Lymphatic System and Immunity Vocabulary

Immunity: The ability of an organism to resist infection.
Antigen: A molecule capable of generating an immune response.
Natural Killer Cells: White blood cells that recognize and destroy infected or abnormal cells.
Antibody: A protein produced by B cells that interacts with a specific antigen.
Pyrogen: A chemical that causes an increase in body temperature (fever).
Phagocytosis: The process by which cells engulf and remove pathogens or debris.
Cytokines: Small proteins that cause changes in other cell types, stimulating immune responses.
Antigen-Presenting Cells (APCs): Cells that display antigens to T cells, such as macrophages and dendritic cells.
Class I Cells: Nucleated cells that present antigens via MHC Class I molecules, indicating infection.
Class II Cells: Antigen-presenting cells (APCs) that present antigens via MHC Class II molecules to activate helper T cells.

Specific vs. Non-Specific Defenses

Non-Specific Defenses: Attack any pathogen, including:
- External Barriers (skin, mucous membranes)
- Phagocytic Cells (macrophages, dendritic cells)
- Natural Killer Cells
- Fever
- Inflammation
Specific Defenses: Attack a specific, identified pathogen, resulting in future protection (immunity).
- Cell-mediated immunity
- Antibody-mediated immunity

Relationship and Function of Immune Cells

Infected Body Cell: Presents antigens via MHC Class I to activate cytotoxic T cells, leading to its destruction.
Macrophages: Engulf pathogens and debris, present antigens via MHC Class II to activate helper T cells, and participate in phagocytosis.
Natural Killer Cells: Recognize and destroy infected or abnormal cells.
Helper T Cells (TH): Activated by antigen-presenting cells (APCs), secrete cytokines to stimulate other immune cells (cytotoxic T cells and B cells), and are required for all immune responses.
Cytotoxic T Cells (TC): Activated by helper T cells and infected cells, kill infected cells displaying specific antigens via MHC Class I.
B Cells: Activated by helper T cells and antigens, differentiate into plasma cells and memory B cells.
Plasma Cells: Produce and secrete antibodies.
Memory (T and B) Cells: Provide a faster response upon subsequent encounters with the same antigen.

Cell-Mediated vs. Antibody-Mediated Immunity

Cell-Mediated Immunity: Involves cytotoxic T cells directly killing infected cells.
Antibody-Mediated Immunity: Involves B cells producing antibodies that target pathogens.

Antigen-Presenting Cells

Class I MHC: Found on all nucleated cells; present antigens to cytotoxic T cells when the cell is infected, signaling "HELP – I’M INFECTED!!! KILL ME!!!"
Class II MHC: Found on antigen-presenting cells (APCs); present antigens to helper T cells, signaling "HEY LOOK WHAT I FOUND. IT’S A FOREIGN ANTIGEN. FIND AND DESTROY!!!"

Learning Objectives

Compare and contrast non-specific and specific defense mechanisms.
Generally describe the roles of the types of white blood cells that we discussed in class (natural killer cells, T-cells, B-Cells, macrophages, dendritic cells)
Describe the barriers that help prevent pathogens from entering the body.
Define phagocytosis and why it is important for the non-specific and specific defenses of the body.
Compare and contrast antibody-mediated and cell-mediated immunity.
Explain the difference between an antigen and an antibody.
Compare and contrast Class I MHC (infected cells) and Class II MHC (antigen- presenting cells) cell types and their roles in the immune system.
Explain the role of antigen-presenting cells in both specific and non-specific defenses.
Define cytokines and their role in the immune system.
With respect to T cells (helper and cytotoxic) and B cells (plasma cells):
- Describe how each cell type is activated.
- Describe the function of each cell type after activation.
- Describe the role of memory cells produced after activation.
- Predict the outcome if any cell type fails to function.
Outline the role of antibodies and their major effect on invading pathogens
Analyze how vaccinations help achieve immunity.

Major Immunity Questions

How do pathogens enter our body?
How does our body “recognize” a pathogen?
What is the difference between non-specific and specific immunity?
How are immune cells activated?
What are antibodies and how do they help with immunity?

Lymph Flow

Interstitial fluid enters lymphatic capillaries, is filtered by white blood cells in lymph nodes, and transported back to the bloodstream at the left and right subclavian veins.

Lymph Nodes

Lymph nodes house white blood cells that help with immunity.
Lymph enters the node and travels through sinuses where white blood cells are located.
Capillaries provide oxygen and nutrients for the cells.

Pathogens

Pathogens are varied and cause disease/infection in a host organism, leading to an immune response.
- Cellular (Living) Pathogens
  - Viruses: Multi-celled but can only reproduce inside a plant, animal, or person.
  - Bacteria: Tiny one-celled creatures that can live inside or outside the body.
  - Fungi: Multi-celled but plant-like, taking nutrition from a plant, tree, or animal.
  - Parasites: Actual complex living organisms that can live in the intestinal tract or bloodstream.
  - Protozoa: One-celled creatures usually spread through water.
- Acellular (Non-living)
  - Virus
  - Prion: Multi-celled but can only reproduce inside a plant, animal, or person.

Nonspecific vs. Specific Defenses

Nonspecific Defenses:
- External Barriers: Integumentary system (skin, dryness, acidity), mucous membranes (trap pathogens).
- Phagocytic Cells: Remove pathogens by engulfing them.
- Natural Killer Cells: Recognize and destroy certain abnormal cells.
- Fever: Increase in body temperature caused by pyrogens.
- Inflammation
Specific Defenses: Target a single pathogen and result in future protection (immunity).
- Cell-mediated immunity
- Antibody-mediated immunity

Antigens

Molecules that have the potential to generate antibodies (create an immune response).
Most commonly proteins or carbohydrates found in the plasma membrane, envelope (virus), or cell wall of pathogens.
Antibodies (proteins) only interact with specific antigens.

Self-Antigens

“Self-antigens” also exist but normally do not trigger a response.

Nonspecific Defenses

Mechanisms that respond to all pathogens in the same way.
- External barriers: Integumentary system (skin): dryness, acidity. Mucous membranes: trap pathogens.
- Phagocytic cells: Remove pathogens by engulfing them. Includes dendritic cells and macrophages, which are critical to specific immunity because they present antigens they engulf.

Phagocytosis and Antigen Presentation

A bacterium is engulfed by phagocytosis into a dendritic cell and is encased in a phagosome.
Lysosomes fuse with the phagosome and digest the bacterium.
Immunodominant epitopes are associated with MHC II and presented on the cell surface.

Natural Killer Cells

Recognize certain types of abnormal antigens presented by cells infected by viruses or by abnormal cells (e.g., cancer).
Results in destruction of the infected cell.

Fever

Increase in body temperature caused by pyrogens (chemicals) released during phagocytosis.
Results in brain “resetting” body’s thermostat.
Increases metabolism to speed up immune response.
Fevers are a natural response to infection and may be beneficial.

What Happens When a Pathogen Enters the Body?

Pathogen enters extracellular space and gets sucked into lymph vessels, then travels to lymph nodes and can interact with B cells.
Pathogen is engulfed by macrophages at the site of injury.
Pathogens “trick” our cells and gain entry into the cytoplasm, then use cells to make more pathogens = infected cells.

Specific Defenses

Target a single pathogen and result in future protection (immunity).
- Cell-mediated immunity: Antigen-presenting infected cells activate and are killed by cytotoxic T-cells.
- Antibody-mediated immunity: Antigens activate the production of antibodies by B-cells.
Two systems above are coordinated and require Helper T-cells.
Helper T-cells are activated by “professional” antigen-presenting cells such as dendritic cells and macrophages.

Antigen Presentation

Both infected cells and “professional” antigen-presenting cells “show” or “present” antigens to cells of the immune system (T cells).
Antigens can be self or foreign.
Presented on 1 of 2 types of MHC proteins: Class I and Class II.
Although both classes present antigens, they use different proteins that affect the type of cell that can recognize the antigen.

MHC – Major Histocompatibility Complex

MHC – family of protein complexes specialized for presenting antigens.
- MHC Class I: found on all nucleated cells. This class presents antigens when the cell reports "HELP – I’M INFECTED!!! KILL ME!!!”
- MHC Class II: found only on antigen-presenting cells (APCs). This class presents antigens when the cell reports “HEY LOOK WHAT I FOUND. IT’S A FOREIGN ANTIGEN. FIND AND DESTROY!!!”
“Professional” APCs:
- Macrophages
- Dendritic cells

Activation of Helper T Cells

This step is required to activate ALL immune responses.
Start with inactive TH (helper) cell. Inactive TH cell binds antigen presented by class II cells (professional APCs).
Activated TH cell divides.
Activated TH cell secretes cytokines, which are small proteins that cause changes in many cell types and help stimulate TC cells and B cells and non-specific responses.
Activation also causes differentiation of memory TH cells, which are stored in lymph nodes for a faster response with the next encounter of the same antigen.

Activation of Cytotoxic T Cells

Occurs at the same time TH cells are being activated but requires TH cells for full activation.
Initiates cell-mediated immunity à TC cells killing infected cells.
Start with inactive TC cell. Inactive Tc cell binds antigen presented by class I cells (infected cells). Further activated by cytokines produced by TH cells.
Activated TC divides to create a specific army of cells.
Activated TC cells attack infected cells (class I) with the same presented antigen, resulting in cell lysis (breaking open).
Activation also causes differentiation of memory TC cells, which are stored in lymph nodes for a faster response with the next encounter of the same antigen.

B Cell Activation

Happens at the same time as other responses.
B cells have antibody receptors for specific antigens on the cell surface.
Sensitization à Receptor binds antigen, engulfs, and presents on MHC II.
Activation à Bind TH cell activated with the same antigen, “Co-stimulation”. This is a required step to prevent an accidental activation of B cells.
Produce plasma cells à make and secrete antibodies.
Produce memory B cells à faster response if exposed to antigen again.

Antibodies

Have several modes of action:
- Neutralization à bind to part of antigen that is toxic.
- Agglutination à antibodies bind to multiple antigens causing them to stick together and prevents transport throughout the body.
- Improved phagocytosis due to the presence of bound antibodies.
- Precipitation of antigens from body fluids.

Specific Resistance Recap

Specific response occurs in lymph nodes, which get swollen when you are sick.
Immunity creates a memory of disease, leading to a quick response if presented with the same antigen because of memory T and B cells in both the cellular and the antibody response.
Vaccines also generate immunological memory, stimulating the immune response using dead antigen or attenuated viruses, so T and B memory cells are produced so if faced with the same disease your immune system launches a fast attack. The vaccines generate the same benefits as memory cells.