Antibodies, Serology, Humoral Responses, and Vaccines

Antibodies & Serology

Viral Meningitis

  • Viral Meningitis is an infection caused by a virus.
  • Diagnosing a patient often involves looking for antibodies rather than the pathogen itself.
  • Doctors may look for antibodies to identify the virus because:
    • The virus may have been cleared from the body or be present in low amounts.
    • Viruses are tiny and replicate inside cells, making them hard to detect.
    • Antibodies remain in the body longer than the virus.
    • Detecting antibodies is like finding crime scene tape, even if the criminal has left.
  • B cells produce specific antibodies, which act as weapons against specific viruses.
  • Finding Polio-specific antibodies indicates the body has been fighting Polio.
  • A high white blood cell count (WBC) indicates something is wrong but doesn't identify the specific virus. Antibodies are more specific.

Antigen vs. Antibodies vs. Antigenic Determinants

  • Antigen: Anything that stimulates an immune response.
    • Can be a pathogen like a bacterium or virus.
    • An antigen only means the immune system responds to it (e.g., an allergy to dust).
  • Antibody: A protein made by the immune system in response to an antigen.
  • Antigenic determinant (epitope): The precise part of the antigen that the antibody binds to.
    • The site on the antigen where the antibody attaches.
    • An antigen can have multiple antigenic determinants.
About Antigens
  • Triggers the immune system.
  • Include microbial cells, foreign cells (human and animal cells causing rejection reactions), and allergens (plant dust mites, peanuts, etc.).
  • "Good" antigen: Stimulates a strong antibody response due to a complex structure with many antigenic determinants.
  • Poor antigen: Does not stimulate a large response.
    • Repetitive antigens with only one antigenic determinant don't stimulate a large response.

Structure of an Antibody

  • Antibodies are proteins called immunoglobulins.
Diagram Explained
  1. Basic Structure of Antibody
    • Contains two heavy chains (long, identical) and two light chains (shorter, identical).
    • Variable Region (Fab): different for every antibody, and is what recognizes the specific antigen (aka epitope)
    • Constant Region: lower part of the Fab region that helps support the structure. Part that is same for all antibodies of the same class.
    • Antigen-binding sites are located at the tips of the variable regions.
  2. Functional Regions of Antibodies
    • The Y-shaped body has two parts:
      • Top arms of the Y (tips) = Fab (Fragment, antigen-binding).
      • These tips vary from antibody to antibody (variable region).
      • Contain antigen-binding sites (two per arm).
      • Physically binds to the epitope (antigenic determinant).
  3. Disulfide Bonds
    • Chemical bonds hold heavy and light chains together.
    • Connect the two heavy chains down the center, maintaining the Y-shape to be sturdy and stable.
  4. Hinge Region
    • Located at the bend of the Y.
    • Provides flexibility so the antibody can adjust its arm to bind multiple antigens at once.
    • Crucial for agglutination (clumping antigens together).
  5. Fc Region (stem of the Y)
    • Fc (Fragment, crystallizable).
    • Same in all antibodies of the same class.
      • Functions:
        • Complement binding site: triggers the complement system.
        • Signals to immune cells like macrophages and NK cells to destroy what the antibodies are bound to.

Antibody Classes

  • Antibody classes approach their jobs differently:
    1. IgG (Immunoglobulin Class G)
      • Monomers, act as memory antibodies.
    2. IgA
      • Dimers connected by a J-chain with a secretory component for secretion.
      • Found in mucus, tears, and cervical secretions.
    3. IgM
      • Pentamer (5 copies attached).
      • Can bind to 10 different antigens.
      • J-chains hold the monomers together.
      • First antibody produced in response to an antigen.
    4. IgD
      • Monomer that acts as a receptor on B cells.
      • Binds antigens to activate B cells (B-cell receptor).
    5. IgE
      • Monomers involved in allergy responses (hay fever, pet allergies).
  • The constant region determines the antibody class (IgE antibodies have identical constant regions).
  • Variable tips differ, allowing IgE to bind to various allergens.

What do Antibodies Do?

  1. Opsonization: Antibodies coat the antigen and increase phagocytosis.
  2. Agglutination: Antibodies bind to multiple antigens, clumping them together and deactivating them.
  3. Complement fixation: Antibodies activate complement, leading to the lysis of the antigen.
  4. Neutralization: Antibodies bind to the surface of the antigen, blocking its ability to attach to host tissues.

Serology

  • In Vitro diagnostic testing of serum.
    • Serum is the acellular portion of the blood.
    • In vitro means testing outside the patient in the lab.
Diagnosing in Serology
  1. Using a known Antigen -> look for antibodies
    • Trying to see if a patient was exposed to something, and if this person has antibodies against this specific pathogen?
      • Use a known antigen (piece of a virus or bacteria).
      • Mix with the patient’s serum (which may contain antibodies).
      • If antibodies bind to the antigen, it indicates a match.
      • Tells you if the patient was exposed/infected in the past or if they got vaccinated.
  2. Use a Known Antibody -> Look for Antigen on a Pathogen
    • Used to identify a mysterious microbe using known antibodies.
      • Take the unknown bacteria/virus growing.
      • Add known antibodies (commercially bought).
      • If they bind, it identifies the antigens on the microbe.
  • Serology is useful because of:
    • Specificity: Incredibly specific for the antigen they bind to.
    • Sensitivity: Can detect even tiny levels of antibodies or antigens.

Examples of Serological Tests

  1. Direct Fluorescence Test: Testing syphilis.

    • Fluid from a lesion is placed on a glass slide.
    • Anti-syphilis antibodies attached to a fluorescent molecule are added.
    • Fluorescence indicates syphilis is present. IF there's no fluorescence, there's no syphilis antigen.

  2. Agglutination Test: Used for blood typing.

    • Antibodies form crosslinks between whole cell antigens, creating complexes that clump together.
    • The clump formation shows there’s been an interaction between the antigen and the antibody.
      • Take the patient’s blood.
      • Mix it with specific antibodies, A antigen, or B antigens.
      • If clumping occurs, then it means the antigen is present on the blood cell. Ex: if clumped with anti-A, blood has A antigen = type A blood
      • Clumping indicates a reaction with the antigen.

  3. Precipitation Test: Looking for individual protein or part of the virus, not an entire cell

    • Detect soluble antigens and antibodies.
    • Sample from a patient is mixed with a known antibody.
    • Antigen-antibody complexes form precipitates and fall out of solution.
      • Agar Plate
        • Center circle contains the antigen, diffusing outward.
        • Outer wells contain different test sera (antibodies).
        • Control Ab = antibody that we know will react
        • Test serum 1 and Test serum 2= patient sample (antibodies unknown)
        • Precipitation band forms if the antibodies match the antigen.
        • Positive: there will be a precipitation band
        • Negative: no band
        • Control Ab = banding (positive control)

  4. Western Blot Test: Looking at Protein

    • Known antigen is broken down and separated via electrophoresis.
    • Proteins are transferred to a membrane.
    • The membrane is incubated with patient antibodies, labeled with a radioactive dye.
      • Proteins from HIV (e.g., gp41, p24, p31) are separated by size and stuck to a membrane.
      • Patient’s serum is added (if it contains antibodies against any HIV proteins, those antibodies will bind to the bands).
      • Secondary antibody with an enzyme is added that lights up the spots.
      • Visible bands form where the patient has antibodies.
      • SRC (Serum Control): Control sample with known HIV antibodies.
      • Day 0: No bands (person hasn’t made antibodies yet).
      • Day 9: Faint bands start to appear (early antibody production).
      • Day 14–30: More bands appear over time as the immune system makes antibodies to more HIV proteins.

  5. Enzyme-linked immunosorbent assay (ELISA)

    • Direct ELISA: Searches for the antigen in the patient’s serum using known antibodies.
      • Plastic plates with wells are coated with a known antibody.
      • Patient’s semen is added.
      • If the antigen is present, it will bind to the antibody.
      • An enzyme is added that changes color, indicating a positive sample
    • Indirect ELISA: Looks for antibodies in the patient’s serum using a known antigen.
      • Plastic wells are coated with a known antigen.
      • Patient’s serum is added. If the antibodies are present, they will bind the attigen.
      • A color change indicates that antibodies against the antigen are present.

Overview of Humoral Responses (Antibody Production)

  • Antibody production is done via B lymphocyte (B cell for short) -> part of those specific immune cells in 3rd line of defense.
  • B cells are made in the bone marrow (like all blood cells are) and then go through a maturation process called clonal deletion that happens in the bone marrow as well.
  • Once mature,- B cell goes to the lymph nodes.
The Big Picture of B Cell Responses
  • Clonal Selection and Differentiation of B Cells
    • B-cells are highlight selective. Has a unique receptor that binds to only one specific antigen
    • In the lymph node, as fluid is flowing over the surface, an antigen shows up, and it is going to bind to the B-cell with the correct B-cell receptor.
    • The moment the antigen binds to the B-cell receptor is called clonal selection.
    • Once the B-cells get activated, they go through many rounds of cell division, which is known as clonal expansion.
    • Two types of cells are made
      • Memory B-cells
        • Cells stick around in lymph nodes
        • Wait for possible reinfection by the same antigen
      • Plasma cells
        • Immediately secretes antibodies, specifically IgM- the first antibody produced in a new immune response.
        • Designed to bind to the same antigen that originally activated the B-cell
  • TLDR: A whole group of B-cells with unique receptors patrols the lymph nodes. When the correct antigen binds to a matching receptor:
    • The B-cell is activated (clonal selection)
    • Divides into memory cells and plasma cells (clonal expansion)
    • Plasma cells produce IgM to attack the antigen ASAP.

Creation and Maturation of B Cells

How to make a repertoire of B-cells
  • B Cells
    • Made and mature in the bone marrow
    • Has one specific B-cell receptor
    • How is it so specific?
      • B-cell receptor is an IgB antibody stuck on the B-cell.
      • Specificity of anti-Boyd is the same as that of IgD.
      • B-cells themselves have the same DNA, but have different receptors on the surface.
      • As a group, they look for a lot of different things.
      • Allows the immune system to respond to just the right antigen
  • How does this happen?
    • MHC- self tag. When we make MHC during development, we randomly select an exon from the MHC genes, and that makes our specific tag. Random selection of an exon is what B-cells use to get their specific receptor.
    • The genes used to make B-cell receptors are called immunoglobulin genes—there are two types: one for the heavy chain and one for the light chain.
    • During development, the B-cell will randomly select exons from these genes and put them together to form its specific B-cell receptor. Much like the MHC. Whatever B-cell receptor is made, that’s what is going to control what kinda of antibodies are made by future plasma cells.
  1. During B-cell development, exons from these genes are randomly selected and stitched together to build that B-cell’s unique receptor, kind of like how MHC is made. Once that B-cell receptor is built, it determines what kind of antibody the B-cell will eventually produce as a plasma cell. For example, one of the heavy chain genes might randomly select 1 out of 80 exons, then 1 out of 12, and 1 out of 4, just to make one side of the receptor. Then, for the other side, it might select from 100 or even 5 different exons. When you do the math, that creates about 1.92 million different combinations, meaning your body can create B-cells with receptors for 1.92 million different antigens using just two genes.
  • One possible downside and danger: There’s a chance a B-cell could accidentally make a receptor that binds to self-tissue, like heart tissue, which would be catastrophic. That’s why B-cell development includes a process called clonal deletion, where B-cells that react to self-antigens are destroyed before they’re released. Only the B-cells that don’t bind to self-tissue are allowed to "graduate" and head to the lymph nodes, where they wait to encounter their specific antigen.

The T helper helps the B Cells

  • T helper cells release cytokines to control the B cell activation
Classes of MHC
  • MHC1 self-tag that’s found in all body cells (except RBC)
  • MHC Class 2 (MHC2) is only made by a few different kinda of cells called antigen-presenting cells
    • B-cells are one of these antigen-presenting cells -> make MHC2
    • T-helpers will bind to MHC2 when they activate the B-cell
Compare & Contrast- MHC1 and MHC2
  • Class I- made and presented by all cells of the body (except RBCs)
    • This is the self tag, and cytotoxic T cells bind to it
  • Class II- made and presented only by certain cells, like B cells
    • Presents bits of digested foreign antigens
    • T helper cells bind to MHC II via their T cell receptors and CD4
Info on T helper Cells
  • T helper cells are a type of T lymphocyte that are WBC
  • T helper cells are made in the bone marrow and mature in the thymus
  • Mature T helper cells can be found in lymphoid tissue, including lymph nodes
  • T-helpers do have T cell receptors that will bind to MHC II in an antigen-presenting cell, like a B cell
  • T helper cells have an additional receptor- Cluster of Differentiation 4 (CD4)
  • T-helpers influence other immune cells by releasing cytokines
  • T helper cells can differentiate into T helper 1 cells or T helper 2 cells

The Specifics of B-cell Activation with T helper cells

  1. As the lymph fluid flows by the lymph node, if the antigen shows up, it will bind to a B- cell receptor.
  2. Because the B-cell is an antigen-presenting cell, it will ingest the antigen and break it down into small fragments, then present those small fragments on its MHC Class 2.
  3. The cell that interacts with MHC Class 2 is a T helper cell, and its T-cell receptor has to recognize both the antigen and the MHC Class II molecule at the same time, because the T-cell receptor needs to see both.
  4. There’s a helper molecule involved called CD4. Which is like a docking protein, assisting the T-cell receptor in binding. Once that connection is made, the B-cell releases a cytokine called interleukin-4 (IL-4). IL-4 tells the T helper cell to differentiate into a T helper 2 (Th2) cell. Now that it’s a T-helper 2 cell is going to release more IL-4 along with another cytokine called B-cell growth factor. The combination of IL-4 and B-cell growth factor causes B-cells to start dividing and going through cell clonal expansion and rapidly dividing and making two types of cells: memory B cells and Plasma cells. Membrane B cells are going to hang out at lymph nodes for future infection. Plasma cells will start to secrete an antibody, called IgM. It is a pentamer antibody. Antibodies will go and bind specifically to the antigen, and when it’s attach, it’s stimulate it’s destruction via opsonization, agglutination, neutralization, and complement fixation.

The Memory Response

  • Memory B cells, what do they do?
  • B cells start colonizing and expanding, producing both memory B cells and Plasma cells.
  • While Plasma cells immediately spew out IgM antibodies to kill the antigen, Memory B cells wait in the lymph nodes in case the same antigen returns.
  • If it does return, the Memory B cell will respond very quickly and in an enormous way by releasing huge quantities of the memory antibody- IgG.
Memory B Cells & Antibody Response
  1. Primary Response:
    • The first interaction the immune system has with an antigen. During primary response, clonal selection (finding the matching antigen) occurs. The B cell interacts with a T helper cell, which helps activate it, and clonal expansion (copies of itself)
    • This process takes time (like days), so there is a lag before any antibodies appear in the blood
    • Most antibodies at this stage will be IgM, but if the infection lasts long enough, few memory cells or long-lasting antibodies will be made as well.
    • Plasma cells die off after doing their job, but the memory B cells stick around the lymph nodes, ready to respond faster if the antigen shows up again.
  2. Second Response
    • If the pathogen returns, the Memory B cells are ready to react
    • Immediately start to release HUGE quantities of their memory antibody, IgG.
    • The entire primary response repeats, so plasma cells eventually release the same amount of IgD and MUCH larger amounts of IgG. This response is so fast and powerful- it usually stops the infection before you feel sick.
  3. Vaccination
    • In vaccination, introduce the antigen (not the pathogen). Vaccination’s goal is to stimulate clonal expansion so your body will have memory B cells against the pathogen; that way, if you’re exposed to the pathogen later in life, memory B cells will protect you with IgG!

Vaccines & Prophylaxis

  • Vaccination is most important, leading to a decrease in disease.
  • The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) often update the schedule of immunization.
  • Vaccines are listed and referred to by the name of the disease (or pathogen).
  • Some immunizations are combos -> one shot protects you from multiple pathogens.
  • The immune system has memory; after the first infection, the immune system learns it. If it tries to infect you again, your immune system can identify it as not JUST a foreign substance but a dangerous one as well. The body gives a stronger, faster response, preventing the disease from being as severe.
  • The vaccine delivers a person to material that is antigenic (generates antibodies and “warns” the immune system) but not pathogenic (disease-causing). This stimulates the primary and secondary response, which prepares the immune system for future exposure to a virulent pathogen.
  • Immunizated people have the benefit of immune response to future exposure will be immediate powerful and substantive.
Different Types of Vaccination
  1. Inactivated Vaccines
  2. Live-attenuated vaccines
  3. Subunit (including recombinant, polysaccharide, and conjugate) vaccines
  4. Toxoid vaccines
  5. Messenger RNA (mRNA) vaccines
  6. Viral Vector Vaccines
Inactivated Vaccines
  • The designed pathogen is grown and then treated with heat, chemicals (like formalin), or some other agent that kills the microbe but doesn’t destroy its antigenicity.
  • Killed or inactivated viruses will still stimulate immunity. Whole cell vaccines often require a larger dose and more boosters to be effective, ex, flu (injection)
Live, Attenuated (weakened) Vaccines
  • The pathogen is alive but weakened, meaning not dead but too weak to cause disease in a healthy person.
  • The pathogen undergoes a genetic mutation that reduces its virulence factors.
  • They are still capable of multiplying and stimulating immunity inside the body, but they will not cause illness. But rather, it can recognize the pathogen and build immunity.
    • Pros
      1. The organism can multiply and produce an infection (not a disease) like a natural organism.
      2. Long-lasting protection
      3. Usually requires fewer doses and boosters
    • Cons
      1. Requires special storage -> since they’re alive, they need to be kept in the cold.
      2. It can be transmitted to other people can cause infection in immunocompromised individuals (since it’s alive, it can replicate and spread to someone else)
      3. Can conceivably mutate back to a virulent strain (revert to a dangerous version)
Subunit or Acellular Vaccine & Conjugate Vaccines
  • In these vaccines, the exact antigenic determinant (specific part of the pathogen that triggers an immune response) is known.
  • Rather than injecting the whole organism, they use those specific molecules.
  • Less risky than exposing someone to the pathogen, but the immune response is usually weaker compared to a live-attenuated vaccine.
  • The antigenic determinant can be taken from a pathogen culture, made from using genetic engineering, or synthesized in the lab. However, sometimes the antigen is so small or simple that the immune system doesn’t react strongly enough.
  • That’s where conjugate vaccines come in. Scientists attach the antigen to an extra protein called an adjuvant to boost the immune response and help the immune system recognize it more easily.
    • Examples
      • Capsule-based vaccines: pneumococcus, meningococcus
      • Surface protein-based vaccines: Anthrax, Hepatitis B
      • Conjugate vaccines: Haemophilus influenzae type B (Hib), where a capsule antigen is paired with a protein to make it more immunogenic
Toxoid Vaccines
  • Made by taking bacterial toxins and inactivating them to not cause disease
  • Used when the bacteria itself isn’t causing the problem, but the toxin it produce is.
  • The toxin (exotoxins) is treated with chemicals like formalin, making it harmless but still antigenic.
  • Your body learns to fight off the real toxins if they ever show up.
  • Ex: zteatnus and Pertussis (whooping cough)
mRNA Vaccines
  • Vaccines that use messenger RNA (mRNA) packaged within a lipid coating
  • When mRNA gets into your cells, it provides them instructions to make viral protein so that your immune system to react to it.
  • In both Moderna and Pfizer/BioNTech vaccines, the mRNA contains information for making the SARS-CoV-2 spike protein. It causes the immune system to produce antibodies against the spike protein. So if the body encounters the actual Coronavirus that causes COVID-19, it’s prepared to fight off the infection.
Viral Vector Vaccines
  • Uses a weakened version of live virus, but a different virus than the ones that cause the disease
  • The virus is called a vector, and scientists insert genetic material from the real pathogen into it.
  • When the viral vector enters the human cells, the genetic material gives instructions to make a protein from the real virus, like the other vaccines. Once the cell makes a copy of the protein, the immune system recognizes it and begins making antibodies against it.
  • Ex: Johnson & Johnson vaccine uses a harmless adenovirus (a type of cold virus) as the vector. It carries DNA instructions for making the SARS-CoV-2 spike protein. Once the cell makes copies of the spike protein, the immune system recognizes it and starts making antibodies against it.

Prophylaxis

  • A form of chemotherapy in which drugs are administered to prevent an infection from happening
  • Used in cases of known or possible exposure
    • Examples
      • In dental procedures, patients are given antibiotics ahead of time to prevent bacteria from their mouth getting into their bloodstream. Since the mouth has a ton of microbes, this precaution makes sure that any bacteria that leak into the blood are killed right away before there is an infection.
      • Another example is during an epidemic. If there’s an outbreak, like meningitis caused by Neisseria meningitidis in a boarding school/military camp, everyone exposed is given mass prophylaxis (usually antibiotics) to prevent them from getting sick.
      • Another form of prophylaxis is immunotherapy. It’s when someone at risk is given prepared antibodies against specific pathogens.
Two types of preparations
  1. Immune Serum Globulin (ISG)
    • Known as gamma globulin. Antiserum that comes from the pooled blood of 1000+ human donors. Since they are vaccinated, their blood contains a mix of antibodies. These are concentrated to protect the immunodeficient patients or people exposed to diseases like measles and Hepatitis A.
    • Given as an injection into the muscle, and provides protection last 2-3 months. ISG gives temporary general protection and is mainly used when a person’s immune system can’t defend itself well.
  2. Specific Immune Globulin (SIG)
    • Comes from a more specific group of donors- people who recently recovered from an infection.
    • Since they have high levels of antibodies, they are called hyperimmune.
    • Serum is full of targeted antibodies against diseases like tetanus, chickenpox, and hepatitis B, or even bacterial toxins.
    • SIG is preferred over ISG because it contains more specific antibodies, but not as easy to find
    • SIG is used when you need fast, strong protection against one specific disease
    • If not available, doctors can use antiserum made from animals (usually horses). Used for emergencies like botulism, rabies, or venom from snakes and slithers. The downside is that some people are allergic to horse protein, which can cause a reaction.n
      • EX: Horse-derived antiserum - made by injecting horses with a small, safe amount of a pathogen like the rabies virus so their immune system produces strong antibodies. These antibodies are then collected, purified, and given to humans exposed to the disease to provide immediate, temporary protection. This is especially useful in emergencies, like after a potential rabies exposure, when the person hasn’t been vaccinated. Since the antibodies come from horses, there’s a risk of allergic reaction, so it’s only used when human-derived antibodies aren’t available.

Antigen Presenting Cells and T helper 1 Cells

  • Remember- B cells are a type of Antigen Presenting Cell (APC) because they activate T- helper cells using their MHC.
  • An Antigen Presenting Cell is any cell that can make MHC. T-helper cells only bind to MHC II, so only APCs can activate them. Only 3 types of APC in the body
    • B Cells
    • Macrophages
    • Dendritic Cell
  • What happens if Antigen antigen-presenting cell is a macrophage or dendritic cell
    • Macrophages/Dendritic Cells do not specifically look for any antigen, just gobble up anything that is non-self.
    • Ingesting and digesting our antigen and presenting pieces of that antigen on MHC class 2.
    • Then T-helper comes, and has a T-cell receptor. Binds to antigen and self MHC class 2. It’s CD4.
    • If it were a B-cell, it would release IL-4. But it’s not, it’s a macrophage/dendritic, it will release IL-1.
    • Interleukin 1 will cause the T helper to differentiate into a T helper 1.
    • T-Helper 1-> releases IL-2, activates cytotoxic T, natural killers, and other T helpers, and macrophages. Gerenuk-like amplifying signal speeding up immune reactions everywhere.
    • This is a general alarm signal to activate many of the immune cells.s

List of Different Cytokines

  1. Cytokines: chemical messenger molecules that communicate between immune cells
  2. Interleukin 1: activates T-helper cells to become T-Helper 1 when produced by bound APC
  3. Interleukin-2: made by Th1 to activate various immune cells like macrophages, natural killers, and cytotoxic T cells
  4. Interleukin-4: Activates T-helper cells to become T-Helpers 2 when produced by the bound APC. Also produced by T-Helper 2 cells to help activate B cells.
  5. B-Cell Growth Factor: Made by T-Helper 2 to activate B cells
Activated T-Helper Differentiation
  • B-Cell: release il04, will differentiate into T helper 2 and would release IL-4 and B-cell growth factor, encouraging clonal expansion
  • Macrophage/Dendrites: releases IL-1 -> causes T Helper differentiation into T-Helper 1 -> releases IL-2 (general activating cytokines that activate many immune system cells)
  • Because the T cell is part of the specific immune system, you get memory T. You get them regardless of whether they become a T-helper 1 or T-Helper 2.
  • T-Helper 2 has an unusual ability, it can secrete inhibitory cytokines that would inhibit the T-helper 1
    • It is important because if the body has long-term immune reactions, it can start to damage its the self-tissue. You need that ability to turn down the immune system, and it’s done by the T-Helper 2. Releasing the inhibitory cytokine and telling the T -helper 1 - knock it off, you’re causing too much damage.

TLDR

  • Macrophages/Dendrites → IL-1 → TH1 → IL-2 → Activates many immune cells
  • B-Cell → IL-4 → TH2 → IL-4 + B-cell growth factor → Activates B cells
  • Memory T cells are made either way.
  • TH2 can shut down TH1 to prevent self-damage