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YOU MUST KNOW:*Elements of INNATE immune response.*Differences between B & T cells (how activated & actions of each)*How antigens are recognized by immune system cells.*Differences in humoral and cell-mediated immunity.*Why Helper T cells are central to immune response.
What is its function? • PROTECTION FROM INVADERS! • Three Lines of Defense: • Innate Immunity- born with it! • 1. Barrier Defenses – NONSPECIFIC • 2. Internal Cellular Defenses - NONSPECIFIC • 3. Acquired Immunity –develops only after exposure to a SPECIFIC pathogen!
Barrier Defenses / 1st line of defense • The Skin and Mucous Membranes • Physical barriers; trap microbes • Secrete substances (oil, sweat, etc.) that makes the skin too acidic (pH= 3-5) for microbes to live there • Also secrete lysozyme, an enzyme that can destroy bacterial cell walls (in saliva, mucous secretions, & tears.) • INNATE=you’re born with it!
Internal Cellular Defenses • If an invader gets inside the body, the internal defenses (2nd line of defense!) take over • Phagocytes (“to eat”/”cell”) • White blood cells that “eat”/engulf invaders • NEUTROPHILS • most numerous phagocyte (60-70%) • Attracted to infected tissue • Tend to destroy self with pathogen • Short-lived • MONOCYTES • Become macrophages • Long-lived
Internal Cellular Defenses • MACROPHAGES • Can patrol lymphatic system/ spleen, lymph nodes for pathogens • Only about 5% of phagocytes • Does not self-destruct after destroying pathogen • EOSINOPHILS • Phagocytize parasitic invaders • They do not engulf parasites, but instead release destructive enzymes • DENDRITIC CELLS • Still act as phagocytic cell, but also • Activates acquired immune system • Invaders (bacteria/virus/etc) are then digested by lysosomes.
Internal Cellular Defenses • Antimicrobial Proteins • Complement System- 30 serum proteins w/ variety of functions. Many lyse invaders. • Interferon= “Warning Protein” sent out by virus infected cells. • Other body cells then make other substances to inhibit viral replication.
Internal Cellular Defenses • Inflammatory Response • Damage to tissue (from physical injury or the entry of pathogens) leads to inflammation • Histamine (signal molecule) is released by basophyls & mast cells (leukocytes). • This causes increased vasodilation & increased permeability of capillaries. • Increases blood flow to site of injury • Carries clotting factors, platelets, phagocytes, etc. • Diffuse into interstitial fluid to help REPAIR • Causes redness, edema (swelling caused by fluid), & increased temperature occur. • The purpose is to limit infection and repair damaged tissue
Internal Cellular Defenses • Example of how to activate the inflammatory response
Internal Cellular Defenses • Natural Killer (NK) Cells- Patrol the body and attack virus-infected cells and cancer cells • Surface receptors (“nametags”) identify these infected/damaged cells • NK cells release chemicals that cause cells to kill themselves, apoptosis (programmed cell death) • Indiscriminate . . . can damage surrounding healthy cells • All 4 of these internal defenses (phagocytes, interferons, inflammatory response, and natural killer cells) occur INNATELY.
Acquired Immunity • Acquired immunity is the third line of defense. • Acquired immunity only comes after EXPOSURE to a specific pathogen. • Receptor proteins in cell membrane provide pathogen-specific recognition. • Acquired immunity occurs more slowly than innate immunity.
Acquired Immunity • Acquired immunity is performed by lymphocytes • Made from stem cells in the bone marrow • B-cells: • mature in the bone marrow • T-cells: • mature in the thymus
Acquired Immunity • Antigen = foreign molecule that is recognized by lymphocytes and causes them to respond • Other phagocytic cells release cytokines (chemical proteins) that activate acquired immunity • An antigen is usually a surface marker (“nametag”) that is “presented” by another phagocyte • Lymphocytes • Have antigen receptors (100,000 on each cell!) that recognize a SPECIFIC portion of the antigen (epitope) by shape • VERY SPECIFIC!!!
Acquired Immunity • B-lymphocytes are responsible for the humoral immune response • They are responsible for pathogens OUTSIDE of cells (in body fluids, etc.) • B-lymphocyte is “activated” when specific antigen binds to its receptors. • Activated B-lymphocytes reproduce using clonal selection in order to destroy the invader (the clones are able to specifically bind to antigens)
Acquired Immunity • These B-lymphocytes produce two types of cloned cells: • Effector cells (Plasma Cells) • Make antibodies! • Special proteins that bind onto the ANTIGENS of the “invaders,” which flags them for destruction (usually by macrophages) • Memory cells • These cells live a long time, and can respond quickly if this same antigen is seen again
Types of Antibodies • IgM • First of the antibodies produced • Responsible for agglutination of antigens • Activates complement • IgG • Most abundant antibody • This is the only antibody that can cross placenta to fetus (discuss later) • Agglutinates and neutralizes antigens • IgA • Found in tears, saliva, mucus, and breast milk • Gives localized defense of mucous membranes by antigen agglutination • Gives passive immunity to nursing infants through breast milk
Types of Antibodies • IgE • Triggered release form mast cells and basophils • Responsible for agglutination of parasites • Also responsible for allergic reactions • IgD • Present on surface of non-differentiated B cells • Acts as an antigen receptor and stimulates the differentiation of and proliferation of B cells (clonal selection)
Primary vs. Secondary Response • Primary Immune Response • When an individual is first exposed to an antigen, it takes time to activate the immune system • Must do a series of recombinant changes in protein synthesis to create the correct antibody that binds to a specific epitope • Secondary Immune Response • After an initial exposure, the memory cells that remain are able to recognize the SAME antigen • Subsequent exposures allow the immune system to RAPIDLY respond to the antigen and create the necessary immune cells • Individual doesn’t fell symptoms and is considered immune
Acquired Immunity • T-lymphocytes are responsible for the cell-mediated immune response • Guard against invaders hiding out inside infected cells • Cytotoxic T cells • They are the effectors (“hit men”) of the cell-mediated immune response by lysing infected cells or “punching holes” in the membrane • They kill infected body cells (present foreign antigens on major histocompatabilitycomplex (MHC) or other cells that don’t belong (like tumors) at the cell membrane • Class I MHCs = on almost all body cells except RBCs. • Class II MHCs= made by dendritic cells, macrophages, & B cells. • Some of these cells will become memory cells, so they can be reactivated if the pathogen “strikes again.”
Acquired Immunity • Helper T Cells • When activated by binding to MHC protein of an antigen presenting cell, Helper T-cells secrete cytokines (like interleukin) which stimulate & activate B cells & Cytotoxic-T cells. • “Master Switch of acquired immunity” • HIV destroys Helper T cells, and shuts down both humoral & cell-mediated immunity!
The Immune System • Key Features of the Immune System • Specificity • Recognizes SPECIFIC invaders – species of bacteria, for example • Due to ANTIGENS displayed on the MHC (Major Histocompatibility Complex) • Diversity • The immune system can respond to millions of different invaders because it has so many different lymphocytes “on reserve”
The Immune System • Key Features of the Immune System • Memory • The immune system can “remember” antigens it’s seen before and react more quickly the second, third, etc. time it sees them • Acquired immunity • Because of memory cells (B & T cells)! • Self/Nonself Recognition • The immune system can distinguish between the body’s own molecules from foreign molecules • Autoimmune disorders (example: lupus, MS, rheumatoid arthritis) means that this part of the immune system is not working – the immune system destroys the body’s own tissues
Passive vs. Active Immunity • Passive Immunity • Transferring antibodies from one person to another, without the B-lymphocytes having to make them! • The person will already have the memory cells and antibodies, so the next response will be quicker! • Example: • Pregnant mother passes antibodies to her fetus through the placenta • Antibodies in breast milk • Immunoglobulins (antibodies) may be given to a person who is exposed to a disease to prevent them from getting the disease.
Passive vs. Active Immunity • Active Immunity • Immunity to a specific pathogen that comes after having come in contact with the pathogen. • Can come naturally • Been sick with the pathogen before • Example: had measles before, 2nd time won’t take as long to respond • Can come artificially • Immunization (weakened or dead form of the pathogen is used to induce immune response.) • Edward Jenner - smallpox • Stimulates B-lymphocytes to make antibodies AND memory cells
Blood Groups and Transfusions • When we discussed Genetics, we discussed blood groups (A,B,O) • The A and B represent different protein markers on the surface of blood cells • If you have an A protein on your blood cell, you have Type A blood • If you have a B protein on your blood cell, you have Type B blood • If you have an A protein and a B protein on your blood cell, you have Type AB blood • If you have neither an A protein or a B protein on your blood cell, you have Type O blood • There is also a factor called the Rh factor • If you have the Rh factor, you are considered “+” • If you don’t have the Rh factor, you are considered “-”
Blood Groups and Transfusions • Your bodies’ immune system is able to “recognize” your blood type • If you get a transfusion that has a surface protein your blood cells are lacking, your immune system will mount a reaction • Example: You have type A blood. If you get a transfusion of type B or type AB, your immune system will attack the blood as a foreign antigen • This is why type O blood is the universal donor, it doesn’t have any surface proteins to activate the immune system
Rh Factor and a Fetus • The Rh Factor can cause some problems for pregnant mother • Take the following scenario: • Rh Factor is dominant to no Rh Factor • Mother is homozygous recessive for Rh factor • Father is homozygous dominant for Rh Factor • Do a Punnett square to determine the Rh Factor phenotype for the infant
ErythroblastosisFetalis • Blood does transfer from mother to fetus (through placenta) • During child birth, the mother is exposed to blood of child • After 1st child, mother has been exposed to Rh factor • For all other fetuses that are Rh+ (does have the Rh factor), the mother, who is Rh- (does not have the Rh factor), has produced antibodies against the Rh factor • REMINDER: IgG antibodies can pass through the placenta • End result, the antibodies produced by the mother will attack the blood of infant • This is called Erythroblastosis Fetalis • NOWADAYS: There are ways to prevent death of fetus through transfusions • Also, the mother can be given a shot of anti-Rh antibodies to destroy any baby blood cells that the mother becomes exposed to . . . prevents the mother form developing memory cells
Organ and Tissue Transplants • MHC markers on cells are unique to everyone (except identical twins) • Therefore when looking for donors, they must have a majority of these markers that “match” • Otherwise, body will recognize the transplant/graft as a foreign antigen and the organ/tissue will be destroyed • Many individuals that have transplants must take immunosuppressive drugs to prevent a “graft vs. host reaction” . . . rejection of the transplant/graft
Allergies • Allergies are hypersensitivies of the immune system to an environmental molecule because of its ANTIGENS • Allergic reactions are caused by the release of IgE antibodies . . . an over-reaction to nonharmful stimuli • Anaphylactic shock • Life-threatening allergic reactions to ingested or injected allergens • Peanuts, shellfish, bee stings, etc.
Autoimmune Diseases • Sometimes a body loses the ability to recognize “self” cells • As a result, the immune system attacks these self cells • Rheumatoid arthritis: immune system attacks cartilage and bone of joints • Insulin-dependent diabetes mellitus: Cytotoxic T cells attack the insulin-producing beta cells in the pancreas
HIV/AIDS • We have already discussed the action of HIV (human immunodeficiency virus) and how it affects cells (retroviruses) • What makes HIV so dangerous is that is targets and eventually destroys the T helper cells • Since the T helper cells are key to activating both cell-mediated and humoral immune responses (through the release of cytokines), the acquired immune system is effectively shut down • HIV does not kill the individual, it is subsequent diseases • Since the host doesn’t have an immune system, they cannot fight off the infection • The condition of a compromised immune system is given the name of the disease, AIDS (acquired immunodeficiency syndrome)
