Ch 8: Imunnology

_________________ contain bright red granules are are primarily involved with invasive parasitic infections. Eosinophils release large amounts of histamine, an dinflammatory mediator. This results in vasodilation. Inflammation is particularly useful against extracellular pathogens.

Eosinophils

___________ are also involved in nonspecific defense. Granulocytes inlcude neutrophils, eosinophils, and basophils (and closelsy related mast cells) . Neutrophils are most populous leukocyte in blood and are very short lived. These cells are phagocytic, like macrophages and target bacteria. Neutrophils can follow bacteria using chemotaxis and can also detect bacteria once they have been____________________, marked with an antibody from a B cell. Dead neutrophil collections form pus.

Granulocytes, opsonized

Cells of adaptive system: Mainly B-cells and T-cells. ________ cells govern humoral space, while T-cells mount cell-mediated response. All cells of immune system are created in bone marrow, but B and T cells mature in dif locations.

Humoral

_____________ refers to the responses cells can carry out without learning; for this reason it is also known as the nonspecific immune response. Adaptive immunity is developed as immune cells recognize and respond to particular antigens, and is often aptly refered to as specific immune response. We can also divide the specific immune system into humoral immunity (driven by B-cells and antibodies) and cell mediated immunity (driven by T cells).

Innate immunity

______________ is composed of defenses that are always active against infection, but lack ability to target specific invaders.

Innate immunity or nonspecific immunity

To protect against viruses, cells have been infected with virus produced _________________, proteins that prevent replication and dispersion. Interferons cause nearby cells to decrease production of both viral and cellular proteins. They also decrease permeability of the cells, making it hard for virus to infect. Interferons also upregulte MHC class I and class II molecules, resulting in increased antigen presentation and better detection of infected cells by the immune system. Interderons are responsible for many "flu-like" symptomns that occur during viral infections, including malaise, fever, etc.

Interferons

_______ can be class 1 or class 2. All nucleated cells in body display MHC class 1 molecules. Any protein produced within a cell can be loaded onto MHC-1 and presented on the surface of the cell. This allows the immune system to monitor the health of these cells and to detect if cells have been infected with a virus or another intracellular pathogen; only those cells that are infected would be expected to present an unfamiliar (nonself) protein on their surfaces. Therefore, MHC-I is often called endogenous pathway because it binds. antigens coming from inside the cell. Cells invaded by intracellular pathogens can be killed by a certain group of T cells (cytoxic T-lymphocytes) to prevent infection to other cells.

MHC

_____________ binds to a pathogenic peptide (also called antigen) and carries it to cell surface where it can be recognized by cells of the adaptive immune system. Additinally, macrophages release cytokines, chemical substances that stimulate inflammation and recruit additional immune cells to area.

MHC

Recognition of self and nonself: __________ are the proteins and carbohydrates present on the surface of every cell in the body. Under normal circumstances, the self-antigens signal to immune cells that the cell is not foreign and should not be attacked, However, when the immune system fails, to make distinction beteween self and foreign, it may attack cells expressing self antigens. This is known as autoimmunity. Autoimmunity is only one potential problem with immune functioning; another problem arises with misidentification of foreign antigens as dangerous, wehn they are not. This is where pet and peanut allergy comes from. Allergies and autoimmunity are part of a family of immune reactions classified as hypersensitivity reactions. The human body strives to prevent immune reactions very early in T and B cell maturing processes. T cells are educated in the thymus, and part of this education involves the elimination of T cells that respond to self antigens, called negative selection. Immature B cells that respond to self antigens are eliminated before they leave the bone marrow. However, this is not a perfect process. Occasionally a cell responding to a self antigen is allowed to survive. Most autoimmine diseases can be treated w a number of therapy. Administering glucocorticoids have potent immunosuppresive qualitites.

self-antigens

________________ are mainly displayed by professional antigen-presenting cells like macrophages. These phaogocytic cells pick up pathogens from the enviroment, process them, and then present them to MHC-II. An antigen is a substance that can be targeted by an antibody. While antibody production is domain of adaptive immune system, it is important to understand that cells of the innate immune system also present antigens. Because antigens originate outside of the cell, the MHC-II pathway is often called exogenous pathway. The presentation of an antigen by an immune cell may result in activation of both innate and adaptive immune systems. Professional antigen=presenting cells include macrophages, dendritic cells in skin, some B-cells, and certain activated epithelial cells.

MHC class-II

Bacterial (Extracellular Pathogen) infections: _________ are like the sentinels of the human body, always on the lookout for possible invaders. If bacteria is introduced into the body, first macrophages and other antigenpresenting cells will engulf the bacteria and subsequently release inflammatory mediators. These cells also digest bacteria and present antigens from the pathogen on their surface in conjugation with MHC-II. The cytokines attract inflammatory cells, including neutrophils and add. macrophages. Mast cells are activated by inflammation and degranulate, resulting in histamine release and increased leakiness of capillaries. This augments the ability of the immune cells to leave the bloodstream to travel to affected tissue. The dendritic cell then leave the affected tissue and travels to nearest lymph node, where it presents the antigen to B-cells. B-cells that produce the correct antibody proliferate through clonal selection to create plasma cells and memory cells. Antibodies then travel through the bloodstream to affected tissue, where they tag bacteria for destruction. At the same time, dendritic cells are also presenting the antigen to T-cells, activating a T-cell response. In particular, CD4+ T-cells are activated. These cells come in two types, called Th1 and Th2. Th1 cells release interferon gamma (IFN-v), which activates macrophages and increases their ability to kill bacteria. Th2 cells help activate B-cells and are more common in parasitic infections. After the pathogen has been eliminated, plasma cells die, but memory B-cells and T-cells remain. These memory cells allow for a much faster secondary response upon exposure to the pathogen at a later time.

Macrophages

__________ are a type of agranulocyte that resides in tissue. These cells derive from blood-borne monocytes and can become a resident pop. in tissue. When a bacterial invader enters a tissue it becomes active. Activated machrophage does 3 things. First in phagocitizes invasers through endocytosis. Then it digest invaders using enzymes. Finally it present little pieces of invader to other cells using a protecting called mahor histocompatibility complex (MHC).

Macrophages

___________________are nonspecific lymphocyte able to detect down regulation of MHC and induce apoptosis in these virally infected cells. Cancer can also down reg MHC so NK cells also protect against cancer growth

Natural Killer (NK) cells

Innate Immune System (all below)First line of defense

skin (integument)

The _______ is a location of blood storage and activation of B-cells, which turn into plasma cells to produce antibodies as part of adaptive immunity. When B-cells leave the bone marrow, they are considered mature but naive. Because these antibodies dissolve and act in the blood and not the cell, this division of adaptive immunity is called humoral immunity.

Spleen

Cytotoxic Immunity: Involves _________ cells. T-cells undergo positive and negative selection. Positive selection refers to allowing only maturation of cells that can respond to presentation of antigen on MHC. Negative Selection refers to causing apoptosis in cells that are self reactive. The maturation of T-cells is facilitated by thymosin, a peptide hormone secreted by thymic cells. Once T cells leave thymus it is mature but naive. Upon exposure to antigen, T-cells will undergo clonal selection so only those with highest affinity for given antigen proliferate.

T-cells

__________,another class of adaptive immune cells, mature on the thymus, a small gland just infront of the paracardium. T-cells are agents of cell-mediated immunity because they coordinate the immune system and directly kill virally infected cells.

T-cells

__________ cells are capable of directly killing viral infected cells by injecting toxic chemicals that promote apoptosis in the infected cell. Tc cells respond to antigens presented on MHC-I molecules. Becuase MHC-I presents endogenous antigens, Tc are most effective against viral ( and intracellular bacterial or fungal ) infections.

Tc

_____ coordinate the immune response by secreting chemicals known as lymphokines. These molecules are capable of recruiting other immune cells (such as plasma, cytotoxic T cells, and macrophages) and increasing their activity. The loss of these cells, as occurs in HIV infection, prevents the immune system from mounting an adequate response to infeection; in advance HIV infections, also called AIDS, even week pathogens can cause devastating consequences as opportunistic infections. Th cells respond to antigens presented on MHC-II molecules. Because MHC-II presents exogenous antigens, Th cells are most effective against bacterial, fungul, and parasitic infection.

Th

_____ cells also express CD4 but also express a protein called FOXP. These cells help to tone down the immune sytem once infection has been adequately contained. These cells often turn off self-reactive lymphocytes to prevent autoimune diseases. This is termed self tolerance.

Treg

GI tract plays a role in nonspecific immunity. The stomach secretes _____________, resulting in the elimination of pathogens. In addition, the gut is colonized by bacteria. Most of these lack necessary characteristics to cause infection. Because there is already such a large bacterial population in the gut, many potential invaders can't compete. Many antibiotics reduce population of gut flora, providing an opportunity for growth of pathogens resistant to them

acid

Remember leukocytes are composed of granulocytes and ________________. Both gran. and agran. can come from a common precursor: hematopoietic stem cells. These also give rise to red blood cells and platelets.

agranulocytes

Other cells like NK, macrophages, monocytes, and eosinophils also contain receptors for ____________ and can attack opsonized bacteria.

antibodies

Innate and adaptive immune systems _________ really disparate entities that functions separately. Proper function of entire immune system depends on interaction between these 2.

are not

5 types of infectious pathogens

bacteria, viruses, fungi, parasites (including protozoa, worms, insects) and, prions (for which there is no immune defense).

Anatomy: The _____________ produces all of the WBC that participate in the immune system through the process of hematopoiesis.

bone marrow

B cells mature in _________ and T cells mature in _____________.

bone marrow, thymus

The ____________ system consist of a number of proteins in the blood that act as nonspecific defense against bacteria. Complement can be activated through a classical pathway (which requires binding of an antibody to a pathogen) or an _______________ (which does not require antibodies.). Complement proteins punch holes in the cell walls of bacteria, making them osmotically unstable. Despite the association with antibodies, complement is considered a nonspecific defense because it cannot be modified to target a specific organism over others.

complement

Skin provides a physical barrier of protection, and antibacterial enzymes called ___________ can be found on the skin. Sweat also has antimicrobial properties. A cut or abrasion on the skin provides an entry point for pathogens into the body. Deeper wounds allow pathogens to penetrate deeper into the body.

defensins

Other immune tissue is found close in proximity to the digestive system, which is a site of potential invasion by pathogens. These tissues are commonly called ___________________ (GALT) and include tonsils and, adenoids in head, Peyer's patch in small intestine, and lymphoid aggregates in appendix.

gut-associated lymphoid tissue.

3 major types of T cells

helper T-cells (Th or CD4+), suppressor T-cells (Treg), and killer (cytotoxic) T-cells(Tc or CTL or CD8+)

The adaptive Immune system: can be divided into ______________ immunity and cell-mediated cytotoxic immunity.

humoral

_____________, which involves production of antibodies, may take as long as a week to become fully effective after initial infection. These antibodies are specific to antigens of the invading microbe. Antibodies are produced by B-cells, which are lymphocytes that originate in bone marrow and are active in spleen and lymph nodes.

humoral immunity

Lymphatic System: intimately related with the _____________ system. B-cells proliferate and develop within the lymphatic system, especially the lymph nodes. Structure: Is a circulatory system. Made of 1-way vessels that become larger as move toward bodies center. These vessels carry lymph, and most join to form the thoracic duct in posterior chest, which delovers fluid inot the left subclavian vein (near the heart).

immune

Antibodies are also called _____________. They can be on cell surface or secreted into body fluids. When antibodies bind to antigen, response depends on location. For antibodies secreted in fluids, there are 3 main possibilites: 1. Once bound antibodies may attract other leukocytes to phagocytize those antigens immediaetly (opsinization). 2. Antibodies may cause pathogens to clump or agglutinate, forming large insoluble complexes that can be phagocytized. 3. Antibodies can block the ability of a pathogen to invade tissue. For cell surface antibodies, binding of antigen to B-cell, causes activation of that cell, resulting in its proliferation and formation of plasma membrane and memory cells. When antigens binds to antibodies on surface of mast cells, it causes degranulation, relasing histamine and causing an inflammatory reaction.

immunoglobulins (Ig)

The immune system relies on interaction between ___________(nonspecific) and ______________(specific) immune system in order to protect itself from disease.

innate, adaptive

____________, a major component of the lymphatic system, provide a place for immune cells to communicate and mount an attack; B-cells can be activated here as well.

lymph nodes

Viral (Intracellular Pathogen) Infections: In a ________ infection, the virally infected cell will begin to produce interferons, which reduce permeability of nearby cells (decreasing the ability of the virus to infect these cells), reduce the rate of transcription and translation in these cells (decreasing the ability of the virus to multiply), and cause systemic problems (malaise, muscle aching, fever...). These infected cells also present intracellular proteins on their surface in conjunction with MHC-I; in a virally infected cell, at least some of these intracellular proteins will be viral proteins. CD8+ T cells will recognize MHC-1 and antigen complex as foreign and will inject toxins into the cell to promote apoptosis. In this way, the infection can be shut down before spreading to nearbye cells. In the event the virus downrgulates and production and presentation of MHC-I molecules, natrual killer cells will recognize the absence of the MHC-I and will accordingly cause apoptosis of these cells. Again, once the pathogen has been cleared, memory T-cells will be generated that can allow a much faster response to be mounted upon a second exposure.

viral

Function of the _______________ system: Equalization of fluid distribution: As the capillaries, fluid leaves the bloodstream and goes to tissue. The quantity of fluid that leaves the tissue at the arterial end of the capillary bed depends on both hydrostatic and oncotic pressures (startling forces). Remember the oncotic pressure of the blood draws waer back into the vessel at the venule end, once hydrostatic pressure has decreased. Because the net pressure drawing fluid in at the venule is slightly less than net pressure pushing fluid out arterial end, a small amount of fluid remains in the tissue. Lymphatic vessels drain these tissues and subsequently return the fluid to the bloodstream. The lymphatic system offers some protection against pathology. For example, if blood has low albumin concentration, the oncotic pressure of the blood is decreased and less water is driven back into the bloodstream at the venule end. Thus, this fluid will collect in the tissues. Provided that the lymphatic channels are not blocked, much of this fluid may eventually return to the bloodstream via the lymphatics. Only when the lymphatics are overwhelmed does edema occur-swelling due to fluid collecting in tissue. Transportation and Biomolecules: The lymphatic system also transports fats from the digestive system into bloodstream. Lacteals, small lymphatic vessels, are located at the center of each villus in the small intestine. Fats, packaged into chylomicrons by intestinal mucosal cells, enter the lacteal for transport. Lymphatic fluid carrying many chlyomicrons takes on a milky white appearance and is called chyle. Immunity: Lymph nodes are a place for antigen presenting cells and lymphocytes to interact. B-cells proliferate and mature in the lymph nodes in collections called germinal centers.

lymphatic

Structure of antibodies

-Part of the reason it takes so long to initiate the antibody response is that each B-cell undergoes hypermutation of its antigen-bonding region, trying to find the best match for the antigen. Only B-cells binding to the antigen with high affinity survive, providing a mechanism for generating specificity called clonal selection. The remaining part of the antibody is known as the constant region. It is this region cells like NK, macrophages, monocytes, and eosinophils have receptors for, and can initiate the complement cascade. Each B cell makes only 1 type of antibody, but we have many B cells so our immune systems can recognize many antigens. Antibodies also come in different isotopes which can be used at dif times. This is called isotope switching.

The respiratory system also has its passages lined with mucous membranes and cilia to trap matter. Other mucous membranes around eyes and mouth produce a nonspecific enzyme called a _____________, secreted in tears and saliva.

lysozymes

Cells of the innate immune system:

macrophages, natural killer cells, granulocytes, dendritic cells, mast cells

Finally, __________ T cells can be generated. These cells lie and wait until next exposure to same antigen. When activated they carry out more robust and rapid response.

memory

______________ refers to the defense that target a specific pathogen. This system is slower to act, but can maintain immunological memory of an infection to mount a faster attack in subsequent infections.

Adaptive or specific immunity

Immunization can be achieved in an active or ____________ fashion. In __________ immunity the immune system is stimulated to produce antibodies against a specific pathogen. Through natrual exposure antibodies are generated by B cells once an individual becomes infected. Artificial exposure through vaccinations also results in antibody production but individual never experiences a true infection. In ______________ immunity immunization, antibodies are transferrred to an individual.

passive, active, passive

While immune system response depends on _____________ identity, we present two classic examples: a bacterial (extracellular pathogen) infection and a viral (intracellular pathogen) infection. Keep in mind these categories are imperfect and have exceptions.

pathogen

Not all _______ are actively or constantly producing antibodies. It is energetically expensive. Instead, Naive B-cells wait in lymph nodes for their particular antigen to come along. Upon exposure, a B-cell will proliferate and produce 2 types of daughter cells. Plasma cells produce large amounts of antibodies, whereas memory B-cells stay in lymph node. This is known as primary response and takes 7-10 days. Plasma cells will eventually die, but memory cells may last organism lifetime. Secondary response is more rapid and robust, and is if same microbe is encountered again. Development of memory cells is the basis of vaccination.

B-cells

___________ contain large purple granules and are involved in allergic response. They are the least popular leukocyte in bloodstream under normal conditions. Mast cells are closely related, but are smoother.

Basophils