Adaptive Immunity: Specific Defenses of the Host

Chapter 17

I. Introduction to Specific Defenses of the Host

• A. Innate immunity (resistance) – An individual’s genetically predetermined resistance to certain diseases. Affected by sex, age, nutritional status, and general health (previously discussed in Chap 16).

• B. Acquired (adaptive) immunity – Ability of the body to counteract specific microbes or foreign substances. Immunity results from the production of protein antibodies and specialized lymphocytes that target a specific antigen that caused their formation. The outcome is destruction or inactivation of the antigen for current or future exposures. The immune system is required for survival, but if misdirected toward self antigens it can be very destructive to the host.

Types of Acquired Immunity - Figure 17.16

I. Naturally acquired active

II.Naturally acquired passive

III.Artificially acquired active and

vaccination

IV.Artificially acquired passive and gamma

globulin fig 17.17

II. Types of Acquired Immunity

Figure 17.17

III. The Duality of the Immune System• A. Mediated by lymphocytes via the lymphatic system.

• Fluid circulates between interstitial fluid, lymphatic vessels and nodes, then returned to the blood. Antigens in this fluid are processed by the immune system. Fig 16.5

• B. Humoral (Antibody Mediated) Immunity

– Protein Antibodies are produced by B Cells (B Lymphocytes) and secreted into extracellular fluids.• Defends against bacteria, viruses, and toxins in body fluids

• C. Cell Mediated by specialized lymphocytes

– Involves T-cells (T lymphocytes) and no antibodies. Act against foreign organisms or tissues. Regulates the activation and proliferation of other immune system cells.• Most effective against intracellular bacteria and viruses, fungi,

multicellular parasites, cancer cells, and transplanted tissue.

IV. Antigens and Antibodies• A. Antigens – Substances that cause the body to produce

specific antibodies and/or sensitized T-cells.

– 1. Foreign – Not part of body chemistry. Nonself vs self recognition so the immune system does not attack the host’s own tissues.

– 2. Proteins or large polysaccharides with a molecular weight greater than 10,000. Combinations can be antigenic: nucleoproteins, lipoproteins, glycoproteins. Most components of an organism are antigenic.

– 3. Antibodies are formed against specific regions on the surface of an antigen called ‘antigenic determinant’ (epitope). Fig 17.1

– 4. Hapten is a low molecular weight compound that cannot induce antibody response by itself, but can if combined with another molecule (often a host protein).

• E.g. penicillin fig 17.2

Figure 17.1Epitopes: antigenic determinanants

Figure 17.2

Haptens

IV. Antigens and Antibodies• B. Antibodies –

Proteins made in response to antigens that can only recognize and bind with the antigen that stimulated their formation.– 1. Structure – Typically

Y-shaped with two light and two heavy chains. Variable region provides for specific antigen recognition and binding.

IV. Antigens and Antibodies

IV. Antigens and Antibodies: Antibodies

• 2. Immunoglobulin Classes– IgG (80% of blood antibodies), crosses placenta

– IgM (5-10% of serum antibodies), used to detect initial infection

– IgA (primarily in mucous and secretions for localized protection), especially important in respiratory and GI tract.

– IgD (antigen receptors on B cells for initiation of immune response)

– IgE (bind to mast cells in tissue), mediates allergies, lysis of parasitic worms.

IV. Antigens and Antibodies: Antibodies

V. B Cells and Humoral Immunity

• A. Bone marrow stem cells give rise to B cells that migrate to lymphoid organs where they come in contact with antigen, which they recognize, via antibody on surface of their cells.

V. B Cells and Humoral Immunity• 1. The antigen is processed and presented with a

MHC class II site on the surface of the B cell where it can be recognized by a TH cell via its specific receptor. – The MHC is a self identity marker that prevents the host

from making antibodies harmful to itself.

– Most antigens elicit this type of response, called a T dependent antigen response.

Figure 17.4 - OverviewActivation of B cells to produce antibodies

V. B Cells and Humoral Immunity

• 2. B cells go through a process of producing a clone of plasma cells (antibody producing cells) and memory cells.

• An individual may recognize about 1015

different antigens determined by their genetic makeup.

V. B Cells and Humoral Immunity• B. Antigen-Antibody Binding and its results

– Agglutination, Opsonization, Neutralization, Complement activation, Inflammation, Antibody-dependent cell-mediated cytotoxicity

Figure 17.14 - Overview

V. B Cells and Humoral Immunity• C. Immunological Memory

– 1. Primary: gradual, several days with no antibody, then IgM, then IgG. Peak titers at 10-17 days.

– 2. Secondary Immune Response: quick via memory cells that persist for years, primarily IgG. Some antibody already present followed by peak in 2-7 days.

– 3. T cell memory is similar and necessary for self vs nonself recognition

Figure 17.15

The primary and secondary immune response to an antigen

VI. T Cells and Cell-Mediated Immunity

• A. Chemical Messengers of Immune Cells

– 1. Cytokines – Chemical way in which cells communicate

– Example: Interleukin 2 (IL-2) stimulates antigen stimulated T helper cells and B cells, activates T cytotoxic cells and natural killer cells.

VI. T Cells and Cell-Mediated Immunity

• B. Cellular Components of Immunity

– 1. Lymphocytes produced in bone marrow migrate to thymus, where under the influence of thymic hormones, differentiate into T-cells.

– In response to antigen, effector T-cells are stimulated to be produced. These cells proliferate and carry out cell mediated immunity.

– The body’s ability to make new T cells decreases with age beginning in late adolescence, so the immune system is relatively weak in old age. Memory cells remain to provide protection.

Figure 17.8Differentiation of T cells and B cells

VI. T Cells and Cell-Mediated Immunity• 2. Types of T cells : APC and T cell

– Classified according to function and cell surface receptors (glycoproteins: clusters of differentiation (CD)).

– Antigen presenting cell (APC) = macrophages or dendritic cells.• Self molecule on surface = Major histocompatibility

complex (MHC).

• Is not a T cell, but is necessary to process antigen to present to T cell

• A T cell only recognizes the antigen if presented with an MHC self surface (Class II) marker close to it that is unique to that person as defined in their genetic code. The immune system uses this to determine self from nonself.

Figure 17.12A dendritic cell

Figure 17.13

Acivated macrophages

VI. T Cells and Cell-Mediated Immunity

• 2. Types of T cells

– T-helper cell (TH, CD4), T-cytotoxic cell (TC, CD8)

• Antigen must be presented by APC to T helper cell. IL-1 secreted by APC to stimulate TH cell. fig 17.9

• Antigen must be closely associated with MHC for successful recognition by T cell. IL-2 secreted by TH

cells to stimulate and differentiate more T and B cells. Amplifies response.

• TC cells attack whole cells (e.g. cancer cells, virus infected cells where antibodies can’t get at them) with surface antigen and MHC class I markers.

– Class I markers are found on nucleated host cells. So, these cells can attack host cells that have an altered surface antigen, such as tumor cells and virus infected cells. Fig 17.10

Figure 17.9 - Overview (1 of 4)Activation of CD4 helper T cell by exogenous antigen

Figure 17.10 - Overview

Activation of CD8 cytotoxic T cell by endogenous antigen

VI. T Cells and Cell-Mediated Immunity

• 2. Types of T cells

– Regulatory T cell (TR ) – Turns off (suppresses) the immune response when antigen no longer present.

• May be involved with regulation of tissue rejection and auto immune reactions.

VI. T Cells and Cell-Mediated Immunity

C. Interrelationship of Cell-Mediated and Humoral Immunity. Fig 17.18