3 - Clinical Immunology Flashcards

1
Q

name the four cardinal effects of acute inflammation

A

Rubor (redness), Calor (heat), Dolor (pain) and Tumor (swelling)

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2
Q

acute inflammation

A

normal, healthy, temporary process; designed to eliminate damaging stimuli and heal damage

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3
Q

Why does chronic inflammation occur?

A

the body is unable to get rid of the damaging stimulus and therefore healing is unable to occur.
results in necrosis and repetitive organisation and tissue repair.

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4
Q

What are the histological features of chronic inflammation?

A
  • necrotic cell debris
  • acute inflammatory exudate
  • vascular and fibrosis granulation tissue
  • lymphoid cells and macrophages
  • collagenous scar
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5
Q

What is the main effector cell in chronic inflammation?

A

Macrophages

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6
Q

What is the main effector cell in acute inflammation?

A

Neutrophils

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7
Q

Acute inflammatory response

A
  • Acute injury releases chemicals mediators that stimulate the production of acute inflammatory exudate
  • Infective agents (bacteria) destroyed and eliminated by components of the exudate
  • Damaged tissue broken down, partly liquefied and the debris is removed from the site of damage
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8
Q

exudate

A

fluid, proteins, blood cells that mobilise local defences

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9
Q

give some of the components of acute inflammatory exudate.

A

salt containing fluids
fibrin
neutrophils - phagocytic cells
macrophages - phagocytes + produce cytokines, 2nd wave response
lymphocytes
dendritic cells - present antigen to T-cells
• Enter tissues as a result of blood vessels becoming leaky

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10
Q

Which two types of cells are involved in acute inflammation?

A

Neutrophils and monocytes/macrophages
Neutrophils are the MAIN EFFECTOR CELLS OF ACUTE RESPONSE
monocytes in blood become macrophages in tissue
• Both capable of phagocytosis
• The neutrophil only lives a few days
• Neutrophils far outnumber monocytes in acute inflammation

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11
Q

Give some examples of chronic inflammation

A

Tuberculosis, Crohn’s disease and leprosy

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12
Q

How do the blood vessels change in the acute immune response?

A

The blood vessels dilate and blood flow slows down, and the blood cells swell and partially retract.
This allows water, salt and proteins to leave the blood cells and enter the tissue as well as allowing neutrophils to trans migrate into the tissues. Later, monocytes and T cells will also leave the blood vessels.

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13
Q

Describe the process of transmigration of leukocytes out of the blood vessels

A
  1. Selectins of endothelial cells cause the leukocytes to tether Ti the endothelial cells
  2. Chemokines and cytokines (released by macrophages) trigger activation of the leukocytes
  3. Integrins on the leukocytes mediate the leukocytes adhering to the endothelial cells
  4. The leukocyte forms pseudopodia and produces proteases which allow it to trans migrate out the the blood vessel
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14
Q

Cellular mediators of immune response

A

macrophage secretes cytokines (mins)
• Cytokines attract and activate B +T-cells to trigger the adaptive immune response (days)
• Acute immune response peaks within 2 days
• By 12 days, should have repair and elimination of pro-inflammatory process, so should resolve within ~2 weeks

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15
Q

How does acute exudate leave the tissue?

A
  • majority of cells re-enter circulation via lymphatic system, stimulate adaptive immune response in lymph nodes
  • neutrophils do not re-circulate, they stay at site = pus buildup
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16
Q

Tuberculosis-infected lung

A

• Mycobacterium tuberculosis
• Invades, and replicates within macrophages
• Evades acute immune response
“Caseous” (cheese-like) necrosis
Granuloma (tubercle) in the lung surrounded by necrotic tissue

17
Q

Innate vs. Adaptive immune response

A
  • Innate responses are (usually) more rapid, particularly if no ‘memory’ cell clones present.
  • Adaptive immunity involves generation of antigen-specific antibodies and T-cells (B- and T-cell clones) and confers lasting immunity
  • Memory clones confer ‘immunity’
  • generated via natural exposure (person-person contact), artificial = active vaccination
18
Q

Innate immune response

A
  • initial rapid response; triggers adaptive arm
  • highly conserved across plant, fungi and animal kingdoms
  • triggered by receptors, such as Pathogen-associated molecular patterns (PAMPs) and Damage-associated molecular patterns (DAMPs)
  • involves phagocytes (neutrophils, macrophages), cytokine/chemokine production and complement cascade
19
Q

Immunodeficiency

A
  • inherited, acquired (infection), or from exposure to certain damaging stimuli (e.g. radiation and chemotherapy)
  • Inherited - Severe combined immunodeficiency (SCID) = rare genetic disorder where there is little or no function of white blood cells
    • Acquired: Human Immunodeficiency virus (HIV) = infects and destroys T-lymphocytes (lymphocytopenia)
    • Can lead to unusual infections (e.g. from commensal microbes) and cancer (e.g. Kaposi sarcoma)
20
Q

Diagnosis of immunodeficiency

A

White blood cell (WBC) count:
Normal ranges
• WBC 4,000 to 11,000 cells/ µL of blood
• Neutrophils 2,000 to 7,500 cells/ µL of blood
• Lymphocytes 1,300 to 4,000 cells/ µL of blood
• Variation normally due to infection, but sustained irregularities may indicate immunodeficiency or leukaemia.

21
Q

Immunophenotyping

A
  • Technique used to study protein expression on cells
  • Can be performed on tissue sections or in cell suspensions
  • Can distinguish specific immune cell populations
  • Can detect specific proteins (e.g. tumour antigens) on cell
  • Expression can be detected either by microscopy or flow cytometry
22
Q

Microscopy

A
  • Subjective interpretation; prone to human error
  • Cost of human labour
  • Microscopy widely available
  • Relatively little training to use, but training in interpretation
  • Can use antibodies for specific labelling
  • More difficult to assess multiple types of antigens at same time
  • Can preserve tissue structure during processing
  • Low throughput
23
Q

Flow cytometry

A
  • Automated, reduce possible error
  • Cost of equipment
  • FACS less available (particularly in rural/low income settings)
  • Requires training in use & interpretation
  • Can use antibodies for specific labelling
  • Multiple cell types can be assessed at the same time
  • Loss of tissue structure during processing
  • High throughput