Chapter 22: Immunity

• Immunity is covered in Chapter 22.

Primary Locations of Immune

• Primary immune locations include the adenoids, thymus, tonsils, bronchus-associated lymphoid tissue, and bone marrow.
• Inguinal and axillary lymph nodes, spleen, intestine, Peyer’s patches, and the appendix are also primary locations

Innate vs Adaptive Immunity

• Vary based on cells involved, specificity of cell response, mechanisms of eliminating harmful substances and amount of time for response

Innate Immunity

• Rapid responses include species resistance, mechanical and chemical barriers, natural killer cells, inflammation, phagocytosis, and fever.
• Innate immunity is present at birth
• It protects against a variety of different substances and is nonspecific
• No prior exposure to a substance is needed
• Includes barriers of skin and mucosal membranes as well as nonspecific cellular and molecular internal defenses
• It responds immediately to potentially harmful agents.

Adaptive Immunity

• It is acquired/specific immunity involving specific T- and B-lymphocytes that respond to specific antigens.
• A particular cell only responds to one specific foreign substance.
• Effective within several days
• Innate and adaptive immunity work together in body defense.
• Adaptive immunity are specific defenses, that develop slowly, and are carried out by lymphocytes that recognize a specific invader.

Lines of Defense

• The defense strategies of the immune system are divided into three categories: first, second, and third line of defense.
• The first and second lines of defense are specific to the innate immune system.
• The adaptive immune system possesses the third line of defense strategies.

First Line of Defense: Mechanical Barriers

• The unbroken skin and mucous membranes of the body create mechanical barriers that prevent the entry of certain pathogens.
• Hair, mucus, and sweat are also part of the mechanical barrier
• Mechanical barriers represent the body's first line of defense.
• The rest of the innate defenses are part of the second line of defense.

Second Line of Defense: Chemical Barriers

• Chemical barriers include the highly acidic environment of gastric juice, and lysozyme in tears; these kill many pathogens.
• Interferons are hormone-like peptides that serve as antiviral substances; they are produced by cells infected with viruses and induce nearby cells to produce antiviral enzymes to protect them from infection as well as stimulate phagocytosis
• Complement stimulates inflammation, attracts phagocytes, and enhances phagocytosis.

Natural Killer (NK) Cells

• NK cells are a type of lymphocyte that defend the body against viruses and cancer cells by secreting cytolytic substances called perforins.
• NK cells secrete chemicals that enhance inflammation.

Inflammation

• Inflammation is characterized by redness, swelling, heat, and pain.
• Major actions during an inflammatory response include dilation of blood vessels, increase of blood volume to affected areas, and invasion of white blood cells into the affected area.

Phagocytosis

• Active phagocytes are neutrophils and monocytes; these leave the bloodstream at areas of injury by diapedesis and are attracted to the injured area by chemotaxis.
• Neutrophils engulf smaller particles, while monocytes attack larger ones.
• Monocytes give rise to macrophages; which become fixed in various tissues.
• Phagocytosis removes foreign particles from the lymph

Fever

• Fever offers protection against infection by interfering with the proper conditions that promote bacterial growth
• During fever, the amount of iron in the blood is reduced, so fewer nutrients are available to support the growth of pathogens.
• Phagocytic cells attack with greater vigor when the temperature rises.

Innate Immunity - Phagocytes

• Neutrophils, macrophages, and dendritic cells are phagocytic cells.

Apoptosis-Initiating Cells: NK Cell (Innate Immunity)

• Apoptosis initiating cells trigger apoptosis of unhealthy or unwanted cells.

Innate Immunity - Phagocytes

• Neutrophils, macrophages, and dendritic cells are phagocytic cells.

First Line of Defense

• Mechanical barriers like skin and mucous membranes

Second Line of Defense

• Chemical barriers like enzymes, pH, salt, and complement
• Natural killer cells
• Inflammation
• Phagocytosis
• Fever

Third Line of Defense

• Cellular immune response
• Humoral immune response

Overview of the Immune System

• The innate immune system provides innate immunity with multiple components that protect against a wide array of substances.
• Skin and mucosal membranes prevent entry, while nonspecific internal defenses like cells (macrophages, NK cells) and chemicals (interferon, complement), cause physiological repsonses (inflammation, fever)
• Adaptive immune system provides adaptive immunity
• Lymphocytes will replicate and respond when stimulated by a specific antigen by using T-lymphocytes and B-lymphocytes which make plasma cells to synthesize and release antibodies.

Effects of Interferon (IFN)

• Infected cells release interferon and signals nearby cells
• NK cells causes apoptosis

Complement System

• Part of innate immunity
• Includes 30 plasma proteins that work along with antibodies and is identified with the letter "C" and a number such as C2.
• Synthesized by the liver, it is continuously released in an inactive form where activation occurs by enzyme cascade.
• It is especially potent against bacterial infections

Innate Immunity: Inflammation

• Injured tissue, basophils, mast cells, and infectious organisms release chemicals that initiate the response with chemicals like histamine, leukotrienes, and prostaglandins
• Released chemicals cause vascular changes like vasodilation, increased capillary permeability, and endothelial expression of molecules for leukocyte adhesion
• Recruitment of leukocytes where leukocytes release cytokines stimulating leukopoiesis in marrow

Events of Inflammation (cont.)

• Macrophages release pyrogens (fever-inducing molecules).
• Delivery of plasma proteins to site, immunoglobulins, complement, clotting proteins, and kinins
• Clotting proteins form clots that wall off microbes, and kinins stimulate pain receptors and increase capillary permeability

Cardinal Signs of Inflammation

• Redness follows increased blood flow
• Heat follows increased blood flow with increased metabolic activity
• Swelling follows increase in fluid loss from capillaries
• Pain follows stimulation of pain receptors in response to compression (extra fluid) and chemical irritants
• Loss of function from pain and swelling in severe cases
• Acute inflammation lasts 8-10 days.

Innate Immunity: Fever

• Fever (pyrexia) is an abnormal body temperature elevation, or 1°C or more from normal (37°C)
• Results from the release of pyrogens from immune cells or infectious agents.
• Pyrogens circulate through blood and target hypothalamus, then hypothalamus releases prostaglandin E2; this raises the temperature set point that leads to fever

Benefits of Fever

• Inhibits reproduction of bacteria and viruses, promotes interferon activity, increases activity of adaptive immunity, accelerates tissue repair, and increases immune cells migrating out of blood
• It is recommended to leave a low fever untreated

Risks of a High Fever

• High fevers potentially dangerous
• Changes in metabolic pathways and denaturation of proteins pose risks
• Possible seizures
• Irreversible brain damage can occur at greater than 106 F (41.1°C), and death is likely if the temperature is greater than that.

Adaptive Immunity

• Adaptive Immunity involves specific lymphocyte responses to an antigen.
• Contact with antigen causes lymphocyte proliferation.
• The immune response consists of lymphocytes and their products.
• Adaptive immunity requires a longer response time than innate immunity:
• Since it takes days to develop, adaptive immunity is considered the third line of body's defense.
• The two branches of adaptive immunity are cell-mediated immunity involving T-lymphocytes and humoral immunity involving B-lymphocytes.

Adaptive Immunity

• Cell-Mediated immunity uses T-Lymphocytes that are effective against antigen within the cells and requires an antigen presenting cell.
• Humoral Immunity uses B-Lymphocytes that are effective against antigens outside the cells and does not require an antigen-presenting cell.

Formation of Lymphocytes

• Naive immuncompetent T and B-lymphocytes
• T-lymphocytes (helper and cytotoxic)
• Primary lymphatic structure responsible for production of lymphocytes is the red bone marrow.
• Primary lymphatic structure responsible for maturation of T-lymphocytes is the Thymus

T-Lymphocytes

• T-Lymphocytes must be able to bind to MHC molecule
• Needs to not recognize self-antigen;
• Helper T-lymphocytes (retains only CD4 protein), while Cytotoxic T-lymphocyte (retains only CD8 protein)
• Regulatory T-lymphocytes (T-Regs) are CD4+ cells formed from T-cells that mildly bind self-antigens; these aid in inhibiting immune response

T-Lymphocytes and B-Lymphocytes

• Helper T-Lymphocytes (Helper T Cells/CD4+) are a type of immune cell that stimulates Cytotoxic T cells, macrophages, and B cells to make immune responses.
• Cytotoxic T-Lymphocytes (Cytotoxic T-Cells/CD8+ Cells) are a type of immune cell that can kill certain cells, including foreign cells, cancer cells, and cells infected with a virus

Activation of T-Lymphocytes

• T-lymphocytes require that another cell displays the foreign antigen on their plasma membrane
• Antigen Presenting Cells (APCs)
• The body's own cells present self-antigens, which are recognized by T-Cells and aren't attached
• These self antigens are attached to MHC Class 1 molecules on the cell surface
• When one of the body's cells is damaged or infected, it will change the self antigen on the MHC 1 molecule for a foreign antigen, which will be recognized by the T-Cells, and they will mount an immune response to destroy it.

Immune Antigen Presenting Cells (APCs)

• Dendrites and macrophages are professional APCs in the body
• When these professional APCs come in contact with a foreign cell, they will engulf the cell (phagocytosis)
• After engulfing, they will present that foreign cell's antigens on specialized MHC II (MHC class 2) receptors on their cell surface
• These will be recognized by the T-Cells, which will cause them to activate an immune response.

Antigen Recognition by T-lymphocytes in Unhealthy Cell

• viral peptide fragments attach to MHC Class I molecules, causing the production of secretory vesicles which display foreign antigens

T-Lymphocytes

• Helper (T-)lymphocytes use cytokines
• Cytotoxic (T-)lymphocytes perforin and granzymes to signal for apoptosis

B-Lymphocytes

• B-cells are produced in the red bone marrow and migrate to secondary lymphoid structures where they await activation from foreign antigens.
• They do not require antigen presentation from another cell in order to be activated.

Activation of B-Lymphocytes

• When B-Cells come in contact with a foreign cell, they will engulf it (phagocytosis).
• These B-Cells will then differentiate into Plasma Cells and Memory B-Cells.
• Plasma cells begin to produce antibodies.
• Memory B-Cells are activated upon subsequent exposures to the same infectious/foreign cell.

Antibodies

• Immunoglobulin (lg) proteins are produced against a particular antigen
• They “tag” pathogens for destruction by immune cells and are a good defense against viruses, bacteria, toxins, yeast spores.

Antibody Functions

• Functions of antibodies includes precipitation agglutination, neutralization, inflammation, and complement
• May cases Enhances Opsonisation & Phagocytosis

Types of Antibodies

• Five types of antibodies (immunoglobulins) are the gamma globulin fraction of the plasma. -IgG is in tissue fluid and plasma and defends against bacterial cells, viruses, and toxins, can cross the placenta, and activates complement. -IgA is in exocrine gland secretions (breast milk, saliva, tears, nasal fluid, gastric and intestinal juices, bile, urine); it prevents attachment of bacteria to mucous membranes. -IgM is found in plasma and activates complement, while reacting with blood cells during transfusions. -IgD is found on the surface of the most B lymphocytes and functions in B cell activation. -IgE is found in exocrine gland secretions and promotes allergic reactions while also defending against worm infections.

Active and Passive Immunity

• Naturally acquired active immunity occurs after exposure to the antigen itself.
• Artificially acquired active immunity occurs through the use of vaccines, without the person becoming ill from the disease.
• Artificially acquired passive immunity involves the injection of gamma globulin containing antibodies (antiserum) and is short-lived.
• Naturally acquired passive immunity occurs as antibodies are passed from mother to fetus and

Clinical View: Vaccinations

• Weakened or dead microorganism or component
• Stimulate immune system to develop memory B-lymphocytes
• Provide relatively safe means for initial exposure to microorganism
• If later exposed, secondary response triggered as the immune system response predominantly from the humoral branch.

Clinical View: Hypersensitivities

• It is an abnormal and exaggerated response of immune system to antigen.
• Acute hypersensitivities occur within seconds (anaphylactic).
• Subacute hypersensitivities occur within 1 to 3 hours (or a bit longer) and involve humoral immunity.
• Delayed hypersensitivities occur within 1 to 3 days and involve cell-mediated immunity.