Comp 1 (P1 Fall)

missing foundations of practice

What is the immune system?

A network of tissues, cells and molecules that protect again infection, injury, and malignancy

What are the recognition mechanisms of the innate immune system?

• rapid responses (within hours)

• fixed responses

• limited number of responses

• constant during response

What are the recognition mechanisms of the adaptive immune system?

• slow response (days to weeks)

• variable responses

• numerous types of responses

• improve during response

NEED TO ADD CELL DERVITIVES

What are the 3 types of granulocytes (WBC)?

neutrophil, eosinophil, basophil

Neutrophils target…

micros through phagocytosis

Where are neutrophils stored? How do they migrate?

• Stored: in the bone marrow

• Migrate to infected tissue where they engulf micro. They die in the tissue and are degraded by macrophages

Eosinophils

kill antibody coated parasites through release of granule contents

Basophils

control immune response to parasites

Mast cells

expulsion of pathogens from body through release of granules containing histamine and other active agents

Myeloid-derived professional antigen presenting cells (APCs) include

macrophages and dendritic cells

Macrophages kill by

• phagocytosis and killing of micros

• activate T cells and initiation of immune responses (alarm signals)

Dendritic cells

activate T cells and initiation of adaptive immune response

Lymphocytes include

plasma cell, effector T cell, and NK cell (all have anitbodies)

Natural Killer (NK) cell

kills cells infected with certain viruses

CD8

cytotoxic T cell

CD4

helper T cell

After viral infection, CD8 T cells

reduce in population, but stay in cell memory

Primary lymphoid tissues include

bone marrow (B cell) and thymus (T cell)

secondary lymphoid tissues include

spleen, lymph nodes, Peyer’s patch (small intestine)

Purpose of T cells

destroy virus infected cells and help run immune response

Purpose of B cells

make antibodies to tag foreign invaders

Lymphocytes are the only cells that will circulate from lymphatic to blood. What happens if a lymphocyte encounters a pathogen that it recognizes?

it stops circulating

Infectious microbial disease

colonization of a human host by a microbe that results in pathology

Pathogen

biological agent that can cause disease to its host. (colonization of microbes does not necessarily mean pathology…ie gut bacteria)

Virulence

relative capacity of a pathogen to cause disease (based on number of microbes, entry route to body, ability to damage the host)

Portals of entry

• respiratory tract

• GI tract

• urogenital tract

• skin and mucous membranes

• vertical transmission (placenta, birth, milk)

• bloodborne

Modes of transmission

• direct contact (touching)

• indirect contact (touching contaminated objects…fomites)

• airborne + droplet

• vector borne (infected ticks)

• contaminated food and water

Cellular (living) pathogens include

parasites, protozoa, fungi, prokaryote

All bacteria are

prokaryotes

Acelular (non living) pathogens include

virus, prion

coccus

round

bacillus

rod

Gram + have

lipoteichoic acid (toll like receptor 2)

Gram - have

Lipopolysaccharides (toll like receptor 4)

Mechanisms of bacterial injury include

• toxins (endotoxins, exotoxins)

• host immune mediated tissue damage (granuloma formation)

Bacterial damage to host tissue is dependent on

ability to adhere to host cells, invade, and deliver toxins

Endotoxins (components of bacterial cell walls in gram -)

activate protective immunity but can cause septic shock

Exotoxins (secreted by bacteria)

enzymes, toxins and neurotoxins, and superantigens

Gram + Corynebacterium Diphtheriae causes

Diphtheria

Signs of Diphtheria

• pharyngotonsillitis (airway obstruction)

• Bulk neck (lymphadenopathy)

• Cutaneous diphtheria (blisters/rash/sores)

After toxins are released:

• Myocarditis

• polyneuritis

• kidney failures

Gram - Bordetella Pertussis causes

Whooping - pertussis (whooping cough)

Whooping cough (pertussis) vaccines include

• DTaP vaccine (5 doses at 2, 4, 6, 15-18mon, and 4-6 yrs)

• Tdap booster: age 11/12. Adults every 10yrs

• During pregnancy in the 3rd trimester to pass antibodies to newborns

Gram - Treponema Palladium causes

Syphilis

Syphilis has 3 stages:

• primary: 3 weeks / painless sore (chancre) (treatable phase)

• secondary: months later / non itchy rash, swollen lymph nodes (needs medical care)

• Tertiary: 10 - 30 yrs later: CV, neuro, and gummatous

Gummatous syphillis

tumor like growths on skin, bones, liver, causing tissue destruction and pain

Gram + Mycobacteria tuberculosis stages

• primary complex: initial exposure; becomes dormant or heals

• secondary TB (reinfection/reactivation): causes lesions on lungs

• Disseminated spread (Miliary TB): TB spreads in bloodstream causing liver and spleen damage

What is caseous granuloma?

Accumulation of macrophages, which causes tissue necrosis (common in TB)

Anaerobic bacteria Clostridium Difficile (C.Diff) leads to

Pseudomembranous colitis

Pseudomembranous colitis

• severe colon inflammation, causing dehydration due to diarrhea, kidney failure, megacolon, and bowel perforation

• Happens after taking antibiotics which allows C. Diff to flourish

C. Diff risk factors

• antibiotics

• 65+

• immunosuppression

• previous infection

Virus structures include

• capsid

• envelope

• tropism

Nucleic acid is protected by a protein coat called a

Capsid

Capsid is sometimes encased by a lipid membrane called an

envelope

Tropism is the

tendency to infect certain cells (ex. viral glycoproteins target receptors)

Virus gain entry and once they are inside the cell they

replicate using cellular machinery

Acute/transient infection example

measles

Measles

• affects breathing

• causes rash + fever

• spreads easily

Chronic laten infection example

• chickenpox (acute)

• shingles (latent)

Latent varicella (shingles)

in dorsal root ganglia is reactivated and infects sensory nerves supplying the skin

Chronic productive infections such as HIV and HBV

have a high mutation rate, escaping the immune system. This leads to continued viral replication.

HBV can lead to

chronic hepatitis, cirrhosis, hepatocellular carcinoma

Transforming infections such as Epstein Barr Virus (EBV) is transmitted by saliva and causes

• mononucleosis kissing disease

• lymphadenopathy, hepatosplenomegaly

• Burkitt lymphoma (B cell lymphoma in immunodeficient people)

Fungal infections can be caused by

candidiasis

Malaria is caused by protozoan…

plasmodium falciparum

First lines of defence

• commensal micros (microbiota)

• physical and mechanical barriers

• antimicrobial substances

Skin

tight juunctions skin epithelium with stratified squamous epithelium (surface keratinization)

Mucociliary Escalator

mechanical system to trap air pollutants and microbes in bronchi

• cilia moves mucus up throat → swallowed → destroyed in stomach

Gut mucosa

tight epithelial junctions; damaged by bowl disease

Innate immunity acts when

physical / chemical barriers are evaded/overcame ; acts within minutes

PRRs (used in detection)

Pathogen Recognition Receptors (TLR, NLRS)

Innate signals with

cytokines, chemokines, or type 1 IFNs

Innate responds with

macrophages, neutrophils, and NK cells

Innate bridges (hands off to adaptive imm) with

dendritic cells to T cells

B cells and plasma cells make

antibodies

Macrophages (first responders)

• phagocytose virus and infected debris

• present antigens

• release cytokines and chemokines (IL 1, IL 6)

• Initiate local inflammation

• embryonic origin

Neutrophils

• phagocytose pathogens

• Release ROS, antimicrobial enzymes, and granules

• Short lived first recruited responders

NK

• Recognize stressed of MHC 1 deficient infected cells

• Kill infected cells using perforin and granzymes

• Produce IFN-y to enhance antiviral response

Dendritic Cells

• Capture and process viral antigens via phag

• Migrate to lymph nodes after activation

• Activate and prime T cells

What is recruited first?

Neutrophils

Inflammatory Macrophages

originate from monocytes that migrated to tissues

Granulocytes include

neutrophils, eosinophils, and basophils

Eosinophils and basophils

defend against parasites and involved in allergies

Mast Cells

• protect internal surfaces

• produce vasoactive and inflammatory mediators

Dendritic Cells

antigen engulfment, presentation, T cell activation

Endothelial Cells

facilitate extravasation (draining) of leukocytes in inflammation sites

Drug

Substance intended for use in the diagnosis, mitigation, treatment, cure, or prevention of disease in humans or other animals

Small Molecules Drugs

(includes most drugs) <900 daltons; compounds that are manufactured via chemical synthesis

Biologics (biopharmaceuticals, macromolecules)

Large molecules that are made in bacteria, plant, or animal cells using recombinant DNA tech

Prodrug

Inactive compound that becomes active in the body through enzymatic or biochemical transformation

Pharmaceutics

the science of designing dosage forms and drug delivery systems — turns an active ingredient into usable medicine

Dosage Form

the final physical form of the drug which may be used by the consumer without requiring any further manufacturing

Why is a dosage form needed?

• to admin an accurate dose that is convenient

• ensure patient compliance

• conceal unpleasant taste/odor

• Protect drug again decomposition from external environment

• control the release of drugs into the body

A finished dosage contains…

inactive and active ingredients

Active ingredients

substances that are responsible for pharmacological effects

Inactive ingredients

have well-define, non-therapeutic function in a drug product (contributes to texture, stability, taste, appearance)

Excipients

are intended to be inert and listed as inactive ingredients, but they can have risks/cause adverse events

Examples of excipients

fillers, thickeners, sweeteners, flavors, solvents, etc.

Why do you need to be careful when considering pediatric dosages?

Children are not born with fully functional organ and enzyme systems — Infants also have immature hepatic and renal function.

Compounding

Preparation, mixing, assembling, altering, packaging, and labeling of a dosage form by a licensed pharmacist