NOTES: CH 43, part 1 The Immune System - Nonspecific & Specific Defenses

The lymphatic system is closely associated with the cardiovascular system.

LYMPHATIC PATHWAYS Lymphatic capillaries ● microscopic, closed-end tubes that extend into intercellular spaces ● receive LYMPH through their thin walls (LYMPH = the fluid of the lymphatic system) ● lymphatic capillary networks parallel blood capillary networks

Functions of lymph: 1) returns to the bloodstream small proteins that leaked out of blood capillaries 2) transports foreign particles, such as bacteria or viruses, to lymph nodes

**if lymph movement is impaired, it may accumulate within the intercellular spaces and produce EDEMA, or swelling (example: after surgery, the lymphatic vessels and lymph nodes around the wound may be damaged, causing fluid to accumulate around the surgery site and lead to swelling)

Lymph Nodes: Structure of a Lymph Node: ● lymph nodes are subdivided into nodules ● nodules contain masses of lymphocytes and macrophages

Locations of Lymph Nodes: ● lymph nodes aggregate in groups or chains along the paths of larger lymphatic vessels

Functions of Lymph Nodes: ● filter potentially harmful foreign particles from lymph ● are centers for the production of lymphocytes (attack invading viruses, bacteria, parasites, etc.) ● contain phagocytic cells (engulf and destroy foreign substances, damaged cells, cellular debris)

THYMUS AND SPLEEN Thymus: ● shrinks slowly after puberty ● contains large numbers of LYMPHOCYTES which mature into T CELLS (T lymphocytes) – important in providing immunity (more on these later…)

Spleen: ● largest lymphatic organ ● resembles a large lymph node (divided into lobules)

Spleen: ● spaces within splenic lobules are filled with blood ● contains many macrophages, which destroy/remove foreign particles and damaged RBCs from the blood **the spleen filters blood as the lymph nodes filter lymph!**

So, how does the body defend itself???

The body has nonspecific and specific defenses against infection / pathogens. Why don’t YOU have mold on your skin???

● PATHOGEN: a disease-causing agent; causes infection -pathogens include: viruses fungi bacteria protozoans

Nonspecific Defenses: ● general defense ● provide protection against many different pathogens ● involve physical and chemical barriers, fever, inflammation, phagocytosis

Specific Defenses: ● very precise ● target certain pathogens ● also known as IMMUNITY ● involve specialized lymphocytes (T cells and B cells) that recognize and respond to specific pathogens **nonspecific defenses are quick to respond; specific defenses are slower-to-respond

NONSPECIFIC DEFENSES 1) Species Resistance ● each species is resistant to certain diseases that may affect other species ● examples: measles, mumps, gonorrhea, and syphilis infect humans but not other animal species ● one species may be resistant to a disease that affects another species because its tissues somehow fail to provide a suitable environment for the pathogen (temperature, chemical environment, receptors, etc.)

2) Mechanical Barriers = FIRST LINE OF DEFENSE ● mechanical barriers / physical barriers include: -skin (and associated hairs) -mucous membranes -fluid (sweat and mucus) ● as long as they remain intact, they can keep out many pathogens

SKIN MUCUS SALIVA

**all other “nonspecific defenses” are considered the SECOND LINE OF DEFENSE

3) Chemical Barriers ● gastric juice: contains hydrochloric acid and enzymes (e.g. pepsin) that are lethal to pathogens ● tears: contain the enzyme LYSOZYME (which has antibacterial action) ● the salt in perspiration accumulates on the skin and kills bacteria on the skin

3) Chemical Barriers (cont.) INTERFERONS: chemicals released by virus-infected cells; they stimulate other immune cells to: -synthesize antiviral proteins that stimulate phagocytosis, block virus replication

Interferons: ● most effective against cold and flu virus ● now mass-produced by recombinant DNA technology to be potentially used as treatment for viral infections and cancer!

3) Chemical Barriers (cont.) COMPLEMENT SYSTEM: ● group of 20 proteins; ● catalyze a series of steps resulting in lysis of invading microbes and/or inflammatory response

4) Fever ● higher body temperature increases the rate of phagocytic cells ● also lowers iron levels in the blood (bacteria and fungi require iron, so this slows their growth)

5) Inflammation ● produces: localized redness, swelling, heat and pain ● HISTAMINE and prostaglandins released by damaged tissues attract WBCs to the site  the mass of WBCs, bacterial cells, and damaged tissue forms a thick fluid called PUS

6) Phagocytosis – removes foreign particles from the lymph and blood ● the most active phagocytes in blood are NEUTROPHILS and MONOCYTES ● Monocytes give rise to MACROPHAGES

● MACROPHAGES are found in the linings of blood vessels in the: -bone marrow -liver -spleen -lungs -lymph nodes

EOSINOPHILS: ● kill antibody-coated parasites

Specific Defenses / Immunity

Immune System… ● the body’s “third line of defense” ● characterized by:  specificity  diversity  self / non-self recognition  memory

ANTIGENS… ● ANTIGENS: specific foreign molecules that trigger an immune response; usually located on a cell’s surface -antigens include: proteins glycoproteins polysaccharides glycolipids

ANTIGENS… ● before birth, body cells sort “self” proteins and other large molecules ● lymphocytes develop receptors that allow them to differentiate between nonself (foreign) and self antigens ● nonself antigens combine with T cell and B cell surface receptors and stimulate these cells to cause an immune reaction

LYMPHOCYTES (T and B Cells) ● originate in the red bone marrow ● some reach the THYMUS, where they mature into T CELLS ● others, the B CELLS, mature in the RED BONE MARROW ● both T cells and B cells reside in lymphatic tissues and organs (lymph nodes, spleen, etc.)

LYMPHOCYTE FUNCTIONS **a lymphocyte must be ACTIVATED before it can respond to an antigen**

*CLONAL SELECTION:  antigen-specific selection of a lymphocyte;  activates lymphocytes to divide and differentiate to produce CLONES of effector cells (& memory cells) designed to eliminate the antigen that provoked the initial response SPECIFICITY & MEMORY!

T CELLS and the CELLULAR IMMUNE RESPONSE * T cells are activated when an antigen-presenting cell displays a foreign antigen antigen T cell! Antigen Presenting Cell (APC)

Antigen Presentation: ● Carried out by a group of approx. 20 glycoproteins that make up the MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)

Two main classes of MHC molecules: ● Class I MHC: located on all nucleated body cells *cytotoxic T cells (TC) bind to fragments of antigens displayed by class I MHC   ● Class II MHC: found only on specialized cells (macrophages, B cells, activated T cells) *helper T cells (TH) bind to fragments of antigens displayed by class II MHC

Antigen-Presenting Cells (APCs): -cells that take up antigens (B cells, macrophages); -engulfed foreign matter binds to a class II MHC molecule and is conveyed to the outside of the APC; -foreign antigen is recognized by a helper T cells (TH); -this interaction is enhanced by CD4, a membrane protein on TH cells.

CD4

T CELLS and the CELLULAR IMMUNE RESPONSE Example: 1) a macrophage engulfs and digests a pathogen 2) the macrophage displays the antigens on its cell membrane using class II MHC.

3) the macrophage encounters a HELPER T CELL with the appropriate antigen receptor  activates T cell 4) activated helper T cell stimulates B cell to produce antibodies specific for the displayed antigen

**Activated TH cells secrete CYTOKINES: -CYTOKINES = factors that stimulate other lymphocytes; -Interleukin-2 (IL-2): stimulates B cells to differentiate into antibody-secreting plasma cells and induces cytotoxic T cells to become active killers. -Interleukin-1 (IL-1): secreted from APCs; promotes activation of helper T cells.

**Other T cells: CYTOTOXIC T CELLS:  recognize nonself antigens on cancer cells or virus-infected cells;  antigen-activated TC cells kill body cells that are infected by pathogens (or are cancerous).   TC cells recognize and bind to antigen-class I MHC markers (host cells display antigens with class I MHC molecules); (TC cells have special plasma membrane proteins called CD8, which have an affinity for class I MHC molecules…remember that class I MHC is found in all nucleated body cells)

Cytotoxic T Cell Response: -cytotoxic T cells then bind to the surfaces of the antigen-bearing cells, and release a protein (PERFORIN) that cuts openings in these cells, causing them to burst (LYSE)

Before…..…..After A fully intact cancer cell surrounded by the immune systems killer t-cells. The cancer cell is surrounded and attacked by  the killer T-Cells of the immune system. Scanning electron microscope pictures shows killer t-cells attacking the cancer cell. Notice the tentacles of the cancer cell. Notice how the cancer is completely flattened and totally destroyed. During the killing process, granules in a T-Cell fuse with the cell membrane and release units of the protein PERFORIN. These combine to form pores in the target cell membrane. Thereafter fluid and salts enter so that the target cell eventually bursts.

T cells… *Some T cells do not respond to the antigen on the first exposure…they remain as MEMORY T CELLS; upon a second exposure to the same antigen, they respond quickly

B CELLS and the HUMORAL IMMUNE RESPONSE * B cells are activated when they encounter an antigen that fits its antigen receptors

B CELLS and the HUMORAL IMMUNE RESPONSE Example: 1) a B cell encounters an antigen that fits its antigen receptors 2) the activated B cell divides, enlarging its clone (especially when stimulated by a helper T cell!)

3) some activated B cells specialize into PLASMA CELLS (antibody-producing cells) *(antibodies react against the antigen that stimulated their production!)…more on this later 4) some activated B cells differentiate into MEMORY B CELLS (respond to subsequent exposures)

TYPES OF ANTIBODIES ● antibodies are soluble proteins called IMMUNOGLOBULINS (Ig) ● 5 major types of antibodies: IgG, IgA, IgM, IgD, and IgE.

Antibody Structure and Function: ● epitope: a localized region on an antigen’s surface that is recognized by antibodies   ● structure:

ANTIBODY ACTIONS ● antibodies work by: attacking the antigens directly (attaching to antigen) -cause them to clump together (AGGLUTINATION) or form insoluble masses (PRECIPITATION) -makes it easier for phagocytes to engulf the antigens / antigen-bearing agents & eliminate them

AGGLUTINATION!

ANTIBODY ACTIONS 2) activating COMPLEMENT -a group of proteins that work together to produce a variety of effects: ● attract phagocytes ● rupture foreign cell membranes ● coating the cells, making them more susceptible to phagocytosis

Complement System

ANTIBODY ACTIONS 3) stimulate changes in local areas that help prevent the spread of the antigens (i.e. promote inflammation)