Immune and Lymphatic Systems

Introduction to Immune and Lymphatic Systems

• Immunity refers to the diverse processes that protect the body from cellular injury and disease-causing cells and molecules (pathogens).
• The immune system defends the body against internal and external threats
• It consists of cells and proteins in the blood and tissues, including leukocytes and immune proteins in the plasma.
• The lymphatic system works with the immune system and participates in fluid homeostasis
• It includes lymphatic vessels (blind-ended tubes) and lymphatic tissue/organs (tonsils, lymph nodes, spleen, thymus).

Functions of the Lymphatic System

• The lymphatic system regulates interstitial fluid volume by collecting excess fluid and returning it to the cardiovascular system.
• Net filtration pressure in blood capillaries favors filtration and Water is lost from the plasma.
• Lymphatic vessels pick up excess fluid (lymph) that ensures that blood volume and blood pressure do not drop and transport it back to the bloodstream.
• Lymphatic system aids in the absorption of dietary fats.
• Lymphatic system carries out immune functions.

Lymphatic Vessels and Lymph Circulation

• Lymph is collected in lymph-collecting vessels, which merge to form lymph trunks.
• Nine lymph trunks drain lymph from specific body regions.
• The intestinal and lumbar trunks drain into the cisterna chyli, which, along with other lymph trunks, drains into the thoracic duct and right lymphatic duct.
• Lymph drains into the blood at the subclavian veins in the low-pressure venous circuit.
• Lymphatic vessels form a low-pressure circuit as there is no main pump; return to the heart is assisted by valves and muscle contractions.
• Lymphatic capillaries in tissues are blind-ended, creating a one-way system moving lymph away from tissues.
• Cells of lymphatic capillary walls can flap open/closed, and fluid from blood capillaries increases interstitial fluid pressure, forcing endothelial cells apart for fluid entry.
• Endothelial cells flap shut in control to limit fluid between cells.
• Lymph nodes filter pathogens from lymph preventing their spread.

Lymphoid Tissues and Organs

• The predominant tissue type in the lymphatic system is reticular tissue.
• Reticular tissue is a loose connective tissue with specialized cells and fibers that form "nets" to trap pathogens.
• Lymphatic reticular tissue is typically called lymphoid tissue
• Lymphoid tissue are found in lymphoid organs/ independent clusters.
• Lymphoid organs house leukocytes like macrophages, B lymphocytes, and T lymphocytes, also referred to as B cells and T cells.
• Mucosa-Associated Lymphatic Tissue (MALT) protects mucous membranes from pathogens and is found in tonsils, Peyer's patches, and the appendix.
• Lymph nodes are bean-shaped clusters of lymphatic tissue located along lymphatic vessels
• Locations include axillary lymph nodes in the axillae, cervical lymph nodes in the neck, inguinal lymph nodes in the groin, and the mesenteric lymph nodes in the abdominal cavity around the abdominal organs.
• Lymph flows into lymph nodes through afferent lymphatic vessels.
• Pathogens in the lymph are trapped within reticular fibers inside.
• Cleansed lymph exits through efferent lymphatic vessels.
• Pathogens are prevented from entering back into blood by the lymph nodes.
• The spleen, the largest lymphoid organ, protects the body from bloodborne pathogens and is located on the lateralside of the left upper quadrant of the abdominopelvic cavity.
• The thymus generates functional T cells to protect the body from pathogens and is in the superior mediastinum, with two lobes and doesn’t trap pathogens.

Lines of Defense

• The immune system has three lines of defense against pathogens.
• The first line of defense is surface barriers (skin and mucous membranes)
• The second line of defense is innate immunity.
• The third line of defense is adaptive immunity.

Types of Immunity:

• Innate immunity responds to all pathogens the same way, involving antimicrobial proteins and quick-responding cells.
• It is the dominant response for the first 12 hours after exposure
• The cells from this immune system already exist in the blood stream without any simulus.
• Adaptive immunity responds to unique antigens, using glycoprotein markers to identify cells/molecules. It is slower than innate immunity, requiring exposure to a specific antigen to initiate a response.
• Acquired immunity takes 3-5 days to react but is ultimately the dominant response.
• The adaptive immune system has two arms, cell-mediated immunity (T cells) and antibody-mediated immunity (B cells and antibodies).
• Adaptive immunity has immunological memory.
• Innate and adaptive immunity work together for highly integrated response to pathogens.
• Surface barriers, such as skin and mucous membranes, are the first line of defense.

Cells and Proteins of the Innate and Adaptive Immune Systems

• Immune system cells includes leukocytes (agranulocytes and granulocytes)
• Agranulocytes are B/T lymphocytes and monocytes
• Phagocytes "eat" foreign/damaged cells
• Natural killer (NK) cells function in innate immunity and are located in the blood and spleen.
• Dendritic cells activate T cells and are located in lymphoid organs.
• The immune system produces proteins in the forms of antibodies, the complement system, and cytokines.

How the Lymphatic and Immune Systems Work Together

• Both the lymphatic and immune systems are closely connected structurally and functionally.
• Lymphoid organs and tissues are the residence for immune system cells.
• Lymph nodes, MALT, and the spleen are examples of lymphoid organs
• Lymphoid organs and tissues trap pathogens for the immune system using reticular fibers.
• Lymphoid organs activate cells of the immune system, such as dendritic cells activating B and T cells.
• The thymus is involved in T cell selection, required for activation of T cells.
• The lymphatic system is heavily involved in adaptive immunity, greater role than in innate.

Innate Immunity: Internal Defenses

• Rapid innate immunity response includes antimicrobial molecules (complement, cytokines) and cells (neutrophils, macrophages, NK cells).
• Pathogens bypassing surface barriers trigger the second line: cells and proteins of innate immunity.
• Types of cells can be phagocytic or nonphagocytic cells.
• Phagocytes include macrophages, neutrophils, and eosinophils which perform phagocytosis.
• Nonphagocytic cells include NK cells, dendritic cells, and basophils.
• The innate immune response is mediated by plasma antimicrobial proteins like complement proteins and cytokines.
• The complement system consists of 20+ plasma proteins made by the liver.
• Activated complement proteins cause cell lysis, MAC formation, inflammation, virus neutralization, enhanced phagocytosis, opsonization, and immune complex clearance.
• Cytokines enhance the immune response and include tumor necrosis factor, interferons, and interleukins.

Inflammatory Response

• Inflammation is an innate response to cell damage from trauma, bacterial/viral invasion, toxins, heat, or chemicals.
• Damaged cells release inflammatory mediators, then phagocytes clean up damaged tissue.
• Tissue damage initiates inflammation and causes inflammatory mediators, released by damaged and mast cells.
• Mediators include histamine, serotonin, cytokines, bradykinin, prostaglandins, and leukotrienes; activated complement also triggers mediator release and acts as inflammatory mediators.
• The four cardinal signs of inflammation are redness, heat, swelling (edema), and pain.
• They are caused by vasodilation, increased capillary permeability, occurrence of pain, recruitment of other cells (chemotaxis).

Phagocyte Response

• The arrival and activation of phagocytes is is divided into processes
• Local macrophages are activated/contain pathogens and neutrophils migrate by chemotaxis.
• Inflammatory mediators/complement proteins attract neutrophils to the damaged area.
• Neutrophils that adhere to the capillary wall is margination
• Inflammatory mediators increase capillary permeability, allowing neutrophils to squeeze through into tissue (diapedesis).
• Once in the tissue, neutrophils begins to destroy bacteria and pathogens.
• Monocytes turn into macrophages which phagocytize pathogens.
• Bone marrow produces more leukocytes: leukocytosis.
• Fever is high body temperature between 36 and 38° C (or 97–99° F).
• A individual with a fever is referred to as febrile.
• Fever is initiated by pyrogens from damaged cells or certain bacteria which resets the hypothalamic thermostat to a higher range.

Adaptive Immunity: Cell-Mediated Immunity

• Cell-mediated immunity is the first arm of the adaptive immune system.
• helper T (TH) cells or CD4 cells and cytotoxic T (TC) cells or CD8 cells are invovlved (CD = cluster of differentiation).
• T cells respond to cells infected with intracellular pathogens, cancer cells, and foreign cells.
• T cells rearrange genes, creating many, distinct T cells.
• T cells respond to a specific antigen known as a clone.
• The thymus helps the individual to become immunocompetent or able to mount a normal response to antigens.
• Self-reactive cells are destroyed to ensure self-tolerance or prevent T cells from attacking self cells.
• Immunogens are antigens capable of generating a response.
• Self-antigens are not immunogens.

MHC Molecules and Antigen Presentation

• T cells interact with antigens bound to major histocompatibility complex (MHC) molecules which determine compatibility among tissue/organ donors/recipients.
• There are two types of MHC molecules: Class I and Class II.
• Class I MHC molecules are on nearly all nucleated cells interacting mainly with cytotoxic T (Tc) cells to present endogenous antigens or those synthesized inside the cell.
• Class II MHC molecules are only found on antigen-presenting cells which interact with helper T (TH) cells to present exogenous antigens or those the cell takes in by phagocytosis.
• A class I MHC molecule processes through The cell synthesizes either a self antigen or a foreign antigen which is broken down by enzymes in the cytosol.
• An antigen fragment is transported into the rough endoplasmic reticulum (RER) and coupled with a class I MHC molecule.
• The MHC-antigen complex leaves the RER and becomes inserted into the cell's plasma membrane.
• The class II MHC molecule processes through where the cell ingests a pathogen by phagocytosis and the phagocytic vesicle fuses with a lysosome which degrades the antigens
• The lysosome fuses with a vesicle from the RER/II MHC molecules, and an antigen fragment binds to the MHC molecule.
• The MHC-antigen complex is inserted into the cell's plasma membrane.
• Antigens are displayed on the plasma membrane which attach to MHC molecules and activate T cells.
• MHC-antigen complex binds to the receptor of a TH or TC cell clone.
• T cell receptor recognizes/binds this complex which begins activation: clonal selection.

Effects of T Cells

• TH or TC cell binds a co-stimulator and becomes activated to then proliferate/differentiate into memory T cells.
• Memory T cells allow cells to respond quicker/efficiently during exposures from antigens.
• TH and TC cells roles depend on one another to function effectively.
• TH cells secrete cytokines to activate and enhance various immune components.
• TH cells include the stimulation of macrophages, the activation of Tc cells, and the stimulation of B cells.
• Cytotoxic T cells kill cells with foreign antigens that are bound to class I MHC molecules
• TC cells detect abnormalities which is critical for detection for cancer cells, foreign cells, and cells infected with intracellular pathogens.
• An activated TC cell can release perforin to pores in the plasma membrane of a cell.
• TC cell releases enzymes to degrade target cell proteins which leads to cell fragmentation of the target cell's DNA and its death.
• TC bind to proteins of the plasma membrane which induces apoptosis (cell death) which degrades the target cell, the Tc cell detaches and searches for a new target cell.

Organ and Tissue Transplantation and Rejection

• Basic graft transfers: autografts, isografts, allografts, and xenografts.

Adaptive Immunity: Antibody-Mediated Immunity

• Antibody-mediated immunity utilizes B cells and antibodies.
• B cells have B cell receptors to bind to specific antigens.
• B cells clone the antibodies in a way the B cell clone binds to the same antigen as the B cell receptor.
• During the first antibody-mediated immune response a B cell clone recognizes its specific antigen
• This triggers changed and start secreted antibodies.
• During the second antibody-mediated level of the blood also rises
• Antibodies (immunoglobulins/gamma globulins) are directly responsible (binding) to antigens
• The third phase comes in the forms of memory that react rapidly/efficiently later.
• During the B Cell activation clonal selection, B cells mature within the bone marrow as bilions are procuded each day.
• B encounters antigens and becomes activated to sensitize, and present on MHC2 molecules. The B then binds to TH become fully activated,
• B cells differentiate into Plasma Cells (which secrete antibodies) and Memory B cells (respond with antibodies upon a second exposure).

Antibodies

• Antibodies are comprised the Y-shaped molecule that is formed from four peptide chains, heavy and light chains.
• Each Chain includes the Constant region (similar amongst antibodies) while another is the Variable region responsible for antigen bonding).
• Antibody has V regions on the two arms of the molecule and has two antigen-binding sites.
• There are 5 antibody classes that are grouped as the “IgXX” names.
• These include IgG, IgA, IgM, IgE, and IgD
• The antibody is able to bind antigens which lead to multiple effects on pathogens. These effects include agglutination/precipitation, Opsonization, Neutralization, Complement activation, and Stimulation of inflammation.
• Memory B cells work to make antibodies responsive for 2nd interactions

Primary and Secondary Immune Responses

• An antigen first exposes a B cell specific for that antigen; the activated B cell proliferates and differentiates into plasma and memory B cells and secrete to creates what is known as a primary immune response.
• Plasma cells involves the initial 4-5 day long where antibody levels begin to peak after between 7–14 days and feelings of sickness.
• When an b cell is exposed again, memory b is activated and the secondary immune response beings.
• Primrary is IgG While IgM is used in 1. Anti body is stronger and more effective later.

Vaccinations

• A vaccination or immunization helps produce and generate memory cells. If exposed a second time a faster and secondary immune response will occur and symptoms will be minimal.
• A vaccine contains attenuated/killed forms of vaccines and subunit vaccines.
• Active and passive Antibody-Mediated Immunity consists of two types that result in a form of active or passive.
• Active has a fast reaction, comes from natural exposure or vaccination and can also come from vaccines leading memory production that are long lasting.
• Passive is a slow passing reaction and can be used naturally or artifically but only lasts as the length of the antibody in the stream. This is about 3 months on average.

Disorders of the Immune System

• These consist of hypersensitivity, immunodeficiency, or autoimmune.
• Hypersensitivity include disorders which causes damage and types 1-4 which damage the immune components.
• Type 1 is commonly the usual allergy with first exposure to an allergen binds to B cells, which triggers B cell differentiation into plasma cells that secrete antibodies. Subsequent results in second exposure which takes place in minutes. Local reactions in the nasal cavity produce runny nose and itchy eyes.
• Type 2 is antibody-mediated hypersensitivity where where antibodies produced in response to foreign antigens also bind to self antigens.
• Type 3 deals with immune complexes or antigens (not attached to the cell) and has antibodies.
• Type 4 of hypersensitivity has T cells rather than antibodies TH cells recognizing antigens bound to MHC activating , recruiting t cells to mediant the destruction by using macropahages.
• Immunodeficiency are caused by 1 or more components being decreased. Two immune deficiencies consist of
• Primary where genetic is genetic or developmental
• Secondary is by infection, cancer, trauma
• primary immunodeficiency consists of innate/adaptive disorders for complement proteins or abnormalities in phagocytes
• Secondary includes AIDS from viruses

AIDS

• Caused by human immunodeficiency virus 1 (HIV-1), which is spread through contact with infected blood, semen, vaginal fluid, or breast milk. HIV-1 preferentially binds and interacts with cells displaying CD4 molecules.
• Aids has a start and end point but varries from each individual consisting of acute/chronic phases.
• TH is very important because they are destroyed which can lead to having AIDS.
• Medication can however help stop AIDS..

Autoimmune Disorders

• Autoimmune disorders consist of B/T cells that secrete antibodies and by to self-antigens known as autoanitobies. These include the following:
• Self antigens not encountered by t cells - multiple sclerosis
• foreign mimicing antigens - rheumatic fever
• Non appropriate MHC II -
• Random activations of b cells