Chapter 18 Defense Mechanisms of the Body

Chapter 18 Lecture Outline* The Immune System Eric P. Widmaier Boston University

Hershel Raff Medical College of Wisconsin

Kevin T. Strang University of Wisconsin - Madison

*See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes.

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Cells Mediating Immune Defenses

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Cytokines

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Nonspecific Immune Defenses • These defenses recognize some general property marking the invader as foreign and they protect the body as the first line of defense. • The nonspecific defenses include: – Physical barriers – Inflammation – Interferons – Natural killer cells – Complement system 4

Defenses at Body Surfaces • The body’s first lines of defense against microbes are the barriers offered by surfaces exposed to the external environment and their various antimicrobial secretions. • Examples: skin and mucous membranes

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Inflammation

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Phagocytosis

Fig. 18-2

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Role of Phagocytosis

Fig. 18-3

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Oponization

Fig. 18-4

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Complement System • The complement system is composed of plasma proteins that lyse foreign cells, especially bacteria. • Approximately 30 proteins participate in the cascades that result in a Membrane Attack Complex (MAC) on the surface of the invading bacteria.

• The MAC ruptures the bacterial membrane causing lysis of the bacteria and death of the organism.

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Functions of Complement

Fig. 18-5

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Interferons

Fig. 18-6

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Specific Immune Defenses: Overview • Lymphocytes recognize specific foreign molecules called antigens.

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Lymphoid Organs

Fig. 18-714

Lymphoid Tissues • Primary Lymphoid organs: – Bone marrow – Thymus

• Secondary Lymphoid Organs: – – – – – –

Spleen Lymph nodes Tonsils Adenoids Appendix Peyer’s patches 15

Lymphocyte Origins

Fig. 18-8

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Functions of B Cells and T Cells

Fig. 18-9

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Lymphocyte Receptors (Antibodies) Two heavy chains Two light chains

Constant region— same within a class of antibodies Variable region— differs for different antigens, gives specificity to antigen-binding site Two antigen-binding sites

Fig. 18-10

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Antibody Function in Humoral Immunity • The antibody functions to bind the specifc antigen. • This leads to inactivation and destruction of the foreign antigen.

• There are 5 classes of antibodies: – IgG – IgM – IgE – IgD – IgA 19

Antibody Functions • Neutralization • Agglutination • Opsonization • Complement Activation • Enhanced Natural Killer Cell Activity

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Major Histocompatibility Complex (MHC) Molecules • There are two classes of MHC molecules: – Class I MHC are expressed on the surface of all nucleated cells. – Class II MHC are expressed on the surface of macrophages, activated B cells, activated T cells, and thymus cells.

• T cells have antigen receptors which recognize antigens only when they are associated with MHC molecules. This is part of the antigen presentation mechanisms. 21

MHC is the “Self” Recognition • MHC molecules are unique to each individual person and are also known as HLA (human leukocyte antigen). • These markers are important because they mark cells as “self” or belonging to that organism. • Cells that do not match the MHC are foreign and are responsible for tissue or organ rejection because they stimulate the immune response to foreign tissue. 22

Antigen Presentation to T Cells

Fig. 18-11 23

Activation of Helper T Cells

Fig. 18-12

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Cytotoxic T Cells

Fig. 18-13 25

NK Cells • NK cells are a class of lymphocytes similar to cytotoxic T cells, whose major targets are virus-infected cells and cancer cells; however, they are not antigen-specific.

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Development of Immune Tolerance • Immune tolerance develops during fetal and early postnatal life due to clonal deletion or clonal inactivation.

• Autoimmune diseases are caused by failure of self-tolerance.

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Defenses Against Bacteria, Extracellular Viruses, and Toxins

Fig. 18-14

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Enhancement of Phagocytosis by Antibodies

Fig. 18-15

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Activation of Complement

Fig. 18-16 30

Defenses Against Virus-Infected Cells and Cancer Cells

Fig. 18-18 31

Role of IL-2 and Interferon-gamma

Fig. 18-19 32

Memory • Primary immune response: (1st exposure) – Generally takes 10–17 days to occur after exposure – Symptoms of illness occurs during these days – Antigen-selected B and T cells proliferate and differentiate into effector cells • Secondary immune response: (all other exposures) – Takes 2–7 days to occur – Greater response – Occurs due to memory cells 33

Memory

Fig. 18-17

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Systemic Manifestations of Infection

Fig. 18-20

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Factors that Alter the Body’s Resistance to Infection • Factors include nutrition, pre-existing disease, stress, physical exercise, sleep deprivation, and genetic deficiency.

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Immunity • Active immunity is an immune response to vaccine or pathogen in an individual and gives immunity because of the production of memory cells. • Vaccine is the introduction of a microorganism or its antigens in a form not expected to cause disease, which induces an immune response including production of memory cells

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Immunity • Passive immunity comes from the administration of synthetically produced antibodies. • This results in no memory cell production, so there is no long-term memory and immunity. • Passive immunity can also come from mother to fetus or baby because antibodies pass in the placenta (IgG) and breast milk (IgA). 38

Harmful Immune Responses • Graft Rejection • Transfusion Reactions • Allergy (Hypersensitivity) • Autoimmune Disease • Excessive Inflammatory Responses

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Tissue Grafts and Organ Transplantation • HLA molecules (MHC) stimulate rejection by inducing immune response, so there must be as close a match in the MHC between the donor and recipient as possible.

• The recipient will have to suppress the immune system pharmacologically to prevent rejection. – Cyclosporin A – FK506

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Transfusion Reactions • Transfusion reactions are the illness caused when erythrocytes are destroyed during blood transfusion. • It is caused by antibodies rather than cytotoxic T cells. • Erythrocytes do not have MHC proteins, but they do have plasma membrane proteins and carbohydrates that can function as antigens. • The ABO system of carbohydrates is the most important for transfusion reactions. • Another group of erythrocyte membrane antigens of medical importance is the Rh system of proteins. 41

Blood Typing

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Immediate Hypersensitivity Allergic Response

Fig. 18-21a 43

Anaphylactic Shock • Anaphylatic shock is a severe allergic reaction that results from a massive release of histamine from mast cells throughout the body. This causes a massive drop in systemic blood pressure and can cause circulatory collapse.

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Autoimmune Diseases • The immune system treats a part of itself like an invading pathogen. • Examples: – Insulin-dependent diabetes mellitus (type I) – Lupus – Rheumatoid arthritis – Multiple sclerosis

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Immunodeficiency Diseases • Immunodeficiency diseases result from weak or under-active immune systems. • Examples: – SCID = severe combined immunodeficiency disease – Hodgkin’s Disease = cancer of lymphatic system – AIDS = affects helper T cells

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Acquired Immune Deficiency Syndrome (AIDS) • Human immunodeficiency virus (HIV) infects and kills helper T cells resulting in impairment of the immune response to other infectious organisms.

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