The lymphatic system is crucial for draining excess tissue fluid and orchestrating immune responses through various structures, including lymphatic vessels, nodes, and the spleen. It involves both innate and adaptive immunity, where innate responses are quick and non-specific, while adaptive responses are slower and specific, involving T and B lymphocytes. Vaccines mimic natural infections to provide immunity, utilizing different types like live attenuated, inactivated, subunit, and toxoid vaccines to stimulate immune memory.

1. The Lymphatic System
Tissue Fluid and the Immune Response

2. 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

3. Lymphatic Structures
• lymphatic vessels
• lymphoid tissues/organs
– primary or central
• bone marrow and thymus
– secondary or peripheral
• lymph nodes, spleen, mucosal

4. 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

5. 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

6. Thymus
• located behind the sternum
– larger in children
• site of T cell maturation
– migrate from bone marrow

7. 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)

8. 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

9. 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

10. • Found in several locations in the body
– Lungs, digestive tract, nasopharynx, skin, breast,
salivary glands

11. Cells of the Immune System
• broken into two broad groups:
– myeloid
• mostly in innate immune system
– lymphoid
• adaptive immune system

12. 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

13. • 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

14. • 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

15. 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

16. • B lymphocytes (B cells)
– antigen-specific receptors
• B cell receptors (BCRs)
– once activated divides to form plasma cells
• produce antibodies
– secreted form of BCRs

17. • 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

18. The Immune System
• cells and biochemicals responsible for the
surveillance and destruction of non-self
– innate response
• quick, non-specific
– adaptive response
• slower, specific

19. 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

20. 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

21. • 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

22. • complement
– pathogens can trigger activation of complement
proteins
– activation begins a cascade which can result in
destruction of the pathogen
– can also promote inflammation

23. 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

24. 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)

25. 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

26. 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

27. 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

28. 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

29. 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

30. • MHC class I
– proteins synthesized in cytosol
– can display viral proteins
– recognized by cytotoxic T cells

31. • MHC class II
– expressed by APCs
– derived from proteins taken in
through phagocytosis/endocytosis
– activate CD4 cells

32. • 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

33. – 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

34. 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

35. • 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

36. • antibodies are found in plasma and
extracellular fluid
– antibody mediated immunity is called humoral
immunity
• body fluids used to be known as humors

37. 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

38. 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

39. 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

40. 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

41. 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

42. • 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

43. • 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