The Lymphatic System

Tissue Fluid and the Immune Response

 Functions
• drain excess tissue fluid
– not all fluid returns to bloodstream
• extra enters the lymphatic vessels
• immune response
– responds to eliminate pathogens from the body
• innate and adaptive responses
• major structures include:
– lymphatic vessels, lymph nodes, spleen, thymus
 Lymphatic Structures
• lymphatic vessels
• lymphoid tissues/organs
– primary or central
• bone marrow and thymus
– secondary or peripheral
• lymph nodes, spleen, mucosal
 Lymphatic Vessels
• similar structure to veins
– thin with valves
• unlike veins, they are a “one-way street”
– originate as capillaries in the tissues
– end at the veins
 Lymph
• lymph is tissue fluid that has entered the
lymphatic vessels
– excess tissue fluid
• functions:
– transports proteins and other molecules to the
bloodstream
– moves foreign particles to lymph nodes
 Thymus
• located behind the sternum
– larger in children
• site of T cell maturation
– migrate from bone marrow
 Lymph Nodes
• located along lymphatic pathways
– absent in the central nervous system
• functions:
– filter/remove potentially harmful particles before
they enter bloodstream
– immune surveillance (monitoring of fluids by
immune cells)
 Spleen
• located in upper abdominal cavity
• similar to lymph node
• red pulp (majority of spleen)
– site of red blood cell disposal
• white pulp
– houses lymphocytes
– site of antigen presentation
Mucosa Associated Lymphatic Tissue (MALT)
• Lymphatic tissue in the mucosal membranes
throughout the body
– Contains T cells, B cells, and macrophages
– Can encounter antigens passing through the
mucous membranes
• Found in several locations in the body
– Lungs, digestive tract, nasopharynx, skin, breast,
salivary glands
 Cells of the Immune System
• broken into two broad groups:
– myeloid
• mostly in innate immune system
– lymphoid
• adaptive immune system
 Myeloid Cells
• macrophage
– engulf and kill invading microorganisms
– can help induce inflammation
– can activate other immune cells
• mast cells
– play a role in allergic responses
– respond to parasitic worms
– can induce inflammation
• granulocytes
– neutrophils
• most numerous
• phagocytic
• role in bacterial infection
– eosinophils and basophils
• defense against parasites
• contribute to allergic response
– can be more damaging than helpful
• dendritic cells
– can take up and degrade pathogens
– main function is antigen presentation
• activate cells of adaptive immunity
– a bridge between innate and adaptive responses
 Lymphoid Cells
• natural killer cells (NK)
– not part of the adaptive immune system…but come
from lymphoid lineage
– not antigen specific
• can recognize and kill some abnormal cells
– ex: tumor cells and some viruses
• thought to keep viruses at bay until adaptive response
kicks in
• B lymphocytes (B cells)
– antigen-specific receptors
• B cell receptors (BCRs)
– once activated divides to form plasma cells
• produce antibodies
– secreted form of BCRs
• T lymphocytes (T cells)
– three categories
• helper T cells
– provide signals which initiate responses from other cells
• cytotoxic T cells
– kill cells which are infected with a virus or other pathogen
• regulatory T cells
– suppress immune activity and help control immune response
 The Immune System
• cells and biochemicals responsible for the
surveillance and destruction of non-self
– innate response
• quick, non-specific
– adaptive response
• slower, specific
 Cytokines and Chemokines
• chemical signaling molecules
– cytokines
• proteins secreted which affect behavior of nearby cells
• pro-inflammatory, regulatory, or growth factors
– chemokines
• proteins secreted which attract cells to an area
• migrate due to a density gradient
• cells have receptors that bind chemokines
 Innate Immune Response
• macrophages
– recognize pathogens through receptors
– engulf and degrade pathogens
• can present antigens from the pathogen on the surface
– secrete cytokines and chemokines
• inflammation (heat, redness, swelling, pain)
– recruits proteins and cells to infected areas
• macrophages and neutrophils
– increases lymph flow
• brings microbes and antigen presenting cells (antigen
presenting cells – APCs) to lymphoid tissues
– can recruit effectors of adaptive immunity later on
• complement
– pathogens can trigger activation of complement
proteins
– activation begins a cascade which can result in
destruction of the pathogen
– can also promote inflammation
 Innate Immune Recognition
• PAMPs (Pathogen Associated Molecular Patterns)
– cells (macrophages, neutrophils, dendritic cells) have
receptors that recognize simple molecules and
regular molecular patterns
• pattern recognition receptors (PRRs)
– PAMPs are present on microorganisms but not body
cells
 Innate and Adaptive
• innate response initiates adaptive response
– macrophages engulf pathogens and present
antigens to lymphocytes
– dendritic cells triggered to activate T cells
– adjuvants
• bacterial extracts used in vaccines
• initiate an innate response…which in turn activates the
adaptive response
– leads to successful vaccination to the purified protein (antigen)
 Adaptive Immune Response
• initiated by APCs (antigen presenting cells)
– primarily dendritic cells (but also macrophages)
• engulf pathogens, degrade, then move the antigen to the
surface of the cell
– dendritic cells also have costimulatory molecules
• stimulate T cells to proliferate and differentiate
• B cells usually also require a helper T cell
– occurs in secondary lymphoid tissues/organs
 Proliferation
• once activated, naïve lymphocytes become
lymphoblasts
– divide to produce clones
• clonal expansion
– can divide 2-4 times per 24 hours for about 3-5 days
• producing about 1000 cells specific to the target antigen
– these cells become effector cells
• B cells = plasma cells
• T cells = cytotoxic or helper T cells
 Immunological Memory
• most cells generated by clonal expansion die
• some T and B cells are left behind
– memory cells
• reactivated quickly when the same antigen is
encountered again
• provides long-lasting immunity
Mechanisms of Adaptive Immunity
• cell-mediated immune response
– T cells responsible for destruction of intracellular invaders
• humoral immunity
– antibodies detect pathogens in blood and other
extracellular fluid (humor = body fluid)
• other mechanisms are similar to those of innate
immunity
– macrophages, neutrophils, complement
 T Cells and Cell-mediated
Immunity
• T cells
– CD4 = helper T cells
– CD8 = cytotoxic T cells
– recognize peptides on MHC molecules (major
histocompatibility complex)
• complex displayed on surface of cells
• trap peptide during production and transported to
surface
• MHC class I
– proteins synthesized in cytosol
– can display viral proteins
– recognized by cytotoxic T cells
• MHC class II
– expressed by APCs
– derived from proteins taken in
through phagocytosis/endocytosis
– activate CD4 cells
• stimulated effector cells secrete effector
molecules
– mainly cytokines
– recruit other effectors to target area
• CD8 cytotoxic T cells directly kill infected cells
– recognize antigens
• CD4 helper T cells can become different types
of T cells
– TH1 help control bacteria in vesicles of macrophages
• stimulate them to increase intracellular destruction of
bacteria
– TH2 promote response at mucosal surfaces
• parasitic infections
– TH17 promote responses with lots of neutrophils
• extracellular bacteria and fungi
– TFH (follicular helper)
• in lymphoid follicles
• aid in B cell activation
Antibodies and Humoral Immunity
• antibody structure
– secreted B cell receptor
– two variable regions
• antigen binding sites
• almost infinite combination of amino acids
– constant region
• 4 or 5 forms
• determines effector function
– how the antibody will interact with immune cells to dispose of antigen
• antibody actions
– neutralization
• binds to antigens and blocks access to cells
• important in viral infections and against bacterial toxins
– opsonization
• coating pathogens with antibodies
– lead to phagocytosis
• bacterial infections
– some evade innate response because they have an outer coat
– antibodies can recognize the antigens on surface
– complement activation
• constant regions can activate the 1st protein
• coats surface and enables phagocytosis
• antibodies are found in plasma and
extracellular fluid
– antibody mediated immunity is called humoral
immunity
• body fluids used to be known as humors
 Immune Responses
• primary immune response
– T cells and B cells become activated for the 1st
time
– some memory cells remain
• secondary immune response
– if the antigen is encountered again, the memory
cells can mount a more rapid attack since they are
already present
– this ability can be long lasting
 Practical Classification of Immunity
• naturally acquired immunity
– occurs after exposure to the antigen itself
• artificially acquired immunity
– occurs through the use of vaccines
– person does not become ill from the disease
• artificially acquired passive immunity
– injection of gamma globulin antibodies (short-lived)
• naturally acquired passive immunity
– antibodies are passed from mother to fetus
 Vaccines
• first vaccine developed in 1796
– used the cowpox virus to vaccinate against smallpox
– vaccine comes from the Latin word vaccinus
meaning “of cows”
• mimic a natural infection
– immune system responds like it normally would
– left with a supply of memory T and B cells
 Vaccination vs. Immunization
• vaccination
– giving of vaccines to prevent disease
• immunization
– acquiring immunity against a disease
– protection against getting sick
• successful vaccination results in immunization
 Types of Vaccines
• live attenuated vaccines
– contains live microbes that are weakened so they no
longer cause disease
– elicits an immune response involving memory T and
memory B cells
– drawbacks include:
• refrigeration
• there is a risk of mutation of the pathogen which causes disease
– diseases include measles, mumps, rubella, polio,
chickenpox, shingles, flu
• inactivated or “killed” vaccines
– most common type used today
– contains pieces of viruses killed with heat, chemicals,
or radiation
– no risk of mutation (since they aren’t alive)
– stimulates B cells to produce antibodies
– drawbacks include:
• not as potent as live attenuated
• booster shots are needed
– diseases include flu, hepatitis A, polio, rabies
• subunit vaccines
– contain only parts of the microbes that stimulate the
immune system
• mainly the antigens
– tend to cause fewer adverse reactions
– diseases include diphtheria, hepatitis B, pertussis, tetanus
• toxoid vaccines
– used to combat the toxins produced by pathogens
– contain inactivated toxin called toxoids
– stimulate antibody production
– diseases include diphtheria and tetanus