Lecture 11: Immunization and Infection Disease

Pathogenicity

Capacity of a microbe to cause disease

Virulence

Relative capacity of a microbe to cause damage to a host

Is infection synonymous with disease

no

Elimination

Can follow infection by either host defense or therapeutic intervention

Commensalism

Rarely if ever results in symptoms or clinical evidence

Colonization

Microbes with significant pathogenic potential that establish in the host without causing symptoms. Often stimulates immune response to prevent future infection or disease

Persistence/latency

Microbes take up residency and cannot be eradicated despite causing host damage

Outcomes of infection

Elimination

Commensalism

Colonization

Persistence/latency

Disease

Innate mechanisms triggered by virulence

Interferons, early defense mechanism antiviral proteins.

Complement systems proteins damage some viral envelopes

IFNa and IFNb

Produced by virally infected cells and are diffused to adjoining cells. They activate genes that interfere with viral replication. Stimulate MHC class I and proteasome proteins that enhance infected cells to prevent viral peptides. Enhance ability of viral cells to present viral peptide to T cells.

Also activate NK cells that kill infected cells. NK cells produce IFNg that leads to macrophage production and prime for adaptive response.

Humoral response to viruses

Neutralizing antibodies can neutralize or impede against viral invasion.

IgG appears to be most active against viruses (activates NK cells + macrophages + PMNs)

Prevent infection by interfering with viral binding to host cells

Fix Complement

Promote opsonization

Inhibit viral enzymes

Antibody response is usually not sufficient to eliminate a viral infection especially once established

Immunity to bacteria

Includes bacterial lysis via antibody and complement, opsonization and phagocytosis with the elimination of phagocytized bacteria by the liver and spleen and RES/MPS

Primary mechanism is cellular immunity for intracellular pathogens

Primary mechanism is humoral immunity for extracellular pathogens

4 class of bacteria

Gram negative

Gram positive

Mycobacteria

Spirochetes

Gram negative

Complement system, specific antibody, and phagocytic cels dominate immune response

Gram positive

Complement system does not lyse but provide opsonin’s and mediators of inflammation that are critical for host defenses

Mycobacteria

Elicit strong antibody response, but humoral role is uncertain

Spirochese

Complement, specific antibodies, and cell-mediated immunity all play a role

Parasites

Very common. Have a variety of tissue stages that differ in cellular location and antigenic composition so immunologically difficult and diverse responses.

Type 2 parasite response

Characterized by TH2 response induction.

Secretion of cytokines IL-4, IL-5, IL-9, IL-13

Distinct transcriptional factor profiles

Also induced for venoms

Protozoa

Complement activation combined with phagocytosis by neutrophils and macrophages is first line defense. Some cellular immunity and humoral immunity.

Helminths

Notorious for chronic infection that illicit intense immune response. Eosinophils and mast cells. IgE priming for eosinophils for antibody dependent cell mediated cytotoxicity (ADCC)

Immunity to fungi

Different cell wall composition than bacteria. Cross linked polysaccharides. Cell mediated immunity is the first line of defense. Humoral immunity has some antibodies specific to common fungi

Mechanisms of immune evasion

Encapsulated bacteria

toxins

superantigens

Antigenic variation

Intracellular survival

Suppression of immune system

Extracellular enzymes

Expression of antibody binding proteins

Encapsulated Bacteria

Antiphagocytic and protects from ingestion and killing.

This is why children under 2 are vulnerable because they lack B cells

Toxins

Proteins that produce physiological effects at minute concentrations

Effect is variable per pathogen, some toxins don’t injure immune system directly

Superantigens

Toxins able to bind T cell receptors of a large number of T cells. Stimulate T cells to proliferate synthesize and then die. This is what TSS is caused by. B cell super antigens bind to and alter expression of Ig families.

Antigenic Variation

Generating variants with different antigenic composition

Antigenic drift

Result of point mutations in the genome producing antigenic changes

Antigenic shift

Expression of new allele resulting in major antigenic change and emergence of new viral strain

Intracellular survival

Some micro organisms are taken up by phagocytic cells but manage to survive intracellular environments. Inside the cell is a nutrient rich environment beyond the reach of humoral immunity and neutrophils. Need cell mediated immunity

Suppression of immune system

Many viruses include genes capable of modulating the immune response and can down regulate the immune system.

Extracellular enzymes

Enzymes that degrade immune molecules like Igs or complement proteins

Expression of Antibody- Binding Proteins

Cell surface proteins that can bind Igs through Fc region

Active immunization

administration of antigen

passive immunization

transfer of antibodies

Adoptive immunization

transfer of immune cells

Vaccination

Exposes the immune system to antigen in a controlled manner to induce protective immune memory before pathogen exposure

Immunologic goals of vaccination

Generate antigen-specific B cell response

Generate long-lived plasma cells

Establish memory B cells

Generate memory T cells

Achieve rapid secondary immune responses

Immunologic sequence following Vaccination

1. antigen enters tissue

2. innate immune recognition occurs

3. dendritic cells capture antigen

4. migration to lymph nodes

5. antigen presentation to t cells

6. activation of B cells

7. germinal center formation

8. antibody production

9. memory formation

What determines vaccine success

Innate immunity. The adaptive immune system needs innate activation.

Many vaccines work because of the danger signals (PAMPs/DAMPs) they generate

T follicular helper cells and germinal center

Tfh aid in the production of high affinity antibodies, long-lived plasma cells, and durable immunity. They help in germinal center reactions.

Primary response

Building the immune sytsems playbook

Secondary response

Using the immune systems play book

Adjuvants

Enhance the immune systems response by stimulating innate immunity. PRR activation, cytokine production, APC maturation, enhanced antigen presentation, improved germinal center responses.

What do the best correlates depend on

The pathogen

Tetanus antibodies

Flu neutralizing antibodies

TB T- cell response

Cancer vaccines cellular immunity

When is vaccination less effective

Advanced age, immunosuppression, malnutrition, chronic disease

Poor APC function, reduced T-cel help, impaired germinal center formation, defective memory generation,

Goal of cancer vaccines

Generate tumor specific t cell responses capable of recognizing and destroying malignant cells