Immunological Memory and Vaccination

does not include diagrams as of now → study those separately

1. what are the thre major subsets of memory T cells?

1. Central memory T cells

2. effector memory T cells

3. Tissue - Resident memory T calls

what do central memory T cells do?

Express chemokine receptor CCR7 and move to the secondary lymphoid tissues similar to naive T Cells. Upon stimulation, Tcm differentiate into Tem cells

What do effector memory cells do

mostly recirculate between the blood and non-lymphoid tissues. They can rapidly enter in flammed tissue to perform effector T cell functions

what do tissue-resident memory T cells do?

Take up long-term residence in various epithelial sites

They are close by and available in case an infection happens again - they can react quickly

what are the two ways of achieving immunization?

1. Passive Immunization

2. Active immunization

what is passive immunization?

the administration of preformed antibodies in order to give temporary protection against infection

lecture examples of passive immunization:

• Maternal antibodies in a newborn

• Pooled lgG from immunized humans can be used to provide emergency protection

what is the goal of active immunization?

to generate protective immunity and immunological memory so that a subsequent exposure to the pathogen will stimulate a vigorous immune response leading to the elimination of the pathogen

lecture examples of active immunization:

• Natural infection

• Vaccination

Passive immunization risk: Repeated administration of gamma-globulin from foreign species

can cause systemic anaphylaxis (Type I hypersensitivity) if IgE is made against the foreign protein

Passive Immunization risk: serum sickness

(Type Ill hypersensitivity). caused by immune complex deposition if there is an IgM or IgG response to the foreign protein

Passive immunization risk: Human gamma-globulin

can trigger an anti-allotypic antibody response, resulting in Type I or Type Ill hypersensitivity

How do vaccines stimulate adaptive immune responses to a pathogen without developing disease?

• induction of B cells/humoral immune response to neutralization and / or elimination of pathogen

• induction of T Cell /cell mediated immune response to kill infected cells and prevent the spread of infection

T and B cell role in vaccination (generally)

vaccination induces memory T and B cells for long term protection upon re-exposure to the same pathogen

What is herd immunity?

Indirect protection from infectious disease due to a large percent of the population becoming immune to infection.

It is essential to protect the members of the population that cannot be vaccinated like newborn babies, pregnant or breastfeeding women, Immunocompromised individuals

what are the two vaccine component

antigen and adjuvant

what is an antigen in a vaccine? 

Any substance capable of inducing a specific immune response, and is capable of reacting with the product of that response

eg. killed or attenuated whole pathogen, or protein or recombinant protein derived from the pathogen

what is an adjuvant in a vaccine?

a substance that enhances the immunologenicity of an antigen by either stimulating innate immune recognition of antigen, or enhancing stability and interactions of antigens with the immune system.

Examples of adjuvants in vaccines

• Molecules that mimic PAMPs and stimulate the innate immune systems PRRs

• Oil/liposome which prolongs stability and interactions of antigens with the immune system

commonly used types of vaccines

• live attenuated

• Inactive or killed

• subunit

• polysaccharide conjugate

• Virus-like particle

• DNA/RNA

• Recombinant vector

• Peptide-based

live attenuated vaccine concept

• Weaken pathogenicity and growth ability (attenuate) of pathogen to allow for activationof immune response but not disease

• Attenuation achieved through chemical treatment, radiation or molecular manipulation

live attenuated vaccines examples

MMRV (measles, mumps, rubella, vericela), Flumist (influenza) , oral Polio (Sabin)

Live attenuated vaccine Pros and cons

Positives

• Persistence, full spectrum of antigens, humoral and cell mediated immunity, long lasting protection (limited boosting required)

Negatives

• Risk of disease, care to not give to immunodeficient patients

• Require careful storage and handling

Inactivated vaccines concept

• Consist of microbes that are killed by heat or chemical (e.g., formaldehyde) treatment and are therefore unable to replicate but maintain their antigenic constitution and immunogenicity

• Split virus: pathogen particles are inactivated then disrupted with detergent or ether
  (reduces irritation

Inactivated vaccines examples

Inactivated Polio vaccine (Salk), seasonal flu

Inactivated vaccine pros and cons

Positives

• Very safe, wide spectrum of antigens

Negatives

• No persistence, limited cell mediated immunity, often need adjuvant, boosting required, antigens damaged by treatment used to kill pathogen

• Incomplete inactivation of the pathogen may lead to diseas

Subunit vaccines concept

• Isolated protein or recombinant protein derived from pathogen

• Often delivered with adjuvant, commonly alum

Subunit vaccine examples

DTaP (diphtheria, tetanus, pertussis)

Subunit vaccines pros and cons

Positives

• Very safe, easily transported and stored, used for organisms that produce potentially fatal toxins

Negatives

• Weak immunogen, needs adjuvant, needs boosting, no spectrum of antigens, transient (no persistence)

Polysaccharide conjugate vaccines concept

• Used for organisms that have surface polysaccharide coats

• Link polysaccharide to protein for T-dependent antibody production

• T cells are activated by peptide, not polysaccharide

Polysaccharide conjugate vaccine examples

Pneumococcal polysaccharide conjugate to Diphtheria toxoid (pneumococcal vaccine), Hib (Haemophilus influenzae type B) vaccine

Polysaccharide conjugate vaccine pro and cons

Positives

• Activates good antibody response to polysaccharide residues

Negatives

• Weakly immunogenic, limited induction of cell mediated immunity

Virus-like particle (VLP) vaccines concept

Multiprotein structures that mimic the organization and conformation of authentic native viruses but lack the viral genome

VLP vaccine example

HPV vaccines (Gardasil, Cervarix), Hepatitis B (Engerix)

VLP vaccine pros and cons

Positives

• Safe (no risk of infection), present spectrum of antigens for cell mediated and humoral immunity

Negatives

• Requires complete virus genome to be sequenced, complex manufacturing/purification, immunogenicity may vary depending on culture conditions, may require adjuvant, not persistent

DNA/RNA vaccines concept

• Plasmid DNA or RNA that encodes antigenic proteins

• Direct injection of the plasmid DNA or RNA (sometimes coated on microscopic gold beads, or encapsulated in lipid vesicles) into the muscle of the recipient causes the proteins to be expressed by muscle cells and adjacent dendritic cells

DNA/RNA vaccine example

COVID-19 mRNA vaccines (Moderna and Pfizer/BioNTech)

DNA/RNA vaccine pros and cons

Positives

• Safe (no risk of infection), and easy and adaptable manufacturing

• Induce humoral and cell-mediated immunity

Negatives

• Stability – requires ultralow storage temperatures

• no spectrum of antigens

recombinant vector vaccines concept

• Produced by inserting genes coding for the major antigens of a pathogen into attenuated viruses or bacteria.

• Vaccinia virus is a popular vector due to its history of safety

recombinant vector vaccines example

COVID-19 vaccine (Oxford/AstraZeneca), which uses the chimpanzee adenovirus vaccine vector

recombinant vector vaccines pros and cons

Positives

• Safe (no risk of infection)

• Adaptable and easy to manufacture

• Induce humoral and cell-mediated immunity

Negatives

• Careful storage and handling

peptide based vaccines concept

• Uses the smallest synthetic epitope available to generate an immune response

• For T cell epitopes, ‘minimal’ epitope size is ~9-10 amino acids for binding to MHC Class I

peptide based vaccines example

not in clinical use

peptide based vaccines pros and cons

Positives

• Highest level of safety due to its small synthetic nature (no risk of infection)

• Adaptable and easy to manufacture

• Common in newer vaccines that target T cell responses

Negatives

• Vaccine adjuvants and formulations are very important