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BDS 1 > Pathology- INNATE > Flashcards

Pathology- INNATE Flashcards

1
Q

Where do all blood cells derive from?

A

-haematopoetic stem cells.

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2
Q

what are the two haematopoietic stem cell linages?

A

Lymphoid and myeloid.

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3
Q

What are myeloid precursors?

A

Macrophages neutrophils, red blood cells, dendritic cells and basophils.

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4
Q

What are lymphoid precursors?

A

B and T cells.

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5
Q

What is a neutrophil?

A

IS A THE MOST ABUNDANT WHITE BLOOD CELL. Carries out phagocytosis. They circulate into blood and move into tissue when required- chemotaxis. They are granulocytes with degradative enzymes and antimicrobial substances. They are short lived- die when ingesting a few microbes.

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6
Q

What are macrophages?

A

They are called monocytes in blood and when they migrate into tissues they are called macrophages. THEY ARE LONG LIVED. They can present their antigens (APC).

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7
Q

Name some antigen presenting cells.

A

Classical APCs include dendritic cells, macrophages, Langerhans cells and B cells.

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8
Q

What are mast cells?

A

They are granulocytes. Migrate from blood and differentiate into tissues. Protect against antigens )including parasitic worms). ALLERGY! They release granules containing histamine (hayfever etc).

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9
Q

What are eosinophils?

A

GRANLUOCYTES. They defend against parasites as they are bigger and can therefore ingest bigger microbes. Can also contribute to allergies.

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10
Q

What are basophils?

A

GRANULOCYTES. Similar roles to eosinophils- promote allergic responses and augmentation of anti-parasitic immunity.

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11
Q

Where do dendritic cells derive from?

A

Can derive from both myeloid and lymphoid precursors.

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12
Q

Name the different types of dendritic cells from a myeloid precursor.

A

Langerhans DC
Interstitial DC
Myeloid DC

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13
Q

Name the different types of dendritic cells from a lymphoid precursor.

A

Plasmocytoid DC

IFN prod killer DC

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14
Q

What cell is the link between adaptive and innate immune response?

A

DENDRITIC CELLS.

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15
Q

What are dendritic cells?

A

They are APC that migrate from blood to tissue to phagocytose microorganisms. They can ingest large amounts of extracellular fluid by a process called (macropinocytosis). MAIN FUNCTION IS TO PRESENT ANTIGEN TO T CELLS- therefore the link between innate and adaptive immune system.

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16
Q

How does a dendritic cell present its antigens?

A

The dendritic cell ingests and degrades antigen into linear peptides. These peptides are presented on the cell surface and are attached to MHC class 1 or 2. The antigen is then presented to T cells via interaction between MHC and T cell receptor.

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17
Q

What is the difference between dendritic cells and macrophages?

A

Dendritic cells are better at moving from one component to another.

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18
Q

Where do T and B cells mature in?

A

B cels- bone marrow.

T cells - thymus.

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19
Q

What do T cells give rise to and what is their job?

A

T cells give rise to cellular immunity. They help B cell responses. They recognise peptide presented by APC through the T cell receptor. “T cell repertoire”- means that the T cells can recognise numerous antigens. There are checkpoints along the way so the T cells do not respond to self antigens.

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20
Q

What is T cell repertoire?

A

It means that a T cell can recognise numerous different antigens.

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21
Q

What are the two different types of T cells and what antigen do they interact with?

A 
MHC class 1- CD8 positive T cells.
MHC class 2-CD4 positive T cells.
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22
Q

What do CD8 and CD4 positive T cells do?

A

CD8- Destroy infected cells (cytotoxic).

CD4- Play central role in immune protection. Numerous subsets which help support and modulate immune responses according to pathogenic threat. Also roles in regulation of immune responses.

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23
Q

How does a CD8positive T cell destroy infected cells?

A

When the T cell interacts with a MHC 1 I produces granzymes and performs. The performs from holes In the plasma membrane where the granzyme enters an lyses the cell.

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24
Q

Describe the process of CD4 T cell subset generation.

A
  • CD4+ T cells start life as a ‘naïve’ T cell
  • Three signals required for activation of T cells
  • Third signal determines fate of naïve T cell
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25
Q

What does a Th1 (CD4 subset) do?

A

They help and support macrophages to destroy microbes.

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26
Q

What does a Th2 (CD4 subset) do?

A

They produce cytokines that recruit mast cells, eosinophils and promote barrier immunity at mucosal surfaces.

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27
Q

What does a Th17 (CD4 subset) do?

A

They secrete IL-17 family cytokines that induce local non-professional
immune cells to release cytokines and chemokines.

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28
Q

What does a Tfh (CD4 subset) do?

A

They induce specific B cell responses (promote opsonising antibody response).

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29
Q

What does a Treg cell do?

A

Suppress T cell activity to prevent autoimmunity.

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30
Q

What do B cells do once activated?

A

Once activated the B Cells change into Plasma cells which churn out lots of antibody against that specific antigen. Recognise antigens through the B Cell Receptor (BCR) which is the actual antibody against the antigen they respond. In addition binding of antigen to BCR can lead to internalisation and subsequent antigen presentation to T cells.

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31
Q

What are the three major functions of B cells?

A
  1. Multiply in numbers to generate memory.
  2. Activate T cells.
  3. Produce antibodies.
32
Q

What do NK cells do?

A 
Large cells with granules.
• Recognise and kill abnormal cells
• Tumour
• Virus infected
• Important for ‘holding
back’ virus infections until adaptive immunity kicks in.
33
Q

Name some innate immunity mechanisms of the oral cavity.

A
  • saliva
  • barrier functions
  • initiation of immune responses
  • recognition of threats
  • signalling pathways initiating immune responses
  • cytokines and chemokines.
34
Q

What does humeral and cellular components mean?

A

Humoral- driven by macromolecules eg.antibodies.

Cellular-does not involve macromolecules but driven by cells eg. T cells.

35
Q

What are the five groups of disease causing agents?

A

Bacteria, virus, protozoa, fungi, helminths (worms).

36
Q

What molecules does the body remake to respond against infection?

A 
SALIVA
• Antimicrobial peptides
• Immunoglobulins (secretory IgA)
• Lactoferrin
• Lysozyme
• Cystatins
37
Q

What molecules does the body remake to respond against infection in saliva?

A 
IN SALIVA
• Antimicrobial peptides
• Immunoglobulins (secretory IgA)
• Lactoferrin
• Lysozyme
• Cystatins
38
Q

What are the major families of antimicrobial peptides?

A
  • Beta defensives
  • Human Neutrophil peptides
  • Cathelicidins
  • Psoriasin proteins (S100)
39
Q

Name some facts about antimicrobial peptides.

A
  • small, under 50 amino acids.
  • cationic and amphiphatic parts
  • effective in low concentrations
  • attach and disrupt membranes
40
Q

Why do antimicrobial peptides not bind to our own membranes when they are also negatively charged?

A

They contain cholesterol

41
Q

Why do antimicrobial peptides not bind to our own membranes when they are also negatively charged?

A

They contain cholesterol and their membranes have a weak negative charge. They have a weak hydrophobic interaction but a strong electrostatic and hydrophobic interaction (when no cholesterol is present).

42
Q

How do antimicrobial peptides work?

A

It inserts itself into bilayer and the other tries to get away from bilayer, create a hole- this causes sosmotic stress and the cells burst open and die-antimicrobial peptides exposed to.

43
Q

What is Secretory IgA and where is it produced?

A

It is produced at mucosal surfaces and it does not require the interaction between T and B cell.

44
Q

How do S-IgA work?

A

Plasma cells produce IgA in a dimer form. The inner surface binds to a polymeric ig receptor. This rceptor give it a ticket for passing through the cell (secretory piece). When inside the igr receptor receptors removed and released into surrounding environments- binding to antigen then occurs.

45
Q

What does S-IgA do?

A
  • Bings to antigens
  • Binds to flagella
  • Binds to and neutralises bacterial toxins
  • Cross links target macromolecules and bacteria therefore trapping them and preventing effects on mucosa
  • Prevents attachment of bacteria on mucosal surfaces (directly (binds to adhesion specific molecules) and indirectly- “hydrophobic shell created”).
46
Q

How many toll like receptors are there and what are they?

A
  1. TLRs recognize constituents of microbial cell walls
    or pathogen-specific nucleic acids that
    are essential to the integrity, function or replication of
    microbes / viruses that cannot readily be modified.

Microbial (Pathogen) Associated Molecular Patterns =M(P)AMPs.

47
Q

What do TLR recognise on bacterial cell walls?

A

Gram positive- Lipoproteins, lipoteichoic acid and dna.

Gram negative- Lipopolysaccarides, DNA and Flagella.

RNA- rna
DNA- dna

Fungi- Zymosan Beta-glycan and DNA.

Protists- DNA and GPI anchors.

48
Q

Describe the process of a TLR recognising a pathogen/bacteria?

A

TLR (TLR4 and TLR2) on cell surface and recognise constituents of bacterial/pathogen cell membrane.
Coupling even takes place, activation of these receptors.
NF-κ(controls transcription of DNA) found inactivate in cell cytosome. Activates and moves into nucleus. Looks for genes that have a binding sequence= switches on the expression of immune response genes. Cytokine/Chemokine transcription and processing takes place- they are then secreted to produce an inflammatory response.

49
Q

What is a PRR and what cells express them?

A

Pattern recognition receptor. Epithelial and immune cells express these receptors.

50
Q

What is a PRR and what cells express them?

A

Pattern recognition receptor. Epithelial CELLS and immune cells express these receptors.

51
Q

What are the consequences of PRR activation?

A

-Signalling activates immune cells directly (promotes functions eg. phagocytosis).

-Signalling also induces cells to express:
– Cytokines
– Interferons (response to viruses)
– Chemokines
– Antimicrobial peptides
– Other enzymes and inflammatory mediators.

52
Q

Name families of cytokine receptors involved in innate immunity.

A

IL1 family receptors.

Receptors for GM-CSF and other cytokines.

IL6.

TNF.

Chemokines and fMLP.

IFNalpha and IFN gamma.

53
Q

What happens as a result of cytokine signalling?

A
  • Cytokines and chemokines- shapes type of immune response.
  • Growth factors are for tissue modelling and repair.
  • Antimicrobials- protecting against invading microorganisms.
  • Receptors- differentiation and proliferation.
54
Q

What are cytokines?

A

They are small signalling proteins that coordinate immune responses.

They are grouped into families by structures eg.

IL (interleukin).
TNF.
Interferons.

55
Q

How do cytokines act in autocrine response?

A

Alter behaviour of cell from which they were created.

56
Q

How do cytokines act in endocrine response?

A

Enter circulation and alter behaviour of distant cells.

57
Q

How do cytokines act in paracrine response?

A

Alter behaviour of neighbouring cells.

58
Q

What are chemokines and how do they work?

A

Small signalling proteins (chemotactic cytokines). They are involved in recruitment of immune cells to site of inflammation. They diffuse through tissues and create a concentration gradient so immune cells know where to go- “chemotaxis”.

59
Q

What are the four classes of chemokines?

A
  1. C chemokines (2 members)
  2. CC chemokines (31)
  3. CXC chemokines (18)
  4. CX3C chemokines (1).
60
Q

How are chemokines group into their four categories?

A

It depends on the pacing of their first two cysteine residues.

61
Q

How do neutrophils know where to go?

A

They polarise and move towards source. THE NEUTROPHIL SENDS OUT SIGNAL AND ITS BODY ORIENTATES ITELF TO NEW DIRECTION. Neutrophils attracted along A
CXCL8 (IL-8) gradient to site of inflammation.

62
Q

How do neutrophils migrate?

A

The endothelial cells then express selectins on their surface. SELECTIN MEDIATED ADHESION TO LEUKOCYTE SIAyl- lewis is weal. This allows leukocytes to roll along the vascular endothelial SURFACE.

63
Q

What can leukocytes embed into?

A

They embed into veins and not arteries.

64
Q

What are the three main families of adhesion molecules and what do they do?

A

The three main families are selecting, interns and immunoglobulin superfamily. They promote cell to cell interactions and are important for immune trafficking.

65
Q

What are neutrophil nets?

A

They trap pathogens. Activation induces neutrophils to release proteins (granules that contain antimicrobial peptides and enzymes) and some genetic material (chromatin) to form an extracellular matrix.

66
Q

When are granules release by vesicles?

A

P(A)MPS
Compliment proteins
Cytokines and other inflammatory mediators.

-They contain preformed mediators including antimicrobials, proteinases and chemical mediators.

67
Q

What are the two types of antigen presenting cells?

A
  1. Non-professional- epithelial cells/andothelial cell/fibroblasts.
  2. Professional- macrophages, dendritic cells.
68
Q

What are the seven steps of phagocytosis?

A
  1. Chemotaxis and adherence of microbe to phagocyte.
  2. Ingestion of microbe by phagocyte.
  3. Formation of a phagosome.
  4. Fusion of the phagosome with a lysozyme to form a phagolysozyme.
  5. Digestion of ingested microbe by enzymes.
  6. Formation of residual bodies containing indigestible material.
  7. Discharge of waste materials.
69
Q

What are the seven steps of phagocytosis?

A

“Pseudopods” engulf the bacteria and bring it into cell.

  1. Chemotaxis and adherence of microbe to phagocyte.
  2. Ingestion of microbe by phagocyte.
  3. Formation of a phagosome.
  4. Fusion of the phagosome with a lysozyme to form a phagolysozyme.
  5. Digestion of ingested microbe by enzymes.
  6. Formation of residual bodies containing indigestible material.
  7. Discharge of waste materials.
70
Q

How do AOC present their antigens?

A

mhc molecils stick compenents of microorganism to these receptors and they get rid of waste and the little peptide is taken to cell surface and presents the antigen.

71
Q

How do APC present their antigens?

A

mhc molecils stick compenents of microorganism to these receptors and they get rid of waste and the little peptide is taken to cell surface and presents the antigen.

72
Q

What are the four enzymatic cascade systems in plasma?

A

Coagulation factors, compliment, kinins and fibrinolytic systems.

73
Q

The compliment system can only work when it is activated. How is the compliment system activated and what is it?

A

Complement components act as primary defence system against bacterial/viral pathogens (works in conjunction with antibodies – link to adaptive immunity).

  1. Classical pathway (antigen to antibody).
  2. Alternative pathway (foreign cell surface).
  3. Lectin pathway (recognising mannose on pathogen).
74
Q

What is the compliment systems role in innate immunity?

A 
Trigges inflammation.
Attracts phagocytes.
Oponise antigens.
Causes cell lysis.
Activates naive B lymphocytes.
Removes immune complexes/

**can bind to bacteria- they opsomise bacteria- label bacteria to help body recognise its foeign to aid phagocytosis. Intercation with receptor can cause degranulation, also can squeeze through tissues.
Also form antibody …labels antibodies for disposal.

75
Q

What are anaphylatoxins?

A

Anaphylatoxins, or complement peptides, are fragments (C3a, C4a and C5a) that are produced as part of the activation of the complement system. Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defense.

76
Q

What do anaphylatoxins do?

A

-Increase vascular permeability. This allows extra fluid leakage with plasma proteins at site of infection. It also allows migration of monocytes and neutrophils from blood to tissue is increased (microbicidal).

77
Q

What do anaphylatoxins do?

A
  • Increase vascular permeability. This allows extra fluid leakage with plasma proteins at site of infection. It also allows migration/recruitment of monocytes and neutrophils from blood to tissue is increased (microbicidal).
  • Cell recruitment.
  • Act on neutrophils (degranulation),
  • Act of macrophages (promote cytokine and antigen expression, degranulation too).
  • Act on mast cells (histamine release, degranulation).
  • Regulates adaptive immune response.

BDS 1 (14 decks)

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