THE IMMUNE SYSTEM

The Immune System

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3 rd L in e o f D e fen seH u m ora l (B ce lls )

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1st Line of Defense: Surface Barriers

The Skin: heavily keratinized epithelial membrane presents a physical barrier to most microorganisms that swarm on the skin; keratin is resistant to most weak acids and bases and to bacterial enzymes and toxins

1st Line of Defense (cont’d)

Mucous Membranes: serve as physical barriers and produce a variety of protective chemicals acidity of skin secretions (pH of 3-5) inhibits

bacterial growth and sebum contains chemicals that are toxic to bacteria

the stomach mucosa secretes a [ ]’d HCl solution and protein-digesting enzymes to kill microorganisms

1st Line of Defense (cont’d)

Mucous Membranes: saliva and lacrimal fluid (external eye) contain

lysozyme, an enzyme that destroys bacteria sticky mucous traps many microorganisms that

enter the digestive and respiratory passageways the respiratory tract mucosae also have

structural modifications such as vibrissae and cilia

2nd Line of Defense: Internal Defenses

Phagocytes the chief phagocytes are macrophages which derive

from circulating WBCs called monocytes search for cellular debris or foreign invaders; are called free (move about regions) or fixed (permanent to one organ)

neutrophils are the most abundant type of WBC and become phagocytic on encountering infectious material in the tissues; also contain the chemical, defensins, to kill

2nd Line of Defense: Internal Defenses

Phagocytes (cont’d) eosinophils are another type of WBC and are

weakly phagocytic but very important in defending the body against parasitic worms

mast cells, more associated with their role in allergies, have been shown to have an ability to bind with and ingest a wide range of bacteria, and then to kill the internalized bacteria

2nd Line of Defense: Natural Killer Cells

Police the body in the blood and lymphCan lyse and kill cancer cells and virus-infected

body cells before the immune system is activated and enlisted in the fight

Part of large granular lymphocytesNot phagocytic; attack the target cell’s

membrane and release cytolytic chemicals called perforins which causes the nucleus to disintegrate

2nd Line of Defense: Inflammation

Inflammation: tissue response to injury such as a physical trauma, intense heat, and irritating chemicals, as well as to infection by viruses, fungi, and bacteria

(1) prevents the spread of damaging agents to nearby tissues (2) Disposes of cell debris (3) Sets the stage for repair processes

2nd Line of Defense: Inflammation (cont’d)

5 Cardinal Signs of Acute Inflammation:(1) Redness (2) Heat (3) Swelling (4) Pain (5)

Loss of functionThe inflammatory process begins with a flood

of inflammatory chemicals into the ECFInjured tissue cells, phagocytes, lymphocytes,

mast cells, and blood proteins are sources of these chemicals (see following slide)

Inflammatory ChemicalsInclude histamine, kinins, prostaglandins,

complement, and cytokinesCause small blood vessels in the vicinity to

dilate and leads to hyperemia; redness and heatChemicals also increase the permeability of

local capillaries and allows exudate (fluid containing proteins such as clotting factors and antibodies) to seep from the bloodstream into the tissue spaces; swelling and pain (presses on nerve endings)

Inflammation (cont’d)Edema: (1) helps to dilute harmful

substances that may be present (2) brings in large quantities of oxygen and nutrients needed for repair (3) allows the entry of clotting proteins

If an epithelial barrier has been breached, -defensins (antibiotic-like chemicals) increases to help control bacterial and fungal colonization

Inflammation (cont’d): Phagocyte Mobilization

Leukocytosis: chemicals released by injured cells promote rapid release of neutrophils from red bone marrow

Margination: the neutrophils cling to the inner walls of the capillaries; also known as pavementing

Diapedesis: chemical signaling causes the neutrophils to squeeze through the capillary walls

Inflammation (cont’d): Phagocyte Mobilization

Chemotaxis: neutrophils and other WBCs are attracted to the site of injury by chemotactic agents and phagocytosis

2nd Line of Defense: Antimicrobial Proteins

Interferon: a virus-infected cell will help protect cells that have not yet been infected by secreting small proteins called interferons (IFNs); they interfere with viral replication in those cells by blocking protein synthesis at the ribosomes; also has an anti-cancer role by activating macrophages and natural killer cells

Inflammation (cont’d): Antimicrobial Proteins

Complement: a group of at least 20 plasma proteins that, when activated, amplify virtually all aspects of the inflammatory process, kill bacteria and other cell types by cell lysis

2nd Line of Defense: FeverThe body’s thermostat (in hypothalamus) is

normally set at 36.2 °C (98.2 °F) but resets upward in response to chemicals called pyrogens (pyro=fire), secreted by leukocytes and macrophages exposed to bacteria; moderate fever causes the liver and spleen to sequester iron and zinc, which bacteria need to multiply

3rd Line of Defense: Adaptive (Specific) Defenses

Antigens: substances that can mobilize the immune system and provoke an immune response; most are large, complex molecules (both natural and manmade) that are not normally present in the body; eg. bacteria, viruses, mismatched RBCs

Complete Antigens: foreign proteins, nucleic acids, some lipids, and many large polysaccharides; proteins are the strongest antigens

Antigens (cont’d)

Incomplete Antigens: Haptens; small molecules that link up with the body’s own proteins; haptens are reactive but not immunogenic unless attached to protein carriers; include penicillin, poison ivy, animal dander, some detergents, cosmetics

haptens can produce harmful reactions, called allergies

3rd Line of Defense: Adaptive (Specific) Defenses (cont’d)

Antibodies: also called immunoglobulins; soluble proteins secreted in response to an antigen, and they are capable of binding specifically with that antigen; they constitute the gamma globulin part of blood proteins

3rd Line of Defense: Adaptive (Specific) Defenses (cont’d)

Immunocompetent Lymphocytes: arise in red bone marrow and mature into T cells (T lymphocytes) or B cells (B lymphocytes)

T Cells: manage the immune response and some directly attack and destroy foreign cells; oversee cell-mediated immunity

B Cells: produce plasma cells, daughter cells that secrete antibodies into the blood or other body fluids; oversee humoral immunity

3rd Line of Defense: B CellsHumoral immune response (anti-body

mediated) occurs when antigens bind to the B cells

Clonal selection occurs to stimulate the B cell to grow and then to multiply rapidly

Most of the clone become plasma cells, which are antibody-secreting effector cells

B cells secrete limited amounts of antibodies, but plasma cells secrete 2000 molecules per second for 4 to 5 days

3rd Line of Defense: B CellsThe clone cells that do not become plasma

cells become long-lived memory cells which will mount an immediate humoral response if they encounter the same antigen again

Primary immune response occurs 3-6 days after the antigen challenge; secondary immune responses are faster, more prolonged, and more effective because the memory cells are already on alert

3rd Line of Defense: B CellsActive Humoral Immunity: (1) naturally

acquired during bacterial and viral infections (2) artificially acquired when we receive vaccines (contain dead or weakened pathogens); tetanus

Passive Humoral Immunity: antibodies obtained from a human or animal donor egs. breast milk, serum to treat snake bites, botulism, rabies (these would kill before active immunity could be established)

3rd Line of Defense: T Cells2 major populations of effector T cellsT4 Cells: display cell differentiation

glycoprotein 4 (CD4); primarily helper T cellsT8 Cells: display cell differentiation

glycoprotein 8 (CD8); cytotoxic cellsdestroy any cells in the body that harbour

anything foreignthe B cells prepare the antigen for disposal by

the T cells

3rd Line of Defense: T CellsT Cell Activation: (1) Antigen Binding: T cell

antigen receptors bind to an antigen-MHC protein (self body cell) complex on the surface of a body cell; not all T cells can bind to all antigen-MHC protein complexes (2) Costimulation: before a T cell can proliferate and form a clone, it must recognize on or more costimulatory signals; physical or chemical signals that nudge the T cells either to complete their activation process or to abort activation entirely

3rd Line of Defense: T CellsT Cell Activation: (3) Cloning: once

activated the T cells proliferate to form a clone of cells that differentiate and perform functions according to their T cell class; occurs within a week after a single exposure; death of T cells occurs between days 7 and 30; clone members become memory T cells for secondary responses

SummaryT8 cells prevent infectious microorganisms,

hidden within cells from antibody surveillance, from killing their cellular hosts

Helper T4 cells costimulate both other T cells and B cells and recruit nonspecific defenses; without them there is no adaptive immune response because they direct or help complete the activation of all other immune cells (AIDS)

Suppressor T cells prevent undesirable immune reactions

“and the Band Played On”Movie – To be shown in PMD lab