Autoimmunity and Vaccines

self-reactive immune cells

• should be deleted during development, but not all are

• central tolerance: destruction of self-reactive cells (bone marrow=B cells, thymus=T cells)

peripheral tolerance

• primarily maintained by anergy (non-responsiveness to an antigen)

• has T and/or B cells

• Tregs (CD4+, CD25+ T cells) play role in anergy

Autoimmunity

failure of self versus non-self

FoxP3 mutations cause:

autoimmune disease

Insulin-dependent diabetes mellitus

• CTL attack of pancreatic islet beta-cells

• Abs can play a role in C’ lysis of ADCC

Hashimoto’s thyroiditis

• mainly in middle-aged females (esp japanese)

• autoantibodies and Th1 cells

• thyroid damage and lack of Iodine uptake—>hypothyroidism

Mucous membrane pemphigoid

• mainly effects mucous membranes, like oral cavity

• Ab against desmosome Ag (separation of cells in basement membrane)

Pemphigus vulgaris (bullous pemphigoid)

• skin lesions (can be in oral cavity)

• anti-desmoglein: affects connection between cells (desmosomes)

Rheumatoid arthritis (RA)

• primarily affects 40-60yo females

• HLA-DR4 association

• chronic joint inflammation

• IgM antibodies (a rheumatoid factor) binding to Fc of IgG—>contributes to immune complex formation

Arthritus images

anti-inflammatory drugs

NSAIDS, corticosteroids

General T cell suppression

Block IL-2 production (cyclosporin)

Cytokine blockade

• block antibodies

  • anti-TNF (Humira)

• Receptor agonists/decoys

  • TNF-RA (Enbrel)

T cell functional blockade

CTLA4-Ig=immune checkpoint

T cell ablation

anti-CD3

B cell ablation

anti-CD20

Immune cell ablation ‘nuclear option‘

chemotherapy to destroy bone marrow+autologous stem cell transplant

Tolerance

an important regulatory mechanism of the immune system to prevent activation of self-reactive cells

central tolerance

delete self-reactive cells in development

peripheral tolerance

self reactive cells are silences/suppressed (anergy)

vaccination rationale

herd immunity

• aka population/community immunity

• the more individuals vaccinated=reduced possible spread of infectious disease

• indirect protection (high likelihood to protect those who can’t get a vaccine)

R0

estimated # infected from one person

Threshold %

% of population that needs vaccination to provide herd immunity

Small pox vaccination success

• eradicated in 1977

• virus now kept in liquid nitrogen

Polio vaccine success (2 types)

• OPV (oral polio vaccine)

• IPV (inactivated polio vaccine)

OPV

• protects individual

• prevents person-to-person transmission

IPV

• protects individual

• DOES NOT stop community spread

• some countries use IPV alongside OPV

Passive immunization

• inject performed Abs into individual

• often from another species (antitoxins, maternal Abs)

• used when need immediate response

• NO memory response

• ex: horse antitoxin for botulism

Active immunization

• protective immunity, develop a memory response

• through infection or vaccination

• most common ones in the US: Hep A+B, COVID, measles

Vaccine biological considerations: (4)

• attenuated

• inactivated

• toxoid

• purified macromolecules

Vaccination and immune system status

• age can determine efficacy (some vaccines don’t work in the young)

  • maternal Abs can inhibit response

• immunosuppressed

  • must determine ‘level‘ of

Attenuated vaccines

• lasts longer in body

• bc it’s a living organism and is non-pathogenic

• usually don’t need boosters

• stimulates CMI and humoral immunity

• adverse reactions: can revert to pathogenic strain, or can cause disease in immunosuppressed

Inactivated vaccines

• chemical inactivation or expisure to gamma-radiation (killed organism)

• usually requires multiple boosters

• mostly a B cell response

• problems: if microbe isn’t killed can cause disease

purified macromolecules

• inactivated toxins=toxoids

• bacterial capsular polysaccharides

  • subunit vaccines

  • capsule is anti-phagocytic

  • Abs binding allows APC recognition

• B cell activation without T cell help

  • hapten carrier effect

  • thymic-independent antigen

Nucleic acid based vaccines

• inject plasmid DNA/mRNA (coding for Ag) into muscle cells

• this produces Ag protein

• ex: COVID vaccines

• potential problems: virus mutation

Live, attenuated vaccines

Measles, mumps, influenza(nasal spray), chickenpox

Inactivated, killed vaccines

polio, Hep A, rabies

Toxoid (inactivated toxin)

tatanus (part of DTaP combo immunization)

Subunit/Conjugate vaccine

Hep B, influenza (injection), HPV

DNA/RNA based vaccines

COVID-19

Dental caries vaccines

-dental caries is multifactorial

-mostly aim to vaccinate against streptococcus mutans

-passive immunity is best for now, risk of cross-reactivity with heart tissue

oral administration can preferentially make IgA

Vaccinated individuals can come down with disease

DISPROVEN: autism from vaccine was disproven, based on circumstantial link to DTaP and falsified data

Vaccine limitations (4)

• multiple serotypes (ex: coronavirus)

• antigenic variation (ex: HIV)

• antigenic competition (some vaccines don’t work well together)

• passive antibody interference (esp with live virus)

Vaccine pathology risk

low risk, but adverse reaction can happen