify the protein – hepatitis
“Trojan horse” vaccine – genetic material from a pathogen is inserted into a live carrier nonpathogen; the recombinant expresses the foreign genes
experimental vaccines for AIDS, herpes simplex 2, leprosy, tuberculosis

60. Genetically Engineered Vaccines
DNA vaccines – create recombination by inserting microbial DNA into plasmid vector
Human cells will pick up the plasmid and express the microbial DNA as proteins causing B and T cells to respond, be sensitized, and form memory cells.
experimental vaccines for Lyme disease, hepatitis C, herpes simplex, influenza, tuberculosis, malaria

62. Route of Administration ad Side Effects
Most administered by injection; few oral, nasal
Some vaccines require adjuvant to enhance immunogenicity and prolong retention of antigen.
Stringent requirements for development of vaccines
More benefit than risk
Possible side effects include local reaction at injection site, fever, allergies; rarely back-mutation to a virulent strain, neurological effects.

63. Herd Immunity
Immune individuals will not harbor it, reducing the occurrence of pathogens – herd immunity.
Less likely that an nonimmunized person will encounter the pathogen