Immunology Fundamentals and Vaccination

Adaptive & Innate Immunity, Antibodies, Vaccines

Immunosupression

• Someone’s immune system has a reduced ability to fight infection

• Ex) Someone has a genetic mutation that leads to cancer

1st Line of Defense

• Innate Immunity

• Constant, non-specific

• Use of epithelial cells

• Ex) Skin, mucus, saliva, microbiome,ciliary activity

2nd Line of Defense

• Inflammatory Response

• Generalized, rapid, non-specific

• Immediately cccurs after physical barrier breach or cellular injury has occurred

• Ex) Swelling and redness that occurs within minutes of spraining ankle

3rd Line of Defense

• Adaptive Immunity/Acquired Immunity

• Slow, specific

• Has memory

Inflammatory Response - 2nd line of defense

• Rapid, NON-SPECIFIC — same response regardless of pathogen type

• Key microscopic changes: vasodilation, ↑ capillary permeability, WBC influx, hemostasis

• Localized s/sx: erythema, warmth, swelling, pain, loss of function

• Systemic s/sx: fever, leukocytosis (↑ WBC), ↑ ESR (liver makes acute-phase proteins)

Adaptive Immunity - 3rd Line of Defense

• Initiated when innate immune system signals cells of adaptive immunity

• Slow onset on first exposure, fast on re-exposure (memory)

• Very specific to target antigen

• T&B lymphocytes retain immunologic memory

• Active molecules: antibodies, complement, cytokines

• Protection includes:

  • Activated T and B lymphocytes

  • Cytokines

  • Antibodies

1st Line - Physical and Biochemical Barriers

• Physical: epithelial cells (skin, GI lining) — minimize pathogen entry points

• Chemicals: mucus, sweat, earwax, tears, saliva — trap microorganisms

• Microbiome: 'good' bacteria on body surfaces (e.g., gut microbiome, yeast on skin)

Antigen

• Molecular targets of antibodies and lymphocytes that evokes immune response

• Can bind with antibodies or antigen receptors on lymphocytes

• Includes exogenous antigens & endogenous antigens

• Adaptive immunity recognizes and attacks these antigens to protect body

Antigen-Presenting Cell (APC)

• Capture antigens, process them, and then display them through the MHC to immune system

• Includes:

  • Dendritic cells:

    • Highly mobile due to unique structure

    • Located in tissues like the skin for easy access to potential exogenous antigens

  • Macrophages

  • B cells

Antigen Presentation Process

1. Antigen (protein) is present in cell

2. Antigen processed/broken down

3. Antigen fragments are presented on the surface of the cell by a MHC molecule

Antigen Presentation - Goal

Present foreign antigen in such a way that immune system knows exactly how to respond by drawing in the proper cells through the activation of the adaptive immune response

Major Histocompatibility Complex (MHC)

•     Presents antigen to immune system on surface of cell

• Has two types

Type I MHC

• Presents endogenous antigens (viruses, tumors)

• Ex) Found on all nucleated cells and platelets

Type II MHC

• Presents exogenous antigens

• Ex) APCs

Cell-Mediated Immunity

• Directly target and destroy infected cells

• Key players:

  • Helper T Cells (CD4+)

  • Cytotoxic T Cells (CD8+)

  • Regulatory T Cells (Treg)

  • Natural Killer Cells (NK)

Cell-Mediated Immunity - Helper T Cells (CD4+)

Activate other immune cells to come to the site

Cell-Mediated Immunity - Cytotoxic T Cells (CD8+)

Kill infected cells directly

Cell-Mediated Immunity - Regulatory T Cells (Treg)

Stop an over-activation of immune system (so body does not attack itself)

Humoral Immunity (B-cells)

• Immune response mediated by antibodies

  • B-CELLS PRODUCE ANTIBODIES

• Antibodies are secreted into the bloodstream and they ciruclate to detect the invader

• Key players:

  • Plasma Cells

  • Memory B Cells

  • Antibodies

Humoral Immunity (B-cells) - Plasma Cells

Produce antibodies

Humoral Immunity (B-cells) - Antibodies

• Immunoglobulins

• Specific class of proteins that bind to specific antigens to destroy them

• Found in general circulation and lymph structures

• Produced by B cells in response to an antigen

Immunoglobulins structure

• 2 identical heavy chains

• 2 identical light chains

• Structure gives it the ability to bind to a certain antigen

• Has 5 difference classes

Immunoglobulins function

1. Circulate through blood

2. Detect and bind directly to antigen

3. Tag antigen

4. Allows antigen to be recognized by immune system for targeted destruction

IgE

• Allergic reactions

• Binds mast cells → releases histamines (Type I hypersensitivity)→ inflammation

IgG

• Most common antibody produced in the primary and secondary immune response

• Most abundant in blood

• Crosses placenta (neonatal immunity)

• Enhances phagocytosis

IgM

• First antibody produces in response to an antigen

• Fixes complement and promotes target cell-lysis

• Present on the surface of mature B cells where it serves as a receptor for antigen recognition (along with IgD)

IgA

• Mucous membranes

• GI/respiratory tract

• Breast milk → protects infant against microbes in GI tract

IgD

• Found only on the surface of mature B cells, where it serves as a receptor for antigen recognition (along with IgM)

• Attaches to B cells and activates them

Active Immunity

• Formed thorough actual exposure to antigen

• Body capable of producing its own antibodies

• Acquired through infection or through vaccination

• Takes longer to develop

• Long-term protection

• Memory Present → can mount secondary response to subsequent exposure

Passive Immunity

• Occurs if antibodies outside of the body are transferred to the individual who needs them

• Recipient of the antibodies cannot form them on their own

• Commonly seen in newborns, who receive maternal antibodies from their mother through breast milk (offers immediate protection to baby)

• Short-term protection (only persist if antibodies remain in the body)

• Immediate onset

• No memory

Vaccine - description

• Preparation containing whole or fractionated microorganisms

• Stimulates the recipient’s immune system to manufacture antibodies directed against the specific microbe from which the vaccines were made

• Cannot cause disease itself in individuals with a healthy immune system

Vaccines produce active immunity

• Directly expose recipient’s immune system to an antigen associated with the disease it may cause

• Allows immune system to form memory against antigen

Inactivated vaccine

• Contain a killed pathogen/microbe unable to cause an infection but can still trigger immune response by the immune system

• Ex) Inactivated polio vaccine

Live, attenuated vaccine

• Contain a weakened version of a live pathogen unable to cause an infection but can still signal immune response

• Ex) MMR vaccine (Measles, mumps, rubella)

• Avoid in those who are immunocompromised

Subunit vaccine

Non-viable or weakened fragments of microbe

Toxoid vaccine

Inactivated toxin (e.g., Td/Tdap)

mRNA vaccine

Codes for antigen; body produces it to trigger response (e.g., COVID-19)

Vaccination

Giving any vaccine to produce active immunity against particular microbe

Immunization

The process of becoming immune, includes both active and passive immunity

Natural immunization

Active immunity or an acquired response through infection and recovery

Artificial immunization

Active immunity from vaccinations

Vaccines - Mild Adverse Effects

• Local reaction at injection site

  • Discomfort

  • Swelling

  • Erythema

• Fever and flu-like symptoms

  • Immune system recognizes microbe as antigen -> activates inmune response (fever)

Vaccines - Severe (rare) Adverse Effects

• Anaphylaxis

• Acute encephalopathy

• Seizures

• Guillain-Barré Syndrome

• Vaccine-associated paralytic poliomyelitis

Vaccines - Severe (rare) Adverse Effects - Anaphylaxis

severe, rapid allergic reaction -> shock, airway constriction, dramatic drop in blood pressure

Vaccines - Severe (rare) Adverse Effects - Acute encephalopathy

a rapid-onset, often reversible syndrome causing global brain dysfunction due to systemic issues like infections, toxins, or metabolic failure

Vaccines - Severe (rare) Adverse Effects - Guillain-Barré Syndrome

autoimmune disorder, immune system attacks peripheral nerves -> rapid onset muscle weakness, tingling, potential paralysis

Vaccines - Severe (rare) Adverse Effects - Vaccine-associated paralytic poliomyelitis

caused by live-attenuated virus in the Oral Poliovirus vaccine (OPV); occurs weakened vaccine virus reverts to a virulent form, causing paralysis in recipients or their contacts

True Contraindications for Vaccines

• Anaphylactic reaction to a specific vaccine: Contraindicates further doses of that vaccine

• Anaphylactic reaction to a vaccine component: Contraindicates use of all vaccines that contain that substance

• Moderate or severe illnesses with or without a fever (places strain on immune system)

• Live, attenuated vaccine should be avoided in those who are immunocompromised

False Contraindications for Vaccines

• Mild to moderate local reaction (soreness, erythema, swelling) after a dose of an injectable vaccine

• Mild acute illness with or without low-grade fever

• Diarrhea

• Current antimicrobial therapy

• Convalescent phase of illnesses

• Prematurity (same dosage and indicates as for normal, full-term infants)

• Recent exposure to an infectious disease

• Personal or family history of with penicillin allergy or nonspecific allergies