Microbio Midterm 4

Immunity

resistance; the ability to ward off disease caused by microbes and their products and protect against environmental agents

Susceptibility

Lack of immunity

Innate Immunity

Recognizes patterns- not specific microbes; defenses from prior to birth; immediate response; no memory response; 1st and 2nd line defense

Adaptive Immunity

Acquired immunity; slower to respond; specific response to microbes; memory component for future infections; 3rd line of defense

First line of defense

Skin, mucous membranes, antimicrobial substances

Second line of defense

Inflammation, fever, phagocytes

Third line of defense

Humoral and cellular immunity

Lymphatic System

Contains cells involved in the immune system and fibers that trap microbes; contains red bone marrow

Phagocytosis

The ingestion of a microorganism or other substance by a cell; cell eating

Red bone marrow

Where stem cells develop into blood cells

Phagocyte

Cells that perform phagocytosis

Hematopoiesis

The formation of new blood cells

Pluripotent

Capable of giving rise to several different cell types

Neutrophils (PMNs)

Highly phagocytic; motile; active in initial stages; can leave the blood and enter infected tissue; destroyer of microbes and foreign particles

Eosinophils

Somewhat phagocytic; can leave blood; can discharge peroxide ion; kills certain parasites

Basophils and Mast Cells

Release histamines; important for inflammation and allergies; mast cells located in connective tissues and mucosa and are not a PMN

Natural Killer cells

Found in the blood, spleen, lymph nodes, and red bone marrow; toxic substances released from lytic granules; kills wide variety of infected body cells; perforin creates channels in cells that lead to cytolysis; granzymes- protein digesting enzymes lead to apoptosis

Macrophage

Phagocytosis; can be activated by adaptive system leads to high levels of phagocytosis

Monocytes

Not actively phagocytic until they leave the blood mature into macrophages

Dendritic Cells

Long extensions; abundant in epidermis of skin, mucus membranes, thymus, and lymph nodes; phagocytosis; initiate adaptive immune response

Perforin

Creates channels in cells that lead to cytolysis

Granzymes

Protein digesting enzymes that lead to apoptosis

Which cell types are Leukocytes?

Neutrophils, basophils, mast cells, eosinophils, natural killer cells, T cells, B cells, monocytes, macrophages, and dendritic cells

Which cell types are not Leukocytes?

Erythrocytes and platelets

Which cells have myeloid stem cells as precursor cells?

Neutrophils, basophils, mast cells, eosinophils, monocytes (macrophages and dendritic cells), and erythrocytes

Which cells have lymphoid stem cell as precursor cell?

Natural killer cells, T cells, and B cells

Which cell type has megakaryocytes as precursor cells?

Platelets

Which cells are granular?

Neutrophils, basophils, mast cells, and eosinophils,

Which cells are agranular?

Natural killer cells, T cells, B cells, monocytes, macrophages, and dendritic cells

Which cells contribute to innate immunity?

Neutrophils, basophils, mast cells, eosinophils, natural killer cells, macrophages, dendritic cells, and platelets

Which cells contribute to adaptive immunity?

T cells and B cells

Which cell type contributes to both innate and intermediary immunity?

Dendritic cells

What are the relative amounts of each type of cell in the white blood cells?

Neutrophils > lymphocytes > monocytes > eosinophils > basophils

What are the 3 sectors of the first line defenses?

Physical barriers, chemical factors, and normal microbiota

Physical barriers

Barriers to block entry of microbes into the host; skin and mucus membranes

Chemical factors

Chemicals associated with skin and mucous membranes help host resist microbes

Normal microbiota

Protection against invaders; competitive exclusion

How does skin prevent microbial entry into the host?

* arrangement and structure: closely packed cells and keratin
* shedding of dead cells
* dry surface inhibiting microbial growth

Skin

the body’s largest organ in both surface area and weight

* epidermis: the outer, thinner portion
* dermis: the inner, thicker portion made of connective tissue

Mucous membranes

epithelial layer and the underlying connective tissues that line the:

* gastrointestinal tract
* respiratory tract
* genitourinary tract

secretes mucous- a slightly viscous glycoprotein

Ciliary escalator

Lacrimal apparatus

physical barrier; drains tears; washes eye

Saliva

physical barrier; dilutes and washes microbes away from teeth

Earwax

physical barrier; prevents microbes from entering the ear

Vaginal secretions

physical barrier; move microorganisms out of the vaginal tract

Epiglottis

physical barrier; prevents microorganisms from entering lower respiratory tract while swallowing

Peristalsis

physical barrier; intestine wave like motion; defecation, vomiting, diarrhea

What are common themes in chemical factors of the first line of defense?

* Lysozyme- destroys cell bacterial walls; in perspiration, tears, saliva, nasal secretions, and urine destroys
* Acidic pH- inhibits microbial growth

Sebum

chemical factor; produced by sebaceous gland and forms a protective film; fatty acids and lactic acid in sebum lowers the pH (3-5) of skin; unsaturated fatty acids help inhibit some bacterial growth

Earwax

chemical factor; fatty acids and sebum in earwax lowers the pH (3-5)

Saliva

chemical factor; contains lysozyme, uric acid, urea; slightly acidic (6.55-6.85)

Gastric juices

chemical factor; HCl, enzymes, and mucous; highly acidic (pH1.2-3) destroys most bacteria and most toxins

Vaginal secretions

chemical factor; have a low pH (3-5) due to Lactobacillus spp. and inhibit microbes; cervical mucus has some antimicrobial properties

Urine

chemical factor; lysozyme; acidic pH (average 6)

Normal Microbiota

microorganisms that establish a more or less permanent residence but do not produce disease under normal conditions

What are the 3 features of the normal microbiota?

competitive exclusion, production of antagonistic substances, and building an immune system

Competitive exclusion

Adapted for living where they live and have a competitive advantage over pathogenic bacteria; ex. normal gut microbiota outcompeting clostridium difficile

Production of antagonistic substances

Produces substances that inhibit or kill other bacteria

Building an immune system

Building an immune system is dependent on microbiota

* hygiene hypothesis: overclean conditions limit the immune training that happens early in life

Probiotics

Live microbial cultures administered to exert a beneficial effect

Prebiotics

Chemicals that selectively promote the growth of beneficial bacteria

Basis of innate immunity

Activated by protein receptors in the plasma membrane of defensive cells

* pattern recognition receptors- recognize elements frequently found on microbes but different from the host

Toll Like Receptors (TLR)

A class of pattern recognition receptors; attach to components commonly found on pathogens called Microbe-associated molecular patterns (MAMPs)

Examples of MAMPs

* LPS (gram -)


* Flagellin proteins (on flagella)
* Peptidoglycan (Gram +)
* DNA (bacteria and viruses)
* RNA (viruses)
* Some components of fungi and parasites

Cytokines

Proteins that regulate the intensity and duration of immune responses

What do TLRs that are bound to MAMPs do?

Induce the release of cytokines from the host cell

What are the 3 blood cell types?

1. Red blood cells
2. Platelets
3. White blood cells

What is the role of red blood cells?

Transport O2 and CO2

What is the role of platelets?

Blood clotting

What are the 4 components of the second line of defense?

1. Defensive cells (ex. phagocytic cells)
2. Inflammation
3. Fever
4. Antimicrobial substances

Infection

Neutrophils, eosinophils, and monocytes migrate to the area; monocytes develop into macrophages; early in infection neutrophils are dominant phagocytes, as infection progresses macrophages dominate

Fixed vs Wandering macrophages

* Fixed- reside in particular tissues
* Wandering (free)- roam and gather at sites of infection

What are the 4 main phases of phagocyte mechanism?

1. Chemotaxis
2. Adherence
3. Ingestion
4. Digestion

What is the chemotaxis stage of phagocyte mechanism?

movement toward signal; microbial products; components of damaged tissue and white blood cells; cytokines released by white blood cells; peptides (complement proteins)

What is the adherence stage of phagocyte mechanism?

Adherence to microbe; PAMPs bind to receptors (TLRs); causes phagocyte to release cytokines; opsonization (coating) using opsonins can make recognition easier

What is the ingestion stage of phagocyte mechanism?

Pseudopods surround microbe; pseudopods meet and fuse creating a vesicle: phagosome (phagocytic vesicle)

What is the digestion stage of phagocyte mechanism?

Fusion of the phagosome with a lysosome to create a phagolysosome; lysosomal enzymes and toxic oxygen products used to kill organism and break down the contents; undigested material is discharged

What are the roles of Neutrophils in the second line of defense?

* Phagocytic
* First responders after signal is sent out
* Can form NETs- Neutrophil Extracellular Traps
* Dump DNA and antimicrobial substances out of the cell
* traps and kills wide variety of microbes
* Have plus sides and downsides to human health

Inflammation

Damage caused by microbes, physical, or chemical agents triggers inflammation, a local defense mechanism

What is the function of inflammation?

To destroy injurious agent and remove it; if it cannot be removed and destroyed, then limit its spread

What are the signs and symptoms of inflammation?

Pain, redness, immobility, swelling, heat

Vasodilation

Dilation of blood vessels → redness and heat (inflammation)

Increased permeability

Increased permeability → defensive substances can enter the injured area through the blood vessel walls, also causes the edema (fluid accumulation) (inflammation)

Acute inflammation

Rapidly develops; lasts short period (days-weeks); mild self limiting; neutrophils principal mechanism

Chronic inflammation

Slower developing; lasts longer period (months-years); severe and progressive; monocytes → macrophages

What happens when MAMPs bind to TLRs on macrophages?

Cytokines (such as TNF-alpha) produced → acute phase proteins produced

What are histamines roles in inflammation?

Vasodilation and increased permeability of blood vessels

What are kinins roles in inflammation?

Vasodilation and increased permeability; chemotaxis of neutrophils

What are prostaglandins roles in inflammation?

Intensifies histamines and kinin response; helps phagocytes move through capillary walls; associated with pain

What are leukotrienes roles in inflammation?

Increased permeability; helps phagocytes attach to pathogen

What are cytokines roles in inflammation?

Produced by fixed macrophages; vasodilation and increased permeability of blood vessels; chemotaxis of phagocytes and adaptive immune cells

What is the process of inflammation?

1. Blood clot forms → prevents spread of agent
2. Blood flow decreases and neutrophils and monocytes migrate to the area and stick to the lining of blood vessels, this sticking is called margination
3. Phagocytes squeeze through blood vessel cells; migration called diapedesis (motion) or extravasation
4. Phagocytes destroy via phagocytosis; neutrophils are first and monocytes follow later
5. Tissue repair

What are the impacts of chronic inflammation?

* persistent presence of a foreign body
* permanent tissue damage
* body tries to wall off the foreign body
* fibroconnective tissue attached to the “walled off” area
* causes tissue hardening → fibrosis

Fever

Systemic (full body) response of abnormally high body temperature; facilitated by cytokines (some interleukins, interferon, and TNF) cause the hypothalamus to release prostaglandins which increase body temperature

What are the impacts of fever?

* may slow the growth of bacteria


* speeds up the body’s reactions → may help tissues repair faster
* speeds up antiviral interferons


* decreases iron available to microbes
* helps increase T cell production

Complement system

30+ proteins produced by the liver; proteins circulate throughout the blood serum and within tissues; enhances cells of the immune system in destroying microbes; does not adapt; helps prevent excessive damage to the host

What are the 3 mechanisms of microbe destruction via the complement system?

1. Cytolysis
2. Opsonization
3. Inflammation

How does the complement system work?

complement proteins are inactive until split into fragments or activated; cascade reactions amplify the effects

Complement activation

The cascade of the complement system

What are the 3 complement activation pathways?

1. Classical
2. Alternative
3. Lectin