2Immunity – The War Against Infection Immunity: ability of an organism to resist disease.Antigen: any substance that elicits an immune response.Antibodies: made in response to specific antigens; can inactivate the antigen that triggered the antibody formation.
3The Body Fights Back: 2 Ways Surface Barriers Keep Intruders OutPrevents entry of antigens inside our bodySkin, MucosaTwo immune mechanisms:Cell Mediated Immunity: Cell activates itself to defend against the attackHumoral Immunity: Cell produces antibodies carried in blood to combat the intrusionPicture1: (bottom)ANTIBODY RESPONSE IMAGE: in the antibody (or humoral) arm of the the acquired immune response, the destruction of invaders is done by antibodies (proteins called immunolglobulins), shown as brick red "Y" shaped molecules at right of picture. Invading microorganisms are shown at top as golden ovoids. They are engulfed (phagocytosed) by a macrophage (green cell at top). The macrophage then presents antigens to a (purple) Helper T-Cell which in turn activates a B-Cell causing it to divide and differentiate into Plasma Cells (large bluish cells at lower left). Plasma cells have a great deal of rough endoplasmic reticulum and are devoted to protein synthesis (of antibodies). The antibodies that are released lock onto their corresponding antigens and lead to the inactivation or destruction of the invader. A dendritic cell is shown at upper left.Picture 2: (top)CELL MEDIATED IMAGE: in the cellular immune response, the destruction of infected or altered cells is done by Cytotoxix T-Cells, shown as purple spikey cells arcing at left of picture. The cell targeted for destruction is shown as a large green sphere at the bottom of the picture. This cell crumples and disintegrates and the cytotoxic cell leaves to attack further target cells. Antigen presentation is shown at the top of the picture where a green macrophage presents viral antigens to a helper T-Cell. The Helper T-Cell then releases cytokines that activate the cytotoxic T-Cells. A dendritic cell is shown at upper left.
4The InvadersThe Antigen The Enemy InvaderUsually a bacteria or virus
5Three Defense Systems: The WarriorsThree Defense Systems:Macrophage cellsLymphocyte (white blood cell) T cellsLymphocyte (white blood cell) B cells
6The Warriors The Macrophage Body's Radar Type of cell normally present in the bloodDetects the enemyand engulfs (eats) itThis is cell-mediated immunity.
7The Warriors The T-Helper Cell Communication Link Communication Link Between the body's macrophages and B-cellsA subtype of lymphocyte that activates macrophages and B cells. Does not directly inactivate antigens.They are called T cells because they original in the thymus (but later migrate to all lymph nodes. In children, the thymus is a huge gland in the neck; later is shrinks. In HIV infections, towards the end of infection, T helper cells become inactive, leading to a breakdown of immunity in general, leading to AIDS (acquired immunity deficiency syndrome).This is inactivated in HIV infections!
8Macrophage Presents Antigen to T Cells (white blood cells) VirusVirusVirusWhen a macrophage ingests a viral particle (blue blobs), it presents the antigen (green arrow) of the virus on its outer surface. Then, a T-cell with the correct t-cell receptor (yellow y-shaped structure) can bind to the viral antigen on the surface of the macrophage. This activates the T-cell. The activated T-cell can then assist in the immune response.
9The Warriors The B-Cell (white blood cell) The War Factory Produces antibodies custom tailored for the type of enemy antigen
11Antibodies Need Help Antibodies Antigen Busters Designed to seek and destroy the specific enemy antigenComplement Support TroopsAssists the antibodies to neutralize the enemy antigenComplement is actually a system of about 20 blood-borne proteins that can be recruited during an immune response to help inactivate antigens. The system is not specific for specific antigens, but it “complements” the action of specific antibodies.
12Antibody Protein & Humoral Immunity Since antibodies circulate through the body fluids(humours),the protection afforded by B cells is called humoral immunity.Structure of antibodies (Y-shaped proteins)The variable portion is created to be a specific match to a specific antigen. The rest of the protein is non-active, just serving to “carry” the active portion of the molecule.
13So what does an antibody do? Binds to molecules (antigens) on the surface of invading organism.Inactivates or renders the microorganism susceptible to destruction by the immune system.
14ELISA TEST-One Way to Test for Antibodies Remove blood cells and use the fluid (serum) to test for presence of antibody.Place target sample on a support.Add serum that has antibody against antigen being tested for. Antibody, if present, binds the antigen.Add a second antibody that was separately developed to react with the antibody/antigen complex in step B and binds it to the complex. Second antibody was also prepared with an enzyme attached to it.This new complex is made visible by reacting it with an enzyme that converts it to a colored compound that you can see.ELISA - Enzyme-Linked Immunosorbent Assay; this is an assay that uses an enzyme linked to an antibody. In this experiment, a colorless substrate is turned into a colored product by the bound enzyme. The amount of activity of this enzyme (as determined by detection of the amount of colored product) is used as a measurement of the amount of bound antibody. ELISA tests make it possible to see and quantify the presence of antiboides in body fluids.Courtesy The Howard Hughes Medical Institute: The Virtual Immunology Laboratory. Students can actually run a computer simulation of the test by going to the following website:http://www.hhmi.org/biointeractive/vlabs/Teachers may also request a CD that is free to teachers and is called The Virtual Lab Series. Other simulations on the disk include a bacterial ID lab, a cardiology lab, a neurophysiology lab, and a transgenic fly lab.
15Cell-mediated immunity It is an immune response that does not involve antibodies, but rather the cells act as the killers themselves.It protects the body by:Activating antigen-specific T-cells that destroy infected cells.Activating macrophages that destroy intracellular pathogens.Activating NK (Natural Killer) cells that release a protein that kills the target cells
16Review 1 What is the enemy called that invades the cell? What keeps intruders out?What are the two kinds of immunity?Pathogen, the portion of the pathogen which causes an immune response is known as an antigenSurface Barriers, like skinCell-mediated and Humoral
17Surface Barriers or Mucosal Immunity SkinCiliaTears, Saliva, Urine.Sticky mucusStomach:Hydrochloric AcidThen why do certain bacteria cause food poisoning? They are resistant to hydrochloric acid. But it does kill many other kinds of organisms. The digestive tract also destroys most proteins, which is why you can’t treat genetic diseases by eating synthetic proteins that are made to compensate for defective proteins caused by the genetic disorder.
18Analogy Suppose the classroom is a body. All students are cells. Rats are Antigens.Doors and Windows prevent them from entering - Surface Barriers.Some of you Tough ones (T-cells) will capture the rodents - Cell-mediated Immunity.Some of you Brainiacs (B-cells) will call pest control (Antibodies) to capture the rodents – Humoral Immunity.
19What do these components look like? White Blood Cells:Other Blood Components:Source: National Library of Medicine
20The Role of Neutrophils When a wound occurs, neutrophils migrate out of blood to rush to the wound and phagocytize (“eat”) the bacteria. This is what pus is made of.BUT, recent research shows that neutrophils can harbor a blood-borne parasite, without killing it. When the neutrophil dies, it releases the parasite and helps it spread into its real target, macrophages (Science. 321 (2008): ). It’s like the Trojan horse story in ancient Greece.“old” neutrophil surrounded by red blood cells
21The Role of Monocytes Eosinophils Turn into Macrophages Attack Internal ParasitesNote the notch in the nucleus. Otherwise, it looks like a lymphocyte.Note the red granules in the cytoplasm.
22Role of LymphocytesThey play a major role in defending the host from both tumors and virally infected cellsThere are two main types of lymphocytes: B cells and T cells.The B cells make antibodies that attack bacteria and toxins while the T cells attack body cells themselves when they have been taken over by viruses or have become cancerous.They are often present at sites of chronic inflammation.
23The Role of Macrophages Engulf and then digest cellular debris and microbes in the body tissues.Note the irregular cell membrane. These are monocytes in the bloodstream and once they migrate into the tissues they become macrophages.Picture from:
24The Role of Platelets Blood Clotting They can clump together to form clots.No role in immunity.In this micro-photo of blood cells, platelets are stained purple. A T-Lymphocyte white cell is stained green, and a Monocyte white cell is stained gold. Red blood cells are red.
25Stop and Review What are the types of white blood cells? What is the function of each of the types of white blood cells?What is the role of platelets?
26Complete Blood Count (CBC) Whether it is a human, dog, cat, steer, bird or even ferret, when sick, their doctors typically draw a blood sample and perform some tests to help determine a diagnosis.The first test generally used is the complete blood count (CBC), which determines the number and types of blood cells present.This test can provide information about the status of the patient’s immune system.Information from:
27Complete Blood Count (CBC) Blood is tested for several things:Red Blood CellsWhite Blood CellsTotal count and percent values for each type of white blood cellPlateletsOther blood componentshemoglobinhematocritMore information about Complete Blood Count:Click Here for a chart of normal blood values in dogs and cats
28LeukocytosisLeukocytosis: white blood cell count increased above the normal range.It is not a disorder or a disease, but a sign of illness.It occurs in response to a wide variety of conditions, includingviral, bacterial, fungal, or parasitic infectioncancerHemorrhage (internal bleeding)exposure to certain medications or chemicals including steroids.Picture from:
29LeukopeniaLeukopenia: a decrease in the number of circulating white blood cells in the blood.As white blood cells get “used up” during infection, leukopenia can place patients at higher risk for infection.Causes:Influenza, typhus, malaria, HIV, tuberculosis, dengue, Rickettsial infections, enlargement of the spleen and folate deficiencies.chemotherapy, radiation therapy, leukemia , myelofibrosis and anemia.many common medications like minocyclen.Picture from:
30Immune Disorders in Humans and Animals: HIV (Human Immunodeficiency Virus) HIV infection in humans causes AIDS (Acquired Immunodeficiency Syndrome).AIDS causes the immune system to fail, leading to life-threatening opportunistic infections.Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk.The four major routes of transmission areunprotected sexual intercourse,contaminated needlesbreast milktransmission from an infected mother to her baby at birth.What’s the difference between HIV and AIDS? One is the name of the virus; the other describes the eventual effect of the disease.
31AIDS (Acquired ImmunoDeficiency Syndrome) Virus infects vital cells such as helper T cells and macrophages.When T cell numbers decline below a critical level, cell-mediated immunity is lost, and infections with a variety of opportunistic microbes appear.Illustration of the AIDS virus penetrating a white blood cell and duplicating.Picture Caption: AIDS VIRUS AIDS - penetration and duplication of the virus in the host cell. Illustration of the AIDS virus penetrating a CD4 white blood cell and duplicating. The close-ups on the left show how the virus harpoons the cell in order to penetrate it.Picture from:
32Feline Immunodeficiency Virus (FIV) Similar to HIV, FIV is a condition in cats that is caused by a virus and causes a reduction in the ability of the immune system of the cat to fight infection and illness.It is sometimes known as Feline AIDS.You can't catch AIDs from a cat and a cat can't catch AIDs from an HIV infected person. This is not a zoonotic disease.For a flier from the American Association of Feline Practitioners please visit:Click here for more information about FIVSee slide note for more resources
33FIV continuedTransmission: Bite wounds from infected cats, especially during cat fights, rarely by milk or during birth.Infected cats may appear normal for years. However, infection eventually leads to a state of immune deficiency. The same agents found in the everyday environment--where they usually do not affect healthy cats--can cause severe illness in cats with weakened immune systems.There is now also a vaccine to help protect cats from FIV, however it does not provide complete protection.Cat with Feline Immunodeficiency Virus
34Feline Leukemia Virus (FeLV) Caused by a virus similar to HIV and FIV.Transmitted in the saliva and nasal secretions of infected cats.Also transmitted by urine, feces and milk.Unsupervised outdoor cats are most at risk.This infection can lead to cancer in cats, blood disorders, and immunodeficiency which causes cat to be unable to protect itself against infections.There is a vaccine available for FeLV.Picture from:Click here for more information on FeLV
35Severe Combined Immunodeficiency Disease in Animals (SCID) A recessive genetic disorder that affects Arabian horses. This condition is fatal, as the animal inevitably succumbs to an opportunistic infection within the first four to six months of life.Carriers, who themselves are not affected by the disease, can be detected with a DNA test. Careful breeding practices can avoid the risk of an affected foal being produced.Dogs are also known to have SCID. There are two known forms, an X-linked SCID in Basset Hounds, and a recessive form seen in one line of Jack Russell Terriers that is similar to SCID in Arabian horses.Arabian Horse picture from:Bassett Hound picture from:http://dogsbreed.net/basset-hound/Jack Russell Terrier picture from:
36Review 3 What is a CBC? What is Leukopenia and what are its causes? What is Leukocytosis and what could it be an indicator of?Name four immune disorders and tell what causes them and what species they affect