Blood & Immunity

Biology 11

A. Allen

C.P. Allen High School

• There are about 5.5 million red blood cells per cubic millimetre of blood in a healthy adult male. (4.5 million in a female).

• insufficient iron in your diet may cause anemia; decreased ability of your blood to transport oxygen.

• The average body (70 kg) contains about 5 L of Blood.

• Your body mass is about 8% blood.• All iron in your body amounts to the same mass as

a 2.5 cm iron nail.

Blood…Interesting Facts

• A human needs 24 hours to recover plasma levels following a blood donation, but it takes three to four weeks to replenish red blood cells.

• Red Blood Cells carry oxygen in the blood. They last for about 4 months before they are replaced.

• A red blood cell will travel through about 1100 km of blood vessels in its lifetime.

• The replacement rate of red blood cells is about 5 million cells per minute!

Blood…Interesting Facts

• Years ago, before the days of modern medicine, it was believed that cutting a person so they bled would help them get rid of sickness. This was called bloodletting.

• The first U.S. president, George Washington, died from a throat infection in 1799 after being drained of nine pints of blood within 24 hours.

Blood…Interesting Facts

http://webpub.allegheny.edu/employee/l/lcoates/CoatesPage/FS101/FS101_Images/BloodLetting.jpg

• Oxygenated blood is bright red. Deoxygenated blood is a darker red. It looks blue in your veins due to a yellow pigment in your skin.

Blood…Interesting Facts

Components of Blood• Blood cells come from stem cells in bone

marrow.

functions of blood;

• transport of life sustaining nutrients, O2 hormones

• transport of wastes such as CO2 and urea.

• protection from disease.

• Clotting.

• maintaining constant body temperature.

• helps with regulation of fluid levels in body.

Blood

Blood Types: Antibodies and Antigens

Why is it important for Doctors to know your blood type when you

receive blood?

Antibodies and Antigens

• antibody: immune substances in the blood and body fluids. They protect

you against foreign bodies.

• antigen: substances, usually proteins, that stimulate the formation of antibodies in the fluids. (can be a foreign body)

Antibodies and Antigens

Clumping (agglutination) is a problem…

Antibodies and Antigens

Blood Type

Antigen Antibodies Who can this blood type receive from safely?

Who can this blood type safely give to?

A A anti-B A, O A, AB

B B anti-A B, O B, AB

AB AB None A, B, AB, O AB

O none anti-A and anti-B

O A,B,AB,O (everyone)

1

14

3 45

11

7

9

6

10

8

12

2

13 15 16

How Common is Your Blood type?

Alleles 0.2   A 0.1   B 0.7   O

0.2   A AA    4% AB    2% AO    14%

0.1   B AB    2% BB    1% BO    7%

0.7   O AO    14% BO    7% OO    49%

Blood Processing

• Donated blood is usually processed after it is collected, to make it suitable for specific uses. Examples include:

• Leukoreduction is the removal of white blood cells from the blood product by filtration. Leukoreduced blood is less likely to cause alloimmunization (development of antibodies against specific blood types).

Rh Factor

• Rh factor is antigen present on RBC of 85% of pop. of US.

• Rh positive and Rh negative• Rh neg pregnant woman may

develop antibodies to the Rh protein of her Rh-positive fetus.

• hemolytic disease of the newborn• prevented with RhoGAM (anti-RhD

immune serum)

Erythroblastosis Fetalis• Toward the end of pregnancy (usually during delivery), fetal blood may leak

through the placenta and mix with the mother’s blood.• If the mother is Rh- and the baby is Rh+, the mother usually produces antibodies

against the baby’s Rh+ antigens.• These antibodies do not usually cause a problem during the first pregnancy because

the baby is usually born by the time the mother produces sufficient antibodies.• In subsequent pregnancies, antibodies may be produced quickly and in large

numbers. These antibodies cross the placenta and cause clumping (agglutination) of the fetus’ red blood cells (erythrocytes). This condition is called Erythroblastosis Fetalis, commonly refered to as “blue baby” caused by decreased O2-rich blood flow to tissues.Treatment:

• slowly removing the newborn’s blood and replacing it with Rh- blood. This removes the mother’s antibodies and provides RBC’s that will not be attacked by the remaining antibodies.

• Erythroblastosis Fetalis can be prevented if the mother is injected with an preparation that contains antibodies against Rh+ antigens. It will bind to the fetus’ red blood cells that crossed over to the mother. Therefore the mother will not produce Rh+ antibodies.

Erythroblastosis Fetalis

Erythroblastosis Fetalis and ABO Blood Groups

• Incompatible ABO blood types can also cause erythroblastosis fetalis.

• Rh incompatibility disease and ABO incompatibility disease diseases have similar symptoms. Rh disease is much more severe, because anti-Rh antibodies cross over the placenta more readily than anti-A or anti-B antibodies. Therefore, a greater percentage of the baby's blood cells are destroyed by Rh disease.

The IMMUNE System

The IMMUNE SystemLymph: A transparent, slightly yellow fluid that carries lymphocytes, macrophages and microorganisms. Lymph is derived from tissue fluids collected from all parts of the body and is returned to the blood via lymphatic vessels.

Lymph vessels: A network of vessels that circulate lymph and branch into all the tissues of the body. Because of high pressure near the arteriole end of capillaries, fluid seeps through these tiny blood vessels and into the tissues. This is tissue fluid. Some of this tissue fluid enters lymph vessels (closed-ended vessels). This fluid is now called lymph fluid.

Spleen: An organ that filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach.

Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone

Lymphatic Vessels

The lymphatic system is a complex system of fluid drainage and transport, and immune response and disease resistance. Fluid that is forced out of the bloodstream during normal circulation is filtered through lymph nodes to remove bacteria, abnormal cells and other matter. This fluid is then transported back into the bloodstream via the lymph vessels. Lymph only moves in one direction, toward the heart.

Neutrophils deal with defence against bacterial infection and other very small inflammatory processes and are usually first responders to bacterial infection; their activity and death in large numbers forms pus.

Eosinophils primarily deal with parasitic infections and an increase in them may indicate such.

Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing inflammation.

Monocytes are able to develop into the professional phagocytosing macrophage cells after they migrate from the bloodstream into the tissue and undergo differentiation.

Lymphocytes are much more common in the lymphatic system

B cells make antibodies that bind to pathogens to enable their destruction. (B cells not only make antibodies that bind to pathogens, but after an attack, some B cells will retain the ability to produce an antibody to serve as a 'memory' system.) B Cells mature in the bone marrow

Helper T cells co-ordinate the immune response and are important in the defence against intracellular bacteria.

Killer T cells are able to kill virus-infected and tumour cells.

(T cells mature in the Thynus gland)

• located in lymph vessels• small round or oval structures (filters)• depositories for cellular debris• bacteria and debris phagocytized.• Can become swollen: may be caused by increased number of lymphocytes

locally as a response to stimulation with a foreign substance (antigen) such as during an infection.

Lymph Nodes

Animation-lymph nodes

The Immune System

• Your immune system has non-specific and specific components…– Non-specific immune responses: does not

distinguish one microbe from another.– Specific immune responses: DOES distinguish

one microbe from another.

Non-Specific Immune ResponsesThe First Line of Defense• The body's first line of defense against pathogens uses

mostly physical and chemical barriers such as…• Skin secretes acids kills bacteria• Tears, saliva, mucous secretions contain lysozyme

(enzyme)destroys cell walls of bacteria.• Mucus - can trap pathogens, which are then sneezed,

coughed, washed away, or destroyed by chemicals.• Cilia are tiny hair-like structures that line the

respiratory tract. They move bacteria & viruses caught in mucus up towards the throat.

• Sweat – has chemicals which can kill different pathogens.

• Stomach Acid – destroys pathogens• Earwax-Traps particles and microorganisms• Digestive Acids-HCl kills most pathogens in stomach• Urine-slightly acidic. Flushes urinary tract• Defecation-removes pathogens from digestive tract

Non-Specific Immune ResponsesThe Second Line of Defense• Second-Line Defenses - If a pathogen is able to get past the body's first

line of defense, and an infection starts, the body can rely on it's second line of defense.  This will result in what is called an inflammatory response.

Inflammatory response causes…

• Redness - due to capillary dilation resulting in increased blood flow

• Heat - due to capillary dilation resulting in increased blood flow

• Swelling – due to passage of plasma from the blood stream into the damaged tissue

• Pain – due mainly to tissue destruction and, to a lesser extent, swelling.

Animation:non-specific inflammatory response cellsalive.com/ouch1.htm

Non-Specific Immune ResponsesThe Second Line of Defense

Share with a Partner!

• Summarize Inflammatory response using the following terms/phrases….

• Leak

• Damaged cells

• Complement proteins

• plasma

• histamine

• Blood vessels

• Dilation

• Phagocytes

Specific Immune Response The Third Line of Defense

• Recognizes and targets “specific” pathogens or foreign substances.

• Has a “memory,” the capacity to store information from past exposures to respond more quickly to future invasions of the same pathogen.

• Protects the entire body, the immunity is NOT linked to the site of infection.

• Specific immunity arises when barriers (first line of defense) and inflammation (second line) do not control the infection.

Specific Immune Response The Third Line of Defense

Foreign organisms in the body activates antimicrobial plasma proteins (complement proteins). Marker proteins from invading microbes activate the complement proteins, which, in turn, serve as messengers. The proteins aggregate to initiate an attack on the cell membranes of fungal or bacterial cells. There are three groups of complement proteins that have different functions:

(a) Form a protective coating around the invader coat/seal the invading cell & immobilize it. (b) Puncture the cell membrane. Water enters the cell through the pore created by the protein, causing the cell to swell and burst.(c) A third group of proteins attaches to the invader. The tiny microbes become less soluble and more susceptible to phagocytosis by leukocytes.

• Antigen: (antibody generator) any substance that the body regards as foreign (virus, bacterium, toxin).

• Antibody: a Y-shaped disease fighting protein developed by the body in response to the presence of an antigen.

Antigen-Antibody Reactions

• Antibodies are specific. An antibody produced to attack an influenza virus will not work against a measles virus. The attachment of antibodies to antigens

…Antigen-Antibody Reactions

• Remember: cells have receptor sites designed to match a certain hormone or nutrient.

• Toxins also can get into cells via receptor cites. They may have a shape similar to a hormone or nutrient. The cell ‘thinks’ the toxin is a needed substance and ingests it!

• Antibodies interfere with the attachment of the toxins to the cell membranes by binding with the toxins. Now the toxins cannot interact with the cells.

…Antigen-Antibody Reactions

• Viruses use receptor cites as entry ports to inject its hereditary material. The virus then forces the cell to make more viruses.

…Antigen-Antibody Reactions

• The attachment of antibodies to antigens increases the size of the complex wandering macrophages can find and engulf them more easily.

…Antigen-Antibody Reactions

The human immune system includes tonsils, thymus gland, spleen, lymph vessels and fluid, lymph nodes, and bone marrow. Blood contains many different types of cells including white blood cells. Lymphocytes and macrophages are types of white blood cells.

Lymphocytes: recognize antigens and then destroy pathogens. They are produced in the bone marrow. If they mature within the bone marrow, they are called B cells. Some lymphocytes migrate to the thymus gland and then mature. These lymphocytes are called T cells.

Macrophages: reside in lymph nodes, spleen, tonsils. They eat pathogens

Lymph vessels and Lymph fluid: Because of high pressure near the arteriole end of capillaries, fluid seeps through these tiny blood vessels and into the tissues. This is tissue fluid. Some of this tissue fluid enters lymph vessels (closed-ended vessels). This fluid is now called lymph fluid.

Lymph fluid contains lymphocytes, macrophages and microorganisms. Lymph nodes contain macrophages which filter microorganisms in the lymph fluid.Some pathogens are present in the blood and are filtered by the spleen. Others are inhaled and are trapped by your tonsils.

Specific Immune Response The Third Line of Defense

Specific Immune Response The Third Line of Defense

Animation-Immune response

Major Histocompatibility Complex

• Aka. - MHC• These proteins act as "signposts" that

display fragmented pieces of an antigen on the host cell's surface.

• The immune system is able to distinguish between self and non-self

• Almost all body cells carry molecules that identify it as ‘self’

Allergies

• An allergy is the result of an over-reactive immune system.• Substances such as peanut protein, dust, pollen, ragweed etc are mistakenly

recognized by your immune system as something harmful.• Cells ‘believe’ they are endangered and release bradykinin which

stimulates release of histamine. Histamine is produced by mast cells and basophils (circulating WBCs)

• Histamine increased permeability of capillaries redness. proteins and WBCs leave capillary osmotic pressure changed so less water is absorbed into capillaries.

• Anaphylactic reaction is a severe allergic reaction.

Asthma• may be chronic or acute• involves respiratory system. The

airways (the bronchi and bronchioles) become inflamed and constrict, and are lined with large amounts of mucus

• trigged triggered by such things as exposure to an environmental stimulant such as an allergen, environmental tobacco smoke, cold or warm air, perfume, pet dander, moist air, exercise or exertion, or emotional stress.

• In children, the most common triggers are viral illnesses such as those that cause the common cold.

• Narrowing of airways causes such as wheezing, shortness of breath, chest tightness, and coughing. The airway constriction responds to bronchodilators

Autoimmunity

• Autoimmunity is when the body’s immune system mistakenly attacks cells of the body. Antibodies are made to attach to the cells’ membranes.

• It is believed that most people have renegade T cells and B cells that attack the body. In most of us, these misguided T cells and B cells are stopped by supressor T cells.

Examples of Autoimmunity

• Rheumatoid arthritis• The arthritis of rheumatoid

arthritis is due to which is inflammation of the synovial membrane that covers the joint. Joints become red, swollen, tender and warm, and stiffness prevents their use

Examples of Autoimmunity

• Type I Diabetes

• Insulin-producing cells of the pancreas are destroyed

• High blood sugar

Examples of Autoimmunity

• Multiple Sclerosis (MS)• Myelin sheath around nerve axon

deteriorates.• Symptoms: changes in sensation,

muscle weakness, abnormal muscle spasms, or difficulty in moving; difficulties with coordination and balance; problems in speech or swallowing, visual problems, paralysis in advanced stages.

Specific Immune ResponsesDefinitions:Antigen: A substance that is foreign to the body which causes the immune system to produce antibodies to fight it.Antibody: Produced by plasma cells. They bind to the specific antigen that has stimulated the immune system.

Once bound, the antigen can be destroyed by other cells of the immune system.

Close your binder. Explain to a partner the difference between an antigen and an antibody.

B Cells and T Cells

B Cells• Lymphocytes that mature in Bone marrow• Involved in antibody formation• Protect against bacteria/viruses/chemicals in blood or tissue fluid.• Has antibodies embedded in membrane. Antibodies are Y-shaped proteins. Each B cell has antibodies of a

slightly different shape.• B cells ‘recognize’ antigens on a pathogen when the shape of its antibodies matches the shape of an antigen on a

pathogen.• Each ‘branch’ of the Y has the same shaped bonding site. It can therefore bond to two like antigen molecules.

………..cont.

Specific Immune ResponsesHow B Cells Work…

• When a pathogen i.e. bacteria (with antigens) enters your body, it may get past your first line of defense and into your lymph fluid.

• B cells are in lymph nodes. They have antibodies that link to antigens.

• B cell enlarges and divides many times to form plasma cells and memory cells (more on memory cells later).

• The plasma cells produce thousands of antibodies per second! These antibodies are the same as those on the original B cell that recognized the antigen.

• The antibodies are released into the bloodstream and lymphatic system and move to the site of invasion.

• The free antibodies then bind to the matching antigens. One antibody (has two bonding sites) can bond to antigens on two different bacteria.

• The bacteria clump. Macrophages then engulf the bacteria via phagocytosis and digest them (lysosomes).

• This battles happens in lymph nodes. Have you ever noticed your glands being swollen and sore when you are sick?

T Cells• There are tens of millions of different T Cells, each designed to identify different antigens. There

are 4 types of T Cells. Three of these types are…

• Helper T Cells: initiate the immune response

• Suppressor T Cells: terminate the immune response.

• Cytotoxic T Cells: lyse (break open) infected cells.

Types of LeukocytesType Image

Diagram

Approx. % in humans

Description

Neutrophil

65%Neutrophils deal with defense against bacterial infection and other very small inflammatory processes and are usually first responders to bacterial infection; their activity and death in large numbers forms pus.

Eosinophil

4% Eosinophils primarily deal with parasitic infections and an increase in them may indicate such.

Basophil <1%Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing inflammation.

Lymphocyte

25%

Lymphocytes are much more common in the lymphatic system. The blood has three types of lymphocytes: B cells: B cells make antibodies that bind to pathogens to enable their destruction. (B cells not only make antibodies that bind to pathogens, but after an attack, some B cells will retain the ability to produce an antibody to serve as a 'memory' system.) T cells:

oCD4+ (helper) T cells co-ordinate the immune response and are important in the defence against intracellular bacteria. oCD8+ cytotoxic T cells are able to kill virus-infected and tumor cells. oγδ T cells possess an alternative T cell receptor as opposed to CD4+ and CD8+ αβ T cells and share characteristics of helper T cells, cytotoxic T cells and natural killer cells.

Natural killer cells: Natural killer cells are able to kill cells of the body which are displaying a signal to kill them, as they have been infected by a virus or have become cancerous.

Monocyte 6%

Monocytes share the "vacuum cleaner" (phagocytosis) function of neutrophils, but are much longer lived as they have an additional role: they present pieces of pathogens to T cells so that the pathogens may be recognized again and killed, or so that an antibody response may be mounted.

Macrophage

(see above)Monocytes are able to develop into the professional phagocytosing macrophage cell after they migrate from the bloodstream into the tissue and undergo differentiation.

How Helper T Cells work…

• Growth and division of B Cells depends on binding with helper T Cells….

T Cell induces the

B cell to undergo

mitosis.

Role of Cytotoxic T Cells

Autoimmune Disease

• Sometimes, a person’s own immune system can attack their own body cells. Certain T Cells attack healthy body cells. This is bad.

• This may cause a variety of autoimmune diseases.

• Scientists are not positive why this happens.

Some such diseases can be treated…

• Scientists can produce an antibody that matches these offending T Cells.

• The antibody is then linked to a toxic chemical.

• These antibodies (with toxin) are injected into the body.

The antibody that was made to match the T Cell bonds

with these T cells. The attached toxin kills the T Cell.

Immunity and the Prevention of Diseases

….The IMMUNE System: Immunity and the Prevention of DiseasesActive Immunity

• The first response to a particular antigen can take a few days for your immune system to produce plasma cells or cytotoxic T Cells. Eventually, your immune system rids your body of the pathogens and you feel better.

• After the first exposure to a particular antigen, memory cells are produced which may stay in your body for months, years or for the rest of your life. (you need a tetanus shot every 10 years).

• Memory cells allow your body to react very quickly if you’re exposed to the pathogen in the future. The pathogen is destroyed before you feel sick! You are “immune”. (active immunity) Ex chicken pox, measles.

….The IMMUNE System: Immunity and the Prevention of Diseases

Vaccines

• The principle of active immunity is used in the administering of vaccines.

• A vaccine is a solution prepared from weakened or dead microorganisms, viruses or toxins.

• Injection of the vaccine tricks the body into forming antibodies, or cytotoxic T Cells.

• The vaccine may make a person feel a bit ill.

• If a person later is exposed to the real pathogen, a quick response is made by your immune system to destroy it.

• We have vaccines for polio, measles, mumps tetanus, etc.

• We have no vaccine for the common cold. There are many different kinds of cold viruses and the viruses that cause the common cold keep mutating, changing their antigens.

….The IMMUNE System: Immunity and the Prevention of Diseases

Passive Immunity• Immunity resulting from the transfer of antibodies

or antiserum (a serum that contains antibodies) produced by another individual.

• It works quickly.

Examples:• Human infants have passive immunity at birth.

Some antibodies crossed from mother to baby through the placenta.

• Breastfeeding is good for babies because the mothers antibodies are passed to the infant along with the breast milk.

• Influenza is highly contagious and is more common during the colder months of the year. Contrary to traditional belief, however, the climate itself is not directly to blame for the increase in incidence, but rather is attributable to the greater amount of time spent indoors in close proximity to other individuals during inclement weather. The influenza virus is chiefly transmitted through airborne respiratory secretions released when an infected individual coughs or sneezes. Incubation typically is from one to two days from the time of infection, and most people begin to naturally recover from symptoms within a week. The vast majority of influenza-related deaths are caused by complications of the flu rather than the actual influenza virus.

Immunity DefinitionsTerm Definition

Leukocyte

Lymphocyte Specialized white blood cells that produce antibodies

antibodyA protein that is formed within the blood that inactivates or destroys antigens

antigen Substances, usually proteins, that stimulate formation of antibodies

NeutrophilNeutrophils deal with defense against bacterial infection and other very small inflammatory processes

and are usually first responders to bacterial infection; their activity and death in large numbers forms pus.

Eosinophil Eosinophils primarily deal with parasitic infections and an increase in them may indicate such.

BasophilBasophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine

causing inflammation.

Lymphocyte

Lymphocytes are much more common in the lymphatic system. The blood has three types of lymphocytes:

B cells: B cells make antibodies that bind to pathogens to enable their destruction. (B cells not only make antibodies that bind to pathogens, but after an attack, some B cells will retain the ability to produce an antibody to serve as a 'memory' system.)

T cells: o CD4+ (helper) T cells co-ordinate the immune response and are important in the defence

against intracellular bacteria. o CD8+ cytotoxic T cells are able to kill virus-infected and tumor cells. o γδ T cells possess an alternative T cell receptor as opposed to CD4+ and CD8+ αβ T cells

and share characteristics of helper T cells, cytotoxic T cells and natural killer cells. Natural killer cells: Natural killer cells are able to kill cells of the body which are displaying a

signal to kill them, as they have been infected by a virus or have become cancerous.

MonocyteMonocytes share the "vacuum cleaner" (phagocytosis) function of neutrophils, but are much longer

lived as they have an additional role: they present pieces of pathogens to T cells so that the pathogens may be recognized again and killed, or so that an antibody response may be mounted.

MacrophageMonocytes are able to develop into the professional phagocytosing macrophage cell after they migrate

from the bloodstream into the tissue and undergo differentiation.

• http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/B/B_and_Tcells.html#B_Cells