LESSON PLAN Sheet 1



PART 5: IMMUNITY

INTRODUCTION

Two Types of Immunity

• We have two general types of immunity against disease

1. Innate immunity

▪ Is “innate” – we are born with it

▪ Is “nonspecific” - it acts against all microbes in the same way

▪ Includes physical and chemical barriers, cells, and physiological mechanisms organized into “lines of defense:

• First line of defense

o Physical and chemical barriers of the skin and mucous membranes

• Second line of defense

o Antimicrobial substances

o Natural killer cells

o Phagocytes

o Inflammation

o Fever

▪ Represents immunity’s early warning system: designed to prevent microbes from gaining access into the body and to help eliminate those that do gain access

2. Adaptive Immunity

▪ Provides immunity against microbes that have breached innate immunity defenses

▪ Is “adaptive” – it adapts or adjusts its immune response to handle a specific microbe

▪ Is “specific” – it involves recognition of a specific microbe by a specific immune cell

▪ Involves two types of cells:

• T lymphocytes

• B lymphocytes

INNATE IMMUNITY

• Innate immunity: refers to a wide variety of body responses against a wide range of pathogens and their toxins; is present at birth.

First Line of Defense: Skin and Mucous Membranes

• The skin and mucous membranes are the first line of defense against pathogens. These structures provide both physical and chemical barriers to infection.

Physical Factors

• Epidermis of skin – forms physical barrier to entrance of microbes

• Mucous membranes – inhibit entrance of many microbes; not as effective as skin

• Mucus – traps microbes in respiratory and gastrointestinal tracts

• Hairs – filter out microbes and dust in nose

• Cilia – together with mucus, trap and remove microbes and dust from upper respiratory tract

• Lacrimal apparatus – tears dilute and wash away irritating substances and microbes

• Saliva – washes microbes from surfaces of teeth and mucous membranes of mouth

• Urine – washes microbes from urethra

• Defecation and vomiting – expels microbes from body

Chemical Factors

• Sebum – forms protective acidic film over skin surface that inhibits microbial growth

• Lysozyme – antimicrobial substance in perspiration, tears, saliva, nasal secretions, and tissue fluids

• Gastric juice – destroys bacteria and most toxins in stomach

• Vaginal secretions – slight acidity discourages bacterial growth; flush microbes out of vagina

Second Line of Defense: Internal Defenses

• The second line of defense involves internal antimicrobial proteins, phagocytic and natural killer cells, inflammation, and fever.

Antimicrobial Proteins

• Interferon (IFN); secreted by virus-infected cells

o Stimulates uninfected neighboring cells to synthesize antiviral proteins

• Complement: A group of about 20 proteins present in blood plasma and on cell membranes

o Are activated by microbes

o Causes cytolysis of microbes; promotes phagocytosis; contributes to inflammation

• Iron-binding proteins: sequester iron from body fluids, which inhibits microbial growth

Natural Killer Cells and Phagocytes

• Natural killer (NK) cells

o A type of lymphocyte (but not T or B)

o “Kill” a wide variety of infectious microbes and “sick” body cells.

o Release perforins that cause microbe or cell to cytolysis

• Phagocytes

o Specialized WBCs that “eat” other cells and microbes

o Include neutrophils and macrophages.

o Phagocytosis has 3 phases (Figure 22.9):

▪ Chemotaxis ( Adherence ( Ingestion

Inflammation

• A physiological response to tissue damage

o Confines and destroys microbes; initiates tissue repair

• Characterized by 5 symptoms:

1. Redness

2. Pain

3. Heat

4. Swelling

5. Loss of function

• Three basic stages of inflammation (Figure 22.10):

o Blood vessel vasodilation ( Migration ( Tissue repair

Fever

• A physiological response to bacterial/viral infection

• Intensifies effects of interferons; inhibits microbial growth; speeds up tissue repair

ADAPTIVE IMMUNITY

• Immunity – the body’s ability to defend against specific foreign antigens (bacteria, toxins, viruses, and foreign tissues).

• Two properties distinguish adaptive immunity from innate immunity:

1. Specificity for particular antigens

2. Memory of previously encountered antigens

Maturation of T Cells and B Cells

• T cells and B cells derive from stem cells in red bone marrow (Figure 22.11).

o B cells remain in the red bone marrow and become immunocompetent

o T cells migrate to the thymus and become immunocompetent

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Types of Adaptive immunity

• Cell-mediated immunity refers to destruction of antigens by T cells.

o Directed against intracellular pathogens, some cancer cells, and foreign tissue transplants.

• Antibody-mediated immunity refers to destruction of antigens by antibodies.

o Directed against extracellular pathogens

• Both types of immunity are stimulated by recognition of specific foreign antigens by specific T and/or B cells

Foreign Antigens Versus Self-Antigens

• Our immune systems can recognize at least a billion different foreign antigens.

o Due to our immune system’s billion (or more) different foreign antigen receptors; each B cell or T cell has a unique foreign antigen receptor.

• Self-antigens are located on body cell plasma membranes and are unique to an individual

o Our immune systems have “learned” that self-antigens are not foreign and thus do not mount an immune response against them

o Self-antigens help phagocytes and infected cells “show” T and B cells foreign proteins

o Two types of self-antigens:

1. MHC-I antigens – on plasma membranes of all body cells except RBCs

2. MHC-II antigens - on plasma membrane of antigen-presenting cells immune cells:

a. Macrophages – process and present foreign antigens to T cells; stimulate helper T cells to secrete interleukin; induce proliferation of B cells

b. Dendritic cells – process and present antigen to T cells and B cells; found in mucous membranes, skin, lymph nodes

c. B cell – process and present antigen to helper T cells

Pathways of Antigen Processing

• For an adaptive immune response to occur, foreign antigens must bind to B and T cell antigen receptors

o B cells can recognize and bind directly to antigens.

o T cells must be presented foreign antigen that has been processed by antigen-presenting cells or infected body cells

▪ Antigen processing – APC breaks antigen down into fragments and binds it to its MHC.

▪ Antigen presentation – APC inserts antigen-MHC complexes into its plasma membrane.

Processing and Presentation of Exogenous Antigens by APCs

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Processing and Presentation of Endogenous Antigens

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Clonal selection

• Clonal selection is the process by which a B or T cell proliferates and differentiates in response to presentation of a specific antigen.

• Two major types of cells result from clonal selection:

1. Effector cells are the cells that actually do the work to destroy the antigen. They include: helper T cells, cytotoxic T cells, and plasma cells (a clone of B cells)

2. Memory cells, with long life spans, provide a faster second invasion response by proliferating and differentiating into effector cells. They include memory helper T cells, memory cytotoxic T cells, and memory B cells.

CELL-MEDIATED ADAPTIVE IMMUNITY

• A cell-mediated immune response begins when an antigen activates a T cell by binding to its antigen receptor.

• Activated T cells proliferate (divide several times) and differentiate (form specialized cells) into a clone of cells that can recognize the same antigen as the activated T cell.

• Effector cells carry out immune responses that eliminate the antigen (intruder).

Activation of T Cells

• Two steps are required for a T cell to become activated:

1. Antigen recognition - T cell receptor “recognizes” and binds to antigen-MHC complex. CD4 or CD8 coreceptors bind to MHC and help maintain coupling during antigen recognition. This step is analogous to starting a car but not putting it into gear.

2. Costimulation – The T cell must receive at least one other signal to become activated. The signal may be chemical (e.g. interleukins) or mechanical (e.g. T cell binding to other receptors on the APC). This step is analogous to putting the started car into gear.

• Two-step activation may prevent cell-mediated immune responses from occurring accidentally.

Activation and Clonal Selection of Helper T Cells

• T cells that display CD4 protein develop into Helper T cells (TH) when activated by an APC.

o TH cell receptor “recognizes” and binds to antigen-MHC-II complex presented by APC.

o APC costimulates TH cell.

• Once a TH cell is activated it forms a clone of active helper T cells and memory helper T cells (Figure 22.15).

o Active TH cells secrete interleukin-2 (IL-2), which is needed for costimulation of virtually all immune responses:

▪ Costimulates TH cells (positive feedback).

▪ Costimulates cytotoxic T cells

▪ Costimulates B cells (part of antibody-mediated immunity)

▪ Enhances natural killer cell activity (part of innate immunity)

o Memory TH cells remain in the body after the immune system destroys the antigen that stimulated their production.If the antigen returns, memory TH cells can quickly proliferate and differentiate into more active TH cells and memory TH cells.

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Activation and Clonal Selection of Cytotoxic T Cells

• T cells that display CD8 protein develop into cytotoxic T cells (TC) when activated.

o TC cell receptor “recognizes” and binds to antigen-MHC-I complex presented by:

▪ A microbe-infected body cell

▪ Some tumor cells

▪ Cells of a tissue transplant

o Cytokines (e.g. IL-2 costimulates TC cell.

• Once a TC cell is activated it forms a clone of active cytotoxic T cells and memory cytotoxic T cells (Figure 22.16).

o Active TC cells fight foreign invaders by killing the target cell (the cell that bears the same antigen that stimulated production of the TC cells; Figure 22.17).

▪ TC cells release granzymes that trigger apoptosis and perforins that trigger cytolysis of infected target cells.

o Memory TC cells remain in the body after the immune system destroys the antigen that stimulated their production.

▪ If the antigen returns, memory TC cells can quickly proliferate and differentiate into more active TC cells and memory TC cells.

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ANTIBODY-MEDIATED IMMUNITY

• The body contains not only millions of different T cells but also millions of different B cells, each capable of responding to a specific antigen.

• An antibody-mediated immune response begins when an antigen activates a B cell by binding to its antigen receptor.

• Activated B cells proliferate and differentiate into a clone of cells (plasma cells and memory B cells) that can recognize the same antigen as the activated B cell.

• Plasma cells secrete antibodies that help the immune system eliminate the antigen (intruder).

Activation and Clonal Selection of B Cells

• As with cell-mediated immunity, antigen recognition and Costimulation are required for B cell activation and proliferation (Figure 22.18):

1. Antigen recognition – B cell receptor “recognizes” and binds antigen.

2. Costimulation - Some antigen is taken into the B cell, combined with MHC-II, and moved to the B cell surface. A TH cell recognizes the antigen-MHC-II combination and secretes IL-2, which costimulates the B cell.

• Once a B cell is activated it forms a clone of plasma cells and memory B cells.

o Plasma cells secrete antibodies that help the immune system eliminate the antigen.

o Memory B cells remain in the body after the immune system destroys the antigen that stimulated their production.

▪ If the antigen returns, memory B cells can quickly proliferate and differentiate into more plasma cells and memory B cells.

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Antibodies

• An antibody (immunoglobulin) is a protein that combines only with the epitope on the antigen that triggered its production.

• Antibodies are grouped into five principal classes each with specific biological roles:

1. Immunoglobulin G (IgG) – most abundant blood antibody; also found in lymph, and GI tract; protects against bacteria and viruses; only antibody to cross placenta; confers considerable immune protection to newborns

2. Immunoglobulin A (IgA) - Found in blood and secretions like sweat, tears, saliva, mucus, breast milk, and GI secretions; protects mucous membranes against bacteria and viruses

3. Immunoglobulin M (IgM) – Found in blood and lymph; first antibody secreted by plasma cells after antigen exposure; includes anti-A and anti-B antibodies

4. Immunoglobulin D (IgD) – Located on B cells; act as B cell receptors

5. Immunoglobulin E (IgE) – Located on mast cells and basophils; involved in allergic and hypersensitivity reactions; provide protection against parasitic worms.

• Table 22.3 summarizes the structures and functions of these five classes of antibodies.

Antibody actions

• Antibodies disable antigens through several actions:

1. Antigen neutralization

2. Bacterial immobilization

3. Antigen agglutination and precipitation

4. Complement activation

5. Phagocytosis enhancement

Role of Complement System in Immunity

• The complement system is a group of about 20 proteins present in blood plasma and on cell membranes

• When activated, complement proteins enhance phagocytosis, cytolysis (via membrane attack complex), and inflammation (Figure 22.20).

Immunological Memory

• Immunological memory is due to the presence of long-lived antibodies and very long-lived memory cells that arise during proliferation and differentiation of antigen-stimulated B and T cells.

• Immunization against certain microbes is possible because memory B cells and memory T cells remain after the primary response to an antigen (Figure 22.21).

• The secondary response (immunological memory) provides protection should the same microbe enter the body again. There is rapid proliferation of memory cells, resulting in a far greater antibody titer (amount of antibody in serum) than during a primary response.

Ways to Acquire Immunological Memory

1. Naturally acquired active immunity – primary response to an attacking microbe’s antigens; forms antibody-secreting plasma cells and cytotoxic T cells; forms memory B cells, and memory T cells (secondary response)

2. Naturally acquired passive immunity – Transfer of antibodies from mother to baby; IgG via placenta, IgA via breast milk

3. Artificially acquired active immunity – primary response to a vaccination; has same effects as naturally acquired active immunity

4. Artificially acquired passive immunity – Intravenous injection of antibodies; has same effects as naturally acquired passive immunity

• Table 22.4 summarizes the various types of naturally and artificially acquired immunity.

SELF-RECOGNIZITON AND SELF-TOLERANCE

• T cells undergo positive selection to ensure that they can recognize self-MHC antigens (self-recognition; Figure 22.22).

o T cells that recognize self-MHC antigens survive.

o T cells that cannot recognize self-MHC antigens are destroyed.

• T cells that survive positive selection undergo negative selection to ensure that they do not react to other self-proteins (tolerance).

o T cells that do not react with self-proteins survive.

o T cells that do react with self antigens undergo either deletion or anergy

▪ Deletion – the T cell is destroyed

▪ Anergy – the T cell is inactivated

• B cells also develop tolerance through deletion and anergy (Figure 22.22).

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