Patho Exam 3

Patho Block 3 Exam

Compare and contrast key components of the first, second, and third lines of defense; timing, specificity; cells involved, memory, and peptides / active molecules involved.

What are the three plasma proteins systems?

Complement system, Clotting (coagulation) system, Kinin System

Complement System

destroys pathogens directly activates every component of inflammatory response.

Clotting (coagulation) system

prevents infection spread by trapping microorganisms at site of inflammation, stops bleeding/ creates clots, framework for repair.

Kinin system

activate and assist inflammatory cells by producing bradykin.

Sequence events in the acute inflammatory response

1. Initiated by guardian cells located near epithelial surfaces, lymph nodes, or blood vessels

2. Release of inflammatory mediators

3. Vascular and cellular responses

4. Migration of leukocytes, platelets, plasma proteins and other biochemical mediators

Local signs of acute inflammation

Redness (Rubor): 

• Caused by increased blood flow due to vasodilation.

Heat (Calor): 

• Also due to increased blood flow and metabolic activity in the inflamed area.

Swelling (Tumor): 

• Resulting from increased vascular permeability and the accumulation of fluid in the tissues.

Pain (Dolor): 

• Induced by the release of inflammatory mediators that sensitize pain receptors and pressure on surrounding tissues.

Systemic signs of acute inflammation

Fever

• Caused by exogenous and endogenous pyrogens

• Acts directly on the hypothalamus

Leukocytosis

• Increased numbers of circulating leukocytes

• Increase in circulating immature leukocytes (bands)

Increased plasma protein synthesis

• Acute-phase reactants

Fatigue and Malaise: 

• General feelings of discomfort and fatigue due to the body's systemic response to inflammation.

What are the 3 cytokines?

Interleukins, Interferon, Tumor Necrosis Factor-Alpha (TNF-alpha)

Who forms TNF-Alpha?

Activated Macrophages (via secretion) 

Mast cells, lymphocytes, and neutrophils to a lesser extent

Who forms Interleukins (IL)?

Macrophages and Lymphocytes as a response to microorganisms or stimulation by inflammation

Who forms Interferons (IFN-alpha, IFN-beta, IFN-gamma)?

Virally-infected host cells

Function of TNF-alpha

Major proinflammatory cytokine

Induces fever 

Increases acute phase protein synthesis in the liver

Function of Interleukins (IL)

Regulation of CAMs

Chemotaxis

Production of leukocytes in the bone marrow

Modulation of the innate and adaptive immune responses

Function of Interferons

Prevents viruses from infecting additional healthy cells (does not directly kill viruses)

alpha and beta: induce the production of antiviral proteins in neighboring cells 

gamma: increases microbicidal activity of macrophages

Causes of Mast Cell Degranulation

• Activated by: physical injury, chemical agents, PRRs, complement, IgE - antibodies

• chemicals released in two ways: degranulation, synthesis of lipid-derived chemical mediators 

Effects of the released mediators from degranulation

• Degranulation

  • releases histamine

    • H1 receptor (proinflammatory): causes vasodilation, endothelial cells that line the capillaries are retracted to create space (so leukocytes can squeeze through and infiltrate tissue)

    • H2 receptor (anti-inflammatory): downregulates release of histamine, negative feedback 

    • can be expressed on same cell, work antagonistically 

  • releases chemotactic factors 

    • neutrophil chemotactic factor attracts neutrophils

    • eosinophil chemotactic factor of anaphylaxis (ECF-A) attracts eosinophils 

  • cytokines 

    • promote inflammation 

    • active adaptive immune response 

Effects of Leukotrienes

similar effect as histamine, later stages of inflammation, made from arachidonic acid

Effects of Prostaglandins

• similar effect as histamine, induces pain, made by cyclooxygenase (COX)

  • meds that inhibit COX: NSAIDs, aspirin, acetaminophen (tylenol)

  • ouch!

Effects of Platelet-activating factor

blood vessel dilation and platelet aggregation, mediates allergic responses (airway inflammation) and shock

Effect of histamine binding to H1 and H2 Receptors

 H1 receptor (proinflammatory)

• Histamine binding to H1 causes vasodilation 

• Endothelial cells that line the capillaries are retracted

• H2 receptor (anti-inflammatory)

- Can be expressed on the same cell

Work antagonistically to each other

Process of Phagocyte Migration

1. phagocytes arrive

2. newly expressed CAMs allow for margination on epithelial cells

3. diapedesis occurs

4. chemotaxis occurs

5. migration toward higher concentrations of chemokines

6. phagocytosis!

Process of Phagocytosis Migration

1. Opsonization (glue between the phagocyte and the target cell by C3b, making the foreign cell more susceptible to phagocytosis), recognition, and adherence 

2. Engulfment: small pseudopods surround the adherent microorganism 

3. Phagosome formation

4. Fusion with lysosomal granules: creates phagolysosome

5. Destruction of the target

Role of Neutrophils in Inflammatory Process

1. also called polymorphonuclear neutrophils (PMNs)

2. predominate in early inflammatory responses 

3. ingest bacteria, dead cells and cellular debris 

4. short lived, become components of purulent exudate (pus)

5. primary roles: removal of debris in sterile lesions, phagocytosis of bacteria in nonsterole lesions

Role of Monocytes in the Inflammatory Process

monocytes become activated and become macrophages.

Role of Macrophages in the Inflammatory Process

1. Kuppfer cells in liver 

2. Alveolar macrophages in lung 

3. microglia in brain 

4. are either proinflammatory or antiinflammatory 

5. actions are pleiotropic: same molecule may have large variety of different biologic activities, depending on the target cell to which it binds

6. includes interleukins, interferons, tumor necrosis factor (TNF)

Role of Eosinophils in Inflammatory Process

1. provide defense against parasites and regulate vascular mediators

2. help control vascular effects of inflammation

Characteristics of Chronic Inflammation/Differs from Acute

• Chronic inflammation: 2+ weeks in duration, usually related to unsuccessful acute inflammatory response

  • differs b/c inflammatory response doesn’t stop when infection/threat is eliminated, body keeps receiving inflammatory signals

  • subtler signs/presentation than acute inflammation

  • periods of getting better then worse, can fluctuate in severity

What is immunity?

Innate and adaptive (body line of defense)

What are immunogens?

Specific antigen that can induce an immune response

What are antigens?

Any substance that can bind to antibody or T cell receptor (an immune receptor)

What are antibodies?

(Immunoglobulins) Protein made by the immune system in response to an immunogen (antigen)

What is Hapten?

Non-immunogenic antigen; must bind with something else to become an immunogen (too small to trigger its own immune response)

Ex. Penicillin is a hapten

What is an immunoglobulin?

AKA Ig and antibody interchangeably, made by B cells

What is an allergen?

triggers an inappropriate immune response

What is an Antigen determinants (epitotes)?

Specific area of the antigen recognized by a particular antibody

Similarities and differences between Cellular and Humoral Immunity

• cellular:

  • T-cytotoxic cells, activated when their receptors detect cellular antigens presented on MHC I molecules that are foreign

• primarily protects against viruses and cancer

• humoral: B cells and circulating antibodies are primary cells

• B cells become activated to become antibody-producing plasma cells

• causes direct inactivation of microorganisms or the activation of the inflammatory mediators

• primarily protects against bacteria and viruses

• similarity: works together to provide immunity and memory

What are the five classes of immunoglobulins (antibodies)?

IgG, IgM, IgE, IgA, IgD

Role and structure IgG

• most protective activity against infections, most active/important in vax response

  • monomer with 4 isotopes

Role and structure IgM

first antibody production in response to antigen (both fetus and adult) with complement activation on mature and immature B cells

Role and Structure IgE

•  defense against parasitic infections and hypersensitivity reactions in tissues

  • monomer

Role and Structure IgA

• antibody secretions and mucosa, first line of defense against microorganism infection

  • monomer dimer

Role and Structure IgD

•   on mature B cells, no bio effector function known

  • monomer

What are the four stages of a clinical infection?

Incubation, Prodromal Stage, Invasion Period, an Convalescence

Incubation

1. Period of initial exposure to the infectious agent and the onset of the first symptoms 

2. Microorganisms have entered a person → undergone initial colonization → begun multiplying (not enough at this stage)

3. May last from several hours to years

4. Clinical latency- time between exposure and symptoms

Prodromal Stage

1. Occurrence of initial symptoms, often mild and include a feeling of discomfort and tiredness

2. Pathogens continue to multiply

Invasion Period

1. Pathogen is multiplying rapidly, invading farther and affecting tissues at the site of initial colonization and other areas

2. Immune and inflammatory responses triggered

3. Symptoms may be specifically related to the pathogen or to inflammatory response

Convalescence

1. Individual’s immune and inflammatory systems successfully remove the infectious agent (in most cases) → symptoms decline

2. Disease may be fatal or enter latency phase with resolution of symptoms until pathogen reactivation at a later time

Infectivity

the ability of an organism to infect the host.

Pathogenicity

Ability of an organism to produce disease.

Depends on infectivity, virulence, toxigenicity, etc.

Virulence

the degree of pathogenicity  (disease severity)

Can measure by case fatality, hospitalization, etc

Portal of Entry

How the pathogen enters the body

Ex: Open wound: group A strep or Staph Aureus

Infective Dose

The number of organisms required to cause infection

Ex: 10-100 for Shigella and norovirus

Phases of Pathogenesis of Bacterial Infections

Transmission, colonization, invasion, evasion

Transmission

• direct transmission: through direct contact with infections of another individual 

• indirect transmission: contact, respiratory, airborne, ingestion, vector-borne

Colonization

ability of pathogenic microorganisms to survive and multiply within the human body. Bacteria adhere to tissue and stabilizes without symptoms 

Invasion

ability of pathogens to cross surface barriers (skin, mucous membranes), also referred to as penetration. Either invading locally or getting into the bloodstream

Evasion

 bacteria evades, replicates, cause disease, Bacteria “hide” via various mechanisms 

ex: TB evades killing by hiding in host macrophages

Routes of transmission

Contact, respiratory, airborne, ingestion and vector-borne

Contact (Route of Transmission)

- physical touch

• direct (person-to-person)

• indirect (contaminated fomites), vertical (mother to infant)

Respiratory (Route of Transmission)

direct large droplet nuclei spread or mucus/saliva

Airborne (Route of Transmission)

 - indirect small droplet transmission

• human-to-human (spreads through air when someone expels droplets)

• environmental (spores inhaled like anthrax)

Ingestion (Route of Transmission)

- through direct oral intake

• fecal-oral transmission

• ingestion of uncooked food

Vector-Borne (Route of Transmission)

-living organisms transmit illness to others by contact 

• ticks, mosquitos, fleas, bugs, flies

Endotoxin Mechanism

(lipopolysaccharide) heat-stable antigen of gram-negative cell wall, released during lysis (destruction) of bacteria

-elicits the inflammatory response by activating complement via alternative pathway, and induce fever

Exotoxin Mechanism

enzymes that can damage the plasma membranes of host cells, or by entering cells and changing their function 

-mainly produced by gram-positive organisms

-usually protein-based and heat-labile

-often may be neutralized by antibodies or inactivated by enzymes

Capsules Mechanism

-a “slime layer” mostly consisting of simple polysaccharides

-an envelope of loose gel surrounding a bacterial cell

- Keeps the bacterium from being phagocytized by the host’s immune cells

Antigenic Variation Mechanism

the altering of a microorganism’s surface antigens to elude detection by the host’s immune system

Methods for Classification of Bacteria

Gram Negative Bacteria

thinner cell wall, have outer membrane containing lipopolysaccharides 

after last step of counter stain safranin: stains pink 

have pilli

ex. E. Coli, Klebsiella, Bacteroides, Brucella

Gram Positive Bacteria

thick peptidoglycan cell wall, no outer lipid membrane 
after last step of counter stain safranin: stains blue/purple (retains crystal violet stain)

Bacteria Lacking Cell Walls

instead of rigid cell wall, they have a trilaminar unit membrane 

require complex lipid cholesterol in growth medium

Mycoplasma species, ureaplasma species

Acid fast Bacteria

unique cell wall composition: 60% of cell wall comprised of waxy lipid, mycolic acid (making them resistant to ordinary dyes), also made of  peptidoglycan & glycolipids 

primary stain: carbol fuchsin, binds to mycolic acids in the cell wall 

counterstain: methylene blue 

non acid-fast: blue

acid-fast: red

ex. mycobacteria, TB

flexible thin walled cells

long, helically coiled, resulting in spiral shaped cells 

gram negative, but do not stain well enough for clinical use

T. palladium = syphilis

B. burgdorferi = Lyme disease

Spore-forming Bacteria

produces spores, which are highly resistant, dormant structures

allows bacteria to survive in unfavorable environmental conditions: heat (boiling temp), chemical, radiation resistance, desiccation (dry conditions)

can remain dormant for years until favorable conditions return

has thick layer of peptidoglycan, outer layer that contributes to spore resistance

ex. C. diff, Bacillus anthracis

Obligate Aerobes

require oxygen to survive and multiply

Gather at the top in test (where oxygen concentration is highest)

Facultative Anaerobes

Can toggle between aerobic metabolism if O2 is present, but can switch to anaerobic metabolism if O2 is absent.

Gathers mostly at the top because aerobic respiration generations more ATP, has some at bottom

Obligate Anaerobes

Cannot survive in an oxygen-containing environment

gathered at the bottom in the test (presence of O2 leads to cell death)

Staphylococcus aureus

 - gram-positive spherical shape cocci, coagulase positive, creates exotoxin called enterotoxin B, TSST-1

• major cause of human infection - sepsis, toxic shock syndrome, food poisoning, cellulitis, skin abscesses, osteomyelitis, endocarditis, pneumonia

• MRSA=methicillin-resistant staph aureus

Clostridium difficile

-gram-positive, spore-forming

• hospital-acquired infection - diarrhea, pseudomembrane colitis

Escerichia coli

- gram-negative bacteria, gut/urine colonizer, pili is tool of evasion

• UTI, bacteremia, sepsis, pneumonia, neonatal meningitis

• STEC (shiga toxin-producing E. coli) - dysentery, hemorrhagic colitis, hemolytic uremic syndrome (HUS)

• ETEC (enterotoxigenic) - traveler’s diarrhea

Mycobacterium tuberculosis

- weakly gram-positive, acid-positive

• TB

Borrelia Burgdorferi

- gram-negative spirochete, non-stainable

• Lyme disease, relapsing fever

Normal Flora Means?

AKA the microbiome

• assemblage of microbes constituting a microbial community and occupying a specific habitat

• protective 

• varies widely by body site and impacted somewhat by age, sex, diet, nutrition, early development changes, puberty, menopause, etc.

Bacterial Flora in Skin

1. proptonibacterium

2. corynebacterium

3. staph

Bacterial flora in Mouth/ Upper Respiratory Tract

1. mouth- strep, haemophilus, prevotella, veillonella 

2. anterior nares- propriobacterium, cor

Bacterial flora in gastrointestinal tract and rectum

stool: bacteroides

Bacterial Flora in Genitalia

Vagina: lactobacillus

Bacterial Flora in Eye

Staph epidermidis

Bacterial Flora in Urinary Bladder

1. urine is normally sterile in young, healthy adults, BUT

2. asymptomatic bacteriuria is common and expected in elderly, diabetics, & catheterized

3. Enterococcus

Key Characteristics of Amoeba

Jelly-like cytoplasm

Thin outer plasma membrane

Central granular endoplasm. 

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The endoplasm contains food vacuoles, a granular nucleus, and a clear contractile vacuole.

Food vacuoles are necessary for digestion as there is no mouth/anus.

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Make pseudopodia (fake feet) for locomotion

Characteristic of Flagellate

Cell or organism with one or more whip-like appendages called flagella

Characteristic of Ciliate

a coating of cilia on their cell surfaces

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 two types of nuclei within single cells: micronucleus and the macronucleus.

Characteristic of Sporozoa

Single-celled 

Parasitic 

Non-motile

Spore forming

Helminths

• multicellular 

• complex life cycles 

• free-living or parasitic 

• 3 subgroups (nematodes, trematodes, cestodes)

Nematodes (roundworms)

• various lifecycles 

  • can be transmitted directly person-person 

  • some require soil phase for development 

  • some require egg to mature outside the host

• intestinal infections: strongyloidiasis, enterobiasis (pin worm), ascariasis

Trematodes (flukes)

• flukes - found in liver, lung, blood

• transmission through 

  • eating undercooked fish/crabs (liver flukes)

  • direct penetration of skin (blood flukes 

• schistosomiasis 

  • adult flukes in mesenteric or bladder veins

Cestodes (tapeworms)

• intestinal infection

  • attaches to lumen of intestines, feeds off food the host is digesting 

• ingested through: undercooked pork, beef, fish

Pathogenesis of Toxoplasma gondii (obligatory intracellular parasite)

• Pathogenesis: sporozoa

  • cats shed oocysts in sexual development

  • ingestion of oocysts, replicates using host system -> release of sporozoites into intestines -> turns into tachyzoites in acute infection

    • asymptomatic in most people