1. The Lymphatic System
a. Consists of lymphatic vessels and lymphoid organs
b. Four main homeostatic functions:
i. Lymphatic capillaries take up and return excess fluid to bloodstream
ii. Lacteals (in intestines) absorb fats in form of lipoproteins and transport them to blood
stream
iii. Responsible for production of lymphocytes
iv. Helps defend body against pathogens
c. Lymphatic Vessels
i. Form a one-way system that begins with lymphatic capillaries
1. Take up fluid that’s been diffused from blood capillaries; fluid inside these
vessels is called lymph
2. Vessels have valves (like veins) that are dependent on skeletal muscle for
movement
3. Edema- localized swelling because of tissue fluid accumulating and not being
collected by lymph system
d. Lymphatic Organs
i. Primary Lymphatic Organs (first line of defense)
1. Red Bone Marrow
a. Site of stem cells that divide to produce all types of blood cells
b. Found in adults in skull, sternum, ribs, pelvis, vertebral column and
heads of femur and humorous
c. Place where B cells mature
2. Thymus Gland
a. Located along trachea behind sternum in upper thoracic cavity; largest
in children (shrinks throughout life)
b. T cells mature here and can tell “Self” from “nonself”
c. T cells that could possibly hurt your own cells are destroyed by apoptis
ii. Secondary Lymphatic Organs
1. Lymph Nodes
a. Avoid structures occurring along lymphatic vessels
b. Cleanse lymph
i. Macrophages engulf debris and pathogens
ii. T cells fight infections and attack cancer cells
c. Lymph nodes named for their location
2. Spleen
a. Located in abdominal cavity behind stomach
b. Macrophages remove old blood cells
c. Lymphocytes cleanse blood of foreign particles
3. Tonsils
a. Patches of lymphatic tissue located in pharynx
b. First to encounter pathogens that enter the body via nose and mouth
4. Peyer’s patches and appendix
a. Located in intestines
b. Encounter pathogens that enter the body through the intestinal tract
2. Immune System
a. Immunity is the body’s capability to remove foreign substances and to kill pathogens and cancer
cells
b. Nonspecific Defenses
i. occur automatically and no memory is involved (no specific antibody)
ii. Barriers of entry serve as mechanical barriers
1. Skin (epithelium)
2. Mucous membranes that line respiratory, digestive, and urinary tract
3. Antimicrobial molecules (oily secretions on skin, lysozyme enzymes, acidic pH of
stomach)
iii. Inflammatory Response – occurs whenever tissue is damaged by physical or chemical
agents/pathogens
1. damaged cells release histamine which causes capillaries to dilate and become
more permeable
2. enlarged capillaries lead to more blood flow which causes sin to redden and
become warm
3. increased permeability allows fluids to escape
4. swollen area stimulates free nerve endings causing pain
iv. Inflammatory Reaction
1. Fevers serve to
a. Inhibit growth microorganisms
b. Promote tissue repair
c. Aids phagocytosis
d. Stimulates immune cells to divide more rapidly
e. Increases production of interferon
2. Neutrophils and monocytes migrate to site of injury
a. Neutrophils and mast cells phagocytize pathogens
b. Monocytes differentiate into macrophages
c. Macrophages release cytokines, chemical signals that stimulate other
white cells
d. Some phagocytes die. These, with dead tissues, bacteria and living white
cells form pus
3. Natural Killer cells – large lymphocytes that kill virus-infected cells and cancer
cells
v. Complement System
1. This is a collection of plasma proteins
a. Activated when pathogens enter the body
b. Amplify the inflammatory response
i. Proteins bind to mast cells and trigger histamine
ii. Others attract phagocytes to the scene
c. Some bind to pathogens coated with antibodies which ensure they will
be phagocytized
2. Interferon binds to non-infected cells and causes them to prepare for possible
attack (interfere with replication)
3. Other compliment proteins join to form membrane attack complex
a. Produce holes in surface of bacteria and viruses; fluids and salts enter
the cell then cause it to lyse
vi. Proactive Proteins
1. Interferons – proteins produced by virus infected cells as a warning to healthy
cells
2. Interferon binds to receptors of non-infeDcted cells
a. Causes them to prepare for possible attack
b. Non-infected cells produce substances that interfere with viral
replication
c. Specific Defenses
i. When nonspecific defenses haven’t been adequate, specific defenses are used
ii. Specific defense requires immune system to recognize specific molecule called antigen;
any foreign substance that that stimulates the immune system to react
iii. immune system can respond to antigen (5-7 days) and can remember antigen
iv. specific defenses primarily depend on B-cells and T-cells
1. lymphocytes can be capable of recognizing specific antigens
2. lymphocytes have antigen-receptors with specific shapes allow it to combine
with particular antigens
3. lymphocytes only have one type of receptor
4. B Cells
a. B cells give rise to plasma cells
b. Plasma cells produce antibodies which can combine with/neutralize
antigens
5. T Cells
a. Directly attack cells that bear non-self proteins
b. Don’t produce antibodies
c. Differentiate into helper T or cytotoxic T cells
3. B-cells and Antibody-Mediated Immunity
a. B cells have receptors on their cell membrane called B cell receptors
i. Virgin B cells are activated when they bind to specific antigen that matches receptor
ii. Specific B cell divides by mitosis many times creating clones of itself
1. Clonal Selection theory
a. Antigen selects which lymphocytes either undergo clonal expansion or
produce more lymphocytes
b. Proliferation of cells based on exposure of antigen
iii. Most clones become plasma cells which circulate plasma and lymph
iv. Plasma cells can secrete millions of antibodies per hour
v. Some clones become memory cells which confer long-term memory and rapid response
the next time antigen is found
b. Antibodies (Immunoglobins/Igs)
i. Antibodies – proteins coded for by genes; responsible for tagging antigen
1. Y-shaped molecules with 2 arms
2. Consist of 4 polypeptide chains
a. 2 “heavy” (long) chains
b. 2 “light” (short) chains
3. These chains consist of
a. Constant regions where AA sequence is set; divided into five antibody
classes by tail area
b. Variable regions where AA sequence varies between different
antibodies located at tips and arms of antibodies
ii. Immunoglobin – proteins that target things for destruction
1. not as specific a response as antibodies
2. Types
a. IgG – main antibody
b. IgM – largest antibody (circulation)
c. IgA – in mother’s milk (secretions)
d. IgD – on surface of immature B cells
e. IgE – found as antigen receptors on basophils in blood and on tissue
mast cells
c. Antibody-Mediated (humoral) response
i. Once antibody production by plasma cells begins, antibodies bind to antigens in plasma
or lymph
ii. each antibody can bind 2 antigens so they begin to clump together creating antibody
antigen complexes
1. Agglutination – the clumping of particles
2. Agglutination triggers three reactions:
a. Macrophages or neutrophils may come and engulf complexes
b. Natural killer cell lymphocytes destroy invader
c. Complement system is triggered and can lead to pathogen destruction
d. T Cells
i. T cells have T-cells receptors (TCR); Each virgin T cell that leaves the thymus has a
unique T-cell receptor, but T-cells can’t bind to pathogen without help
ii. For a Virgin T cell to bind to an antigen:
1. Antigen must be presented by an antigen presenting cell (APC), such as a
macrophage, a B cell, or infected body cell
a. APC phagocytizes a phatogen, then breaks it down to lysosome
b. Pieces of pathogen (antigen) are displayed on an MHC (major
histocompatibility complex) protein on cell’s surface
iii. Two types of T-cells
1. Cytotoxic T-cells (killer T cells)
a. Destroy antigen bearing cells
b. Contain perforins
2. Helper T-cells
a. Regulate immunity by secreting toxins
iv. MHC proteins
1. MHC I
a. Found on all nucleated human body cells
b. Cells with these proteins can be killed by cytotoxic T-cells
2. MHC II
a. On B cells, phagocytes (like macrophages)
b. Stimulate immune response
c. Cells with these proteins aren’t killed by cytotoxic T-cells
3. Each MHC protein has two chains (Their tips are variable)
a. Bind to antigens and present them on surface of cell
b. Then bind to T-cell receptors on a T-cell; called “self-makers”
c. T cells bind to antigen and MHC protein simultaneous
4. T-Cell or Cell-Mediated Response
a. Steps
i. Virgin T cell sees APC presenting specific antigen that binds to its T cell receptor (Tcell is
activated and will clone itself)
ii. Two types of T cells produced: (based on type of cell and MHC)
1. If APC is an immune cell with MHC II, helper T cells are produced
2. IF APC is an infected body cell with MHC I, cytotoxic T-cells will be produced
b. Cytotoxic T-cells
i. Have storage vacuoles containing perforins
1. After cyto-t cells bind to an infected cell, they release perforin molecules which
form pores in infected cell
2. The cytotoxic T-cells then deliver granzymes into pore cause the cell to undergo
apoptis
c. Helper T cells
i. Can bind to cells with MHC II proteins (macrophages or B cells) that engulfed and
processed antigens of invading pathogen
1. Helper T-cells divide into clones of helper T cells and memory T cells
2. Activated helper cells secrete cytokines, one cytokine, interleukin-2 stimulates
other cells
a. Stimulates division of B cells into plasma cells
b. Helps cyto-T cells become active killers
c. Stimulates phagocytosis of pathogens
d. Causes helper T cells to grow and divide
5. HIV infection
a. Primary hose for HIV (human immunodeficiency virus) is helper T cell (and some macrophages)
b. After a HIV enters a host, it reproduces inside then the offspring buds from cell
i. Host cell reproduces inside then the offspring buds from cell
1. Host cell reproduces, viruses go to destroy more helper T’s
2. Helper T cell count drops, comes down with opportunist infections – AIDS
(acquired immunodeficiency syndrome)
6. Induced Immunity
a. Immunity happens naturally through infection or by medical means (Active or Passive)
b. Active Immunity
i. Active immunity develops after a person is infected with pathogen
ii. Immunization – done so future infection won’t take place; involves vaccines
(substances containing an antigen to which the immune system responds)
iii. Primary immune Response
1. Occurs when body is first exposed to an antigen; takes several days to recognize
antigen (artificially or naturally)
a. 2 weeks to reach peak response
b. The antibody concentration (titer) then gradually declines
iv. Secondary Immune Response
1. Secondary exposure to same antigen causes faster and stronger response
a. Antibody titer rises higher during primary response and antibodies work
more effectively (high response lasts longer period of and antibody titer
doesn’t return to zero
b. Due to presence of memory cells, that can last a lifetime
c. Passive Immunity
i. Occurs when one is given prepared antibodies (immunoglobins) to combat disease
ii. Short-lived since antibodies were not produced by own body
1. Newborns are passively immune because of mother’s placenta antibodies
2. Breast feeding also passes antibodies (IgA antibodies)
d. Monoclonal antibodies
i. Every plasma cell from same B cell secretes specific antiboes
ii. These monoclonal antibodies can be produced in vitro (in lab)
1. B cells removed from animal & exposed to antigen; resulting plasma cells fuse
with malignant myeloma cells
a. Fused cells are called hybridomas
2. Hybridomas divide and produce antibody (used in urine test for pregnant
women and in delivering radioisotopes or drugs to cancer areas
7. Immunity Side Effects
a. Allergies
i. Hypersensitivities to substances that ordinarily don’t harm
1. Immediate response
a. Antigens attach to IgE antibodies on mast cells then release histamine
(symptoms of hay fever)
b. Constriction of bronchioles is response in asthma
2. Anaphylactic shock
a. Occurs when allergen is injected into bloodstream
b. Causes sudden blood pressure loss
c. Bee stings and penicillin shots are frequent cause
ii. Blood type reactions
1. ABO blood typing
a. 2 self-antigens – A & B are on A, B, and AB blood types
b. People make antibodies against blood they don’t have
c. If same antigen and antibody are in blood, agglutination occurs and can
block small vessels and lead to organ damage
2. Rh Blood Typing
a. Rh+ people have Rh factor (85% of people)
b. Rh- don’t have factor and produce antibodies to the factor
c. Hemolytic disease of the newborn
i. Rh- woman is pregnant with Rh+ child; cells from child leak into
mother’s blood and she could produce antibodies against the
child
iii. Tissue rejection
1. Antibodies/cytotoxic T cells destroy foreign tissues in the body
2. Immune system knows self from nonself
iv. Autoimmune diseases
1. Cytotoxic t cells and antibodies mistakenly attack body’s own cells
2. Mult. Sclerosis, rheumatoid arthritis, lupus
a. Lupus – red spots, attack heart and lungs; doctors give you
immunosuppressants