Immune System Study Notes

B Cells and Antibodies

• B cells are primarily responsible for producing plasma cells.
• Plasma cells create antibodies against specific antigens.
• T cells and antigen-presenting cells identify foreign substances and present them to B cells.
• B cells create clones of themselves to produce antibodies targeting those specific substances.
• Innate Response Activating B cells (IRA B cells) contribute to the innate immune response, but the main function of B cells is antibody production.

T and B Cell Maturation

• T cells mature in the thymus and are dependent on its function; hence the name T cells.
• T cells possess:
  • CD3 marker.
  • CD4 or CD8 markers.
  • CD4 binds to MHC class II molecules, while CD8 binds to MHC class I molecules.
• B cells mature in the bone marrow.

Immunoglobulins (Antibodies)

• Immunoglobulins are proteins commonly known as antibodies with broader roles in the body.
• They are large glycoproteins consisting of four polypeptide chains: two heavy and two light chains.
• The heavy and light chains have variable regions that allow for a vast number of unique combinations, potentially millions.
• Basic immunoglobulin structure is Y-shaped and functions as an antibody in various ways.

Functions of Antibodies:

• Attaching to the surface of bacteria to mark them.
• Causing bacteria to clump together (agglutination).
• Enhancing phagocytosis by adding "grippy handles" (opsonization).
• Neutralizing viruses by binding to viral landing molecules, preventing cell entry.
• Binding to toxins and neutralizing them (antitoxins), as in tetanus shots or antivenom.
• Initiating the complement system.

Five Forms of Immunoglobulins:

• IgG: Basic memory antibodies.
• IgA: Secreted in mucous membranes as a dimer molecule.
• IgM: Large pentamer, first response antigen marker, B cell receptor.
• IgD: Receptor on B cells.
• IgE: Primarily used in helminth infections and allergies; high IgE levels usually indicate an allergy or autoimmune reaction.

Antibody Titer

• Antibody titer refers to the concentration of antibodies in serum.
• It indicates exposure to an illness or immune system priming.
• Examples include titers for Epstein Barr virus or COVID-19 to assess protection levels.

Antigen Binding Sites

• Immunoglobulins have antigen-binding sites with heavy and light chains that combine to form two pockets.
• The variable region within these sites is changeable, allowing for different fits for various antigens.
• This variability is created through genetic recombination.
• The constant region is unique to each type of immunoglobulin.

T Cell Receptors

• T cells, like B cells, have receptors modified by genetic recombination, featuring both variable and constant regions.
• Unlike immunoglobulins, T cell receptors are not secreted.
• T cell receptors have antigen-binding sites similar to B cells.

Genetic Recombination for Receptor Diversity

• Variable chains combine in light and heavy chains through mix-and-match sections.
• Transcription combines different regions, creating multiple options and combinations.
• This allows for a large amount of variability in receptor structure.

Antigen Presentation and B Cell Activation

• When the body encounters an invader, antigen-presenting cells (APCs) process and chop it up.
• APCs project antigen fragments to B cells.
• Each B cell expresses a unique immunoglobulin on its surface.
• The APC presents the antigen to a "grand council" of B cells until a B cell recognizes and binds the antigen.
• This initiates proliferation and cloning of that specific B cell.
• Some clones differentiate into plasma cells that secrete immunoglobulins, while others become memory cells

Antigenicity

• Only certain molecules can serve as antigens.
• Proteins are commonly antigenic, with specific types more likely to trigger an immune response.
• Antigens can be whole microbes, partial microbes, cell substances, or molecules from other humans, animals, or plants.
• Any non-self protein-based compound can be a potential antigen.

Alloantigens

• Alloantigens are human-against-human antigens, as seen in blood typing.
• Blood types (A, B, O, etc.) have markers; for example, type A blood has anti-B antibodies in the plasma.
• Receiving a mismatched blood type can cause clumping and immune reactions.
• Blood type matching is crucial in blood transfusions and organ transplants.
• Besides ABO, the Rh factor (positive or negative) is another major marker.
• MHC compatibility is also tested for organ transplants to minimize immune rejection.
• Humans can react to another human's tissues because we aren't highly genetically diverse.
• Organ transplants typically last 10-20 years due to immune system rejection, often requiring immunosuppressant drugs to delay the process.

T Helper Cells (CD4+)

• T helper cells bind to MHC II molecules and the antigen epitope on antigen-presenting cells.
• They confirm something is wrong and produce cytokines, including interleukin-2, to promote growth and recruit cytotoxic T cells.
• T helper cells also clone themselves.

B Cell Activation by T Helper Cells

• B cells bind to an antigen, process it, and present it on MHC II receptors on their surface.
• A previously activated T helper cell matches with the B cell, activating it.
• The activated B cell clones itself and differentiates into:
  • Plasma cells: Secrete immunoglobulins.
  • Memory cells: Remain for future response.
  • Regulatory cells: Oversee the process.
• Each cell type further clones itself to fight the infection.
• Cytokines from activated T cells help B cells proliferate, and then B cells tone down the T cell response in a cellular baton-waving process.

Cytotoxic T Cells (CD8+)

• Cytotoxic T cells are mercenary cells that hunt and kill infected cells.
• They have CD8 markers.
• They secrete:
  • Porphyrins: Hole-punching molecules that cause leakage.
  • Granzymes: Attack and eliminate cell functionality.
• These cells can identify cells presenting foreign antigens on their surface.
• Cytotoxic T cells are effective against virally infected cells and play a role in cancer cell surveillance.
• They are also responsible for tissue rejection in transplants.

Other Types of T Cells and Natural Killer Cells

• Gamma delta T cells respond to PAMPs and help produce memory cells.
• Natural killer (NK) cells are lymphocytes that function similarly to cytotoxic T cells but are part of the innate immune system.
• NK cells monitor the body and kill cancerous cells.
• NK cells lack antigen receptors and primarily distinguish self versus non-self and cancerous versus non-cancerous cells.

Primary vs. Secondary Immune Response

• Primary Response: Occurs during the first antigen exposure; slow antibody production with a latency period during which the body gets sick.
• Innate immunity starts fighting, and then adaptive immunity kicks in; antibodies eventually wipe out the pathogen; antibody titer wanes over time.
• Secondary Response: Occurs upon subsequent exposure to the same antigen; faster and stronger response due to memory cells rapidly proliferating into plasma cells pumping out antibodies.
• Higher rate of antibody synthesis, higher titer rate, and faster response.
• Vaccines work by exposing the body to an antigen the first time to create memory cells for a quicker response upon actual infection.

Four Types of Immunity:

• Classified as Natural or Artificial, and Passive or Active.

Natural Immunity:

• Passive: Maternal transfer of antibodies to the baby in the womb and through breast milk.
• Active: Exposure to an illness leading to the creation of antibodies.

Artificial Immunity:

• Passive: Receiving immunoglobulins from donated plasma, often given to immunosuppressed individuals.
• Active: Vaccination, which stimulates an immune response artificially before exposure to an infectious agent.

Vaccination

• Involves exposing a person to antigenic material that is typically non-pathogenic.
• Vaccines might contain: live viral particles (attenuated), partial or killed/inactivated viruses or cells, cloned antigenic molecules or mRNA.
• The term vaccination originates from vaccinia (cowpox) because exposure to cowpox provided safety against smallpox.

Vaccine Considerations:

• Which antigens to use, particularly relevant for strains of viruses like the flu.
• Ease of administration, e.g., whether the vaccine needs to be refrigerated.
• Safety and cost-effectiveness.
• Many vaccines also include adjuvants to stimulate the immune system, such as Alum.
• Adjuvants serve to keep the antigen in the tissue longer for a better immune response; slight inflammation indicates immune activation.

Hypersensitivity

• Overactivity of the immune system can cause illness. There are four types of hypersensitivity.

Type I: Immediate Hypersensitivity

• Mediated by IgE, mast cells, and basophils.
• Primarily drives anaphylaxis and atopic conditions like eczema, asthma, and rashes.

Type II: Antibody-Mediated Hypersensitivity

• Involves IgG and IgM antibodies that act against the body's own cells.
• Can activate the complement system, resulting in significant inflammation.
• Examples include blood group incompatibility, pernicious anemia, and myasthenia gravis.

Type III: Immune Complex-Mediated Hypersensitivity

• Antibody-mediated inflammation becomes a major issue.
• Circulating antibodies cause widespread inflammation.
• Examples include systemic lupus erythematosus, rheumatoid arthritis, and rheumatic fever.

Type IV: T Cell-Mediated Hypersensitivity

• Involves delayed hypersensitivity and cytotoxic reactions.
• Examples include contact dermatitis, graft rejections, and some infection reactions.

Allergies

• Exaggerated immune response to an allergen, which is an antigen that typically wouldn't cause a response.
• The body is primed to recognize many things as food; sometimes the wrong kind of exposure can cause allergies.

Types of Allergic Reactions:

• Atopic/chronic local allergies: Hay fever, asthma, eczema.

• Anaphylaxis: Systemic, potentially life-threatening reaction. (Throat closing)

• There is a genetic component to allergies; one may be predisposed based on family history, though not necessarily to the same allergen.

Hygiene Hypothesis:

• Increased allergy diagnoses correlate with decreased exposure to parasites and dirt.

• Kids in rural areas and farms are less likely to develop allergies. (Maybe go play in the mud)

• A less diverse microbiota may also play a role.

• IgE is mostly associated with helminthic infections and allergies.

• Eat sushi!

• Mast cells and basophils bind IgE and release inflammatory chemicals, critical in anaphylaxis.

Histamine

• Key chemical released by mast cells and basophils.
• Benadryl shuts off histamine; this is an antihistamine and will reduce inflammation caused by histamine.

Allergic Conditions

• Allergic rhinitis (hay fever): Small allergic reaction to plant pollen.
• Chronic rhinitis: Allergic to household allergens like pet dander and mold.
• Asthma: Severe bronchoconstrictions triggered by allergens, food, or infectious agents. (Not feeling well + inflamed + airways constricted leads to severe difficulty breathing; allergies are often triggers)
• Eczema (atopic dermatitis): Allergies manifested on skin, causing weeping, red crusts, and thick scaly skin.
• Food Allergies: Reactions to food
  • Milk, Eggs, Fish, Shellfish, Tree Nuts, Peanuts, Wheat, Soybeans, and Sesame are required to be labeled.
  • Reactions can range from gastrointestinal symptoms to skin reactions.
  • Elimination Diets for diagnosis.
• Drug Allergies: Can cause rashes or anaphylaxis; some drugs more commonly cause allergies: penicillins, sulfa drugs, aspirin, opiates, and contrast dye.

Anaphylaxis

• This systemic throat closing issue was Essentially first named because when animals would be injected with a foreign protein, they would have no response the first time. And then the second time, they would essentially have serious complications and die.

Autoimmunity

• Occurs when the immune system reacts to the body's own tissues.
• Can be systemic (involving multiple organ systems) or organ-specific.
• Autoimmune disorders are much more likely to develop if you're female.

Potential Causes:

• Hormonal modulation with menstrual cycles.
• Trauma.
• Infection such as Epstein Barr.
• Overactive immune system due to lack of parasites.

Important facts:

• There is a strong genetic component, but not to specific tissue. The propensity to develop one often means that there is an increased genetic change. (You might not develop one, but likely another.)
• Some tissues in the body are immunologically privileged. For example, during the process for eye injuries the tissue is not tested against the immune system. Blindness in both eyes could then be triggered from autoimmunity.
• The clonal selection process can react to self tissues.
• Exposure to microbiome also can cause
• There are a number of known autoimmune disorders (estimated to be 10 percent of the population)

Specific Autoimmune Diseases:

• Lupus: Butterfly rash.
• Rheumatoid Arthritis: Joints.
• Graves' Disease: Thyroid.
• Type 1 Diabetes: T cells kill pancreas.
• Myasthenia Gravis: Muscles.
• Multiple Sclerosis: Body attacks myelin sheath.

Underactive Immune System

• DiGeorge syndrome is a syndrome caused by small deletions in chromosome twenty two or embryonic errors, and it essentially creates a lack of cell mediated immunity. People here often have to avoid live vaccinations (especially as children) to avoid regular childhood illness.
• Severe combined immunodeficiency syndrome (SCID) is a syndrome where your BNT cells do not function normally. Usually there are several forms of SCID and usually this is identified at birth.
• Acquired immunodeficiency syndrome (AIDS) Impacts helper T cells. The health and documentary here on aids is phenomenal in covering the public health response to how This impacts the immune system.