1. Objectives 8 Characteristics of Immune Responses
Every immune response has these characteristics:
1. It is antigen specific
2. It is systemic in scope
3. It has memory

2. Objective 9 Cell Mediated and Humoral Immunity
There are two interacting mechanisms in the immune response:
Cells Involved Mechanism
Humoral Immunty  plasma cells secrete (Antibody Mediated) antibodies into body fluids  antibody is transported in body fluids to the site of infection  antibodies form complexes with antigens and may activate complement, neutralize the antigen or immobilize the antigen by precipitation or agglutination
B lymphocytes and plasma cells

3. But first a word about antigens!
Examples of antigens:
Bacteria
Viruses
Transplanted cells
Cancer cells
Incompatible blood transfusion
Pollen (for some of us)

4. Neutralization: the antibody combines with the antigen and blocks an active site, preventing antigen binding to receptors on tissue cells
Agglutination: antibodies are divalent (have more than one binding site); they can bind to more than one antigen at a time, forming cross linked clumps of antigen/antibody complexes
Precipitation: same as agglutination, but the antigen is a soluble molecule; clumping causes the soluble antigen to fall out of solution

5. Precipitation
Aggultination
Neutralization

6. All the ways antibodies work in immunity:
Remember PLAN OP
Precipitate
Lyse (via complement)
Agglutinate
Neutralize
Opsonization
Phagocytosis

7. Cell Mediated Immunity
Cells Involved Mechanism
T lymphocytes T lymphocytes travel directly to the site of infection and act directly to lyse the invader or indirectly by secreting chemicals which activate other immune mechanisms
Cell Mediated Immunity

9. Objective 10 Cells of the Adaptive IS
Antigen Presenting Cells: include dendritic cells, macrophages, B lymphocytes

10. APCs engulf antigens and present fragments of the engulfed antigens to B cells and/or T cells

12. Objective 16 (page 4.42) MHC
Major histocompatibility (MHC) antigens are self antigens that are tolerated by the host, but not by other genetically different individuals. There are two classes of MHC surface markers, MHC class I and MHC class II

14. MHC Class I:
Location:
Recognized by: cytotoxic T cells (CD8)
Function activate cytotoxic T cells if body cells are infected with intracellular parasites such as viruses, if body cells become malignant, or by non-self antigens (eg, transplants)
MHC Class I antigens allow activated cytotoxic T cells to interact with the target cell
All cells except RBCs ( all nucleated cells)

15. How MHC Class I and Endogenous Peptides are displayed on all cells (except RBCs)

16. MHC Class II:
Location: Dendritic cells, macrophages, B cells (all APCs)
Recognized by:
Function: present antigens to helper T cells
CD 4 cells (T cell subtype)

17. How MHC Class II and peptide derived from extracellular antigen is displayed on an APC surface

18. MHC Class I
MHC Class II
All nucleated cells
Antigen presenting cells
Binds endogenous antigens synthesized in a cell
Binds exogenous antigens
Presents antigen to cytotoxic T cells (CD8)
Presents antigen to helper T cells (CD 4)

19. autograft isograft allograft xenograft
The MHC Class I antigens of a donor will stimulate a recipient to reject a transplanted tissue causing tissue incompatibility; it is the class I proteins that are typed and matched prior to transfusion
: tissue is grafted from an individual back to himself
: tissue is transplanted between genetically identical individuals
: tissue is transplanted between two members of the same species (not genetically identical)
: tissue is transplanted from a member of one species to a member of another species
autograft
isograft
allograft
xenograft

20. a. A porcine (pig) derived ligament (Z-lig)
A young female soccer player tears her ACL during practice and decides to have it replaced with a graft. She is given several surgical options – decide which category each graft below falls in to:
a. A porcine (pig) derived ligament (Z-lig)
A section of the patient’s own patellar tendon:
A section of hamstring from a cadaver (not a relative):
xenograft
autograft
allograft

21. Birth Education Job Search Job interview A job!
Back to objective 10 page 4.30
Cells of specific immunity: B Lymphocytes and T Lymphocytes
The overall plan
Birth
Education
Job Search
Job interview
A job!

22. B Lymphocytes Are born and develop immunocompetence in bone marrow
Acquire B cell receptor (surface antibody) to a specific antigen
They then travel to lymph nodes and other lymphoid tissues

23. . Self reactive B cells are deleted in bone marrow or are
 Self reactive B cells are deleted in bone marrow or are inactivated in peripheral lymphoid tissues (anergy)

24. B lymphocyte activation
Activation occurs when antigens bind
Clonal proliferation means that many copies of this cell are produced
Maturation

25. Plasma Cell: antibody secreting cell that is a descendant of an activated B lymphocyte
Memory Cell descendant of a B lymphocyte that is programmed to respond quickly to the same subsequent encounters with the same antigen

26. T Lymphocyte:
 lymphocyte that has differentiated in the thymus gland where it acquires a T cell receptor (TCR)
 It later travels to lymph nodes and other lymphoid tissues

27. T cells must acquire two properties while in the thymus gland:
1. Must be able to bind to MHC class 1 antigens found on the surfaces of nucleated body cells (positive selection)
2. Must not react to self antigens bound to MHC class 1 molecules on the surface of nucleated body cells
T cells that fail to meet these criteria are removed from the pool of developing T cells via apoptosis

29. Specific Glycoprotein:
Helper T Cells:
Specific Glycoprotein:
Activating Cell: APC presentation of antigen
Requires MHC class II antigen and processed antigen
CD 4
Generally, they activate macrophages, attract WBCs, assist in B cell and T cell activation and stimulate B cell and T cell division
Functions:

30. TH1 subset
TH2 subset
Is involved in stimulating inflammation, activating macrophages, and promoting cytotoxic T cell activation
Is involved in eosinophil recruitment ; stimulates B cell division and antibody production activation

31. Cytotoxic T Cells Specific Glycoprotein: CD8
Activating Cell: APC presentation of antigen
Cytotoxic T Cells
Functions:
Directly attack and kill body cells infected with virus or other intracellular parasites, cancer cells and transplanted tissue cells
Cytotoxic T cells kill their targets by:
Inducing apoptosis
Releasing cytokines

32. CD8 Regulatory T Cells Specific glycoprotein:
Function: Regulate the immune response by releasing inhibitory cytokines (IL 10, transforming growth factor ,  interferon)
CD8

33. Objective 11 Antigens (Immunogens)
Immunogens (antigens) are substances which evoke immune responses
 Typically, antigens are:
1. Large, complex molecules – the larger and more complex the more immunogenic they are
2. Natural or man-made substances
3. Are non-self (normally)
Chemically (in order of highly to less immunogenic)
Proteins
Polysaccharides
Nucleic acids
Lipids

34. Examples of antigens:
Pathogens
Toxins
Foreign RBCs
Pollen
Food
Transplants
Fungus

35. Immunogenicity Reactivity A complete antigen has two properties:
can activate B cells and/or T cells
can react with activated T cells or antibodies
Immunogenicity Reactivity
Immunogenicity
Reactivity

36. . An incomplete antigen (hapten) is a molecule that is too small by
 An incomplete antigen (hapten) is a molecule that is too small by itself to be immunogenic; it can become immunogenic if it attaches to a larger carrier protein and becomes part of a larger complex

37.  Antigenic determinants (epitopes):
the portions of the antigen that are actually immunogenic, the portion to which antibodies or T cells bind

38. Objective 14 (page4.39) Antibodies (Immunoglobulins)
Antibodies (immuoglobulins) are glycoproteins secreted by plasma cells. They are located in interstitial fluid, plasma (gamma globulins) and in body secretions
 Four polypeptide chains (two heavy, two light)
 Chains are held together by covalent disulfide bonds (S=S)
Antibody Structure

39.  each heavy and light chain has two functional areas:
consists of highly variable amino acid sequences and forms the basis of antigen specificity; antigen binds here
more conserved amino acid sequences, which define the 5 antibody classes: IgA, IgD, IgE, IgG, IgM
each class has its own effector functions
Variable region
Constant region

40. Antibody Classes: Think “GAMED” Class Structure Function(s) IgD
IgM
IgG
(75-85 %)
IgA
IgE
(0.1%)
Structure
Function(s)
B cell activation
First antibody released during a primary infection; potent agglutinator; activates compliment
Monomer is involved in B cell activation
Effective against bacteria, extracellular viruses and toxins; activates complement and crosses the placenta
Protects body surfaces and prevents the attachment of pathogens
Triggers the release of histamine and other mediators of inflammation during allergic reactions
Location(s)
Attached to B cell surfaces antigen receptor
Pentamer is found in IF and plasma
Monomer is attached to B cell surfaces
Plasma and IF
Body Secretions
Attached to mast cell and basophil surfaces

41. What do antibodies do?
Think “PLAN OP”

42. Objective 12 (page 4.34) Humoral Response To Antigen
Activation: antigen binds to B cell receptor
Clonal expansion: binding of the antigen to the B cell receptor induces proliferation of identical B cells
Effector cells: B cells become antibody secreting plasma cells
Memory B cells: increased number of antigen specific B cells ready for next encounter with the specific antigen
Note: co-stimulation by IL-2, secreted by T helper cells is required

44. Objective 13 Acquired Immunity
Immunity can be innate or acquired through exposure to antigens:
generated when an individuals B cells encounter antigen and manufacture antibodies as part of an immune response (IR); long lasting protection is generated
generated when an individual receives antibodies produced by another organism (human or animal donor); shorter duration because no memory is generated
Active Immunity
Passive Immunity

45. Naturally Acquired Immunity
Immunity that is acquired as a result of a natural process (e.g., infection, placental transfer of antibody)
Immunity that is acquired when the antigen is introduced as part of a clinical process (e.g., vaccination)
Artificially Acquired Immunity

46. Acquired Immunity specifically obtained through the transfer of serum from one individual to another individual in order to fight a disease is an example of:
Immunity that is passive and artificial

47. Objective 15: The Cell Mediated Response
T lymphocytes are the cells (helper T and cytotoxic T)
Cell-mediated immune response is effective against:
Virus infected cells
Tumor cells
Grafted tissues
Fungi
Intracellular parasites
Some intracellular bacteria (slow growing e.g. tuberculosis)

48. Antigens are presented to T cells by
APC cells with MHC class II protein complexed with foreign antigen
Infected body cells with MHC class I protein complexed with foreign antigen

50. What are the steps in activating cell mediated immunity ?
This diagram illustrates the activation of T helper cells.
What is different in the process of activating cytotoxic T cells?

51. What do activated helper T cells do?
Stimulate cytotoxic T cells via secretion of interleukin 2 (IL-2)
Stimulate B cells via IL- 2, IL4, IL-5, IL-6
Activate macrophages
Stimulate helper T cells via IL-2
And remember….

52. TH1 subset
TH2 subset
Is involved in stimulating inflammation, activating macrophages, and promoting cytotoxic T cell activation
Is involved in eosinophil recruitment ; stimulates B cell division and antibody production activation 52

53. What do activated cytotoxic T cells do?
Destroy:
virus infected cells
cancerous cells
intracellular parasites
some bacterial infected cells
non-self cells 53

54. Cytotoxic T cells kill target cells by binding to the target cell and releasing:
Perforin which causes pore formation
Granzymes which stimulate target cell apoptosis

55. Cytotoxic T cells also:
Bind to Fas receptor on target cell which induces apoptosis in target cell
Release the cytokines tumor necrosis factor beta and gamma interferon which stimulate macrophages