MICROBIO ENTIRE COURSE

pathogen classifications (from most infectious to least)

1. bacteria

2. fungi

3. worms

4. viruses

5. parasites (protozoa)

outbreak, endemic, epidemic, and pandemic

• outbreak

  • the occurrence of disease cases in a community, region, or specific group (ex. school/hospital) at a frequency clearly in excess of normal expectancy

• endemic

  • disease is always present in a population within a region

• epidemic

  • a rapid increase in cases higher than expected in a population within a region

  • ex. SARS, ebola

• pandemic

  • an epidemic that becomes widespread over several countries or continents

  • ex. COVID

6 steps of the chain of infection

1. infectious agent

   1. bacteria, virus, fungi, protozoa, parasite

2. reservoir

   1. people, equipment, water

3. portal of exit

   1. excretions, secretions, droplets

4. mode of transmission

   1. contact, droplet, airbourne, or vectorbourne

5. portal of entry

   1. resp tract, GI tract, mucous membranes, skin

6. susceptible host

   1. people with chronic disease, immunocompromised, babies, elderly

5 opportunities to break the chain of infection

1. the infectious agent is eliminated, inactivated, or cannot survive in the reservoir

   • disinfecting the environment

2. the portal of exit is managed through good infection prevention and control practices

   • hand hygiene, PPE

3. transmission does not occur due to good infection prevention and control practices

   • hand hygiene, isolation of infected pts, air flow where necessary

4. the portal of entry is protected

   • aseptic non-touch technique, safe catheter care, wound care

5. reducing the susceptibility of pts receiving healthcare

   • treating underlying diseases, recognizing high risk pts

what is infection

infection: the invasion of the host by microorganisms, which then multiple in host tissues - NOT disease

• dependent on 3 main factors

  • number of organisms in or on the host

  • virulence of the organism

  • host defences or degree of resistance

what is virulence

• the ability of an organism to cause infectious disease

• the reason why some pathogens cause disease, and others done

  • some infectious agents are easily transmitted, but they are not very likely to cause disease (contagious, but not virulent)

  • ex. ebola vs. polio (COVID is both)

5 factors that contribute to host susceptibility

dependent on physiologic and immunologic conditions of the host

• immune system

• age - infants and elderly!

• nutrition

• genetic defecits

• medications (chemo)

what is host resistance

the ability of the host to prevent infection from occuring and infectious diseases from developing

• non-intact barriers (skin, mucous membranes, Gi and resp tract)

• chemical (gastric juices, saliva)

• immunity against a particular agent (natural and artificial)

  • chicken pox

what are antigens

• antigens: chemical substances that identify as foreign that continually challenge the immune system

  • can be bacteria, viruses, etc

  • OR from the environment like blood transfusions, vaccines, transplant tissue, or bee venom

  • OR pre-cancerous cells

innate vs adaptive immune system mechanisms

• has 2 systems to protect against pathogens

1. innate immune system

   1. barriers - 1st line of defence

   2. innate cells - 2nd line of defence

2. adaptive immune system

   1. B lymphocytes (humoral)

   2. T lymphocytes (cell-mediated)

what is the function of the immune system

• main function is to protect body from pathogens that can make you sick

• destroy abnormal cells (cancerous)

• has 2 systems to protect against pathogens

  1. innate immune system (barrier and innate cells)

  2. adaptive immune system (B and T lymphocytes)

properties of the innate immune system

• innate = in body since birth

• does not require memory and does not have memory (non-adaptive)

  • responds immediately and the same strength every time

  • is always initiated when pathogen contacts body, is non-specific

• uses Pattern Recognition Receptors (PRRs) that recognize microbial structures

  • this is to identify self and ensure the immune system does not destroy its own cells marked by PRRs

• has first and second lines of defence

what are portals of entry + examples

• microbes enter in body by various methods

• most pathogens have specific portals of entry

  • skin (anything that breaks skin layers - trauma/burns)

  • GI tract (fecal-oral, or contaminated food)

  • resp tract (airbourne droplets, or contact)

  • urogenital (local invasion/STI or ascending infections/UTI)

7 main barriers in the body

• skin

  • tightly knit epithelial cells that keep bacteria out

  • provides physical barrier to the entrance of microbes

  • acidic pH discourages the growth of organisms

  • fatty acids, sweat and oil gland secretions kill many bacteria

  • sloughing off of old skin

• tears

  • wash away irritating substances and microbes

  • lysozyme kills many bacteria

• saliva

  • washes microbes from the teeth and mucous membranes of the mouth

• resp tract

  • mucus traps organisms

  • cilia sweep away trapped organisms

  • goblet cells that secrete mucous, that protect structures and trap microorganisms

• stomach

  • acid kills organisms

  • antibacterial peptides (pepsin)

  • microflora and good bacteria to help keep foreign bacteria in check

• large intestine

  • normal bacterial inhabitants keep invaders in check

• bladder

  • urine washes bacteria out

NOTE: microflora associate with epithelial cells that line all pathogen entry points

the WBCs of the innate immune system

• mainly leukocytes

  • neutrophils

  • monocytes

  • macrophages

  • eosinophils

  • basophils

• dendritic cells - bone marrow derived WBCs

• mast cells - found in connective tissues

• NK cells - innate and adaptive immune system

what are phagocytes

• defensive cells, white blood cells

• eat unwanted invaders of the body and dead/damaged cells

• non-specific (will eat any pathogenic organisms)

• main function: destroy extracellular pathogens

the 3 main phagocytes

NOTE: these destroy extracellular pathogens by phagocytosis

• neutrophils

  • first responders

  • live in blood

• macrophage

  • arise from blood monocytes

  • can consume larger particles that neutrophils cannot handle

• immature dendritic cells

  • an important intermediary between the innate and adaptive immune system

  • a mature dendritic cell is more involved in adaptive immunity

what is phagocytosis + 3 steps

• ingesting and killing invading pathogens

  • recognition and adherence

  • engulfment

  • intracellular killing

phagocytosis - recognition and adherence

occurs when a pathogen-associated molecular pattern (PAMP) expressed by a microbe, binds will a PRR receptor on the membrane of a phagocyte

phagocytosis - engulfment

• extension of the cytoplasm move around and eventually enclose the particle in a phagosome (membrane)

phagocytosis - intracellular killing

1. phagosome fuses with the cytoplasmic lysozome, forming a phagolysozome

   1. contains antibacterial molicles and enzymes that can kill and digest microbes

2. accomplished through toxic reactive oxygen species (hydrogen peroxide) and nitrogen containing species (nitric oxide)

3. any indigestible material is then removed through exocytosis

what are eosinophils

• type of leukocytes

• defence against parasitic infections

  • able to digest much larger particles

• also have role in allergic reactions

what are natural killer cells

• goal is to survey the whole body and identify + destroy virally-infected cells and tumour cells

• each NK cell has an activating receptor and inhibitory receptor

• all healthy cells have an MHC1 complex sticking out of their cell, while infected cells do not - when NK cells connect with healthy cells, they are inhibited by MHC1 and do not kill this healthy cell

  • if not inhibited (with infected cells), the NK injects toxic cytoplasmic granules which perforates the cell resulting in viral DNA and RNA destruction, or apoptosis

• kills INTRAcellular viruses

what are defence proteins

• complement system (works with antibodies)

• 30 or more plasma and cell surface proteins that work in concert to fight invading microorganisms through OIL

  • opsonization → easier phagocytosis

    • complement system acts as a glue to help attach antigens to macrophils/neutrophils for easier phagocytosis

  • inflammation

    • histamine release by mast cells/basophils to dilate blood vessels and making more them leaky

  • lysis

    • complement system induces bacterial lysis/burst due to water entering

pro-inflammatory cytokines

• type of defensive protein

• part of an integrative signalling network to encourage inflammation and innate immunity via chemotaxis of leukocytes

  • chemotaxis: the movement of an organism in response to a chemical stimulus

• main types of cytokines

  • chemokines

  • interferons (IFN)

  • interleukins (IL)

  • tumor necrosis factor (TNF)

the process of inflammation

• recruits circulating immune cells and plasma proteins into infected tissue to encourage immune defences

• occurs in 3 main steps

  1. activated phagocytes secrete chemokines and pro-inflammatory cytokines

  2. vasodilation and increased vascular permeability cause redness, heat, and swelling

  3. inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain

fever = higher temp to kill off bacteria, helps slow bacteria growth, and speed up body defences

properties of adaptive immunity

• can distinguish one specific microbe from another

• develops memory for subsequent exposures of that same microbe

• two types:

  • humoral immunity (B lymphocytes)

  • cell-mediate immunity (T lymphocytes)

• autoimmune (AI) disorders → cannot distinguish microbial antigens from self antigens

what is humoral immunity

• involves the production of antibodies by plasma cells in response to a pathogen

• main function is to produce specific antibodies to fight against the particular EXTRAcellular pathogens

• arise in the fetal liver and from stem cells in the bone marrow where they mature

  • once the mature, they enter the bloodstream where they migrate and are stored in the lymphoid tissue (spleen + lymph nodes)

the process of B cell activation

• they must be activated before maturation - exposing them to an antigen

  • antigens binds to the B cell surface receptor

  • activates the B cell

  • B cell proliferate to make identical cell copies

  • these copies then differentiate to become either antibody-producing (plasma) cells or memory cells

    • plasma cells secrete antibodies; non-dividing B cells and only last about a few weeks + die by apoptosis

    • memory cells live for many years and recognize + respond to multiple exposures of the same microorganism that initially stimulated their formation (primary and secondary responses)

the 5 antibodies

• IgG

  • most abundant, crosses placenta for 3 months of neonatal immunity, neutralizes and opsonizes pathogens

• IgA

  • dominant mucosal antibody in bodily secretions, blocks pathogen entry at GI and resp tract, provides passive protection to breastfed infants

• IgM

  • prominent in the primary antibody response, main function is to neutralize pathogens

• IgE

  • triggers mast cell-mediated type i rxns and some antiparasitic responses, does not neutralize pathogens or promote phagocytosis

• IgD

  • mostly remain bound to naive B cells - main function is to bind antigens (b cell receptor)

2 ways antibodies eliminate pathogens

1. neutralization

   1. blocks pathogen receptors that are used to gain entry into a cell or tissue

1. phagocytosis

   1. express surface receptors that bind Ig - Fc repectors → triggers phagocytosis

**only EXTRACELLULAR pathogens

the process of antibody production

• primary response

  • the rxns of the immune system when it contacts an antigen for the very first time

  • 5-7days (IgM) to 14 days (IgG/A/E)

  • low number of mainly IgM → IgGAE

• secondary response

  • the run of the immune system when it contacts an antigen for the second or subsequent times

  • 1-3 days of high IgGAE

IgM and IgG lab differential

• IgM vs. IgG

  • its got me vs its gone

  • acute infection (many symptoms) vs. previous infection (almost gone)

• IgM resonds first, and then IgG secondarily

• this helps us understand the level of infection for certain patients

IgM in ABO blood compatibility

• IgM works as an anti-A and anti-B antibody

• types A, B, and O all have antibodies (anti-…) without having prior contact

• AB don’t have any antigens so are the universal recipient

• O has both antigens, so are the universal donor

what is cell-mediated immunity

• deals with INTRAcellular bacteria, viruses, and any bacteria that are out of reach of antibodies and have escaped phagocytosis

• T cells arise in the bone marrow → migrate to the thymus to undergo several steps of maturation

  • TCR (T cell receptors), CD4, and CD8 co-receptors

• destroys invading microorganisms and helps B cells produce antibodies

• two types:

  • helper T cells (CD4+)

  • cytotoxic T cells (CD8+)

what are the main defences in T cell immunity

• helper T cells (CD4+) - MHC2

• cytotoxic T cells (CD8+) - MHC1

• MHC class 1 and class 2 - proteins that play a pivotal role in the adaptive branch of the immune system

  • both share the task of presenting peptides on the antigen cell surface for T cells to recognize

  • T cell receptors can only bind to protein antigens (peptides) - all microbes present these peptides

• for a T cell receptor to be activated it must be presented with a peptide by an MHC

• each T cell expresses a variable region and antigen binding site, specific for one unique peptide or antigen

2 classes of MHC molecules

the process of T cell activation

• APC = antigen presenting cells

• prior to activation, T cells are known as naive T cells

1. activation of T cells begins with recognition and binding of that T cell receptor to the MHC antigen complex (costimulation)

2. proliferation and differentiation requires interleukin 2 (IL2) which is produced by naive T cells and send signals for the T cells to duplicate

3. differentiation into either effector or memory cells

how do helper T cells work

• CD4+

• remember: bind with MHC2

• the “alarm bell” of the immune system

• once activated, Th cells release cytokine

• this stimulates other parts of the immune system to react

  • NK cells, macrophages, cytotoxic cells to proliferate, B cell proliferation

how do cytotoxic T cells work

• CD8+

• remember: bind with MHC1

• once binding occurs, proliferation into effector and memory cells

• the effector cytotoxic T cells release toxic enzymes that degrade nucleic acids in the cells

  • latching onto the abnormal cell to release molecules, forming pores and forcing apoptosis

  • very similar to NK cells!!!!!

• NOTE: some viruses block the presentation of MHC1 molecules to evade cytotoxic T cell response

  • ex. herpes and HPV

what is a hypersensitivity rxn

• refers to sensitization of the immune system by repeated exposure to an allergen (when the immune system goes wrong)

• hypersensitivity disorders refer to excessive or inappropriate activation of the immune system

4 types of hypersensitivites

• type I

  • IgE-mediated response

  • within 1 hr

  • ex. anaphylaxis

• type II

  • antibody-mediated response

  • specifically IgG and IgM cytotoxic

  • hours-days

  • ex. hemolytic anemia or blood incompatibility

• type III

  • complement-mediated immune responses

  • 1-3 wks

  • ex. lupus or glomer nephro

• type IV

  • T-cell-mediated responses

  • days-weeks

  • metal sensitivity or TB tests

atopic conditions

• atopy refers to the genetic tendency to develop allergic diseases such as allergic rhinitis (hay fever), atopic asthma, and atopic dermatitis (eczema)

  • most common with IgE responses

• people with one atopic condition are more likely to develop another atopic condition

type 1 hypersensitivity rxns

• begin rapidly, often within minutes of an antigen challenge through inhalation, ingestion, injection, or skin contact

• allergen is met by phagocytic cell that ingests it, chews it up, and spits it out

• an APC then creates a cascade where B cells are created → secreting IgE

• IgE then binds to mast cells (called first exposure/sensitization)

• re-exposure to the same allergen = memory response occurs immediately

• allergen-IgE binding activates the mast cell to degranulate

• releases histamine and cytokines → atopic symptoms

allergen route of entry rxns

• inhale

  • resp tract

  • mucus buildup, sneezing, nasal congestion, bronchial smooth muscle constriction

  • asthma/rhnitis

• inject

  • skin & bloodstream

  • local and systemic inflammation

  • hives or anaphylaxis

• ingest

  • GI tract

  • intestinal smooth muscle constriction, systemic inflammation

  • NVD or anaphylaxis

what is anaphylaxis

• provoked by any allergen that enters the bloodstream - injected directly into blood or rapid absorption across the epithelial surface of the skin/gut

• a severe, potentially life-threatening allergic reaction requiring immediate attention characterized by widespread edema, vascular shock secondary to vasodilation, and dyspnea

• level of severity depends on level of previous sensitization

anaphylactic shock

anaphylactic shock: the catastrophic loss of blood pressure due to extensive fluid loss from blood vessels

3 ways to diagnose allergies

• serum bloodwork to reveal increased IgE levels

• biopsies during endoscopies and colonoscopies (for GI intolerances)

• skin prick/patch tests

  • local inflammation at injection site with 10-15 mins

allergy desensitization immunotherapy

• aka allergy shots

• principle: divert immune response from IgE to IgG

• a form of long-term treatment that decreases symptoms for those with rhinitis, asthma, pink eye, or stinging insect allergies

• works like a vaccine - gradually increase dose to develop immunity

• risks: local rxns, systemic rxns, anaphylaxis (within 30 mins usually)

what are type ii hypersensitivities

• mediated by IgG or IgM antibodies directed against target antigens on cell surfaces

  • can be endogenous on cell membranes or exogenous absorbed on membrane surface

• the rxn destroys the antigen in 3 different ways

3 steps of type ii hypersensitivity

1. opsonization and phagocytosis

   1. cells are coated (opsonized) with molecules that make them attractive to phagocytes

2. antibody dependent cellular cytotoxicity

   1. IgG binds to surface antigen on infected cell and NK cell kills the infected cell

3. complement activation

   1. the binding of a IgG can activate the complement system and cause lysis of the antigen by membrane attack complex or by phagocytosis

   2. complement activation recruits neutrophils and monocytes which release specific enzymes → inflammation and tissue damage

Rh incompatibility

• example of type ii hypersensitvity

• a condition that occurs during pregnancy if a woman has Rh- blood and her baby has Rh+

  • Rh factor is a protein on RBCs that is inherited

• the baby’s blood can pass through to the mother through the bloodstream/placenta and mom’s body will react and begin producing antibodies against baby → hemolytic anemia

type iii hypersensitivities

• mediated by the formation of insoluble antigen-antibody complexes which activate the complement system and localized edema

• the immune complexes formed damage vessel linings as they are delivered and deposited into desired tissues

• once deposited, inflammatory response is activated→ complement system → neutrophils recruited → inflammation

  • the neutrophils try to damage complexes, but destroy target tissues with them

• responsible for vasculitis

  • seen in AI disorders like lupus or acute glomerulonephritis/kidney damage (due to post-strep infections)

post-strep glomerulonephritis (PSGN)

• example of type iii hypersensitivity

• characterized by rapid deterioration of kidney function due to inflammatory response (type III rxn) following a strep infection

• affects the glomeruli and small blood vessels of the kidneys

  • most frequently in children 1-2 wks after a sore throat or 6wks after a skin infection

• the body responds to nephrogenic streptococcal infection by forming immune complexes containing the strep antigen with human antibody → complement pathway

• complement pathway causes infiltration of leukocytes and proliferation of other cells in glomerulus → reduction in GFR and perfusion → renal failure, acid-base imbalance, electrolyte abnormalities, volume overload, edema, and HTN

• PSGN triad: hematuria, edema, and HTN

type iv hypersensitivities

• aka delated-type hypersensitivity (DTH)

• cell-mediated NOT antibody-mediated

  • immune rxn in which T cells are activated by antigens

• there must be a previous exposure to mount an immune response

• subsequent exposures on SQ tissue = rash

  • local APC deem these cells normal, but T effector cells are activated and release cytokines → phagocytes, fluid, protein are recruited to the site → physical lesion

• ex. TB test, poison ivy, nickel, latex

immune self tolerance

• the immune system being able to differentiate foreign antigens from self-antigens

• results from central and peripheral mechanisms that delete self-reactive immune cells that cause autoimmunity

• two types: central and peripheral tolerance

immune self-tolerance: central

• derived from the deletion/inactivation of self-reactive T cells (eliminated in thymus) and B cells (eliminated in bone marrow)

immune self tolerance: periphipheral + what is anergy

• maintenance of tolerance in secondary lymphoid tissue (spleen or lymph nodes)

• these processes work through deletion/apoptosis of autoreactive cells or anergy that escaped central tolerance

• anergy = a state where cells become unresponsive to antigen stimulation and suppression of effector T cell activation

what is autoimmunity

• results from a loss of self-tolerance

• reason is unknown, however gender and genetics play a role, as well as self-reactive lymphocytes (HLA)

  • more women have AI disorders (5:1)

classification of autoimmunity

**a spectrum

• organ-specific AI diseases

  • AI response targets an antigen present in a specific organ

  • ex. DM1 (pancreas-beta cells), Graves Disease (thyroid-TSH receptors), MS (neurons/brain)

• systemic AI diseases

  • AI response targets an antigen present at many different sites (can involve multiple organs)

  • ex. Systemic Lupus Erythematosis (many cell types)

what is graves disease

• organ specific autoimmune disorder

• immune system attacks thyroid → overactive thyroid/increased T3 and T4

• immune system makes thyroid-stimulating immuniglobulin (TSI) that attaches to thyroid cells - acts like TSH, but makes the thyroid produce even more TSH and TSI

DM1

• organ-specific autoimmune disorder resulting from a chronic AI destruction of the beta cells

• autoreactive Cytotoxic T Lymphocytes (T cells) kill Islets of Langerhans → reduced insulin production → hyperglycemia + unk. inflammatory response

MS

• organ-specific autoimmune disorder

• immune system attacks myelin sheath that covers nerve fibers → communication problems between brain and rest of body

• inflammatory process that causes T cells and their mediators triggering injury of axons and their myelin sheath

  • the T cell-mediated inflammation is driven by the AI process, which triggers a degenerative phase that is immune dependent

5 main treatments for autoimmune disorders

1. immunosuppression

2. plasmapheresis (remove antibodies) - temp

3. block MHC with similar peptide (mimic)

4. use antibodies that block B or T cells

5. disease-specific treatments (ex. insulin or joint replacements for RA)

• based on effector mechanism, bodily tissues/organs involved, magnitude, and chronicity of effector processes

• treatment should target underlying mechanisms

4 key goals of immunization

1. prevent

2. control

3. eliminate

4. eradicate

• by directly protecting vaccine recipients and indirectly protecting vulnerable populations

what is vaccination + purpose

• the intentional exposure to pathogens in a form that cannot cause an infectious disease

• purpose: for the recipient to develop long-term immune protection against the pathogen

key time stamps of vaccination

• 1774 - Ben Jesty

  • innoculated family with pus from cowpox clister of a cow to protect from smallpox

• 1796 - Ed Jenner

  • demonstrated immunity to smallpox by innoculating an 8yr old with cowpox virus

• 1798

  • smallpox vaccine was developed - the first vaccine!

• 1870 - Louis Pasteur

  • created vaccines against chicken cholera, anthrax, rabies

  • principle: isolate, inactivate using heat and inject

the UK MMR controversy

• Dr. Andrew Wakefield claims the MMR vaccine causes autism

• “no causal link was established between MMR vaccine and autism as the data was insufficient”

• Wakefield had been funded by lawyers who had been sued by vaccine manufactures - study was fraudulent in favour of his lawful argument

• faking data

herd immunity

• parents excuse as to why they will not vaccinate their child

• protects susceptible individuals by stopping transmission

• the risk of infection is reduced when the number of individuals who can spread that pathogen is reduced

**herd immunity is only effective when a sufficient number of people are immune

can vaccines cause disease (live and inactivated)

• NEVER

• inactivated vaccines

  • killed viruses or bacteria

  • cannot cause disease

• live vaccines

  • may cause mild symptoms, but full blown-disease is extremely unlikely

why do children get multiple vaccine doses

• inactivated vaccines

  • build immunity in phases

  • multiple doses

• live vaccines

  • one dose - sufficient immunity

  • not all children respond to the first

common rxns to vaccines

• minor rxns

  • redness/pain at injection site

  • fever

  • prolonged crying

  • vomiting

  • headache

• moderate rxns

  • febrile seizures

• severe rxns (very rare)

  • anaphylaxis

  • encephalitis/encephalopathy from measles vaccine

what are in vaccines

• the live or non-live bacteria (or parts)

• adjuvants

  • help boost immune response

• *multi-dose vials contain preservatives

  • may include thimerosal, formaldehyde, aluminum

what is vaccine hesitancy

• a delay in acceptance or refusal of vaccination despite availability of vaccine services

• the WHO declared vaccine hesitancy as one of the top 10 threats to global health in 2019

9 reasons why people are vaccine hesitant

1. mistrust in government and the medical system

2. not believing that vaccine are safe

3. too many vaccine

4. philosophical or religious belief

5. thinking that alternate healthcare can replace vaccines

6. vaccine myths are prevalent

7. it is hard to understand vaccine information

8. worried about vaccine side effects

9. diseases that vaccines prevent aren’t a serious threat to their health

5 Cs of vaccine hesitancy

1. complacency

2. convenience

3. confidence

4. calculation

5. collective responsibility

what is immunization

immunization: the process by which a person becomes protected against a disease through exposure to immunizing agents

what is immunoprophylaxis

• prevention of disease using immunizing agents

• agents are classified as active or passive immunization

passive immunity

• involves the natural transfer of pre-formed antibodies from one person to another (or from an animal product) to provide immediate, temporary protection from infection, or reduce severity of illness

• most commonly can occur by transplacental transfer

  • an infant receives antibodies from the mother through the placenta in the last 1-2 months of pregnancy

  • the newborn will have the same antibodies as the mother for up to a year

• artificial/systemic admin of immunoglobulins can also provide protection when vaccines aren’t available or exposure has already occurred

active immunity

• the stimulation of immune system to produce antibody and cellular immunity

• lasts for many years-lifetime

• can occur through getting infected or getting vaccinated

  • the memory B cells remember the disease and already have the antibodies to protect to the best of their ability (immunologic memory)

• vaccines give the same immunity without the individual having the infection + also provide immunologic memory

how do vaccines work

• admin of a vaccine antigen triggers an inflammatory rxn that is initially mediated by thew innate immune system, then works its way to the adaptive immune system through B and T cells

• most vaccines provide humoral immunity (through B cells), most live vaccines act through cell-mediated immunity (T cells) - or both

• long-term immunity requires the persistent of antibodies, or creation + maintenance of antigen-specific memory cells (priming) that will produce an immune response when needed

guiding rule of vaccines

the more similar a vaccine is to the disease-causing form of the organisms, the more effective the vaccine

classification of vaccines

1. live attenuated

   1. viral

   2. bacterial

2. inactivated

   1. whole

      1. viruses, bacteria

   2. fractional

      1. protein-based (toxoid, subunit)

      2. polysaccharide-based (pure, conjugate)

live attenuated vaccines

• contain whole, weakened bacteria or viruses

• because the vaccine is so similar to the agent, this vaccine will last longer and be more effective than non-live vaccines

• to produce an immune response, the live vaccines must replicate/grow in the body

  • underattenuated → causes disease

  • overattentuated → does not provoke immune response

• usually one dose, rarely 2 doses

• require careful storage and handling to avoid inadvertent inactivation (heat, light, etc)

• contraindicated for immunocompromised

examples of live vaccines

• viral: measles, mumps, rubella, vaccinia, varicella, zoster, yellow fever, rotavirus, intranasal influenza, oral polio

• bacterial: BCG, oral typhoid , rotavirus

inactivated (non-live) vaccines

• contain the whole inactivated (killed) bacteria or virus, their parts/products secreted that are modified to remove their toxoids (what makes them infectious) with heat or light

• cannot replicate or cause disease (even in immunocompromised)

• require adjuvants + primary series and booster doses

• the addition of adjuvants enhances the immune response and extends the B and T cell activation

• subunit vaccines include toxoid, recombinant, polysaccharide, and conjugate vaccines

  • these use pieces of the germ like its protein, sugar, or capsid (casing around the germ) to provide immunity

polysaccharide vaccines - pure

• unique type of inactivated subunit vaccine composed of long sugar molecule chains that make up the casing of certain bacteria - making the vaccine more potent

• available for pneumococcal, meningococcal, and Salmonella Typhi

• usually T-cell independent - can stimulate B cells without Th cells

• should not be given to children under 2

• do not require booster shots due to predominantly IgM being produced, rather than IgG

  • this is why conjugate vaccines were made

polysaccharide vaccines - conjugate

• pure polysaccharides are chemically combined with a protein molecule

• conjugation changes the immune response from T-cell independent to T-cell dependent

  • this allows children under 2 to receive this vaccine + requires booster shots now

• pneumococcal, meningococcal, and Hib

toxoid vaccines

• use a protein-based toxin to create immunity strictly to the toxin in the germ - rather than the entire germ

• the toxoid is absorbed to the Al or Ca salts

• toxoid is harmless, cannot cause disease

  • do not actively multiply or spread + less susceptible to damages by light or heat

• usually require several doses

• ex. TDAP

nucleic acid-based vaccines

• mRNA vaccines contain material from the virus that causes disease that gives our cells instructions for how to make a harmless protein that is unique to the virus

• after our cells make copies of this protein, they destroy the genetic material from the vaccine

• our bodies recognize that the protein should not be there and build T cells and B cells that will remember how to fight the virus if we are infected in the future.

4 main challenges with vaccines

1. not effective in immunocompromised ppl

2. high costs of vaccine development

3. inadequate access to vaccines

4. constant disease evolution will cause constant updating of vaccines

hx of mRNA vaccines

• 1960 mRNA discovered

• 1974 liposomes used for drug delivery

• 1978 first liposome mRNA delivery to cell

• 1993 first mRNA vaccine tested (influenza in mice)

• 2005 discovery of modified RNA that evades immune detection

• 2013 first clinical trial of mRNA vaccine (Rabies)

• 2018 first drug with lipid nanoparticles approved

• 2020 mRNA based COVID vaccines

how mRNA vaccines work

1⃣ What the Vaccine Contains

• mRNA that codes for the spike protein of SARS-CoV-2

• Lipid nanoparticle system to:

  • Protect the mRNA

  • Help it enter cells

2⃣ What Happens After Injection

• Lipid nanoparticles help mRNA enter dendritic cells

• mRNA stays in the cytoplasm (does NOT enter nucleus)

• Ribosomes read the mRNA

• Cells produce the spike protein

3⃣ Immune System Activation

• Spike protein is displayed on the dendritic cell surface

• Dendritic cell travels to nearby lymph node

• In lymph node:

  • Helper T cells activate B cells

  • B cells produce large amounts of antibodies

  • Cytotoxic T cells learn to kill infected cells

pros of mRNA vaccines

• easier and safer to produce than vaccines that require a weakened or inactivated pathogen

• mRNA can be easily altered for different protein spikes/common viral mutations

cons of mRNA vaccines

• mRNA can be a challenge to deliver to cells as the innate immune system can identify and destroy mRNA, hence the use of lipid nanoparticles to protect the mRNA

• these lipid nanoparticles require uninterrupted refrigeration/freezing and are easily damaged.

  • stringent protocols are required for transportation and vaccine preparation for delivery

bacterial suface structures - capsule

• only in some bacteria

• extra outer covering

• protects against phagocytosis

• helps retain moisture

• aids in adhesion to surfaces and nutrients

bacterial suface structures - cell wall

• rigid outer layer

• gives cell its shape

• protects from the envirpnment

• prevents dehydration

• controls permeability

• provides attachment site for flagella and pili

bacterial suface structures - plasma membrane

• thin layer beneath the cell wall

• semi-permeable

• controls movement of substances in and out of the cell

bacterial internal structures - cytoplasm

• gel-like substance (mostly water)

• contains enzymes, salts, organic molecules, and cell components

• house ribosomes and nucleoid

bacterial internal structures - ribosomes & nucleoid

ribosomes

• responsible for protein synthesis

nucleoid

• region containing the single circular bacterial DNA molecule (plasmids)