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Chapter 17 Specific Immunity
- Thirdline of Defense Lymphocytes - B cells - T cells Other cells Macrophages Dendritic Cells Eosinophils -
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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
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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
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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
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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
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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 )
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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
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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
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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
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Summary of the different acquired immunities.
Fig Categories of acquired immunities
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Two Arms of the Immune System
Humoral Immunity B-lymphocytes produce antibodies Antibodies in fluids ( blood, lymph, etc.) Defense against Bacteria Toxins Circulating viruses
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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
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Cell-Mediated Immunity
Defends against Bacteria or viruses that are within the host cells Fungi, protozoa and helminths Transplanted tissue cancer
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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.
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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
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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
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An overview of the stages of lymphocyte development and function.
Fig Overview of the stages of lymphocyte development
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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
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Antigens Foreign material that is recognized by the immune system and activates the immune response Size and shape are important
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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
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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)
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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
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Examples of different antigens and their characteristics.
Fig Characteristics of antigens.
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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
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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.
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The complete structure of an IgG antibody.
Fig Working models of antibody structure.
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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
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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
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5 Classes based on the structure of the constant region
Immunoglobulin (Ig) IgG IgA IgM IgD IgE
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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
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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
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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
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IgD Single Y – shape Important in B & T cell maturation
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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
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The characteristics of the different immunoglobulin classes.
Table 15.2 Characteristics of the immunoglobulin classes.
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B cells Activation Cell Division Antibody production
Antibody-antigen interaction Response
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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
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The clonal selection theory of lymphocyte development and diversity.
Fig Overview of the clonal selection theory of lymphocyte development and diversity.
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The stages of B-cell activation and antibody synthesis.
Fig Events in B-cell activation and antibody synthesis.
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Antibody-antigen interactions
Opsonization Agglutination Neutralization Activation of the Complement system
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The different functions of antibodies.
Fig Summary of antibody functions
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Agglutination Antibodies cross-link cells or particles into clumps
Renders microbes immobile Enhances phagocytosis Principle for certain immune tests (RBC typing)
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Opsonization Microbes or particles coated with antibodies
Enables macrophages to recognize and phagocytize microbe more efficiently
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Neutralization Antibody binds to
The microbe, virus or toxin surface Prevents any further binding of microbe or toxin to your cells
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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.
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Response Primary Secondary
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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
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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
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The stages of primary and secondary responses to antigens.
Fig Primary and secondary responses to antigens.
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Cell mediated immunity
Activation Antigen presenting cells T cells recognize antigen Cytokines Helper T cells Cytotoxic T cells
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Cell-mediated immunity
Direct involvement of T cells Produce and react to cytokines Activated simultaneously with B cell activation
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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
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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
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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
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Types Helper T cells (TH) Cytotoxic T cells (TC)
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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
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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
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An example of helper and cytotoxic T cell activation and differentiation.
Fig Overall scheme of T-cell activation and differentiation into different types of T cells.
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An example of a cytotoxic T cell destroying a cancer cell.
Fig A cytotoxic T cell has mounted a successful attack on a tumor cell.
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