principles immunology Flashcards

1
Q

What is the immune system

A

Network of specialised cells, tissues and soluble factors that co-operate to kill and eliminate disease-causing pathogens and cancer cells

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2
Q

variolation definition

A

Exposure of an individual to the contents of dried smallpox pustules from infected patient

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3
Q

two major classes in the immune system

A

cells (leukocytes, white blood cells) and soluble factors (humoral factors)

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4
Q

the main classes of soluble factors

A

Antibodies
Complement System Proteins
Cytokines
Acute Phase Proteins

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5
Q

the main classes of cells

A

phagocytes, lymphocytes, mast cells, eosinophils and basophils

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6
Q

what is an antibody

A

protein produced in response to an antigen

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7
Q

overview of the complement system

A

family of approx 30 proteins, produced in liver and circulate blood as inactive, the enter infected/inflamed tissues and become active. Complement proteins can enzymatically cleave and activate other downstream Complement proteins in a biological cascade.

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8
Q

overview of cytokines

A

collection of small proteins and peptides, produced in response to infection, inflammation and tissue damage, they modulate the behaviour of cells and play a key role in coordinating the immune system

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9
Q

functions of monocytes, macrophages and neutrophils

A

phagocytosis - they ingest and kill bacteria and fungi, ingest and clear debris from the body, and are also important sources of cytokines

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10
Q

what do monocytes do

A

circulate in blood and then migrate to peripheral tissues and differentiate into macrophages

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11
Q

what do macrophages do

A

they are long lived tissue resident cells that have the additional functions of:
Limit inflammation
Involved in tissue repair and wound healing
Involved in Antigen Presentation

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12
Q

what do neutrophils do

A

circulate in blood and are rapidly recruited into inflamed, damaged and infected tissues

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13
Q

what do dendritic cells do

A

in peripheral tissues in immature state mature and migrate into secondary lymphoid tissue where the play a key role in antigen presentation

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14
Q

mast cells, basophils and eosinophils

A

highly granular cells, release histamine, heparin and cytokines which results in acute inflammation, they are they defence system against large pathogens

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15
Q

what do mast cells do

A

reside in tissues and protect mucosal tissues

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16
Q

what do basophils and eosinophils do

A

circulate in blood, recruited to sites of infection by inflammatory signals

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17
Q

what do natural killer cells do

A

large granular lymphocytes, kill tumour cells and virally infected cells can also kill antibody -bound cells and pathogens

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18
Q

overview of T and B cells

A

circulate in blood, lymph and secondary lymph tissue, inactive and mature, active when in come into contact with pathogen/antigen

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19
Q

what do B cells do

A

Responsible for production and secretion of antibodies to defend against extracellular pathogens

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20
Q

what do T cells do and what are the two types of T cells

A
Key role in defense against intracellular pathogens (viruses, mycobacteria)
Helper T cells
Key regulators of the immune system
Cytotoxic T cells
Kill virally infected body cells
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21
Q

what is immunological memory and what cells regulate it

A

Once the adaptive immune system has recognised and responded to a specific antigen, it exhibits life-long immunity to this antigen
regulated by memory T cells and B cells

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22
Q

what is the innate immune system

A

rapid and general response to different pathogens

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23
Q

what is the adaptive immune system

A

Slow response (days)
Response is unique to each individual pathogen
Mediated by T and B lymphocytes
Responsible for generating Immunological Memory

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24
Q

what is primary lymphoid tissue the sight off

A

leukocyte development

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25
Q

what is secondary lymphoid tissue the sight off

A

Sites where adaptive immune responses are initiated

Contain T cells, B cells and Dendritic cells

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26
Q

overview of the lymphatic system

A

System of vessels draining fluid from body tissues (‘lymph’)

Lymph nodes are positioned regularly along lymph vessels – trap pathogens and antigens in lymph

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27
Q

what is lymphoedema, what are the causes and what does it increase the risk of

A

Also known as lymphatic obstruction, is a condition of localized fluid retention and tissue swelling caused by a compromised lymphatic system, which normally returns interstitial fluid to the thoracic duct and then the bloodstream.
causes are - inherited, cancer treatment and parasitic infections
increases risk of infection

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28
Q

what are the two major mechanisms of cell to cell communication in the immune system

A
  1. direct (receptor to ligand contact)

2. indirect (production and secretion of cytokines)

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29
Q

what is direct cell to cell communication

A

receptor to ligand interactions, ligand can be another immune cell, pathogen or tissue cell.

30
Q

what is indirect cell to cell communication

A

injured tissue cells and activated immune cells can produce and secrete cytokines which causes biological effects

31
Q

what are the 3 main stages the innate immune cells need to recognise and respond to pathogens

A
  1. recognition phase
  2. activation phase
  3. effector phase
32
Q

what occurs during recognition phase

A

Pathogens express ‘signature’ molecules not found in human cells:
“Pathogen associated molecular patterns” (PAMPS)
Innate immune cells express specific receptors for these PAMPS:
Pattern-recognition receptors (PRRs)
Found on cell surface and intracellularly (detect extra- and intra-cellular pathogens)

33
Q

some examples of pattern recognition receptors (PRRs)

A

e.g. Toll-like receptor 4 (TLR4)
(cell surface) and NOD2
(intracellular)

34
Q

some examples of pathogen associated molecular patterns (PAMPs)

A

e.g. Lipopolysaccharide (LPS)
Gram-ve Bacteria and Muramyl dipeptide
M. tuberculosis

35
Q

what mainly occurs during activation and effector phase

A

acute inflammation and pathogen killing

36
Q

describe the 4 main steps in phagocytosis

A
  1. Receptor binding to ‘eat-me’ signals on apoptotic cell - formation of a phagocytic cup
  2. Cup extends around the target and pinches off, forming a phagosome
  3. Fusion with lysosomes to form a phagolysosome - degradation of contents (acidification, lysosomal hydrolases)
  4. Debris released intro extracellular fluids
37
Q

what happens when physical barriers are breached by pathogens

A

pathogens and injured cells cause macrophages, mast cells and NK cells to be released causing pathogens and infected tissue cells to be killed and the release of inflammatory mediators

38
Q

what do the macrophages do when physical barriers breached

A

Pathogens and infected tissues killed and production of inflammatory mediators

39
Q

innate immune response of macrophages killing mechanisms

A

Pathogen Killing Mechanisms:

Phagolysosome - acidification, lysosomal hydrolases
Production of toxic reactive oxygen and nitrogen species

Killing ability (and other functions) are enhanced by cytokines - e.g. IFNg
Produced by NK cells (and some T cells)
Acts on macrophages to
Increase production of toxic reactive oxygen and nitrogen species
Increase microbicidal activity
Boost Antigen Presentation capability

40
Q

what do mast cells do when physical barrier is breached

A

production of inflammatory mediators

41
Q

innate immune responses of mast cells

A
  1. De-granulation - Release of pre-formed pro-inflammatory mediators
  2. Gene expression - Production of new pro-inflammatory mediators
42
Q

what do NK cells do when physical barrier is breached

A

Infected tissue cells killed
Production of inflammatory mediators

Function: specifically kill virally infected cells and abnormal cancer cells

43
Q

key points from lecture 3

A

Two major mechanisms of communication in the immune system:
Receptor / Ligand interactions
Cytokines

Early events mediated by tissue-resident innate immune cells:
Recognition and activation of innate immune cells by invading pathogens and injured cells:
PAMPs, Pattern recognition receptors and ‘Danger’ signals
Macrophages
phagocytosis, killing and clearance of pathogens/apoptotic cells, cytokines
Natural Killer cells
killing of tissue cells infected with intracellular pathogens, cytokines
Mast cells
cytokines

Cytokines:
IFNg: enhances macrophage responses (local effect)
TNFa, IL-1, IL-6: stimulate Acute Phase Responses, neutrophil production and fever (systemic effects)

The Acute Phase Response and CRP
Results from the action of cytokines on the liver
Limits spread of infection and prevents systemic inflammation

44
Q

major functions of some acute phase proteins -
C reactive protein (CRP)
SAP (serum amyloid protein)
Complement proteins

A

Preventing the spread of infection
Diagnostic marker
note - CRP is also involved in preventing systemic infection

45
Q

major functions of some acute phase proteins - Fibrinogen

A

Wound healing

Coagulation

46
Q
major functions of some acute phase proteins - 
C reactive protein (CRP)
Haptoglobin
Manganese superoxidase dismutase
Proteinase inhibitors
A

Preventing systemic inflammation

47
Q

what is the 3 things CRP is important in

A
  1. Diagnosis
  2. Enhance phagocytosis
  3. Complement System Activation
48
Q
effects of pro inflammatory mediators produced by macrophages, NK cells and mast cells - 
Nitric oxide
Prostaglandins / leukotrienes
Histamines
cause...
A

Vasodilation
increase Vascular permeability
Smooth muscle contraction
Pain

49
Q

effects of pro inflammatory mediators produced by macrophages, NK cells and mast cells -
Cytokines - TNFa, IL-1, IL-6, IFNg

A

increase Vascular permeability

Endothelial cell activation

50
Q

effects of pro inflammatory mediators produced by macrophages, NK cells and mast cells -
Chemokines

A

Leukocyte recruitment and activation

51
Q

what are the 4 main effects you get during inflammation

A
  1. Increase vascular permeability
  2. Vasodilation and ↑blood flow
  3. Endothelial cell activation - is the expression of cell adhesion molecules, selectins (receptors) and ICAM-1/VCAM-1
    (ligands)
    4.‘Transendothelial migration’ and ‘Chemotaxis’ of Neutrophils
52
Q

describe what happens during transendothelial migration and chemotaxis of neutrophils (5 main stages)

A
  1. Neutrophils bind weakly to Selectins expressed on the activated endothelium
  2. Selectin-mediated rolling of neutrophils
  3. Neutrophils bind strongly to ICAM-1/VCAM-1 ligands present on the activated endothelium via receptors known as ‘Integrins’
  4. Neutrophils squeeze between the endothelial cells (‘Diapedesis’)
  5. Neutrophils migrate to site of inflammation within affected tissues (‘chemotaxis’)
53
Q

what are the characteristic features and functions of neutrophils

A

Characteristic features
intracellular granules + multi-lobed nucleus
Functions:
Kill extracellular pathogens
Produce pro-inflammatory cytokines (e.g. TNFa)

54
Q

what are the 3 main killing mechanisms of neutrophils

A

phagocytosis, degranulation and NETs

55
Q

what 2 distinct mechanisms once pathogen is encapsulated in phagosome do neutrophils kill by

A
  1. Anti-microbial proteins

2. NADPH oxidase-dependent mechanisms

56
Q

describe mechanism of degranulation and what is causes

A

Release of anti-bacterial proteins from neutrophil granules directly into the extracellular milieu
→ Direct killing of extracellular pathogens bacteria and fungi
→ Tissue damage and (potentially) systemic inflammation

57
Q

describe the mechanism of NETs and what they cause

A

Activated neutrophils release intracellular structures (NETs) into the extracellular environment

NETs serve to immobilize pathogens:
prevents them from spreading
Facilitates their phagocytosis

58
Q

some immunodeficiency diseases that affect neutrophils -

Chédiak–Higashi syndrome

A

defective phagocytosis

59
Q

some immunodeficiency diseases that affect neutrophils -Chronic granulomatous disease

A

Deficiency in NADPH-oxidase

60
Q

some immunodeficiency diseases that affect neutrophils -Leukocyte Adhesion Deficiency

A

Defective integrin expression

61
Q

what stage of the innate immune response are neutrophils involved in

A

late stage

62
Q

what stage of innate immune response is the complement

A

late stage

63
Q

overview of the complement in inflammation

A

occurs by 2 pathways:

  1. mannose-binding lectin pathway
  2. alternative pathway

results in 3 main things:

  1. pathogen killing
  2. pathogen opsonisation
  3. leukocyte recruitment and inflammation
64
Q

describe complememt mediated killing

A
  1. C5b binds to surface of pathogens
  2. C6, C7, C8 and C9 assemble with C5b to form the Membrane attack complex
  3. Inserts into target cell walls → osmotic cell lysis of cells
65
Q

describe complement mediated opsonisation

A

The process by which bacteria and other cells are altered in such a manner that they are more readily and more efficiently engulfed by phagocytes.

66
Q

what do dendritic cells do

A

Dendritic cells are ‘professional’ antigen presenting cells
and act as a bridge between the innate and adaptive immune response

they also are:
Present in peripheral tissues in an ‘immature’ state

Phagocytose antigens, cell debris, particles

Mature and migrate into secondary lymphoid tissues where they play a key role in antigen presentation

67
Q

what are adaptive immune responses stimulated by and define the stimuli

A

stimulated by antigens, an antigen is any substance which can cause an adaptive immune response by activating B cells and T cells

68
Q

where do T and B cells reside

A

they circulate in the blood in, inactive form until they meet an antigen

69
Q

what is the function of B cells

A

Defense against intracellular pathogens via production of antibodies

70
Q

what is the functions of helper and cytotoxic T cells

A

helper T cells -Key regulators of the entire immune system

cytotoxic T cells - Kill virally infected body cells