IMMUNOLOGY 2

Polysaccharide conjugate subunit vaccine

Pneumococcus PCV20 vaccine

Genetic RNA vaccine

Moderna COVID-19 vaccine

Attenuated whole pathogen

Sabin polio vaccine

Toxoid subunit vaccine

Diphtheria vaccine

Recombinant DNA-generated subunit vaccine

HPV vaccine

Inactivated whole pathogen

Injected flu vaccine

Give one advantage and one disadvantage of using an inactivated whole pathogen vaccine compared to an attenuated whole pathogen vaccine for polio

Advantages: safer, easier to make
Disadvantages: less potent immune response, vaccine is not delivered by normal routes of infection, harder to deliver (requires syringes and needles for injection).

Give one advantage and one disadvantage of using a conjugate polysaccharide vaccine
compared to a native polysaccharide vaccine for bacteria that cause meningitis.

Advantages: conjugates give a more potent immune response and are more effective in
children.
Disadvantages: more expensive, vaccines will cover fewer serotypes and will therefore provide less overall protection.

What is antigenic drift, and why is it a problem for development of influenza vaccines?

Over time, natural random mutations in an antigen cause it to longer be recognized by the
immune system. This is a problem for influenza vaccines because they become ineffective as each new variant of influenza virus arises, and new vaccines need to be made for each flu
season

What is the difference between a recombinant subunit vaccine and a genetic vaccine?

To make a recombinant subunit vaccine, the gene for a pathogen protein is put into an
expression system such as yeast, so that large quantities of the protein can be made to use as a vaccine. In a genetic vaccine the genetic information for a pathogen protein (DNA or
RNA) is injected directly into body, so that our own body cells make the protein.

Widening of blood vessels called _______ increases blood flow to an infected area and results in the heat and redness often associated with inflammation

vasodilation

During an inflammatory response, leaky blood vessels allow fluid to leak from the blood into
tissues, causing a swelling that is referred to as _________

oedema

An infection in the blood can result in blood vessels becoming leaky throughout the body,
leading to a massive loss of blood pressure and insufficient delivery of oxygen to the body that is
referred to as __________

shock

Blood clotting is an essential part of wound healing to stop bleeding, but an inappropriate
clotting response called _____ can occur during inflammatory disease

thrombosis

Repair of the extracellular matrix of tissues is an essential part of wound healing, but
uncontrolled deposition and destruction of extracellular matrix called _______
can occur during inflammatory disease.

fibrosis

An inflammatory disease of the liver.

hepatitis

A genetic disease that causes persistent activation of the inflammasome, leading to the
symptoms of severe infection even when there is no infection.

familial Mediterranean fever

The presence of pathogens in the bloodstream results in an inflammatory response that is
systemic (occurs throughout the body) instead of being localized.

sepsis

An inflammatory disease of the skin.

dermatitis

Recruitment of monocytes into arterial walls leads to the formation of lesions called plaques that obstruct blood flow.

atherosclerosis

The classic definition of inflammation

redness, hear, swelling, pain associated with innate immune response

Modern Definition of Inflammation

Tissue damage caused by an immune response, even without classic symptoms

Detection of Bacteria

Mast cells detect infection and release chemical signals

increased permeability

blood vessels become leaky, allowing fluid into tissues

chemoattraction

neutrophils and monocytes migrate to infection site

Pathogen Destruction

Monocytes mature into macrophages and assist in clearing infection

Causes of tissue damage

• ROS and antimicrobial enzymes attack pathogens but also harm normal tissue

• Proteases break down extracellular matrix, causing tissue damage

Acute Inflammation

• rapid response, resolves quickly

• Ex: bronchitis, tonsillitis

Chronic Inflammation

• long-term immune activity leads to tissue damage

• Arthritis, hepatitis, vasculitis

Pulmonary Emphysema

Chronic lung inflammation caused by tobacco smoke or genetic defects

Autoinflammatory Disorder

genetic diseases causing unprovoked inflammation

Effector cells

Attack pathogen, limited life span

Memory cells

Long lived, persist in body after infection, so a second
exposure to the pathogen is dealt with more quickly

Whole pathogen vaccines

Inactivated and live attenuated
pathogens (examples: influenza,
polio, measles, mumps, rubella)

Subunit vaccines

A component of the pathogen is
isolated (examples: diphtheria,
meningitis) or made by recombinant DNA techniques (examples: HPV, HBV)

Genetic vaccines

• DNA (gene) encoding
  a pathogen protein is
  put in a viral vector
  (examples, J&J and
  Oxford COVID-19)

• RNA encoding a
  pathogen protein is
  packaged in a lipid
  nanoparticle
  (examples: Pfizer and
  Moderna COVID-19)

Adjuvants

substance that enhances the immunogenicity of the
vaccine; They are needed for subunit vaccines that lack normal PRR ligands and inactivated whole pathogen vaccines

Dendritic Cells

Migrate to lymph nodes, activating helper T cells, B cells. cytotoxic T cells

Primary Response

First exposure takes ~2 weeks for adaptive immunity to develop

Secondary Response

Faster and stronger due to memory B and T cells

Outcome

Mild or no symptoms upon re-infection, leading to effective immunity

How Vaccines work

Vaccinations mimic infection without causing disease

stimulates production of memory cells

Developed cowpox-based smallpox vaccine

Edward Jenner 1798

Criteria for an Ideal Vaccine

Safe, Effective, Ease of Administration and affordable

Major Successes

Smallpox, poli

Available vaccines

Measles, mumps, rubella, influenzas, yellow fever

Challenges

No effective vaccines yet for HIV, Hep C, tuberculosis, malaria

Advantages of attenuated vaccines

• More potent and longer-lasting immune response
• More effective because the vaccine can be delivered by normal
routes of infection, for example oral or nasal delivery.
• Easier to administer without the need for syringes and needles

Advantages of inactivated vaccines

• Inactivated vaccines are safer. Attenuated vaccines have more risk
of the pathogen reverting to a virulent form and are a particular risk
to immunodeficient patients.
• Inactivated vaccines are usually easier to make.

Antigenic drift

Mutations in an antigen cause
it to no longer be recognized
by the immune system

epinephrine, agonist

Injected medication to reverse the potentially lethal effects of systemic anaphylaxis

albuterol, agonist

Inhaled medication specifically used to relieve asthmatic patients who are finding it difficult to breathe:

antihistamines, antagonist

Used to treat generic short-term allergic symptoms such as itching, sneezing, and watery eye

NASAIDs such as aspirin are used as general anti-inflammatory drugs for many diseases,
including allergies. Why does aspirin make the symptoms of allergy worse in some patients?

Aspirin inhibits an enzyme called cyclooxygenase (COX) that converts arachidonic acid into inflammatory mediators called prostaglandins. If aspirin is inhibited, arachidonic acid metabolism is diverted to the pathway that makes leukotrienes. This results in the production of more leukotriene C 4 (LTC 4 ) that makes allergy symptoms worse in some patients

Give one reason why systemic anaphylaxis can be lethal if not immediately treated

Loss of fluid (oedema) from the blood into tissues throughout the body results in a massive loss of blood pressure that can cause heart failure or insufficient oxygen delivery to tissues. Contraction of smooth muscle can lead to asphyxiation due to sustained constriction of the airways.

Poison ivy reaction

type IV

Production of IgG against soluble antigens (for example, non-human therapeutic proteins)
forms immune complexes that promote inflammation

type III

Production of IgG against modified cell surface proteins (for example, proteins that have been “haptenized” by chemical attachment of drugs) promotes inflammation

type II

A typical allergy such as allergic rhinitis:

type I

Histamine and leukotriene C 4 are inflammatory mediators with similar biological activities.
What is different about the time course of production of these mediators in an allergic reaction,
and what accounts for this difference?

Histamine is released immediately following exposure to allergen, because it is preformed and released from storage in secretory granules in mast cells. Leukotriene C 4 is a lipid that has to be synthesized following mast cell activation, so it requires a longer time period (several hours) to take effect

Herd Immunity

Immunity in just a proportion of the population can help the whole community

Technological advances that made RNA vaccines possible

• Lipid nanoparticle technology:
Enabled the stabilization of RNA in a form that can be taken up by cells.
• Modified RNA: A simple chemical modification prevented the mRNA from causing extensive inflammation as a side effect when
injected into the body.
• Structural biology: Understanding the 3D structure of the spike protein was crucial the the development of an efficient vaccine.

Molecular Mimicry

One hypothesis is that there is structural similarity between allergens and the immunogenic peptides in parasites

Epitope Spreading

• Epitope spreading is a
  process whereby epitopes distinct from and non-cross-reactive with an inducing epitope become major
  targets of an ongoing
  immune response.

• DNA cannot be presented on MHC (it is not a protein and therefore cannot be
  broken down into peptides) but antibodies to DNA can be made by epitope spreading.

• The inducing epitope is from a histone protein that forms a complex antigen with DNA.

Placental Immunity

• IgG autoantibodies can cross the placenta, so pregnant women with Graves’ disease, myasthenia gravis, pemphigus vulgaris, and some other autoimmune diseases transmit disease symptoms to their babies.

• Autoantibodies can be removed from babies by plasmapheresis (exchange of the infant’s blood or plasma).

Genetic Susceptibility to autoimmune disease

• Most genetic susceptibility to autoimmune disease is not caused by single gene defects but is multifactorial and arises from natural alleles
  (“versions of genes”) that make development of autoimmunity more or
  less likely.

• Genetic risk depends on the overall combination of “good”
  and “bad” alleles that are inherited.

• Susceptibility to autoimmune disease is most consistently associated
  with MHC (HLA) genotype: certain MHC alleles (usually MHC class II)
  are more common in patients with autoimmune disease than in the
  general population.