zhvilllimi i limfociteve

Microbiology: A Systems Approach

Chapter 15Specific Immunity and Immunization

PowerPoint to accompany

Cowan/Talaro

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– Stages– Self and nonself– Clonal selection– Antigens

4

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

5

An overview of the stages of lymphocyte development and function.

Fig. 15.1 Overview of the stages of lymphocyte development

6

Self and nonself• Markers

– glycoprotein– located on the cell surface – Eg. Major histocompatibility complex

(MHC)

7

Markers• Host cells receptors (ex. MHC)

confer specificity and identity• Role – detection, recognition, and

communication• Lymphocyte cells recognize the

host cell receptors as “self”• Lymphocyte cells recognize

microbe receptors as ‘nonself’

8

Major histocompatibility complex (MHC)

• Self receptor• Glycoprotein• Found on all nucleated cells• In humans – Human leukocyte

antigen (HLA) is equivalent to the MHC

• Classes of MHC

9

Classes of MHC• Each individual has a unique MHC

profile– Expression of a particular

combination of MHC genes • Class I – all nucleated cells• Class II – macrophages, dendritic

cells, B cells

10

The Class I and II MHC for humans are surface receptors consisting of glycoproteins.

Fig. 15.2 The human major histocompatibility complex.

11

Clonal selection• The synthesis of varied receptor types

– 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

12

B cell clone• Application of immunology• Propagate a single clone in order

to synthesis monoclonal antibodies• Monoclonal antibody

– possess a single specificity for antigen

13

The clonal selection theory of lymphocyte development and diversity.

Fig. 15.3 Overview of the clonal selection theory of lymphocytedevelopment and diversity.

14

Mature T and B cells migrate to the lymphoid tissue, where they encounter antigens.

Fig. 15.4 Major stages in the development of B and T cells.

15

Receptors• Present on B and T cells

– Immunoglobulin molecule• Light chain• Heavy chain• Variable region• Constant region

• B cell receptors are secreted as antibodies

16

The structure of a receptor for B cells.

Fig. 15.5 Simplified structure of an immunoglobulinmolecule on the surface of B cells.

17

The structure of the receptor for T cells.

Fig. 15.6 Proposed structure of the T cell receptor for antigen.

18

Antigens• Foreign material• Size and shape• Alloantigens• Superantigens

19

Foreign material• Proteins and polypeptides

– enzymes, cell surface structures, hormones, exotoxins)

• Lipids – cell membranes

• Glycoproteins – blood cell markers

• Nucleoproteins – DNA complexed to proteins

• Polysaccharides – capsules, LPS)

20

Size and shape• Immunogen

– Less than1000 daltons – no immune recognition– Greater than 1000 daltons – immune recognition– Proteins are better immunogens than

polysaccharides • Epitope

– portion of the antigen (ex. Amino acids) recognized by lymphocyte receptor

• Haptens – antigens that are too small to elicit an immune

response

21

A hapten can complex with a larger carrier protein in order to stimulate an immune response.

Fig. 15.8 The hapten-carrier phenomenon.

22

Alloantigens• Cell surface markers that occur in

some members of the same species– blood typing (transfusion) – MHC profile (organ grafting)

23

Superantigen• Bacterial toxins• T cell activation much greater than

normal antigens• Large release of cytokines• Results in toxic shock syndrome

and some autoimmune diseases

24

Examples of different antigens and their characteristics.

Fig. 15.7 Characteristics of antigens.

25

B cells• Activation• Antibody• Antibody-antigen interaction• Response

26

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

27

The stages of B-cell activation and antibody synthesis.

Fig. 15.10 Events in B-cell activation and antibody synthesis.

28

Antibody• Product of B cell (plasma cell)

activation– Immunoglobulin (Ig) or antibody

• Structure– Four polypeptides – Connected by disulfide bonds– Antigen binding fragment (Fabs)– Crystallizable fragment (Fc)

• Classes

29

Fab• Variable (N-terminal of the heavy

and light chains)• Binds to the antigenic determinant • Swiveling enables more efficient • Held together by disulfide bonds

30

Fc• Constant (C-terminal of heavy

chain)• Binds to macrophages• Anchors Ig to lymphocyte• Held together by disulfide bonds• Responsible for class identification

31

The complete structure of an IgG antibody.

Fig. 15.11 Working models of antibody structure.

32

Classes• Isotypes – based on the Fc fragment• Immunoglobulin (Ig)

– IgG– IgA– IgM– IgD– IgE

33

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

blood

34

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

35

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

36

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

37

IgE• Allergies• Parasite infections• Fc portion binds to mast cells and

basophils– release chemical mediators that aid

inflammation

38

The characteristics of the different immunoglobulin classes.

Table 15.2 Characteristics of the immunoglobulin classes.

39

Antibody-antigen interactions

• Opsonization• Agglutination• Neutralization• Complement fixation

40

A complementary fit between an antibody and antigen involves hydrogen bonds and electrostatic attractions.

Fig. 15.12 Antigen-antibody binding

41

Opsonization• Microbes or particles coated with

antibodies• Enables macrophages to recognize

and phagocytize microbe

42

Agglutination• Antibodies cross-link cells or

particles into clumps• Renders microbes immobile• Enhances phagocytosis• Principle for certain immune tests

(RBC typing)

43

Neutralization• Antibody binds to

– The microbe or virus receptor– Antigenic site of a molecule (Eg.

Exotoxin)• Prevents further binding of

microbe or toxin

44

Complement fixation• Antibodies interaction with

complement proteins (Eg. Classical pathway)

• Lysis of microbial cell

45

The different functions of antibodies.

Fig. 15.13 Summary of antibody functions

46

Response• Primary• Secondary

47

Primary• First exposure

– Latent period• Lack of antibodies synthesis

– Synthesis of antibodies • Level of synthesis (titer)• IgM first• Followed by IgG, and some IgA and IgM

48

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

49

The stages of primary and secondary responses to antigens.

Fig. 15.15 Primary and secondary responses to antigens.

50

T cell• Activation• Types

51

Activation• Cell-mediated immunity• Antigen presenting cells • Transformation

52

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)

53

Antigen presenting cells (APC)

• Macrophages and dendritic cells– Process and present antigen in

association with MHC II– T cell CD receptor recognize

antigen/MHC II

54

Transformation• Activated T cells prepare for

mitosis• Effectors cells or types (TH, TC) are

produced• Memory cells are produced

55

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

56

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 .0083 T helper cell dependent antigen

57

TC

• Binds and lyses cells (apoptosis) – 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 .0034 Cytotoxic T cell

58

An example of helper and cytotoxic T cell activation and differentiation.

Fig. 15.16 Overall scheme of T-cell activation and differentiation into different types of T cells.

59

Characteristics of the different subsets of T cells.

Table 15.3 Characteristic of subsets of T cells.

60

An example of a cytotoxic T cell destroying a cancer cell.

Fig. 15.17 A cytotoxic T cell has mounted a successfulattack on a tumor cell.

61

Specific Immunities• Active• Passive• Natural• Artificial• Vaccines

62

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

63

Passive• Natural or artificial• Receive antibodies from another

individual or animal• No memory cells• No antibody production • Short-term protection

64

Natural• Immunity produced by normal

biological experiences, no medical intervention– Natural active

• Eg. Infection– Natural passive

• Eg. Mother to child

65

Artificial• Immune protection through

medical procedures or intervention– Artificial active

• Eg. vaccination– Artificial passive

• Eg. immunotherapy

66

Summary of the different acquired immunities.

Fig. 15.18 Categories of acquired immunities

67

Vaccines• Types

– Killed whole cell or inactivated viruses– Live, attenuated cells or viruses– Antigenic molecules from bacteria or

viruses– Genetically engineered microbes or

microbial antigens

68

Example of how different types of vaccines are designed.

Fig. 15.19 Strategies in vaccine design.

69

New vaccines• DNA vaccines

– Insert microbial DNA into plasmid– Inoculate recipient with plasmid– Host cell expresses microbial DNA– Immune system reacts to microbial

antigen expressed on the host cell surface

70

Benefits of vaccinations• Long-lasting immunity• Herd immunity

– Indirect protection of nonimmune– Prevents epidemics

71

In the U.S., there is a recommended childhood and adolescent immunization schedule.

Table 15.6 Recommended childhood and adolescent Immunization schedule.i

72

In the U.S., there is a recommended adult immunization schedule.

Table 15.7 Recommended adult immunization schedule.

73

In the U.S., there is a recommended adult immunization schedule.

Table 15.7 Recommended adult immunization schedule.

74

The steps associated with the preparation of DNA vaccines.

Fig. 15.20 DNA vaccine preparation