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Microbiology: A Systems Approach

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Presentation on theme: "Microbiology: A Systems Approach"— Presentation transcript:

1 Microbiology: A Systems Approach
PowerPoint to accompany Microbiology: A Systems Approach Cowan/Talaro Chapter 15 Specific Immunity and Immunization Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2 Chapter 15 Topics - Thirdline of Defense - B cells - T cells
- Specific Immunities

3 Thirdline of Defense Specific immunity is a complex interaction of immune cells (leukocytes) reacting against antigens Specific Self and nonself (foreign) Antigens Antibodies & specialized lymphocytes

4 Self and nonself Markers glycoproteins located on the cell surface
Eg. Major histocompatibility complex (MHC)

5 Markers Host cells proteins (ex. MHC) confer specificity and identity
Role – detection, recognition, and communication Lymphocyte cells recognize the host cell markers as “self” Lymphocyte cells recognize microbe markers as ‘nonself’

6 Major histocompatibility complex (MHC)
Self receptor Glycoprotein Found on all nucleated cells In humans – Human leukocyte antigen (HLA) is equivalent to the MHC Different Classes of MHC

7 Specific Acquired Immunities
Active Passive Natural Artificial Vaccines

8 Active Antigen activates B and T cells Memory cells
Long-term protection Natural or artificial

9 Passive Receive pre-formed antibodies from another individual or animal No memory cells No antibody production Short-term protection Natural or artificial

10 Natural Immunity produced by normal biological experiences, no medical intervention Natural active Eg. Infection Natural passive Eg. Mother to child – across the placenta, via breast milk

11 Artificial Immune protection through medical procedures or intervention Artificial active Eg. vaccination Artificial passive Eg. Injection of preformed antibodies (antiserum) Immediate but short-lived protection

12 Summary of the different acquired immunities.
Fig Categories of acquired immunities

13 Duality of the Immune System
Humoral Immunity B-lymphocytes produce antibodies Antibodies in fluids ( blood, lymph, etc.) Defense against Bacteria Toxins Circulating viruses

14 Duality of the Immune System
Cell-Mediated Immunity T-cells (lymphocytes) Acts against foreign tissues or organisms Regulates the activity of other immune system cells

15 Cell-Mediated Immunity
Defends against Bacteria or viruses that are within the host cells Fungi, protozoa and helminths Transplanted tissue cancer

16 Mature T and B cells migrate to the lymphoid tissue, where they encounter antigens.
Fig Major stages in the development of B and T cells.

17 Stages Dual lymphocyte development and differentiation
Presentation of antigens Challenge of B and T lymphocytes by antigens Production of antibodies by B cells (plasma cell) T lymphocyte responses

18 An overview of the stages of lymphocyte development and function.
Fig Overview of the stages of lymphocyte development

19 Receptors Present on B and T cells
Immunoglobulin molecule Light chain Heavy chain Variable region Constant region B cell receptors are secreted as antibodies

20 The structure of a receptor for B cells.
Fig Simplified structure of an immunoglobulin molecule on the surface of B cells.

21 The structure of the receptor for T cells.
Fig Proposed structure of the T cell receptor for antigen.

22 Antigens Foreign material Size and shape are important

23 Antigens Microbial products Non-microbial products
Capsules, cell walls Flagella Fimbria Bacterial toxins Viral protein coats Other surface molecules Non-microbial products Pollen Egg white Blood cell surface markers Serum proteins from other individuals Transplanted tissues

24 Foreign material Antigenic Proteins and polypeptides
enzymes, cell surface structures, hormones, exotoxins) – usu. Glycoproteins - blood cell markers Large Polysaccharides - capsules, LPS) Not very Antigenic Lipids & cell membranes Nucleic acids (DNA)

25 Size and shape Size affects antigenicity Haptens
Too small – no immune recognition Large – immune recognition Proteins are better immunogens than polysaccharides because of their complex shape Haptens antigens that are too small to elicit an immune response

26 A hapten can complex with a larger carrier protein in order to stimulate an immune response.
Fig The hapten-carrier phenomenon.

27 Superantigen Bacterial toxins
T cell activation much greater than normal antigens Large release of cytokines Results in toxic shock syndrome and some autoimmune diseases

28 Examples of different antigens and their characteristics.
Fig Characteristics of antigens.

29 Antibody Product of B cell activation Structure
Immunoglobulin (Ig) family of proteins Produced in response to an antigen Structure Highly specific for the antigen that stimulated the production of the antibody Antigen –binding site on the antibody specifically binds the antigen Has at least two antigen-binding sites

30 Antibody Structure 2 identical heavy chains 2 identical light chains
Linked by disulfide bridges Variable region binds antigen Constant region determines the class of the antibody Fc – stem region binds complement or allow antibody to be attached to the surface of a cell.

31 The complete structure of an IgG antibody.
Fig Working models of antibody structure.

32 V-region Variable (N-terminal of the heavy and light chains)
Binds to the antigen Swiveling enables more efficient binding Held together by disulfide bonds

33 Fc Constant (C-terminal of heavy chain) Binds to macrophages
Anchors Ig to lymphocyte Held together by disulfide bonds Responsible for class identification

34 Classes based on the Fc fragment Immunoglobulin (Ig) IgG IgA IgM IgD
IgE

35 IgG Monomer Primary response Memory cell response
Most prevalent in tissue fluid and blood

36 IgM Five monomers Held together by a J chain
First to be synthesized during primary immune response Associated with complement fixation Receptor for antigens on B cells Circulates in the blood

37 IgA Monomer or dimer (secretory IgA)
Dimer – held together by a J chain Secretory IgA (mucous and serous secretions) Local immunity Salivary glands, intestine, nasal membrane, breast, lung, genitourinary tract Protection for newborns

38 IgD Monomer Small amounts in the serum
Receptor for antigens on B cells

39 IgE Allergies Parasite infections
Fc portion binds to mast cells and basophils release chemical mediators that aid inflammation

40 The characteristics of the different immunoglobulin classes.
Table 15.2 Characteristics of the immunoglobulin classes.

41 B cells Activation Antibody Antibody-antigen interaction Response

42 Activation Clonal selection and binding of antigen
Instruction by chemical mediators Transmission of signal to the nucleus B cell changes into a plasma cells and begins mitosis Clonal expansion and memory cell formation Antibody production and secretion

43 Clonal selection The synthesis of varied receptor types Clone
approximately 500 genes undergo rearrangement eventually one clone recognizes an antigen and expands (proliferates) Clone each mature lymphocyte possesses a single combination or receptor specificity Expansion a single cell is stimulated by antigen recognition Clonal deletion cells that recognize self are removed

44 The clonal selection theory of lymphocyte development and diversity.
Fig Overview of the clonal selection theory of lymphocyte development and diversity.

45 The stages of B-cell activation and antibody synthesis.
Fig Events in B-cell activation and antibody synthesis.

46 Antibody-antigen interactions
Opsonization Agglutination Neutralization Complement fixation

47 A complementary fit between an antibody and antigen involves hydrogen bonds and electrostatic attractions. Fig Antigen-antibody binding

48 The different functions of antibodies.
Fig Summary of antibody functions

49 Agglutination Antibodies cross-link cells or particles into clumps
Renders microbes immobile Enhances phagocytosis Principle for certain immune tests (RBC typing)

50 Opsonization Microbes or particles coated with antibodies
Enables macrophages to recognize and phagocytize microbe

51 Neutralization Antibody binds to
The microbe or virus receptor Antigenic site of a molecule (Eg. Exotoxin) Prevents further binding of microbe or toxin

52 Complement fixation Antibodies interaction with complement proteins (Eg. Classical pathway) Lysis of microbial cell

53 Response Primary Secondary

54 Primary First exposure Latent period Synthesis of antibodies
Lack of antibodies synthesis Synthesis of antibodies Level of synthesis (titer) IgM first Followed by IgG, and some IgA and IgM

55 Secondary Re-exposure to the same immunogen (Anamnestic response)
Antibody synthesis, titer, and length of antibody persistence is rapid and amplified Primarily due to memory cells

56 The stages of primary and secondary responses to antigens.
Fig Primary and secondary responses to antigens.

57 Apoptosis Programmed cell death
Genetic program that is turned on and stimulates the cell to digest itself Debris is cleared away by macrophages without stimulating inflammation The way the body gets rid of unneeded or worn out cells

58 T cell Activation Types

59 Activation Cell-mediated immunity Cytokines Antigen presenting cells
Interleukins – IL-1, IL-2 Gamma interferon Tumor Necrosis Factor ( TNF) Antigen presenting cells Activated macrophages

60 Cell-mediated immunity
Direct involvement of T cells Produce and react to cytokines Activated simultaneously with B cell activation Subset of T cells have unique CD receptors (CD4, CD8)

61 Antigen presenting cells (APC)
Macrophages and dendritic cells Process and present antigen in association with MHC T cell CD receptor recognize antigen/MHC

62 Transformation Activated T cells prepare for mitosis
Effectors cells or types (TH, TC) are produced Memory cells are produced

63 Types Helper T cells (TH) Cytotoxic T cells (TC)

64 TH Regulate immune reactions to antigens by releasing cytokines
CD4 receptor Type of cytokine will determine subset of TH TH1 (activate other T cells, delayed type hypersensitivity) TH2 (B cell differentiation) Cytokines also activate macrophages Most prevalent in the blood Insert animation T helper cell dependent antigen

65 TC Binds and lyses cells (apoptosis) CD8 receptor
microbe, viral infected cells, foreign cells, cancer cells CD8 receptor Perforins – punch holes in the membrane Granzymes – degrade proteins Natural killer (NK) cells related to TC attack virus infected cells and cancer cells Insert animation Cytotoxic T cell

66 An example of helper and cytotoxic T cell activation and differentiation.
Fig Overall scheme of T-cell activation and differentiation into different types of T cells.

67 Characteristics of the different subsets of T cells.
Table 15.3 Characteristic of subsets of T cells.

68 Relationship between Cell-Mediated and Humoral Immunity
T- independent antigens Can stimulate B-cells directly Antibodies will be produced without the need for T-helper cells T-dependent antigens Most antigens are not sufficient to stimulate the B-cells directly A T-helper cell has to recognize the antigen and assist the B-cell Most antigens are T-dependent

69 An example of a cytotoxic T cell destroying a cancer cell.
Fig A cytotoxic T cell has mounted a successful attack on a tumor cell.


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