Microbio Exam 3 Ch. 13-17

Immunodeficiency

Lack of proper immune response (partial, weak, or none)

Primary immunodeficiency

Genetic (born with it)

Rare and more severe

Affects different pathways (B cells, T cells, phagocytes, complement)

SPUR

SPUR (primary immunodeficiency)

Severe, persistant, uncommon, recurring

Secondary immunodeficiency & causes

Acquired (get later in life)

Can be caused by aging, some drugs, some infections, chronic stress

Immunodeficiency can lead to cancer

True

Autoimmune disorders

Immune system too strong, attacks own body

Diagnosed via antibodies

System vs localized autoimmune disorders

Systemic: attacks whole body (lupus)

Localized: attacks one tissue (arthritis)

Autoinflammation vs autoimmune disorders

Inflammation: innate

Immune disorders: adpative

Hypersensitivity

Inappropriate adaptive immune response

Body attacks harmless non-self antigen

Can't be cured, just treated (immunosuppressants)

Hygiene hypothesis

Cleanliness lowers microbiome diversity, decreases training of immune system, can lead to hypersensitivity

Type I hypersensitivity

Allergy (most common)

Triggered by allergens

Activation of IgE & mast cells

Method of exposure determines reaction

Anaphylaxis

Allergen in blood causes response everywhere

Treated with epinephrine to decrease muscle swelling

Primary exposure (Type I)

First time exposed to allergen

B cells make IgE

Sensitization, no reaction

Secondary exposure (Type I)

IgE on mast cells causes degranulation (histamine big driver)

Type I treatments

Avoid allergen

Manage symptoms (like eye drops)

Anti-inflammatory drugs

Type II hypersensitivity

Binds to NON-SOLUBLE antigen

Usually cytotoxic but not always

Activation of IgM & IgG

Cytotoxic type II & example

Antibodies bind to target and INDUCE killing via other immune pathways

Ex: blood transfusion mismatch

Non-cytotoxic type II & example

Antibodies bind to target and BLOCK some crucial signaling pathway

Ex: Grave's disease

Type III hypersensitivity (immune complex)

Binds to SOLUBLE antigens

Antibodies & antigens form large complex

Deposits in tissues

Activation of IgG & IgM

Many are autoimmune (lupus), some not

Recruits complements to cause damage

Type IV hypersensitivity

Requires T cells instead of antibodies

Delayed response (12-72hrs)

Activation of T cells is slow

Reacting to self or non-self antigens, so can be autoimmune or not (MS or contact dermatitis)

Requires sensitization

Categorize the following:

Type I Diabetes

Celiacs disease

Multiple Sclerosis

Contact dermatitis

Type IV

Categorize the following:

Lupus

Rheumatoid arthritis

Scleroderma

Type III

Categorize the following:

Blood transfusion reaction

Hemolytic disease of newborn (baby has Rh, mom doesn't)

Grave's disease

Type II

Categorize the following:

Allergies

(Some) asthma

(Some) skin eczema

Type I

Variolation example

Using smallpox scrapings, inhaling/parental exposure

Herd immunity

Main goal

Preventing spread of pathogen by generating immunity in a population

Childhood vaccination

Skipping/delaying weakens herd immunity

Some need boosters

Some viruses mutate too quickly, new vax needed frequently

Eradication

Ultimate goal

Creating an immune population so that pathogen dies out

In order for eradication to work

Need good vaccine, slowly mutating virus, public supports, only infects a single host

Antivaccination sentinent

Weakens herd immunity

Popularized by debunked study (MMR and autism)

VAERS

Vaccine Adverse Event Reporting System (not reliable)

Vaccine types

Active: some "live pathogen"

inactive: some killed/incomplete pathogen

Active vaccine types

Attenuated: live but weakened, risk of spreading

Vector: piece of pathogen added to harmless virus

Inactive vaccine types

Whole agent: entirely dead pathogen

Subunit: piece of the pathogen, requires separate adjuvant to fully activate immunity

mRNA: temporarily gives body the instructions to make subunit (temporary)

Diagnostics and anitbodies

Many tests use antibodies for their specificity (anitbody-antigen specificity)

Agglutination

If target antigen is present, antibodies will cause clumping (blood typing)

ELISA

Relies on synthetic antibodies with an attached reporter

Create light/color change when bound to sample

Indirect ELISA 7 steps

Looking for patient antibodies to given antigens

1. Plate w bound antigen

2. Patient serum added, patient antibodies that recognize the antigen will bind to it

3. Excess patient antibody is rinsed away before adding detetcion antibody

4. Excess detection rinsed away, substrate added

Sandwich ELISA & steps

Looking for antigens

1. Plate w capture antibody bound

2. Patient serum added, antibodies than ca bind are retained

3. Capture antigen is sandwiched between antibodies

4. Excess detection anitbody is rinsed away, substrate added

ELISA rapid tests

At home

Rather than read samples in a plate reading, colored lines will appear on the testing strip

(Pregnancy test)

Weakness of anitbody-based tests

Can't always test patients for anitbodies or antigens in early stages antigens

(have no antibodies, antigens too low to detect)

PCR

Detecting genomes

If present will be copied several times

Quantitative PCR

Special dye added, makes it glow from bacteria (heat-resistant)

CT value

Threshold cycle, when fluorescence crosses some line

Lower = better

Antimicrobial

Kills microbe or inhibits growth

Antibiotic

Naturally occurring antimicrobial

Selective toxicity*

Antimicrobial should target something that't not also in the host to prevent severe side effects

Spectrum

How many species it targets

Broad: many

Narrow: few

Empiric therapy

Start patient on broad spectrum, ID pathogen, then move to narrow spectrum

Bacteriostatic vs bacteriocidal

Static: prevent growth, rely on host to clear infection

Cidal: kills microbes

Antimicrobial origins

Naturally occurring: defense

Synthetic: human made

Semi-synthetic: modified

Considerations before use

Side effects: common in filtering organs, dosing

Delivery: differs btwn drugs, influences dosing

Half-life how long it remains in system

Common antibacterial targets

Cell wall

Plasma membrane

Nucleic acids

Ribosome

Protein synthesis

Cell wall targeting

Many target transpeptidation (cross-bridge formation)

With weakened wall, cell swells w water and bursts

Beta-lactam family

Inhibits transpeptidation

Resistance common

Can be co-delivered with inhibitor

Beta-lactam examples

Penicillins

Cephalosporins

Carabapenems

Monobactams

Penecillins

Ampicillin, amoxicillin, penicillin

Narrow spectrum (good for gram+)

Minimal side effects

Later gens: expand spectrum, easier delivery

Cephalosporins

Similar to penicillins

Later gens: better at targeting gram-

Carabapenems

Last resort

Can cause renal issues

Monobactams

Only work on gram-

Examples that also target cell wall

Glycopeptides

Bacitracin

Isonaizid

Glycopeptides

Similar action to lactams, different in structure

Resistant to lactamses

IV delivery

Bacitracin

In triple antibiotic ointment

Isoniazid

Targets mycolic acid

DNA targeting

Target bacteria-specific replication enzymes

Ex: quinolones

RNA targeting

Inhibit bacterial RNA polymerase

Ex: rifamycins

Anitfolate drugs

Inhibit folate synthesis (which is needed to make nucleic acid)

Humans don't synthesize, we eat it

Sulfa drugs/sulfonamides (anitfolate)

Mimic PABA

Varied delivery, bacteriostatic

In wound dressing for burn victims

Ribosome targeting & examples

Prevent protein translation

Macrolides

Lindosamides

Phenicols

Tetracyclines

Aminoglycosides

Macrolides**

Broad spectrum and delivery

Ex: azithromycin

Aminoglycosides**

Narrow spectrum, only good for gram-

Short half-life

Second component of triple ointment

Ex: neomycin

Membrane targeting

Tears holes in membrane

Polymyxins**

Final component of triple ointment

Bind to LPS and tear apart membrane (gram-)

Antivirals

Target some step of viral replication

Extremely narrow spectrum

HIV, hepatitis, influenza

Antifungals

Target ergosterol in membrane or cell wall

Azoles, allymines, polyenes: ergosterol

Echinocandin: cell wall

Antiprotozoan

Antimalarials: chloroquine, quinine

Metronidazole: wide variety of protozoa infections - targets nucleic acid

Antihelminthic

Inhibit sugar uptake or paralyze

Albendazole: sugar

Praziquantel: paralyze

Resistance

Selective pressure to mutate

Can pass resistance by horizontal gene transfer

Mechanisms of resistance

1. Alter drug target (rifampin)

2. Break drug (beta-lactmases)

3. Keep drug out (efflux pumps)*

Human activity promotes resistance

Unregulated use

Antibiotic stewardship: reduce unnecessary antibiotic use and use narrow spectrum drug

Upper/lower respiratory tract

Mucocilliary escalator to trap microbes

Lungs are very vascularized

Types of inflammation

1. Sinusitis & Rhinitis

2. Pharyngitis

3. Epiglottitis

4. Laryngitis

5. Tracheitis & bronchitis

6. Pneumonia

Sinusitis & Rhinitis

Runny/stuffy nose

Pharyngitis

Sore throat

Epiglottitis

Breathing difficulty

Laryngitis

Lost voice

Tracheitis & bronchitis

Wheezing

Pneumonia

Inflammation of the lungs

Common symtpoms

Dyspnea (shortness of breath)*

Strider (wheezing)*

Sneezing

Coughing

Runny nose

Sore throat

Respiratory microbiome

No longer though to be sterile

Commensals can out-compete pathogens*

Common cold

Mainly rhinoviruses & coronaviruses

Viral

Spread by droplets and fomites

Runny nose, sneezing, coughing, low fever, etc

Symptoms similar, severity differs

Self limiting, treatment is rest

More severe colds

*RSV: severe pneumonia and high fever in infants & elders

Croup

Severe wheezing and coughing

Parainfluenza can cause

Influenza

Caused by influenza viruses

Viral

Spread by droplets and fomites

Same is colds but with pneumonia (longer to recover)

Strains named have HA and NA proteins

Influenza types

A: most common and severe

B: can be difficult

C: rare

Antigenic shift vs drift

Drift: gradual (why we need flu shots every year)

Shift: sudden, cause of flu pandemics

Influenza treatment

Attenuated vaccine

Cannot give healthy person the flu

Antivirals: inhibit NA spike (mostly)

COVID-19

Sars-Cov-2

Emerged from ? in China 2019

Highly contagious

Severe pneumonia, damage to lung tissue (ARDS)

Many vaccine options

Variant

Viral mutation that changes disease

Increases severity or drug resistance or transmissibility or etc.

If common it becomes new strain*

Eustachian tube

Fluid in ear drains to pharynx

Tube is narrow and more horizontal in children, thats why otitis media (middle ear infection) is more common

Sinusitis constricts tube more bc inflammation