Immunology (Chapter 45)

story of the humoral immune response

1) a bacteria is in the body 2)the bacteria is engulfed by a dendritic cell (the same role that macrophages play in the non-specific) 3)the activated dendritic cell migrates to a nearby lymph node, and the proteins of the bacteria are degraded into molecular bits and pieces that function as antigens 3)the antigens made from the bacteria bind to an MHC II protein (a class 2 major histocompatibility complex), and the MHC II and antigen are presented together on outside of dendritic cell, now called an antigen-presenting cell. 4) a T-cell in the lymph node that has a corresponding specific receptor for that type of bacteria will bind to the dendritic cell 5)the dendritic cell releases cytokine that activates the T-cell 6) the activated T-cell releases even more cytokines and begins "clonal expansion", making an army of identical helper T-cells which all display an identical antigen to the one originally engulfed by the dendritic cell. meanwhile......... 7) a bacteria bumps into one of the standing population of b-cells that are always present in the body, and antigens on the bacterias surface are a match for its specific receptor sites (one of its membrane bound antibodies), so it binds to the b-cell. the antigen is engulfed and then presented on the surface of the B cell with an MHC II protein 8)now there are a few b-cell and many helper t-cells presenting the same antigen on their surface. when two of these come together (usually in a lymph node or the spleen), the b and t cells link together, the t helper cell releases more cytokines, activating the b-cell to proliferate. 9) the activated b cell begins rapidly cloning itself, reproducing the specific activated receptor protein (made exactly for the antibody that is present) along with it 10)some of the reproduced b-cells become memory ( Long lasting B cells in higher quantities than before antigen activation. this is so that you have more b-cells made for things that you have been exposed to in the past than for things you've never been exposed to) 11)most of the reproduced b cells become Plasma cells (Effector B cells). they are basically Antibody factories, they rapidly Secrete lots of specific Antibodies of the type that was activated. 12) The antibodies spread through the blood and do their two jobs: neutralization and agglutination. -bind and tag virus or bacteria for pick up/disposal by phagocytes -neutralize antigen (reduces function of pathogen)

Inflammation

-a process that creates internal conditions that inhibit or kill many pathogens -it is the body's response when tissue is damaged - It isolates damaged area to stop the spread of damage, recruits cells and molecules to the damaged area to kill invaders, and promotes healing -feels like heat, pain, swelling, redness ear the injury

how a vaccine works

-understand the guinea pig diphtheria example from the slides Guinea pig one is not exposed to any amount of toxin. A serum drawn from pig 1 is given to pig 2. pig 2 is then given a lethal dose of toxin strain A, and it dies. :( guinea pig 3 is given a non-lethal dose of toxin strain A. a serum drawn from pig 3 is given to pig 4. then pig 4 is given a lethal dose of toxin strain A. It lives! pig 5 is given a non-lethal dose of toxin strain B. a serum drawn from pig 5 is given to pig 6. then pig 6 is given a lethal dose of toxin strain A. It dies. :( Moral of the story: previous exposure to a small amount of diphtheria allowed the guinea pigs to survive a later, larger exposure, BUT only if the earlier exposure was to the exact same strain of disease.

lymph nodes

Lymph nodes are small, round structures at many sites along the lymph vessels. Lymph nodes contain lymphocytes, a type of white blood cell. As lymph passes through the nodes, lymphocytes initiate an immune response if foreign cells or molecules are detected

lymph

Lymph: Fluid derived from blood and other tissue that accumulates in intercellular space throughout the body Lymph vessels join and eventually form the thoracic duct, which joins the circulatory system at a major vein near the heart. The lymphatic system drains fluid from tissues. You funnel fluids from tissues into lymph nodes, which have lots and lots of lymphocytes (b cells, t cells, and natural killer cells). Anything at all that gets in to the body through skin or wounds (any antigen), etc, gets shunted through the lymphatic system where white blood cells are present to bind to harmful things and start immune response to it

blood and lymph tissue are crucial to our defense

Lymphoid tissues: Thymus, bone marrow, spleen, lymph nodes -Blood plasma: Carry red blood cells (circulatory function) -white blood cells (found in lymph) -platelets (clotting functions, found in lymph)

Phagocytes

They can recognize, adhere and ingest (phagocytosis) viruses, pathogenic cells, or fragments of invaders. a macrophage is a type of phagocyte. phagocytes help to activate lymphocytes so they can then carry out specific immune response. When a phagocyte finds a pathogen, it can a) engulf and destroy it b) send out chemical signals to induce inflammation c) send out chemical signals to induce the complement protein system

lymphocytes

Three types: -B cells -T cells -Natural Killer cells (NK-cells) They all come from multi potent hematopoietc cells in the bone marrow, which make lymphoid progenitor cells, which make B-cells, T-cells, and NK-cells. B-cells mature in the bone marrow and are released from there into the blood stream and then go to lymphatic tissue. T-cells are released into the blood stream while immature, go to the thymus and mature there. The T in t cell refers to the thymus. the two types of t cell are helper t cells and cytotoxic t cells.

Defense (Immune System)

Two types of Defense Mechanisms: 1) Nonspecific Defenses: Innate and rapid 2) Specific defenses (adaptive): Targets specific pathogens, is slow to develop and long lasting (antibodies)

antigens and pathogens (the enemy)

An antigen is any substance that causes your immune system to produce antibodies against it (antigen = antibody generator). An antigen may be a foreign substance from the environment, such as chemicals, bacteria, viruses, or pollen. An antigen may also be formed inside the body, as with bacterial toxins or tissue cells. Antigens are not necessarily actually harmful, and might not stimulate the full immune response against it. Pathogens are antigens that DO cause disease in the body. Animals have various means of defense against pathogens—agents that come into organism from outside and cause disease. Defense systems (immune systems) are based on the recognition of self (one's own) and nonself (foreign) molecules. Enemies of humans and other mammals: -bacteria -viruses -fungi -protozoa -large parasites

epitope

Epitope: Specific sites on antigens recognized by antibodies, B cells or T cells. epitopes are the locations on the surface of the antigen that antibodies, b cells, and t cells are made to bind on to. Antigens can have more than one Epitope.

granular cells

Granulocytes are a sub-category of white blood cells characterized by the presence of granules in their cytoplasm. they are white blood cells, but not lymphocytes. Like red blood cells and platelets, they are made by myeloid progenitor cells, which are made by mutlipotent hematopoietic cells, which are in red bone marrow. we need to know only three types: -mast cells (they release histamine when damaged. histamine begins healing process of trauma wounds) -macrophages (a type of phagocyte. they engulf, digest, and present foreign microorganisms; activate T cells) -dendritic cells (present antigens to T cells; travel to the lymph nodes where they are more likely to hit an important immune cell)

Multipotent hematopoietic cells

Hematopoietic stem cells (HSCs) are the blood cells that give rise to all the other blood cells. They are located in the red bone marrow, which is contained in the core of most bones. They give rise to the myeloid cells (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid cells (T-cells, B-cells, NK-cells). How it works: they differentiate into either myeloid progenitor cells or lymphoid progenitor cells. Myeloid progenitor cells differentiate into all the types of myeloid cells needed in the circulatory system (

Humoral Immune Response (B cells)

Humoral immune response uses B cells to make antibodies. B cells are a type of lymphocyte (white blood cell) found in the blood, lymph and tissue fluids. B cells (a type of lymphocytes) are the basis of the humoral immune response. Antibodies are secreted by B cells and react with antigens in blood, lymph, and tissue fluids.

organ transplants and depression of immune system

-if your immune system gets depressed, you are susceptible to 3 things: Infections (bacteria) Viruses Cancer People who get organ transplants must take imunosupresents. So they are extremely susceptible to all of the above. Your immune system can recognize that the organ has different DNA than your own body and should be rejected/killed by your immune system (whose job is to attack outside things that are in the body). So ppl w/ transplants need to take immunosupressants for the rest of their life. So they need to be extremely careful not to get sick. Even a small fever is a big deal to them.

Specific Defenses (aka Adaptive Immune System or Acquired Immune System)

-takes longer to initiate than non-specific (takes several days after exposure to become protective) -has "memory" of what it has defended against in the past (thus the 'acquired' part; this is how vaccines work) The specific immune system has four key traits: 1)Specificity 2)Ability to distinguish self from non self 3)Diversity—response to a wide variety of nonself molecules 4)Memory The specific immune system has two types of responses: 1)Humoral Immune Response (B cells) 2)Cellular Immune Response (T cells) Humoral immune response uses B cells to make Antibodies. Cellular immune response uses cytotoxic T cells. The two responses operate simultaneously and cooperatively (they also cooperate with non-specific immune system). The Specific Immune response has four overall steps. These are very similar for the humoral and cellular responses: 1)antigen encounter and recogition (lymphocytes encounter and recognize an antigen) 2) lymphocyte activation (lymphocytes are activated by binding to the antigen. they then proliferate by cell division to produce many identical clones of the activated cell) 3) antigen clearance (the many clones of the activated lymphocyte clear the antigen from the body) 4)development of immunological memory (some of the activated lymphocyte clones into memory cells that circulate in the blood and lymph, ready to initiate a more rapid specific immune response if that exact antigen should enter the body in the future)

story of an injury (response to tissue damage and introduction of bacteria)

1) something breaks the skin and introduces bacteria to body 2)macrophages already present in the area recognize and engulf some bacteria and secrete cytokines (which tell nearby cells that antigens are present in the area 3)the tissue damage activates mast cells as well, and they secrete histamine, which triggers inflammation (along with the cytokines) 4)histamine and cytokines dilate the local blood vessels to increase their permeability, so more blood can flow to area, and more fluids and blood cells can leak from capillaries into damaged tissue. (at some point, the complement system could be activated by the pathogens or cytokines, and even more cells and molecules would join in the fight) 5)even more defense cells are attracted to area and can move from capillary to damaged tissue to aid in process of phagocytosis of bacteria and tissue repair

antibody

Antibody (immunoglobulin/Ig): Antibodies are highly specific protein molecules that circulate in the blood and lymphatic system recognizing and binding to antigens to clear them from the body. antibodies are large Y-shaped proteins produced by B cells to identify and neutralize foreign objects and invaders. Antibodies recognize specific antigens and are created to bind with that specific antigen. -antibodies are Y-shaped proteins made by your body in plasma cells. Antibodies bind on to antigens at epitopes on the antigens. Antigens can have many different epitopes on them, and and antibody is made to bind to one exact specific one. Antibodies are Y-shaped, with specific antigen binding sites on the two tips of the Y. the structure of the antibody is always the same except for the variable portion at the tip. Antibodies flow through your body in your blood stream. They can: -bind and tag virus or bacteria for pick up/disposal by phagocytes -neutralize antigen (reduces function of pathogen) Each branch can bond to an epitope of a different viruses/bacteria, so one antibody could bond to two different antigens.

antigen

Antigen: Substance that initiates the production of antibodies (typically a foreign particle or cell or virus that enters the body, but could be something from inside host (as in case of cancer). if it is actually a disease agent it is called a pathogen. a pathogen is called an antigen IF it initiates the production of specific antibodies against it.) Each antigen has multiple sites on it where antibodies could bind (aka epitopes) An antigen is typically a large molecule like a protein or some other type of large molecule coming from a pathogen or from a host cell infected with virus or cancer. they can be on the surface of pathogens or secreted by pathogens. not the entire bacteria or virus or whatever, but it can be a toxin or substance secreted by a pathogenic bacteria or virus. Two types of cells recognize antigens: B cells and T cells

immune system malfunctions

Autoimmunity—clones of B and T cells are produced that are directed against self antigens. Possible hypotheses as to why: -Failure of clonal deletion -Molecular mimicry—self has antigens that resemble nonself and are recognized by T cells Hashimoto's thyroiditis—immune cells attack thyroid tissue Insulin-dependent diabetes mellitus (type I)—occurs most often in children Caused by an immune reaction against proteins in the pancreatic cells that make insulin Insulin-producing cells are destroyed and insulin must be taken daily

B Cells

B cells are a type of lymphocyte (white blood cell) found in the blood, lymph and tissue fluids. B cells (a type of lymphocytes) are the basis of the humoral immune response. A "B cell" first expresses a receptor protein on its cell membrane surface. The receptor proteins on surface of the b cell are quite similar to an antibody. they are basically membrane-bound antibodies (bound in the surface membrane of the b-cells). In humans there are over 10,000 distinct receptor proteins (aka membrane bound antibodies), each one made to bind specifically with one epitope. B cells are all made by the same type of cell (a lymphoid progenitor cell), but different genes are expressed in making the tips of the receptor proteins (the distinct, specific part). Each B-cell comes from the same precursor cell, but during development the DNA that codes for the variable portion is shuffled. Each B-cell has multiple different types of receptor proteins for antigens on its surface. there are over 10 billion different possible combinations! Some B cells get made with combinations that might allow it to incorrectly recognize a host cell as an antigen. Clonal deletion: Any immature B and T cells that show the potential to mount an immune response to self antigens undergo apoptosis. Apoptosis means they mark themselves as a potentially dangerous cell and an NK cell comes along and kills them. Even after removal of self-responding combinations, Humans can respond specifically to about 10 million different antigens.

Cellular Immune Response (T cells)

Cellular immune response uses cytotoxic T cells. Cytotoxic T cells expose "hidden" pathogens to antibodies by destroying infected body cells. 1)Body cells are infected by a virus, or become cancerous. so in case of virus, it is fully concealed by the host cell 2) some of the viral pathogens break down inside host cell. the host cell takes these and presents them as antigens on its surface using class 1 MHC I proteins. 3) the infected antigen-presenting cell encounters a T-cell with receptors that correspond to an epitope of the specific antigen being presented, and they bind together. this linkage, plus the presence of cytokines released during the humoral immune response, activates the T-cell. 4) the activated t-cell proliferates into cytotoxic T-cells and memory cytotoxic T-cells that correspond to the particular antigen which started the process 5) cytotoxic T-cells bind to any body cells which are presenting an MHC I protein with the antigen on their surface 6) the infected cell is killed in much the same way that a NK cell would do it. it undergoes apoptosis, breaks apart, and the pathogens (virus) inside are released to the interstitial fluid where they can be neutralized or agglutinated by antibodies made in the humoral immune response.

Cytokines and complement proteins

Cytokines: Soluble signaling proteins released by many cell types. They bind to cell surface receptors and alter the behavior of their target cells. Complement proteins: Small plasma proteins found in the blood that circulate the body as inactive precursors. When triggered they release cytokines to hugely amplify an immune response. (macrophages in local area of the tissue damage or infection are already releasing cytokines. once complement system is activated, many many more are released and many more proteins come to the aid of that area)

immunology, immunity, immune system

Immunology is the study of host defense mechanisms. Immunity is the ability of the host to protect itself against foreign organisms. The immune system comprises the tissues, cells & molecules which mount the immune response. White blood cells (leukocytes) and some types of plasma proteins are responsible for the functions of the immune system.

MHC Proteins (MHC class 1 and MHC class 2)

MHC I and MHC II proteins have an antigen binding site, which holds a polypeptide fragment. T cell receptors recognizes not just the antigenic fragment, but the fragment bound to MHC I or II. Class I MHC: Present on the surface of every nucleated cell. MCH I and any bound fragments can interact with cytotoxic T cells. Cytotoxic T cells have a membrane protein (CD8) which can recognize and bind MHC I Class II MHC: Mostly found on surfaces of B cells, macrophages, and other antigen presenting cells. T-helper cells have a surface protein (CD4) that binds to MHC II. Any malfunctioning cell will present antigen on MHC I, due to Cancer or Viral infection. MCH I -antigen complex will bind to Cytotoxic T-cells. Like Helper-T cells and B cells, Cytotoxic T-cells have a specific receptor for a specific antigen. Helper T cells and Cytotoxic T cells have effector and memory cells.

Non-specific Defense

Non-specific is the body's 1st line of defense against disease (also called the innate immune system). Much faster than Specific Defense. Types of Nonspecific Defense: - physical barriers (epithelial tissues and mucous: skin, mucous membranes, cilia in lungs) -Molecules that are toxic to invaders (tears, saliva, stomach acid, vaginal secretions) -Phagocytic cells (macrophages) -cytokines and complement proteins -interferons (a type of cytokine) -inflammation (involves histamine released by mast cells) -Natural Killer cells (a type of lymphocyte)

origin of blood cells

Red and white blood cells originate from multipotent stem cells (constantly dividing; able to differentiate) in the bone marrow. Two major families of white blood cells (leukocytes)—phagocytes and smaller lymphocytes. -origin of blood cells involves bone marrow, multi potent hematopoietic cells, and myeloid progenitor cells -red blood cells (aka erythrocytes; transport oxygen and carbon dioxide) -platelets (aka cell fragments without nuclei; initiate blood clotting)

T cells

T cells differentiate into two types of effector T cells: -T-helper cells (in the humoral immune response) -Cytotoxic T cells (in the cellular immune response) T cells possess specific membrane receptors (just like B cells). Diversity of receptors is created in the same manner as B cells.

response to bacterial infection is different than response to viral infection

macrophages can recognize molecular patterns common on the surface of cellular pathogens (living pathogens like bacteria, protozoans, and parasites) that come into the body and stay in the interstitial fluid/extracellular matrix (inside body but outside host cells for the most part). but virus quickly enter host cells. they are actually inside host cells, not in the extracellular fluid. so the body needs a slightly different way of discerning the presence of viral pathogens. the main methods to do this are interferons and natural killer cells.

neutralization and agglutination

the two methods that antibodies use to clear intigens form body. neutralization: toxins produced by invading bacteria are treated as antigens by specific immune system, and specific antibodies bind to them and so stop them form carrying out their damaging functions. agglutination: Works by immobilization. Antibodies just make a big lump by binding to the epitopes on the antigens and then to each other. Then a macrophage will come by and clean up and just have a big feast and break up all the materials in the lump to get rid of the bacteria. Lumping bacteria together simply stops them from reproducing, which neutralizes infection. *antibodies also work in conjunction with the non-specific immune response by helping to stimulate the complement protein response

Natural Killer Cells

they are a class of lymphocyte that can target virus-infected cells and tumor cells and initiate apoptosis. Can also interact with the specific defense system by lysing (destroying) antibody-labeled target cells. Basically their job is to kill the body's own cells when they become dangerous to the body (virus and cancer cells). They can be activated to kill a host cell by interferons or molecular markers on target cell surface. They don't eat the target cells like a phagocyte; rather they puncture holes in it. Your body should be trying to kill 2 types of your own cells: 1)A cancerous cell 2)A cell that has already been infected/invaded by a virus (b/c viruses use human cells to reproduce so you need to kill any cell w/ a virus inside). Human cells actually will put up a little flag or marker on themselves that tells NK cells (or T cells) to kill them

Interferons

when a cell becomes infected with a virus , the host cell releases signaling proteins called interferons Interferons: -they are a type of signaling protein (a type of cytokine) that increase the resistance of neighboring cells to viral infection, and also might call a NK cell to come kill the infected cell -they bind to receptors on uninfected cells stimulating signaling cascades that inhibit viral reproduction if they become infected in the future. -basically they make nearby cells more resistant to viral infection