PH162a MT2

Innate immunity qualities

Rapid, germline encoded, most cells involved

Innate immunity functions

Hold pathogens in check, alert the adaptive immune system

Adaptive immunity qualities

Slower, somatically generated, highly specific, mostly B&T cells

Adaptive immunity functions

Powerful response to clear infection, memory

Immune organs where cells develop

Bone marrow (all immune cells originate here, B cells fully develop) & Thymus (T cell development)

Immune sites where B & T cells are activated

Spleen (infection in blood), lymph nodes (infection in tissues)

Professional phagocytes

Dendritic cell, macrophage, neutrophil

Roles of professional phagocytes

1. Kill pathogens, 2. Initiate inflammatory response, 3. Initiate and influence adaptive immune response

Enzymes in the lysosome

Acid hydrolases that break down phagocytosed pathogens' cell walls

Oxidative burst

Macrophages & neutrophils produce reactive oxygen species to kill phagocytosed pathogens

How do neutrophils kill large pathogens?

They extrude "nets" of their DNA and protein to trap the pathogens (this is called NETosis)

Complement

A system of proteins in the blood that function as part of the innate immune system to combat pathogens

Functions of complement

Inflammation, opsonization, membrane attack complexes (direct killing by forming pores in pathogens)

Opsonization

Tagging a pathogen for phagocytosis by coating it in proteins recognized by other immune cells (antibodies can do this, as well as complement)

Purpose of increased blood flow during inflammation

Allow for plasma proteins (like complement) and immune cells to make their way to the site of infection from the bloodstream

PAMPs

Pathogen Associated Molecular Patterns, invariant components of pathogens that are recognized by the innate immune system

TLRs

Toll Like Receptors that sense PAMPs in extracellular space and endosomes/lysosomes

Location of TLRs

Plasma membrane and endosomal membrane

TLR responsible for sensing LPS

TLR-4

Cytokines

Soluble proteins that travel through blood and activate cells

Canonical inflammatory cytokine

TNF-a (Tumor necrosis factor alpha)

Cells responsible for killing virally infected cells

NK (natural killer) cells (also CD8 T cells are important)

Strategies to kill larger pathogens

"Weep and Sweep", recognition of chitin, cells secrete effectors rather than absorb the worms (chitinases, proteases, toxic granules)

Cells linking innate and adaptive immune responses

Dendritic cells

Purpose of B cells

Secreting antibody to eliminate extracellular pathogens, toxins

Purpose of CD4 T cells

Secreting cytokines to activate the killing of phagocytosed microbes in macrophages; also help activate B cells

Purpose of CD8 T cells

Lysing infected cells with intracellular cytosolic pathogens (mostly viruses)

VDJ recombination

variable-diversity-joining rearrangement, increases diversity of antigen recognition in BCRs/TCRs/antibodies

Function of MHC molecules

present antigen to T cell receptors

MHC I

present cytosolic/intracellular antigen, present on almost all cell types

MHC II

present phagocytosed antigen taken from extracellular space, present on professional antigen presenting cells (DCs, Macrophages, B cells)

MHC molecule presenting to CD8 T cell

MHC I

MHC molecule presenting to CD4 T cell

MHC II

Types of cells that secrete antibody

Plasma cells

Functions of antibodies

Neutralization, opsonization, activation of complement

First type of antibody made

IgM

Process generating different types of antibody

Class switching

Process generating higher affinity antibodies

Somatic hypermutation

Type of antibody important for mucosal immunity

IgA

Stages of vaccine testing

Preclinical trials in animals, Human Phase I (safety), Human Phase II (efficacy)

Active immunization

stimulation of immunized host immune response with microbial product

Passive immunization

providing the host with preformed antibodies (does not generate memory or modify existing immune system)

Vaccine

biological preparation that enhances immunity to a particular disease without causing disease

Antigen

any molecule that is recognized by the immune system (specifically binds antibody or B/T cell receptor)

Epitope

smallest unit of an antigen to which the immune system responds

Adjuvant

compounds used to enhance a vaccine's ability to elicit a stronger immune response

Live attenuated vaccine

contain live bacteria/virus that has been weakened (ex: MMR, polio oral vaccine)

Inactivated vaccine

contain killed bacteria/virus such that it cannot replicate (ex: polio inactivated vaccine)

Protein subunit vaccine

use a protein portion of the bacteria/virus to stimulate an immune response, requires an adjuvant (ex: Hep B)

Toxoid vaccine

neutralize toxin created by bacteria (ex: tetanus)

Polysaccharide and conjugate vaccines

use a protein conjugated to a polysaccharide (combo of the two is more helpful for immune response) (ex: Hib)

mRNA vaccine

mRNA coding for an antigenic protein is delivered in a nanoparticle (ex: SARS-CoV2)

Ring vaccination

vaccination of a "ring" of people surrounding an infected patient, contacts and contacts of contacts are vaccinated (ex: Ebola outbreaks)

Herd immunity

occurs when the vast majority of the population is immune/resistant to disease, means that the small portion of susceptible people are protected

Epidemiology

study of distribution and determinants of diseases in a population

Infection

entry and multiplication of an infectious agent in a person or animal

Infectious disease

clinically manifest disease resulting from an infection

Communicable disease

can be transmitted from one human to another, or from animals to humans

Incidence

number of NEW instances of illness (# new cases per time period / # of persons at risk in population per time period)

Prevalence

number of TOTAL people infected within the population at any time (prevalence @ time/ population at risk @ time); a measure of disease burden

Morbidity

a measure of disease burden

Mortality rate

(# deaths per time period/population @ risk)

Case fatality rate (CFR)

measures severity (# of deaths per time/# of cases per time)

Attack rate

proportion of people who become ill with a disease in an at risk population initially free of the disease (measured from beginning to end of an outbreak)

Endemic

habitual presence of disease or infectious agent within geographic region or population group (ex: malaria)

Epidemic

occurrence of cases of disease (or outbreak) with frequency clearly in excess of normal expectancy (ex: Ebola, measles)

Pandemic

epidemic spreads worldwide (ex: COVID-19, cholera)

Sporadic

random, isolated cases that are unpredictable (ex: meningitis)

Two types of outbreak

Common source (contaminated substances) & propagated (person-person transmission)

Chain of infection

certain conditions must be met in order for an infectious disease to spread - (disease organism, reservoir, mode of escape, mode of transfer, mode of entry, susceptible host)

Reservoir

where an infectious agent normally lives and multiplies (does not experience disease when infected by the pathogen) (ex: human, animal, environmental)

Direct transmission

direct contact (horizontal, vertical, direct exposure)

Indirect transmission

vehicle-borne, vector-borne (mechanical or biological)

Airborne transmission

dissemination of microbial aerosols to a suitable port of entry by the respiratory tract

Ro (Rnaught, the reproductive rate)

the number of people that one sick person will infect (ex: measles=18, ebola=2)

Iceberg concept of infection

what you see as disease cases are only a small part of the whole (many cases are asymptomatic or undiagnosed)

Incubation period

time interval between initial contact with an infectious agent and the first appearance of symptoms associated with the infection

Exotoxins

proteins secreted by the growing cell (ex: AB toxin, superantigen, cytolytic)

Endotoxins

LPS, released when cell lyses

Primary prevention

methods to avoid occurrence of disease

Secondary prevention

methods to diagnose and treat disease in early stages

Etiology

cause of a disease in general (ie the cause of all cases of a particular disease in a population)

Diagnosis

identification of the disease in an individual case of disease

Direct detection

directly detecting the presence of a microorganism from the body or bodily fluids of an infected person (ex: seeing parasites in a blood smear, culturing bacteria from spinal tap, detecting viral DNA by PCR)

Indirect detection

indirectly detecting the presence of a microorganism from the body or bodily fluids of an infected person, typically measuring the host's response to the infection (ex: anti-HIV antibodies in a blood sample, host proteins produced in response to viral infection)

Sensitivity

how many of the TRULY sick people test positive? (test positives/true positives)

Specificity

how many truly NOT sick people test negative? (test negative/true negative)

What does RT-PCR measure in diagnostics?

It measures how many PCR cycles it took a sample to reach a certain fluorescence threshold.

What does a lower Ct value indicate in RT-PCR?

A lower Ct value indicates a higher viral load, meaning it took fewer cycles to reach the fluorescence threshold.

HAIs

Health-care associated infections; infections that become evident after 48 hours in or discharge from a healthcare facility.

Puerperal fever

A HAI affecting postpartum people that Ignas Semmelweis proposed spread due to doctors not washing hands after autopsies.

Sources of HAIs

Endogenous (normal flora, from within one's body) and exogenous (from outside one's body).

Most common site for HAI

Urinary tract.

Candida auris

Emerging multidrug resistant fungi, causes common HAIs.

WaSH

Water, sanitation, hygiene; a public health strategy for reducing gastrointestinal illnesses like Shigella and rotavirus.

Vector

An arthropod that transmits a disease-causing organism from one host to another.

Biological vector

A vector where pathogens complete a part of their life cycle within the organism.

Mechanical vector

A pathogen that does not complete any part of its life cycle during transit.

Dengue

+ssRNA flavivirus, transmitted by Aedes mosquito.

Dengue clinical manifestations

Dengue fever (DF), Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS).