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

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

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

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

Precipitation Aggultination Neutralization

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

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

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

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

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

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)

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

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)

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

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)

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

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

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!

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

. 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)

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

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

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

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

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:

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

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

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

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

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

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

. 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

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

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

 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

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

What do antibodies do? Think “PLAN OP”

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

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

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

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

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)

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

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?

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….

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

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

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

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