Specific Types of Immune System Responses: Comprehensive Study Guide

Overview and Contributors

• Topic: The Immune System: Specific Types of Responses.

• Authors/Contributors: Belinda, Eugenia, Nadine, and Victorio.

Antibodies: Immunoglobulins ($Ig$)

• Definition and Structure: Antibodies, also known as Immunoglobulins ($Ig$), are specialized defender proteins. They are characterized by a distinct $Y$-shaped structure.

• Origin and Purpose: These proteins are created by immune cells to assist in the destruction of harmful antigens.

• Primary Functions:

  • Recognition and Prevention: They help recognize pathogens and prevent them from damaging healthy cells.

  • Triggering Responses: They initiate response mechanisms within the body's defense system.

  • Production: Antibodies are produced specifically by lymphocytes.

• Mechanism of Action:

  • Circulation: They circulate through the blood and lymph, actively searching for foreign cells or pathogens.

  • Marking: They "tag" or mark pathogens so they can be recognized and subsequently destroyed by phagocytes.

  • Binding: Antibodies bind with antigens at an antigen-binding site. This interaction is often compared to a puzzle piece fitting together.

• Phagocytes: These are cells that engulf and digest debris, pathogens, and dead cells.

Antigens: Triggers for Immune Response

• Definition: Antigens are foreign substances on the surface of a pathogen, recognized by the body that trigger an immune response. They typically refer to a small part of a cell or a virus.

• Chemical Components: Antigens can be composed of various chemical structures, including:

  • Proteins: Examples include snake venom and pollen.

  • Polysaccharides: Examples include foreign blood types.

  • Lipids: These are common but usually require a protein to be effectively recognized.

• Main Groups of Antigens:

  • Exogenous Antigens: Originating from the external environment (e.g., bacteria, viruses, fungi).

  • Endogenous Antigens: Originating from within the body (e.g., genetic mutations, internal infections).

  • Allergen: Antigens that specifically trigger allergic reactions.

  • Autoantigens: Components of the body’s own tissues and cells that the immune system mistakenly identifies as harmful, leading to autoimmune diseases.

The Connection Between Antigens and Antibodies

• Structure Specificity: Each $Y$-shaped antibody contains paratopes located at the tips (antigen-binding sites).

• The Look and Key Model:

  • Paratopes: Located on the antibody tips; each paratope has a unique shape.

  • Epitopes: Antigenic determinants found all over the antigen (the "grip points").

  • Binding: Each unique paratope matches a complementary epitope, allowing for precise binding between the antibody and the antigen.

Lymphocytes and Maturation

• Definition: Lymphocytes are a broad category of White Blood Cells (WBC) that are uniform in appearance. The category includes $T$ cells, $B$ cells, and Natural Killer cells.

• Specificity: Different lymphocytes recognize different determinants (epitopes).

• Origin: They originate from hematopoietic stem cells inside red bone marrow.

• Hematopoietic Stem Cells: These are self-renewable cells that differentiate into red blood cells, white blood cells, and platelets (colorless cell fragments in the blood that form clots to stop bleeding and heal wounds)

• Immunocompetence: This state is reached after maturation. It refers to the ability of the cell to recognize particular antigens.

• Surface Receptors: Maturation involves the production of surface receptors devoted to a specific antigen shape.

• Self-Tolerance and Apoptosis:

  • Lymphocytes must be able to recognize the body's own cells and must not attack them.

  • If a lymphocyte is unable to distinguish self from non-self, it undergoes apoptosis (programmed cell death).

• Brief Functional Overview:

  • $B$-Cells: Produce antibodies to tag and neutralize threats.

  • $T$-Cells: Directly destroy infected cells.

Adaptive Immunity

• Definition: Also known as the third line of defense, involving primary and secondary responses.

• Activation: It is activated when the innate (non-specific) immune system fails to eliminate a pathogen on its own.

• Characteristics:

  • It is a specialized and targeted defense system.

  • It responds slower than innate immunity but is highly specific.

• Primary Components: Lymphocytes.

• Types of Responses:

  • Humoral immune response.

  • Cellular immune response.

Humoral Immune Response

• Primary Focus: Attacking germs in the blood and lymph before they can invade the cells.

• Step-by-Step Process:

  1. Recognition: A $B$ Cell discovers a germ where the epitope shape matches the $B$ Cell’s paratopes. The $B$ Cell then engulfs the pathogen, processes it, and displays it on its surface.

  2. Activation: This requires confirmation/verification from an Antigen-Presenting Cell (APC) and a Helper $T$ Cell. The Helper $T$ Cell (derived from a Naive $T$ Cell) releases cytokines.

     • Cytokines: Act as an "alarm" to alert other cells ($B$ cells) of a detected antigen:

     • TH1: releases a molecule that activates macrophages and, to an extent, killer T cells to eliminate foreign substances

     • TH2: activates B-cells that release antibodies, as well as releasing cells to remove foreign substances through coughing, sneezing, etc.

  3. Cloning: The verified $B$ Cell begins to create numerous copies of itself.

  4. Release of Antibodies: The cloned $B$ cells become Plasma cells, which release antibodies into the blood.

  5. Tagging: The released antibodies stick to the epitopes on the germs. This allows other WBCs to identify and destroy the antigens.

Cellular Immune Response

• Primary Focus: Attacking cells that have already been invaded by a virus or have become cancerous.

• Step-by-Step Process:

  1. Signal: A piece of a germ is pushed outside the cell membrane as a "flag" (antigen). The cell places this piece on its surface to become an Antigen-Presenting Cell (APC).

  2. Verification: The APC releases cytokines to attract the Helper $T$ Cells. A Helper $T$ Cell binds its receptors to the antigen on the APC to activate themselves.

  3. Cloning: The Helper $T$ Cell divides rapidly by mitsosis into T memory cells and T killer cells. It releases interleukins that stimulate B cells to produce more antibodies and stimulate T phagocytes to engulf more pathogens. It also releases more cytokines, which activate Killer $T$ Cells (previously Naive $T$ Cells).

  4. Identification: Driven by cytokines, Killer $T$ Cells search for and quickly identify infected cells.

  5. Destruction: The Killer $T$ Cell binds to the infected cell and releases specialized proteins:

     • Perforins: Create holes in the cell membrane.

     • Granzymes: Enter through the holes to trigger apoptosis (cell death).

  6. Memory: Once the infection is cleared, most $T$ cells die, but Memory $T$ cells remain.

Specialized $T$-Cells

• Memory $T$-Cell:

  • Acts as the immune system's memory.

  • Long-lived cells that persist after a pathogen is cleared.

  • During a second encounter with the same pathogen, they multiply much faster than naïve $T$-cells.

• Helper $T$-Cell ($CD4+$):

  • Stimulates other $T$-cells and $B$-cells by releasing cytokines.

  • Subtype $TH1$: Releases molecules to activate macrophages and Killer $T$-cells.

  • Subtype $TH2$: Activates $B$-cells for antibody production and releases cells to remove substances via physical means (coughing, sneezing).

• Killer $T$-Cell ($CD8+$):

  • Also known as cytotoxic $T$ lymphocytes.

  • Frontline defense that identifies and destroys virus-infected or cancerous cells.

  • Utilizes cytotoxic proteins like perforin and granzymes.

• Regulatory $T$-Cell ($Tregs$):

  • Marked by $CD25$. These cells regulate the immune system to prevent overreactions.

  • Induced Tregs ($iTregs$): Target foreign antigens.

  • Natural Tregs ($nTregs$): Target self-antigens to control autoimmune inflammation.

  • Prevention: They prevent diseases like Lupus (organ targeting) and Multiple Sclerosis (destruction of the myelin sheath in the nervous system).

  • Importance of Homeostasis:

    • Balanced Population: Leads to healthy homeostasis and peripheral tolerance, preventing non-specific side effects.

    • Reduction/Loss ($Low\, Tregs$): Leads to loss of homeostasis, loss of immune regulation, and promotes autoimmunity/autoimmune diseases.

    • Increase ($High\, Tregs$): Leads to the loss of cancer immuno-surveillance, suppression of anti-tumor responses, and promotes cancer progression.

Specialized $B$-Cells

• Basic Information: Responsible for producing anti-infective antibody proteins.

• Immature $B$ cells: These are mature cells that have not yet been exposed to antigens. Upon exposure, they differentiate into plasma or memory cells.

• Plasma Cells:

  • Release corresponding antibodies based on specific antigens.

  • Mature plasma cells release approximately $2000$ antibodies per second.

  • They have a shorter lifespan than memory cells.

• Memory $B$ cells:

  • Long-lived cells formed after differentiation.

  • They do not produce large amounts of antibodies initially.

  • They remain in the body for years to trigger faster and stronger secondary immune responses.

Non-Immune Functions of B Cells

• Metabolic Regulation: $B$ cells help regulate motor function via the liver-skeletal muscle metabolic pathway.

• Consequences of $B$ Cell Decrease:

  • Significant decrease in running endurance and grip strength.

  • Reduction in spontaneous activity levels.

  • Decrease in the number of mitochondria in skeletal muscle and damage to their structure.

  • Overall decline in energy metabolism levels.

Audio-Visual Resources Mentioned

• YouTube/External Media:

  • Stocking Up on $T$ Cells that Can Remember the Flu (AAAS_org).

  • Killer $T$ Cell: The Cancer Assassin (Cambridge University).

  • Roles of Regulatory $T$ Cells | Immunology | Immune System (Biology Goal).

  • Regulatory $T$ Cells: Keeping the Immune System in Balance ($iQ$ Biosciences, $2019$).

  • $CD4+$ CELLS - HOW DOES $HIV$ AFFECT THEM? (Video link provided).

  • $B$ lymphocytes ($B$ cells) | Immune system physiology (Khan Academy).

Questions & Discussion

• Question 1: What is apoptosis and its significance in the immune system?

  • Answer: Apoptosis is the process of cell death used to avoid cells damaging self-cells.

• Question 2: Where are paratopes located and what is their function?

  • Answer: Paratopes are located on the tips of antibodies. Their function is to bind with an antigen’s epitope.

• Question 3: What would happen if the Helper $T$ Cells of an individual are unable to produce cytokines?

  • Answer: The individual’s $B$ Cells would be unable to verify the presence of the antigen and continue the response, placing the individual at high risk of their cells being further damaged.

• Question 4: Why is it better for the body to have more memory $T$-cells than naive $T$-cells when you get sick with the same virus a second time?

  • Answer: Memory $T$ Cells have the capability to remember and quickly react to viruses previously experienced, whereas Naive $T$ Cells may take time to completely react towards the virus.

• Question 5: Why can vaccines provide long-term protection?

  • Answer: Vaccines provide long-term protection by helping the immune system recognize certain pathogens to create Memory $T$ Cells for future encounters.