Chapter 21 Immune System Lecture Objectives

Internal Nonspecific Defences: Antimicrobial Proteins (2. Complement System - Completment System Mechanism I + Complement System Mechanism II).

1. Antibodies bind to pathogens. 2. Complement proteins bind to antibody-pathogen complexes. 3. Lysis, phagocytosis and inflammation result. Complement System Mechanism II: 1. Complement proteins bind to polysaccharide molecules on pathogens. 2. Lysis, phagocytosis, and inflammation result.

2. IgA (Dimer)

IgA monomer exists in limited accounts in plasma. The dimer, referred to as the secretory IgA, is found in body secretions and prevents attaching of pathogens to epithelial cell surfaces. 4 binding sites!

3. IgD (Monomer)

IgD is virtually always attached to the external surface of B cells, where it functions as an antigen receptor of B cell. 4 binding sites!

5. IgE (Monomer)

IgE is slightly larger than the IgG antibody. It's secreted by plasma cells in skin, mucosae, and tonsils. Its stem region becomes bound to mast and basophils. It causes the release of histamine and levels rise during allergic attacks or virus. *Allergies

4. IgG (Monomer)

IgG is the most abundant and diverse antibody in plasma, accounting for 75-85% of circulating antibodies. It protects, readily fixes complement, and main antibody of both secondary and primary responses. Crosses the placenta. 3 binding sites!

1. IgM (Pentamer)

IgM exists as monomer and pentamer. The monomer, which is attached to the B cell surface, serves as an antigen receptor. The pentamer circulates in blood plasma and is the first Ig class released by plasma cells during the primary response. It's numerous binding sites make IgM a potent agglutinating agent, and readily fixes and activates complement. 10 binding sites!

List specific examples of immune disorders.

Immune Disorders (3): -Immunodeficiencies: any condition where our immune cells behave abnormally. Ex: not enough -Autoimmune Diseases: Some immune cells lose the ability to differentiate self from non-self. -Hypersensitivities: Immune system is responding to things that aren't really immunogenic. Ex: pollen, dust, etc. (Allergies) 1. Immunodeficiencies A. Sever combined immunodeficiency syndrome B. Acquired immunodeficiencies (AIDS, Severe Combined Immunodeficiency Syndrome: -Congenital (from birth) -Individual doesn't produce enough B or T cells. -Don't have a functional immune system. Get sick a lot. Acquired Immunodeficiency (AIDS) -Exposure to HIV virus which causes reduction in T lymphocytes. -Don't have a functional immune system. Very susceptible to subsequent infections. 2. Autoimune Diseases A. Multiple Sclerosis B. Myasthenia Gravis C. Graves' Disease D. Juvenile Diabetes E. Lupus F. Rheumatoid Arthritis Multiple Sclerosis: -An Autoimmune Disease -Immune Cells attack White Matter in our Brain, axon fibers, myelin sheath. -Reduction in neural transmission. Myasthenia Gravis: -Autoimmune disease that only attacks the neuromuscular junction -Difficulties in neuro-muscular activity Graves' Disease: -An autoimmune disease where the immune system attacks the thyroid gland. -Metabolic activity isn't regulated. Juvenile Diabetes: -An autoimmune disease where the immune cells attack the cells in the pancreas -Insufficient insulin production Lupus: -An autoimmune disease where the immune system attacks the skin, kidney, heart, and lungs. -Gets wolf-bite like marks on their skin and butterfly rashes Rheumatoid Arthritis: -An autoimmune disease where the immune system attack the synovial membranes in our joints 3. Hypersensitivities A. Immediate (Anaphylaxis) B. Subacute (Transfusion Reaction) C. Delayed (Poison Ivy Reaction). Immediate (acute) Hypersensitivity Disorder: -Ex: Anaphylaxis. -Allergic reaction that causes instant response (within seconds) -Response is systemic flood of histamine. Blood vessels dilate, BP drops, etc. -Usually, first exposure is not severe. Subsequent exposures are much faster and stronger. Subacute Hypersensitivity Disorders: -Ex: Blood Transfusion rxn (wrong blood cells) -1 to 3 hours later Delayed Hypersensitivity Disorders: -Response is 1 - 3 days later -Ex: Poison Ivy

Differentiate primary and secondary humoral responses.

Immunological Memory: The cellular proliferation and differentiation constitutes the primary humoral response, which occurs on first exposure to a particular antigen. The primary response typical has a lag period (3-6 days) after the antigen challenge to allow differentiation into plasma cells. If someone is re-exposed to the same antigen, a secondary immune response occurs. The secondary immune responses are quicker, more effective due to being previously primed (memory cells = immunological memory, these persist for months). Summary: A primary response sets up a pool of effector cells (in this case, T cell) and generate memory cells that then mount secondary responses.

Internal Nonspecific Defences: Inflammation

Inflammatory response: It's triggered whenever body tissues are injured by physical trauma, intense heat, irritating chemicals, or irritation from viruses. It has a positive reaction for the following reasons: 1. It prevents the spread of damaging agents to nearby tissues. 2. Disposes of cell debris and pathogens. 3. Sets the stage for repair. The four cardinal signs of short-term, or actor, inflammation are: Redness, heat, swelling, and pain. *Inflammatory Mechanism: 1. Toll-like receptors on macrophages recognize pathogens. 2. TLRs release cytokines. 3. Other cells release other inflammatory mediator chemicals. 4. Vessels in injured area dilate and increase permeability. 5. Hyperemia occurs. 6. Exudate accumulates causing edema. *Results of inflammation. 1. Injured cells release leukocytosis-inducing factors. 2. Causes neutrophil release by red bone marrow. 3. Loss of fluid slows blood flow locally. 4. Inflammation causes production of selectins on endothelial cells. 5. Margination occurs. 6. Neutrophils escape capillaries. 7. Inflammatory chemicals act as chemotactic agents. 8. Monocytes follow neutrophils. 9. Monocytes become macrophages after leaving capillaries.

Internal Nonspecific Defences

Internal Nonspecific Defences: 1. Phagocytes A) Macrophages: B) Neutrophils: C) Eosinophils: 2. Mast Cells 3. Natural Killer Cells 3. Inflammation 4. Antimicrobial Proteins: A) Interferon B) Complement System C) Fever

Identify the reasons for transplant rejection.

Isograft (Identical Twin): Autograft (Individual): Allograft (Non-Identical): Xenograft (Animal): Self vs Non-Self: potential for rejection Autograft: -if a person is burned and they need a tissue graft, can move it from one part of the body to a different part of the body -Immune System won't reject (Same MHC) Isograft: -Identical Twin Allograft: -Transplant from another individual (non-identical to us)-The more closely related the two individuals are, the less likely the person will reject the MHC. Xenograft: -Transplant parts come from a non-human source -Ex: pig heart valves

Internal Nonspecific Defences: Mast Cells

Mast cells: They are a key component of the inflammatory response and release the potent inflammatory chemical called histamine. *In addition, injured and stressed tissue cells, phagocytes, lymphocytes, basophils, and blood proteins are all sources of inflammatory mediators. *These chemicals are histamine, cytokines, kinins, prostaglandins, leukotrienes, and complement. *They are all arterioles in the injured area to dilate. *Hyperemia: Congestion with the blood, occurs, accounting for the redness and heat of an inflamed region. *Exudate: Fluid containing clotting and antibodies, seeps from the blood and into tissue spaces, causing the swelling (edema) and contributing to the pain sensation.

Internal Nonspecific Defences: Natural Killer Cells

Natural Killer (NK) cells, which police the body in blood and lymph, are a unique group of defensive cells that can lyse and kill cancer cells and virus-infected body cells before the adaptive immune system can be activated. Natural Killer cell are a member of the large granular lymphocytes. They are not picky. Natural Killer cells eliminate a variety of infected or cancerous cells by detecting the lack of "self" cell-surface receptors and by recognizing certain sugars on the target cell. "Natural" refers to the non-picky attitude. *Natural Killer cells destroy by direct contact and induces the target cell to undergo apoptosis (programmed cell death). They also secret potent chemicals.

Identify the "self" antigens.

Self-Antigens: These are surface proteins called MHC proteins, which mark cells as self. Assuming that your immune system has been properly programmed, your *self-antigens* are not foreign to you but strongly antigenic to other individuals. Major Histocompatibility Complex: Genes are that complex code for the proteins (only identical twins could possibly share them). Class 1 MHC proteins: These are found on virtually all body cells, but Class II MHC proteins are found only on certain cells that act in an immune response. These each display peptides and also bind fragments of foreign antigens that come from within the infected cells. The peptides displayed by MHC II are displayed on the outside.

Superficial Nonspecific Defenses

Superficial Nonspecific Defenses: 1. Skin: The heavily keratinized epithelial membrane presents a formidable physical barrier to most microorganisms on the skin. Keratin functions as resistant to most weak acids, bases, bacterial enzymes, and toxics. Intact mucosal provide similar mechanism barriers within the body. 2. Mucous Membranes: Mucosal membranes line all body cavities that open to the exterior (digestive, respiratory, urinary, and reproductive tract). The epithelial membranes provide a variety of protective chemicals. A: The acidity of skin against bacterial growth. B: Lipid secretions in sebum and dermcidin in eccrine sweat are toxic to bacteria. C: The stomach secretes a concentrated hydrochloric acid solution and protein-digesting enzymes. They kill microorganisms. D: Saliva cleans the oral cavity and teeth. E: The lacrimal fluid of the eye contains lysozyme to kill bacteria. F: Sticky mucus traps many microorganisms that enter the digestive and respiratory passageways.

Define antigen challenge.

The *antigen challenge*, the first encounter between an immunocompetent but naive lymphocyte and an invading antigen, usually takes place in the spleen or in a lymph node, but can happen within a secondary lymphoid organs. If the lymphocytes is a B cell, the challenging antigen provokes the humoral immune response, in which antibodies are produced against the challenger.

Summary and Function of Adaptive Immune Response

1. B Cell: Lymphocyte that matures in bone marrow. Induced to replicate by antigen binding, usually followed by helper T cell interactions in lymphoid tissues. It progeny (clone members) form memory cells and plasma cells. 2. Plasma Cell: Antibody-producing "machine"; produces huge numbers of antibodies (immunoglobulins) with the same antigen specificity. An effector B cell. 3. Helper T Cell (TH): An effector CD4 T cell central to both humoral and cellular immunity. After binding with a specific antigen presented by an APC, it stimulates production of cytotoxic T cells and plasma cells to help fight invader, activates macrophages, and acts both directly and indirectly by releasing cytokines. 4. Cytotoxic T Cell (TC): An effector CD8 cell. Activated by antigen presented by APC, often with helper T cell involvement. Its specialty is killing viruses-invaded body cells and cancer cells; also involved in rejection of foreign tissue grafts. 5. Regulatory T Cell (TREG): Slows or stop activity of immune system/ Important in controlling autoimmune diseases; several different populations probably exist. 6. Memory Cell: Descendant of activated B cell or any class of T cell; generated during initial immune response (primary response). May exist in body for year after, enabling it to response quickly and efficiently to later infections. 7. Antigen-Presenting Cell (APC): Any of several cells (dendritic cell, B cell, macrophage) that engulfs and digests antigens that it encounter, presenting parts of them on its plasma membrane (bound to an MHC protein) for recognition by T cells bearing receptors for same antigen. This function, antigen presentation, is essential for normal cell-mediated responses. Macrophages + dendritic cells release cytokines. 8. Antigen: Substance capable of provoking an immune response. 9. Antibody: Protein produced by B cell or plasma cell. They are released into body fluids where they attach to antigens, causing complement fixation, neutralization, precipitation, agglutination, which "mark" the antigens for phagocytes or complement. 10. Complement: Bloodborne proteins activated after binding to antibody-covered antigen or certain molecules on the surface of microorganisms; enhance inflammation response and cause lysis. 11. Cytokines: Small proteins that act as chemical messengers between various parts of the immune system.

Compare the origin, maturation, and action of B and T lymphocytes.

1. B Lymphocytes (B Cells) These oversee humoral immunity. They originate within the red bone marrow. They mature within the red bone marrow. 2. T Lymphocytes (T Cells): These are non-antibody producing lymphocytes the constitute the cell-mediated arm of adaptive immunity. They originate within the red bone marrow. They mature within the thymus (circulate freely). *Cell-to-cell interactions. *Activated by antigen binding and co-stimulation. Lymphocytes originate within the red bone marrow from hematopoietic stem cells. 1. Immunocompetence: Lymphocytes must be able to recognize its one specific antigen by binding. 2. Self-tolerance: Lymphocytes must be relatively unresponsive to self-antigens so that they do not attack their own cells. *Primary lymphoid organs: Thymus and bone marrow. All other lymphoid organs are secondary lymphoid organs. *Development of Immunocompetence and Self-Tolerance: They each display particular receptors. They react to only one. *The receptors on B Cells are membrane-bound antibodies. T Cells are not antibodies but products of same gene superfamily. They can respond to the same antigens though. *Must be able to bind MHC molecules and not react strong to self-antigens (positive selection with thymic cortex, negative selection with apoptosis).

Internal Nonspecific Defences: Antimicrobial Proteins (1. Interferon - Interferon Mechanism).

1. Cells infected by virus release interferons. 2. IFNs diffuse to nearby cells. 3. PKR protein synthesis is stimulated. 4. PKR interferes with viral replication. 5. IFRs also activate macrophages and NK cells.

List the various (3) types of T cells, and identify the role each plays in imparting immunity.

1. Cytotoxic T Cells: They are the only T cells that can directly attack and killer other cells. *Circulate within and out of blood, lymph, and lymphoid organs searching for those displaying antigens. *They target virus-infected cells but also those through blood transfusions and organ donations. *They must "dock" by binding to self-nonself complex. *Letha hit with perforin and granzymes. *Immune surveillance 2. Helper T Cells: They help adaptive immunity by mobilizing cellular and humoral arms. *Once primed by APC presentation of antigen: Helper cells activate B + T cells and induce proliferation. *They activate macrophages to become better killers. *Signal for antibody formation after prodding B cells. *Activating CD8 cells to become destructive cytotoxic T cells. *Releases cytokines. 3. Suppressor T Cells: These are also known as regulatory cells. These dampen the immune response by direct contact or by releasing inhibitory cytokines.

Internal Nonspecific Defences: Antimicrobial Proteins (3. Fever - Fever Mechanism).

1. Leukocytes and macrophages exposed to pathogens secrete pyrogens. 2. Pyrogens causes hypothalamus to raise body temperature.

Internal Nonspecific Defences: Phagocytes (A: Macrophages, B: Neutrophils, C: Neutrophils).

1. Phagocytes: Pathogens that get through the skin and mucosal into the underlying connective tissue are confronted by phagocytes (phago = to eat). A) Macrophages: The chief phagocytes are macrophages, which derive from white blood cells called monocytes that leave the bloodstream, enter the tissues, and develop into macrophages (there are free macrophages and fixed macrophages). B) Neutrophils: They are the most abundant type of white blood cells, which become phagocytic on encountering infectious material in the tissues. Neutrophils produce defensins, which pierce the pathogen's membrane. C) Eosinophils: Phagocytic Mechanism: 1. Phagocyte recognizes pathogen's carbohydrate surface markers. They are enhanced with opsonization. 2. Cytoplasmic extensions adhere to pathogen. 3. Pathogen pulled inside cell in vacuole. It's called a phagosome. 4. Lysosome binds with phagosome forming phagolysosome. 5. Lysosomal enzymes digest the pathogen. This can be aided by respiratory burst (additional enzymes activated). 6. Residual body formed and then expelled. *Adherence: The phagocyte must first adhere or cling to the pathogen, which requires recognition. *Opsonization: The process of complement proteins or antibodies coating foreign particles, since the coating causes "handles" for the phagocyte receptors can bind.

Discuss how monoclonal antibodies are produced and how whey are used.

1. Tumor cells are injected into a mouse to stimulate production of B cells, which produce different types of antitumor antibodies. 2. Imortalized myeloma cells are collected. 3. The B cells are fused with myeloma cells to produce immortalized, antibody-producing hybrid cells. 4. The hybrid cell that produces the needed antibody is selected and cloned to produce unlimited quantities of a monoclonal antibody. -Antibodies produced in Labs -Generally used in research, sometimes in medicine -Produced by tumor cells in animals, bacteria, etc. -Commercially prepared. Not naturally prepared

Compare and contrast active, passive, natural, and artificial humoral immunity.

Active Humoral Immunity: It's when you encounter antigen and produce antibodies against them. 1. Naturally Acquired: It's when you get a bacterial or viral infection, during which time you may develop symptoms of the disease and suffer. 2. Artificially Acquired: It's when you receive vaccines. 3. Passive Humoral Immunity: It differs from active immunity, both in the antibody source and in the degree of of protection it provides. The antibodies are harvested from the serum of an immune human or animal donor (borrowed protection, artificial). 4. Active

Identify the general functions of antibodies.

Antibodies: *Produced by plasma cells *Extracellular environments Functions: 1. Formation of antigen-antibody complex. 2. Provide site for binding of complement proteins. 3. Block sites on pathogens. 4. Cause clumping of antigen containing cells. 5. Cause clumping of soluble antigen molecules.

Describe the structure of an antibody.

Antibody Structure: 1. Heavy chains (identical, contain amino acids). 2. Light chains (two identical chains). 3. Variable region (one end, antibodies responding have different v regions). 4. Constant region (one end, antibodies are the same in the given classes). 5. Antigen-binding site (the V regions of the heavy and light form the binding site, which fit specific antigenic determinants - there are 2). -Sometimes called immunoglobulins/gamma globulins -Complex proteins consisting of 4 subunits. 2 subunits are called Heavy Chains (identical proteins), and the other 2 are called Light Chains (identical proteins). -Variable Region: top part of the Y shape. Determines what antigen the antibody is specific for. (the receptor part). Make up the binding sites. (2 binding sites). -Constant Region: bottom part of the Y. Determines what class of antibody and how antigen is destroyed (eventually).

Describe the role of antigen presenting cells.

Antigen Presenting Cells: These function in immunity to engulf antigens and then present fragments of them, like signal flags, on their own surfaces where they can be recognized by T cells. APCs: These are dendritic cells (connective tissue, epidermis, also called langerhan cells), macrophages, and B lymphocytes. 1. Dendritic: These are mobile sentinels. 2. Macrophages: Widely distributed throughout the lymphoid organs and connective tissues. 3. These each activate T cells, which further activate macrophages (true killers).

Define antigen, and describe how antigens affect the immune system.

Antigen: Antigens are substances that can mobilize the adaptive defenses and provoke an immune response. They are the ultimate targets of all adapt immune responses. They are large, complex molecule and considered non self. Antigens are either *complete (containing immunogenicity, ability to stimulate specific proliferation, or reactivity, ability to react with the activated lymphocytes + antibodies). Antigens can also be *incomplete (the small molecule, considered a hasten,which has reactivity but not immunogenicity). *A limitless and various supply of foreign molecules can act as antigens *Proteins are the strongest antigens *If antigens combine with our proteins, the adaptive immune system may recognize the combination as foreign and mount a harmful attack rather than protective The ability to act as an antigen depends on its size and complexity. Only certain parts of an entire antigen, called *antigenic determinants*, are immunogenic. Free antibodies and lymphocytes recognize these sites and bind. *A single antigen may mobilize several lymphocytes and antibodies.

List and define the properties possessed by antigens.

Antigenic Properties: 1. Immunogenicity: The ability to stimulate proliferation of specific lymphocytes and antibodies. 2. Reactivity: The ability to react with the activated lymphocytes and the antibodies released by immunogenic reactions. 3. Antigenic Determinants: The ability of a molecule to act as an antigen depends on both its size and complexity. Only certain parts of an entire antigen, called antigenic determinants, are immunogenic. Binding sites.

Internal Nonspecific Defences: Antimicrobial Proteins (1. Interferon, 2. Complement System, 3. Fever).

Antimicrobial Proteins: A variety of antimicrobial proteins enhance the innate defenses by attacking microorganisms directly or by hindering their ability to reproduce. 1. Interferon: Interferons are small proteins that help protect cells that have not yet been infected. The IFNs diffuse to nearby cells,where they stimulate synthesis of proteins, which then "interfere" with viral replication in the still-heathy cells by blocking proteins synthesis and degrading viral RNA. These aren't virus specific. Lymphocytes secrete game, or immune, interferon but most secrete alpha interferon. Interferons activate macrophages and mobilize NK cells. 2. Complement System: Complement system refers to a group of at least 20 plasma proteins that normally circulate in the blood in an inactive state. It's activated by the classical pathway (antibodies, binding, complement fixation) and alternative pathway (CS, activated B, D, P). 3. Fever: It's a systematic response to invading microorganisms. Our body temperature is regulated by a cluster of neurons in the hypothalamus. It's aided by pyrogens, secreted by leukocytes and macrophages exposed to foreign substances in the body.

Describe the general mechanism of the cell-mediated immune response.

Cell-Mediated Immune Response: It's when antibodies become fairly useless again infectious microorganisms like viruses. It's regulated by CD4 and CD8, which are two kinds of T cells. These are structurally related cell differentiation glycoproteins, which are displayed by mature T cells. They are surface receptors and play with interactions. CD4: Become helper T cells CD8: Become cytotoxic T cells (destroy any foreign cells within the body) Cell-Mediated Immune Response: 1. T cell binds with antigen infected body cell 2. Co-stimulatory signals are present 3. T cell is activated 4. Clones are produced 5. Some clones become memory cells

Differentiate the humoral and cell-mediated specific immune response.

Humoral Immune Response: Cell-Mediated Specific Immune Response: