Chapter 17 Specific Immunity - Thirdline of Defense Lymphocytes - B cells - T cells Other cells Macrophages Dendritic Cells Eosinophils -

Thirdline of Defense Specific immunity -- a complex interaction of immune cells (leukocytes) reacting against antigens Specific – each response is specific for the pathogen that provoked the response Self and nonself (foreign) – the immune system must be able to tell the difference between foreign vs. self tissues, cells, etc. Antigens – activate the immune system Antibodies – made in response to a foreign antigen specialized lymphocytes - carry out the functions of the immune system

Self and nonself “self” Markers Proteins located on the surface of our cells Identify your cells as belonging to you Eg. Major histocompatibility complex (MHC) proteins Found on all the cells of our body EXCEPT RBCs

Markers Lymphocytes recognize the host cell markers as “self” Tolerance -- Your immune system should not respond against “self” cells & tissues Autoimmune disease – when your immune system attacks your own tissues Rheumatoid arthritis, Type I diabetes, lupus Lymphocytes will recognize microbe proteins as ‘nonself’ Your immune system SHOULD respond against “foreign cells & tissues

Specific Acquired Immunities Active vs. Passive Active – you make the response Passive – you receive immune products made by someone else Natural vs. Artificial Natural – acquired by natural biological processes Artificial- acquired by medical process E.g., Vaccines

Active Foreign Antigen activates B and T cells You make a protective immune response Memory cells – provide long-term protection Acquired by Natural ( you get the infection) Artificial processes ( vaccine )

Passive You receive pre-formed antibodies from another individual or animal Short term protection No memory cells You don’t produce the antibodies Natural or artificial

Natural Immunity produced by normal biological experiences, no medical intervention Natural active Eg. Infection Natural passive Eg. Mother to child – across the placenta, via breast milk

Artificial Immune protection through medical procedures or intervention Artificial active Eg. vaccination Artificial passive Eg. Injection of preformed antibodies (antiserum) Immediate but short-lived protection

Summary of the different acquired immunities. Fig. 15.18 Categories of acquired immunities

Two Arms of the Immune System Humoral Immunity B-lymphocytes produce antibodies Antibodies in fluids ( blood, lymph, etc.) Defense against Bacteria Toxins Circulating viruses

Two Arms of the Immune System Cell-Mediated Immunity T-cells (lymphocytes) Acts against foreign tissues or organisms Regulates the activity of other immune system cells

Cell-Mediated Immunity Defends against Bacteria or viruses that are within the host cells Fungi, protozoa and helminths Transplanted tissue cancer

B& T cells are produced in the bone marrow B& T cells are produced in the bone marrow. Mature T and B cells migrate to the lymphoid tissue, where they encounter antigens.

B & T Lymphocytes B&T lymphocytes develop in bone marrow B-cells remain in bone marrow until mature T-cells leave bone marrow at immature stage; complete their development in the thymus Once mature – these cells are released into the lymphatic tissues ( e.g. spleen, tonsils, appendix, gut) or lymph nodes

Stages If foreign antigens are present B and T lymphocytes recognize antigens B cells become plasma cells - Produce antibodies T lymphocyte responses Helper T-cells ( CD4 cells) make chemical messengers called cytokines which help all the cells of the immune system Cytotoxic T-cells (CD8 cells) seek out & destroy your own infected or abnormal cells

An overview of the stages of lymphocyte development and function. Fig. 15.1 Overview of the stages of lymphocyte development

Receptors Mature B and T cells have very specific receptors on their surface that can specific foreign antigens B cell receptors can also be secreted as antibodies These receptors are proteins called immunoglobulins

Antigens Foreign material that is recognized by the immune system and activates the immune response Size and shape are important

Examples of Antigens Microbial products Non-microbial products Capsules, cell walls Flagella Fimbria Bacterial toxins Viral protein coats Other surface molecules Non-microbial products Pollen Egg white Blood cell surface markers Serum proteins from other individuals Transplanted tissues

What makes a good antigen? l Antigenic Proteins and polypeptides enzymes, cell surface structures, hormones, toxins Glycoproteins - blood cell markers Large Polysaccharides - capsules, LPS on gram negative cell wall) Not very Antigenic Lipids & cell membranes Nucleic acids (DNA)

Size and shape Size affects whether a foreign molecule can act as a good antigen Too small – no immune recognition Large – immune recognition Proteins are better antigens than polysaccharides because of their complex shape

Examples of different antigens and their characteristics. Fig. 15.7 Characteristics of antigens.

Antibody Product of B cell activation Structure Immunoglobulin (Ig) family of proteins Produced in response to an antigen Structure Highly specific for the antigen that stimulated the production of the antibody Antigen –binding site on the antibody specifically binds the antigen Has at least two antigen-binding sites

Antibody Structure Typical Y-shaped structure 2 identical heavy chains 2 identical light chains linked to each other Variable region binds antigen Constant region determines the class of the antibody Also allows antibody to be attached to the surface of a cell.

The complete structure of an IgG antibody. Fig. 15.11 Working models of antibody structure.

V-region Variable region Binds to the antigen On every antibody the variable region is specific for only one antigen The antigen & the V region on the antibody must have very specific matching shapes in order to bind

FC OR “CONSTANT” REGION allows the antibody to bind to surface of some cells E.G., can bind to macrophages Can also anchors the antibody to lymphocytes or other cells like basophils or eosinophils Also determines the class of the antibody

5 Classes based on the structure of the constant region Immunoglobulin (Ig) IgG IgA IgM IgD IgE

IgM Five Y shaped units – joined by a protein chain ( Very Large) First to be synthesized during initial immune response Circulates in the blood, but too big to cross into tissues or across the placenta The antibody produced in response to your ABO blood type

IgG Single Y-shaped Monomer Most common antibody in blood Small enough to cross the placenta Primary response –will be produced later in the initial response than IgM After about 10 days you start making less IgM and more IgG Memory cell response – strong memory response – these are the long term antibodies you continue to make after you recover from an infection or receive a vaccine

IgA Monomer (single Y ) Dimer – 2 Y shaped monomers, held together by a protein chain (secretory IgA) Most abundant antibody in the body Secretory IgA (found in most mucous and serous secretions) Salivary glands, intestine, nasal membrane, breast, lung, genitourinary tract Protection for newborns

IgD Single Y – shape Important in B & T cell maturation

IgE Made in response to Allergies Parasite infections The FC portion binds to mast cells and basophils Causes them to release chemicals that aid inflammation, allergic response, destroy parasites

The characteristics of the different immunoglobulin classes. Table 15.2 Characteristics of the immunoglobulin classes.

B cells Activation Cell Division Antibody production Antibody-antigen interaction Response

Activation Specific B-cell finds & binds to the matching antigen B cell divides making multiple copies (clones) Some change into plasma cells and secrete antibody Some form memory cells for future protection Usually also requires chemicals called cytokines produced by T helper lymphocytes that have also recognized the foreign antigen mediators

The clonal selection theory of lymphocyte development and diversity. Fig. 15.3 Overview of the clonal selection theory of lymphocyte development and diversity.

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

Antibody-antigen interactions Opsonization Agglutination Neutralization Activation of the Complement system

The different functions of antibodies. Fig. 15.13 Summary of antibody functions

Agglutination Antibodies cross-link cells or particles into clumps Renders microbes immobile Enhances phagocytosis Principle for certain immune tests (RBC typing)

Opsonization Microbes or particles coated with antibodies Enables macrophages to recognize and phagocytize microbe more efficiently

Neutralization Antibody binds to The microbe, virus or toxin surface Prevents any further binding of microbe or toxin to your cells

Complement fixation Antibodies interaction with protective complement proteins ( these are made in the liver or by WBCs and circulate in the blood) Actived complement proteins lyse the microbial cells.

Response Primary Secondary

Primary Response First exposure Latent period Synthesis of antibodies Lag time until antibodies synthesis begins Synthesis of antibodies Level of antibody made is called the titer IgM first After about 7-10 days, less IgM made and switch is to mostly IgG

Secondary Response Re-exposure to the same antigen produces a Memory response Primarily due to memory cells Antibody synthesis is rapid ( no latent period) Stronger response ( titer is higher) IgG dominates

The stages of primary and secondary responses to antigens. Fig. 15.15 Primary and secondary responses to antigens.

Cell mediated immunity Activation Antigen presenting cells T cells recognize antigen Cytokines Helper T cells Cytotoxic T cells

Cell-mediated immunity Direct involvement of T cells Produce and react to cytokines Activated simultaneously with B cell activation

Cell-mediated immunity Cytokines - Chemical signals produced by T-cells that have recognized foreign antigen Activated macrophages Ex. Interleukins, interferons, Tumor Necrosis Factor ( TNF) Stimulate or assist most cells involved in the immune response

Antigen presenting cells (APC) Like B cells, each T cell has a receptor that can recognize only one foreign antigen. They also have receptors called CD proteins. T-cells only recognize the foreign antigen if it is presented to them on the surface of one of your own cells Macrophages, dendritic cells act as Antigen Presenting Cells

T-cell Activation Activated T-cells begin mitosis and replicate Macrophages, dendritic cells Ingest or trap the foreign antigen and now show it on their surface, next to their MHC proteins. Activated T-cells begin mitosis and replicate Active cells ( TH and TC ) are produced to act now Memory cells are also produced for future protection

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

T Helper cells - TH Have CD4 receptor Regulate immune by releasing cytokines Type of cytokine will direct & determine the immune response activate other T cells allergic reactions drive B cell differentiation also activate macrophages

Cytotoxic T cells (TC) Have CD8 receptor on surface Binds to and lyses cells microbe, viral infected cells, foreign cells, cancer cells Perforins – enzymes that punch holes in the membrane of the target cell Granzymes – degrade proteins Natural killer (NK) cells related to TC attack virus infected cells and cancer cells but are not specific for any one foreign antigen

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.

An example of a cytotoxic T cell destroying a cancer cell. Fig. 15.17 A cytotoxic T cell has mounted a successful attack on a tumor cell.