Module 6 Overall Flashcards

Immune system definition

collection of cells, tissues, and molecules that mediate resistance to infections and eliminate tumors

Immunology definition

study of the immune system and its response to invading pathogens and tumors

Immune response definition

Coordinated and tightly controlled reaction of the immune system to infectious microbes

Immunity definition

Resistance to disease, specifically those caused by bacteria, viral, fungal, or parasitic infections.

• extended recently to include tumor immunity

Immunity not just about killing pathogen but also keep body in working order

What is the function of the immune system

• prevent infections

• eradicate established infections

• detect and eliminate tumors as well as tolerate own cells

Congenital (primary) Immune defeiciency

genetic condition that results in a lack of key cells and molecules of the immune system

• MORE RARE

Acquired (secondary) Immune deficiencies

infections that kill key immune cells and molecules

• MORE COMMON

Overreacting immune system

a condition where the immune system responds excessively to harmless substances, leading to allergies, asthma, or autoimmune diseases

Immune system integrations with other systems

• GI tract

• Cardiovascular

• Respiratory

• Nervous

• Endocrine

• Skin

• Mouth

Where do Immune cells originate and how do they travel

Originate in bone marrow

Travel via blood/lymph vessels

• may travel/migrate or be resident in tissue

Autocrine

mechanism of action on self

Paracrine

mechanism of action on neighboring cells

Endocrine

mechanism of action over long distances

• usually involves travelling via blood/lymph

Physical and Chemical barriers

• Epithelial cells (skin, gut, resp. tract)

• secretions (sweat, wax, tears)

• mucous (nose, trachea)

• urine

• enzymes

• stomach pH

Central immune sites

the lymphoid tissue/organ itself

Primary lymphoid organs

bone marrow

thymus

Secondary lymphoid organs

spleen

lymph nodes

mucosal associated lymphoid tissue

cutaneous associated lymphoid tissue

Peripheral immune sites

all other tissues and systems

• skin, liver, gut, heart, brain, CNS, muscle, lungs, etc.

Thymus

Identifies as a primary lymphoid organ by Jacques Miller

Located right above heart and between lungs

• Site of T cell maturation enable T cells to tolerate host cells

Differentiation of Immune cells

Common myeloid progenitor cells (and what they differentiate into)

Involved in the innate immune system

Differentiate into:

• Megakaryocyte (form thrombocytes)

• Erythrocytes

• Mast Cells (inflammation)

• Myeloblasts - produce:

  • Basophils

  • Neutrophils

  • Eosinophils

  • Monocytes

Basophils

release histamine and other chemical involved in inflammation and allergic responses

Neutrophils

most abundant type and are the first to respond to bacterial infections (via phagocytosis)

Eosinophils

allergic reactions and fighting parasites

Monocytes

become macrophages

Common lymphoid progenitor cells (and what they differentiate into)

involved in the adaptive immunity

Differentiate into:

• Natural killer cells (large granular lymphocytes)

• Small lymphocytes (T Cells, B Cells → plasma cells)

What lymphocyte?

Neutrophils - have sgemented nucleus and granules in cytoplasm

• nucleus divided into 2-5 segments giving multi-lobed appearance

What lymphocyte?

Basophils - large, irregular shaped nucleus, lots of granules in cytoplasm that contain histamine

What lymphocyte?

Eosinophils - have bi-nucleus and large granules in their cytoplasm

What lymphocyte?

Monocytes - large kidney shaped cells with single large oval shaped nucleus. Small amount of cytoplasm and can differentiate into macrophages

What lymphocytes?

T cells - have a round nucleus with a small amount of cytoplasm

What lymphocytes?

B cells - have round nucleus with more cytoplasm than T cells

3 main types of T cells

1. Helper T cells

   • contain CD4+ receptors

   • activate other cells of the immune system

2. Cytotoxic T cells

   • contain CD8+ receptors

   • kill infected/cancerous cells

3. Regulatory T cells

   • prevent autoimmune reactions by suppressing the immune response

B cell action

Have B cell receptors (BCR) which recognize and bind to specific antigens - when BCR binds to antigen, B cells differentiate into plasma cells and produce antibodies to neutralize antigen

Innate Immunity

acts as first line of defence against invading pathogens

present at birth and provides immediate protection

Components of innate immunity

1. Epithelial barriers

2. cells in circulation and tissue

   • Phagocytes: neutrophils & acrophages

   • Exocytes: eosinophils, mast cells, basophils

3. Molecules

   • cytokines

   • blood preoteins

Mast cells

tissue resident cells - first responders to injury

reside in peripheral tissue and often exposed to environment (gut, lung, skin, oral mucosa)

How do mast cells respond to infection

1. degranulate contents (histamine, other soluble factors)

2. increase vascular permeability & promote inflammation

Cascade of events when danger is detected

1. Mast cells and macrophages release histamine, cytokines, protaglandins

2. dilated blood vessels allow for more blood flow and fluid to the area (redness + swelling)

   • carries innate immune cells and plasma proteins to the area

3. Induces expression of adhesion molecules on endothelial cells lining the blood vessels

   • attracts neutrophils to the area for:

     • phagocytosis

     • secretion of inflammatory cytokines

     • extend web-like extracellular trap for bacteria

Characteristics of innate immunity

1. Speed: early and rapid

2. Duration: short-lived (5 days in circulation, 2-6 hours in tissue)

3. Repetitive: responds the same way each time

4. Interactive: interacts with other cells of the innate and adaptive immune system

5. Non-reactive: is tolerant of host cells

How does the innate immune system distinguish between self and non-self cells

Uses Pattern Recognition Receptors (PRRs) expressed on cell surface to identify host cells

Detect Pathogen-associated Molecular Patterns (PAMPs) which are present on harmful invaders

Adaptive immune system

adapts to the presence of microbial invaders

consists of T&B cells that recognize specific antigens

uses effector and memory cells to coordinate immune response

Effector cells

detect and respond to antigens

Memory cells

cells that have encountered the pathogen before and can respond more effectively and rapidly the next time that the pathogen is encountered

B cells reason for name

Bursar of Fabricius

T cell resaon for name

mature in the thymus

Two main types of adaptive immunity

1. Humoral immunity

2. Cell-mediated immunity

Humoral immunity

Involves B cells that secrete antibodies (plasma cells) in response to extracellular pathogens

Cell-mediated immunity

Involves T cells (helper and cytotoxic) that help phagocyte microbes and kill infected cells

3 Main types of T cells

1. Helper T cells (Th)

2. Regulatory T cells

3. Cytotoxic T Lymphocytes

Helper T cells (Th)

help other cells perform their function

Ex, Help B cells produce antibodies, help cyto T cells kill

Mechanism:

CD4 → MHC2

Regulatory T cells

suppress or regulate the immune response to ensure self-tolerance and prevent autoimmunity

Cytotoxic T lymphocytes (CTLs)

kill target cells in highly specific way - they get help from helper T cells and play role in viral infections and anti-tumor immunity

Mechanism:

CD8 → MHC1

Immune cells in the gingiva

• Neutrophils (continually transmigrate through epithelium)

• T cells (resident lymphocytes)

• B cells

• Innate lymphoid cells

• Mononuclear phagocytes

Summary of humoral and cell-mediated immunity

Chemokines

chemical messengers that are important for cell migration - direct cells where to go

Chemotaxis

The migration of leukocytes to a specific area

• Formation of chemokine gradient that guides immune cells to sites of inflammation or injury

Process of leukocyte migration

1. Tissue resident cells promote inflammation

2. TNF and IL-1 stimulate endothelial cells the produce adhesion molecule (E-selectin and P-selectin)

3. Circulating phagocytes express surface carbohydrates that bind weakly to the E-selectin and P-selectin

   • causes cells to “roll” along endothelium

4. leukocytes express integrins on cell surface

5. resident cells produce chemokines

   • stimulates leukocyte integrins to bind ligands on endothelium

6. binding of integrin to ligands stops leukocytes from rolling

7. once leukocyte stops, it squeeze through the endothelium and into the extracellular space (diapedesis)

Primary features and functions of neutrophils

• not normally found in tissues

• recruited to inflamed peripheral sites

• potent anitbacterial function

  • entraps bacteria in “Neutrophil Extracellular Traps” (NETs)

• perform phagocytosis

• secret cytokines to recruit other immune cells

• promotes phagocytosisby macrophages

• short-lived

Primary features and functions of macrophages

• monocytes migrate into inflamed tissue and differentiate into macrophages

• can be resident in tissue

  • Ex, Kupffer cells in the lover or alveolar macrophages in lung

• secrete cytokines

• often long-lived

• act as antigen presenting cells

Phagocytosis

often triggered by microbes binding to phagocyte receptors → once microbe binds to cell phagocyte will form plasma membrane around microbe (phagosome) → phagosome fuses with lysosomes = phagolysosomes → lysosomes kill microbes

PRRs binding to PAMPs

Activates:

• transcription factors that stimulate expression of gene encoding cytokines, enzymes, proteins involved in antimicrobial function

• Toll-like receptors are activated

• phagocytosis and production of soluble mediators

Toll-like receptors (TLR)

type of PRR on host cells

• discovered by Bruce Beutler and Jules Hoffman in Drosophila flies

Locations of TLRs

on Cell surface: recognize extracellular microbes

on Endosomes in cell: recognize ingested microbes

Common types of TLRs

TLR 5: flagella

TLR 2 and 6: recognize diacylinpopeptide

TLR 1 and 2: recognize triaclipopeptide

TLR 4: LPS of gram neg bacteria

TLR 3,7,8,9: located on endocytic vesicles

Nucleotide oilgomerization domain family (NOD proteins)

family of PRRs that can detect pathogens in cytosol and signal pathogen presence to immune system

Abundance of leukocytes

Neutrophils > Lymphocytes > Macrophage/monocytes > Eosinophils > Basophils (most to least abundant)

Never Let Monkeys Eat Bananas

Primary features and functions of Eosinophils

• Contains enzymes harmful to cell walls of parasites and helminths (contents can also harm host cells)

• some found in peripheral tissue (resp, GI, genitourinary)

• increase immune recruitment

• participate as effector cells in adaptive immune response

Primary features and functions of basophils

• not normally found in peripheral tissue

• recruited from the bloodstream during inflammation

• supporting role in the development of the adaptive immune system

Innate lymphoid cells (ILCs)

“lymphocyte-like” cells that live in epithelial tissue and produce cytokines

• acts similar to T cells

• important function in oral mucosa

Main function of ILCs

• provide early defence against infections

• interact with the cells of the adaptive immune system to guide T cells

Major groups of ILCs

Group 1 ILCs (ILC1): defence against pathogens

Group 2 ILCs (ILC2): promote allergic inflammation in skin and airways

Group 3 ILC (ILC3): mucosal barrier function

Natural Killer (NK) cells

• subset of ILC 1

• class of innate lymphocytes

• secrete cytokines to kill infected and stressed cells

Complement system

collection of circulating and cell membrane proteins that are important in host cell defence and antibody-mediated tissue injury

assists the antimicrobial activity of the immune system

Activation of Complement System

sequence of cleavage of complement proteins → triggers effector molecules to kill microbes (can be innate or adaptive)

3 pathways of complement activation

1. Alternative

2. Lectin

3. Classical

All three pathways produce C3b, C3a, C5b, C5a, MAC

C3b

coats bacteria to be recognized by type 1 complement receptor (CR1) so it can be phagocytosed or killed

C3a and C5a

anaphylatoxins that stimulate inflammation and recruits neutrophils to tissue sites

Alternative and lectin pathways

initiated in the absence of antibodies = Innate immune system

Classical pathway

initiated when antibodies attach to antigens = adaptive immune system

Antibiotic definition

a chemical substance produced by microorganisms that have the capacity to inhibit growth and destroy bacteria

Antimicrobial Resistance (AMR)

changes in bacteria and viruses that make the no longer respond to medicine → difficult to treat

How are antibiotics classified

1. What part of the cell they target

2. Whether the drug kills of inhibits the cell (bacteriolytic/bacteriostatic)

3. Range of action

   • Narrow

   • Moderate

   • Broad

4. Species the drug works on

Indications for antibiotic use in dentistry

1. Prophylaxis - preventing bacterial infections before dental procedures in at-risk patients

2. Treatment - usually always required alongside dental surgery

3. Post-operative - to reduce risk in medically compromised patients

Antibody prophylaxis in dentistry

• 1hr before treatment for people with cardiac conditions (congenital heart disease, previous infective endocarditis, prosthetic cardiac valve)

Antibiotics for treatment in dentistry

Used for:

• odontogenic infections

• necrotising periodontal disease

• peri-implantitis

• salivary gland infections

Antibiotics for postoperative in dentistry

Use if patient is:

• immunocomprimised

• past history of infection

• experiences systemic disorders (fever, tachycardia, sweating, etc)

Recommended antibiotics for odontogenic infections

• Metronidazole + amoxicillin

• Amoxicillin + clavulanate

Recommended antibiotics for necrotising periodontal disease

Metronidalzole

Recommended antibiotics for prophylaxis

Amoxicillin or Cefelexin or Clindamycin (depending on patient allergy)

Principles of prescribing antibiotics

• use appropriate antibiotic for presenting infection

• Follow Antibiotic Creed (MIND ME)

M: microbiology guides therapy wherever possible

I: indications should be evidence-based

N: narrowest spectrum required

D: dosage appropriate to the site and type of infection

M: minimize duration of drug

E: ensure monotherapy in most situations

Common antibiotics

Phenoxymethylpenicillin (PenV) - used for majority of odontogenic infections

Amoxicillin - most prescribed antibiotic

Metronidazole - second most prescribed

Amoxicillin + Clavulanic acid - third most prescribed

Innate vs. Adaptive Immunity

Thymic output

the production and release of T cells from the thymus gland into the bloodstream

• output is highest during early life - peaks around 20-30 yrs old

Graph of Thymic output, Memory T cells, Native T cells

Clonal Expansion

Feature of adaptive immunity that involves rapid proliferation

Specific clonal expansion occurs for a specific antigen

Process of clonal expansion

• T cells activated in response to infection

• T cells trigger clonal expansion (24-48 hours)

• produce tons of CD8+ and CD4+ to treat infection

• following treatment of infection remaining T cells become memory cells

Basic antibody structure

Variable region = different for each antibody - gives antibodies their specificity

Constant Region = same for each class of antibody - determines the isotype of antibody (IgM, IgA, etc)

Hinge region: offers light and heavy chain flexibility

Classes of anitbodies

MAEDG (pentamer, dimer, rest are monomers)

• IgM

• IgA - neutralizes antigen

• IgD - capacity to differentiate into any antibody - anchored to cell membrane, therefore not found in serum

• IgE

• IgG - neutralizes antigen - capacity to differentiate into any antibody - most abundant in blood

Mechanism of antibody action

1. blocking penetration of microbe through epithelial barrier

2. blocks binding of microbe and infection of cells

3. blocks binding of toxin to host cell receptor