Ch. 15

Specific Defenses of the Host

Specific immunity

•         When the non-specific defense fails, then the third, specific line of immunity is activated

•         Immunity is not innate but adaptive; it is acquired over time

•         It is characterized with a specificity and memory

–        Specificity – antibodies against chickenpox is not effective against measles virus

–        During the 2nd encounter with a pathogen, the lymphocytes recall the 1st engagement and attack it again

•         Immunity is a defensive response of the body when a foreign organism or foreign substance invades it.

•         Antigens are substances (proteins or polysaccharides) that provoke immune response

•         Antibodies are proteins produced to inactivate the antigens

•         During the immune response, lymphocytes recognize and bind to the antigen

•         The immune system has two components:

1. Humoral immunity – production of

                        antibodies (B-cells)

2. Cell-mediated immunity – activation and proliferation of immune system cells (T-cells)

Overview of lymphocyte development and interaction

There are 5 Stages:

1. Development of B-cells and T-cells

2. Antigen presenting cells present the antigen to lymphocytes (T-helper cells)

3. Lymphocytes activation – formation of B and T cells

4. B lymphocytes become plasma cells – produce antibodies

5. Activated T cells become Helper T cells and cytotoxic T cells

Specificity of the lymphocytes

•         They have receptor sites on the cell surface that can recognize millions of different antigens

•         This great diversity of receptor sites is achieved through genetic recombination of 500 genes

•         The lymphocytes with the receptor sites for “self” cells are eliminated

•         Upon entry of an antigen, only lymphocytes specific to that antigen proliferate – clonal selection

Characteristics of Antigens

•         Not a normal constituent of the body

•         They are components of microbial cells (capsule, cell wall, flagella, fimbriae, microbial toxins, and coats of viruses), humans, plants, animals

•         They belong to: proteins, lipoproteins, glycoproteins

•         Good antigens have complex molecules

•         Poor antigens have small and simple molecules

•         Antigens contain specific regions that are recognized by antibodies – antigenic determinants or epitopes

•         Superantigens (bacterial toxins) can trigger a 100 times greater response of immune system – toxic shock syndrome

Antigen Processing and Presentation

•         Antigen Processing

–        Antigen Processing Cells (APC) ingest a bacterial cell – degrade the antigen into smaller peptides

–        The processed antigens are complexed with a cell glycoprotein MHCII (major histocompatibility complex) – and transported to the cell surface

•         Antigen Presentation

–        The processed antigens are presented to lymphocytes

–        T cells are activated – they release interleukin-2

B-cell activation and antibody synthesis

•         The linked receptor of T-cells and B-cells, and chemical stimulus from the T-cell – stimulates the B-cells

•         Proliferation and differentiation of B-cells

•         Two types of cells are formed: memory cells and plasma cells

–        Memory cells play role in future exposure to the same antigen

–        Plasma cells – synthesize and release the antibodies

Antibody Structure

•         Antibodies are specific proteins (immunoglobulins – Ig) developed by the body that is invaded by a specific microorganism

•         The antibody molecule is Y-shaped. It consists of 4 protein chains:

–        2 identical heavy chains

–        2 identical light chains

•         Each antibody molecule has two binding sites (site that binds to antigen)

•         Antibody molecule is made up of

–        constant region

–        variable region

•         binds the epitope of the antigen

Antibody-Antigen Interactions

•         Complementary fit between antigen and antibody is needed

•         The better the fit the better the stimulation of the lymphocytes

Antigen - Antibody Binding

Antigens are rendered harmless by different mechanisms:

•         Opsonization - antibodies coat the antigens enhancing the phagocytosis

•         Neutralization - antibodies block the active sites on  viruses (or bacteria) preventing their attachment to host cells

Immunoglobulin classes

•         IgG – 80% of all antibodies; effective against bacteria, toxins, trigger the complement system, long term immunity

•         IgA - Abundant in mucus membranes

•         IgM – Large molecule, first to appear, circulate in blood

•         IgD – In small amounts (1%) has no well-defined function, B-cell activation

•         IgE - Play role in allergic reactions

Primary and Secondary Responses to Antigen

•         Primary response

–        There is a latent period

–        Takes longer to reach the maximum

•         Secondary response

–        Memory cells responsible

–        Fast response

–        Higher concentration of immunoglobulins

–        Basis for vaccination

T cells and cellular immunity

•         Produced in the bone marrow, mature in thymus gland, and wait for the encounter with antigens in the lymphoid organs

•         Two populations of T cells:

–        Helper T cells (with CD4 receptor)

–        Cytotoxic T cells

•         Recognize peptides that are presented on dendritic cells

Helper Cells

•         Activated helper cells produce cytokins – Th cells proliferate and produce

–        cytotoxic T cells

–        natural killer cells

–        macrophages

•         Depression of T cell (class CD4) by HIV is responsible for pathology of AIDS

Cytotoxic T Cell

•         Recognize and kill the infected cell (some microorganisms multiply inside the host cell)

•         Recognize and kill nonself (tumor) cells

•         Attaches to the target cell and releases perforin (pore-forming protein)

Natural Killer Cells

•         Lymphocytes related to T cells

•         They do not have specificity for antigen

•         The first to attack cancer cells and virus infected cells

Classifying Specific Immunity

•         Natural active immunity

–        Getting the infection

•         Natural passive immunity

–        Maternal antibodies are transported across placenta

•         Artificial Active Immunity

–        Vaccination

•         Artificial Passive Immunity (Immunotherapy)

–        Administration of specific antibody – obtained by vaccinating animals and extracting the serum

Monoclonal Antibodies

Technique by which large amounts of specific antibodies can

be produced

Vaccines

•         Vaccine is a suspension of microorganisms or their cell components that are injected into a human or animal body in order to induce immunity.

•         The purpose of vaccination is to control microbial diseases and to prevent epidemics

Types of vaccines

Attenuated whole agent vaccine

•         Use of living but attenuated (weakened) or mutant microbes. Measles, mumps, rubella (MMR)

•         Advantage: more closely mimic an actual infection

•         Disadvantage: can backmutate to virulent form and cause a disease

Inactivated whole-agent vaccines

•         Use of killed microbes (rabies, influenza, and polio)

•         Killed by formalin or phenol

Toxoids

•         Chemically or thermally modified toxins used to stimulate active immunity

•         Tetanus, diphtheria toxoids – requires series of injections

•         Require boosters every 10 years

Recombinant vaccines

•         Genetically engineered microorganisms produce the antigenic fraction of the pathogen (Hepatitis B).

DNA vaccine

•         Promising technology in vaccine production

•         Gene coding for an antigen is incorporated into a plasmid – “naked” DNA (plasmid) injected

•         Human cells will take up the plasmid

•         Foreign protein (antigen) will be expressed

•         This will stimulate immune response

Why to Vaccinate?

•         To protect individuals

•         To establish herd immunity

–        Protection of the whole population

•         Prevention of epidemics

–        Protection of non-immunized individual

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