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MY MCD > Immunology > Flashcards

Immunology Flashcards

1
Q

What is the role of the immune system?

A

Detect and respond to threat
Minimising collateral damage
Retaining memory in case of future infection

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2
Q

What does an immunodeficiency lead to?

A

INC infection/cancer susceptibility

Abnormal regulation/function leading to autoimmune disease

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3
Q

What is involved in the normal function of immune system?

A

To identify and eliminate harmful microorganisms/subs by distinguishing self from non-self and abnormal-self (cancer) as well as identifying danger signals e.g. Tissue damage

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4
Q

Compare generation times of bacteria vs viruses

A

Bacteria replicate in mins

Viruses replicate in hrs

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5
Q

What are the 2 strategies for recognising danger?

A 
#1 Germ-line encoded
#2 Random recombination
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6
Q

What is involved in the germ-line encoded strategy for recognising danger

A

Genes code for 100s of specific, non-changing receptor proteins for molecular patterns; many cells have same receptors so v rapid and effective response, yet limited diversity so some pathogens not recognised

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7
Q

What is involved in the random recombination strategy for recognising danger

A

Mills of receptors to recognise specific structs using rand recomb of gene segments; few cells express each receptor, so must replicate for effective response, massive diversity allows for recognition of all structures

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8
Q

Pattern Recognition Receptors (PRRs) use either……

A 
PAMPs
(pathogen associated molecular patterns)
OR
DAMPs
(damage AMPs)
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9
Q

What does PAMP stand for

Eg.s of PAMPs

A

Pathogen-Associated Molecular Patterns

eg. Bacteria, Virus, Fungus, Parasite

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10
Q

What does DAMP stand for

Eg.s of DAMPs

A

Damage-Associated Molecular Patterns

Cell (inv. Necrosis)
Extracell Matrix (inv. Injury- fragments from aggrecan, fibronectin, collagens etc)
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11
Q

What do PAMPs do?

A

Manipulate differences in human and pathogenic cells

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12
Q

What do DAMPs do?

A

Recognise damage through ECM fragments from damage or proteins released after Necrosis

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13
Q

What do B cells do?

A

Bind to intact antigens w surface receptor antibody

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14
Q

What do T cells do>

A

Have T-cell receptors w a/B chains which bind to processed antigen fragments called epitopes that have been presented on cell surfaces

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15
Q

What is innate immunity?

A

Uses PPRs so independent to antigen exposure; fast and depends on rapidly synthesised components that have a limited specificity
- destroys invading nucleic acids in cytoplasm, activates inflammatory pathways and elicits type 1 interferons for anti-viral defence (buys time for adaptive immunity and promotes appropriate immune response)

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16
Q

What is adaptive immunity?

A

Adaptation to exposure that depends on clonal selection so is slower yet highly specific to foreign antigens

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17
Q

Differences between innate and adaptive immuntiy

A

Innate uses PPRs, independent to antigen exposure, fast, limited specificity

Adaptive depends on clonal selection, slower, highly specific to foreign antigens

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18
Q

Innate immune response is ______ specific

Adaptive immune response is ______ specific

A

INN- Pattern

ADAP- Antigen

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19
Q

What 3 cell types are linked to both innate and adaptive immunity types

A

Basophils/mast cells
Dendritic cells
Natural Killer (NK) cells

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20
Q

Define clonal diversity

A

During B / T cell development random genetic recombination occurs within each cell w multiple copies of immunoglobulin gene segments to prod. single, unique antigen receptors

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21
Q

Define clonal response

A

Mills of diff lymphocytes in body expressing Mills of receptors that will lead to proliferation if they bind to their complimentary antigens

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22
Q

Where are the T cells distributed

A

2% T cells in blood,

98% in lymph/organs

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23
Q

Define clonal selection

A

Activation of naïve lymphocyte leads to replication of only this one (antigens typically recognised by 1 in 105 naïve T cells

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24
Q

What is/happens at the primary lymphoid organ?

A

Lymphocytes are prod. by lymphopoiesis (lymphoid stem cells differentiate to mature funct. lymphocytes - thymus and bone marrow)

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25
Q

What is/happens at the secondary lymphoid organ?

A

Lymphocytes interact w antigens and each other eg. Spleen, lymph nodes and mucosal associated lymphoid tissues (MALT)

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26
Q

What does MALT stand for

A

Mucosal Associated Lymphoid Tissues

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27
Q

All lymphocytes are derived from…..

A

Precursor bone marrow stem cells

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28
Q

The Thymus -
Septum divides ____ to lobules and Hassall’s _____ have ______ cells that are involved in the formation of _________; dark staining regions around outside of lobule = cortex; light staining region in middle = medulla (full of maturing/proliferating T-lymphocytes)

A 
lobes
lobules
corpuscles
fibroblast
regulatory T-cells
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29
Q

How does the thymic output change?

A

Declines w age
fewer T-cells prod.
Total no. does NOT change as highly regulated

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30
Q

What is the bone marrow the site of>

A

Haematopoiesis
& INC white cell prod. during infection
(visible change)

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31
Q

How do the organs involved in Harmatopoiesis change from foetus to adults?

A

Foetus: bone marrow very cellular, and liver/spleen involved in haematopoiesis

Adults: large, flat bones involved in haematopoiesis - NO LIVER/SPLEEN

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32
Q

Lymphatic system: fluid drained from ________ are absorbed into lymph with ____ litres returned to blood each day via duct to SVC

A

Btwn tissue cells

2-3

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33
Q

What does the lymph node do?

A

Filters antigens in lymph
Afferent/Efferent lymphatic vessels bring lymph fluid into/out of node
FLuid collected is filtered thru lymphocytes so can react if antigens = present

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34
Q

Lymphoid cells on outside of lymph nodes tend to be…

A

B cell aggregates in follicles

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35
Q

If ongoing immune response, B cells in lymph node will proliferate & prod. _____ in ________

A

Antibodies

Germinal centres

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36
Q

What is a high endothelial venule

A

Specialised area of artery w much thicker endothelium causing T/B-cells to leave circulation & enter the lymph node

B-cells go to follicles on outside whilst T-cells move closer to centre following chem signals (Chemokines)

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37
Q

What is a germinal centre seen as?

A

Distinct spheres of proliferating B-cells

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38
Q

What does the spleen do?

A

Filters antigens in the blood (while lymph nodes do same for antigens in lymph)

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39
Q

In the spleen there is white pulp where _________ and red pulp where ___________
(what colour do red/white stain)

A

WHITE - Lymphocytes reside (stains dark purple)

RED - Erythrocytes present (stains lighter purple)

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40
Q

What does the PALS (Periarterial lymphatic sheath) within the spleen do?

A

Immediately surrounds arteries (in white pulp) w predominantly T-cells

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41
Q

What is the first line of bodily defence against infection?

A

Mucosae and skin (physical barrier) w a large SA & single layer of cells

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42
Q

Gut: _______ lymphocytes reside on villus

A

Intraepithelial

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43
Q

Villi of the gut has lymphatic drains to _________

A

Mesenteric Lymph nodes

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44
Q

What are Peyer’s patches

A

Large aggregates of lymphocytes/follicles espec B-cells that drain to lymph nodes

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45
Q

Specialised mucosal epithelium over Peyer’s patches contain…..

A

Microfold cells which sample antigens in gut to pass to present to lymphocytes in patches to allow for surveillance

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46
Q

WHat does the cutaneous immune system do?

A

Lymphatic vessels drain from skin & intraepidermal lymphocytes present; epidermal langerhans (specialised dendritic cells) - capture & present antigens, migrating through lymphatic vessels to lymph nodes

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47
Q

Define immune system recirculation

A

Primary lymphoid tissues prod. naive lymphocytes that enter blood & circulate btwn blood and secondary/peripheral lymphoid tissues till react or die

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48
Q

WHat happens during extravasation of naive T-cells into lymph nodes:

A

Lymphocytes roll along cell surf & bind to Selectin and CD34, and chemokine receptors on T-cells bind to chemokines on cell surface membrane to change the conformation of integrin

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49
Q

What are the steps involved in extravasation (3 steps involved)

A

1) Naive T-Cell roll along endothelium until they reach the HEV
2) Selectin binds weakly to endothelial CD34
3) Chemokines present on surface of HEV bind strongly to receptors on T-Cell, causing integrins to have a higher affinity, allowing movement over endothelium into lymphoid tissue

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50
Q

Define lymphocytes

A

Small cells w a granular cytoplasm & large nucleus

  • divided into 2 groups depending on where produced (b=bone marrow, t=thymus) - CANNOT be differentially stained
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51
Q

T-lymphocytes all express _____
90% have ……
10% have ……

A

ALL = CD3
2/3 have CD4
1/3 have CD8

90% have an alpha beta T cell receptor
10% have gamma delta T cell receptor

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52
Q

Describe what occurs during T-cell antigen recognition

A

T-cells recognise processed antigens presented @ cell surface using a TCR presented by a major histocompatibility complex (MHC)

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53
Q

What type of receptors do B-lymphocytes have?

A

IG like surface receptors expressing CD19 and CD20 (NOT 3/4/8 as in T),
express MHC Class II so can present to TH cells & prod. antbodies; recognise intact antigens in body fluids not on cell surfaces using a B cell receptor

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54
Q

What do antigen presenting cells do?

A

Present processed antigens to T-Cells to initiate adaptive immune response including B-Cells, dendrite cells and activated macrophages

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55
Q

Define innate immunity

A

Rapid cellular/soluble component immune response present from birth, using PAMPs/DAMPs to detect microbial structures and damage

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56
Q

What are the anatomical defensive barriers?

A

Skin (mechanical barrier, acidic environment) and Mucous membranes (secretions trap microbes and cilia expel)

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57
Q

What are the physiological defensive barriers?

A

Fever (doesn’t favour replication by microbes), Low pH in stomach (kills many ingested microorganisms), Chemical mediators (lysozymes, interferons, complement)

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58
Q

Define neutrophils

A

Phagocytes w multi-lobed nucleus (polymorphonuclear granulocytes) - relatively short lived cells that circulate in blood then migrate to tissues - first cells to be recruited to a site of tissue damage

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59
Q

What are the first cells to be recruited to a site of tissue damage?

A

Neutrophils

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60
Q

Define Eosinophils

A

Phagocytic, releasing granules & defend against parasitic infection; stain w eosin and help w B cell responses in producing IgA

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61
Q

Define Basophils

A

Release granules, may act as antigen presenting cells for “type 2” immunity - antibody mediated

62
Q

Define Monocytes/macrophages

A

Important for phagocytosis, and release cytokines as mediators when do; also present fragments of antigens on surface to T-cells

63
Q

Define what Mast cells do

A

Release granules containing histamine (pro-inflammatory)

64
Q

Define what Dendritic cells do

A

Capture antigens and present these to T-cells

65
Q

Define what Natural Killer cells do

A

Lyse infected cells

66
Q

Neutrophils: exit circulation & enter tissues to bind to pathogens, phagocytose AND kill them:

1) Roll along surface of blood vessels, ____ weakly binds to lining
2) Macrophages release_____ if ingesting microorganisms that bind to surface of endothelium, allowing rolling neutrophil to bind tightly with______ and migrate thru the endothelium
3) More ______ near site of infection, so moves along gradient toward site of infection

A

selectin
chemokines
integrins

chemokine molecules

67
Q

What happens during Opsonisation?

A

Micro-organisms coated w proteins to facilitate phagocytosis - antibody and complement both function as opsonins

68
Q

What are opsonins?

A

Molecules that bind to antigens and phagocytes

69
Q

What is the oxygen independent neutrophil killing mechanism?

A

Enzymes (lysozymes, hydrolytic etc.) and antimicrobial peptides

70
Q

What is the oxygen dependent neutrophil killing mechanism?

A

free radicals, nitric oxide, nitrogen intermediates, singlet oxygen, hydroxyl radicals, hydrogen peroxide and superoxide anion

71
Q

What are neutrophil extracellular traps?

A

Activated neutrophils which release granule net-like materials that form extracellular fibres to trap microbes, in turn killing the neutrophils but allowing phagocytosis

72
Q

Macrophages
_________ in blood
_________ in tissue

A

monocytes
macrophages

-> Granules fuse w phagosomes to digest ingested material

73
Q

What is the function of Macrophages?

A

Receptors for microbes, upon binding & ingesting, release soluble cytokine mediators to recruit further cells

74
Q

What do mast cells secrete?

A

Histamine and other inflammatory mediators eg. cytokines

75
Q

Where are mast cells found?

A

Near mucosa and near connective tissue

76
Q

What type of receptors do mast cells have?

A

Pattern recognition receptors to recognise bacteria for subsequent phagocytosis (can be activated by complement products - anaphylatoxins)

77
Q

Describe what NK cells do?

A
  • No antigen-specific receptors
  • Lyse cells
  • Secrete interferon-y
  • Activatory & Inhibitory receptors
  • Binds Antibody coated cells
78
Q

Target cell recognition: under viral stress, cell upregulates ______ that activate ____ cells and downregulate ___________ so ____ cells are not inhibited to kill cell

A

stress-induced molecules
NK
inhibitory molecules
NK

79
Q

What are cytokines?

A

Small proteins

Secreted for local, short-lived cell-to-cell communication

80
Q

What 5 forms of cytokines?

A
  • Interleukins: btwn leukocytes
  • Interferons: anti-viral effects - interfere with replication
  • Chemokines: chemotaxis (cell movement)
  • Growth factors: help stem cells to differentiate and proliferate
  • Cytotoxic tumour necrosis factors: induce programmed cell death in target cells
81
Q

Steps in cytokine prod:

  1. Stimulus in cytokine prod. cell causes…
  2. Cytokines bind to specific receptors on other cells, affecting….. and causing biological effects
A

Production & granule fusion w the memb

Gene expression in target cell (up/downregulate 100s of genes)

82
Q

Define autocrine

A

Cytokines act on self

83
Q

Define paracrine

A

Works on nearby cells

84
Q

Define endocrine

A

Travel via circulation to distant cell

85
Q

Dendritic cells produce cytokines and are a network of cells located near __________(eg. skin and mucosal surfaces); they have ________ receptors and will capture ________

A

likely Sites of infection

pattern recognition

pathogens before migrating to lymph nodes to present antigens

86
Q

WHat does the complementary system have a major role in complementing?

A

The activity of specific antibody in bacteria

87
Q

The complementary system is a complex series of around 30 proteins and glycoproteins that leads to _____________ in a rapid response

Components are present as __________ by ____, but part of peptide must be cleaved to activate; substrate is next enzyme in pathway, so will cleave and activate, leading to sequential activation of subsequent enzymes to amplify number of activated molecules

Cleavage waste is __________ so signals to nearby cells - causes mast cells to degranulate

A

triggered enzyme cascade system

inactive enzyme precursors

liver

proinflammatory molecule

88
Q

What are the 3x activation methods of the complementary system?

WHat is the same about all of the 3x different activation methods?

A

ALL converge to activated C3b which opsonises antigens/pathogens

Classical Pathway
- AB bound to antigen forming immune complex

Lectin Pathway
- Lectin proteins that bind to carbs on bacteria to trigger complementary system

Alternative Pathway
- Bacteria directly trigger complementary system

89
Q

What is the final common pathway?

A

When C3b is activated, the membrane attack complex forms holes in bacterial cell membrane
-> Causes loss of integrity

90
Q

What are the functions of the complementary system?

A
  • Cell lysis
  • Opsonisation
  • Pro-inflamm effects
  • Clearing of immune complexes
91
Q

What is the system “acute-phase” response?

A

After 1-2 days

fever, INC prod. WBCs and acute phase liver proteins induced by cytokines

92
Q

Define antibody

A

Protein prod. in response to foreign antigen, specifically binds to antigens

93
Q

Define Immunoglobulins

A 
Protein class
Soluble glycoproteins
94
Q

What are Fab fragments?

A

Bind to antigens

Not variable as did not crystallise

95
Q

What are Fc fragments?

A

Will crystallise therefore homogenous sequence (constant region)

96
Q

What does the hinge region of the antibody allow?

A

Flexible binding to antigens, so Fab regions can move to bind to more widely spaced surface proteins/determinants

97
Q

Where are Fab/Fc fragments located on antibody?

A 
Fab= antigen binding site
Fc= heavy chain
98
Q

Both light and heavy chains have constant regions but then variable regions are where ……

A

Where antigens bind

-> allows specificity

99
Q

Explain the hypervariable regions of antibodies?

A

Complementarity determining regions which interact w antigen

-> Ensures specificity, aligned to loops @ end of variable domains; disulfide bridges exist btwn B-pleated sheets

100
Q

What forces are involved in antigen binding?

A

All forces = non-covalent

eg. Hydrogen, ionic, hydrophobic, VDW

101
Q

Define antibody affinity?

A

Strength of total non-covalent interactions btwn single AB binding site and single epitope on antigen

102
Q

WHat is the association constant K for antibodies?

A

K = [Ab-Ag] / [Free Ab] [Free Ag]

103
Q

What is antibody avidity?

A

Overall strength of multiple interactions btwn an AB w multiple epitopes -
eg. Monovalent = low
Bivalent = High
Polyvalent = V High

104
Q

What is an epitope?

A

Part of antibody which binds to the antigen

105
Q

WHat is antibody cross-reactivity?

A

AB which can recognise different similar antigens

106
Q

How do different classes of antibodies differ from each other?

A

Differ in constant region of heavy chains IgG/A/M/E/D with gamma/alpha/upsilon/sigma/epsilon heavy chains and kappa or gamma light chain

107
Q

What are the subclasses of antibodies?

A

IgG has IgG1-4
with gamma 1-4

IgA has IgA1-2
with alpha 1-2

108
Q

What is the most abundant class of antibody?

A

IgG - gamma heavy chain

109
Q

Describe the IgG class of antibodies:

A
  • Variability btwn subgroups usually in hinge region
  • Actively transported over placenta to give baby passive immunity
  • Found mainly in blood and ECF
  • Major activator of classical complement pathway
110
Q

What is the 2nd most abundant class of antibody?

A

IgA - alpha heavy chain

111
Q

Describe the IgA class of antibodies:

A
  • Occurs in monomer in blood & dimer in secretions
  • Major secretory immunoglobulin to protect mucosal surfaces
  • J chain forms!!!
  • Binds to basolateral surface of epithelial cells (onto Poly-Ig receptor), allowing endocytosis to vesicle where receptor is cleaved, yet part remains that forms a dimer secretory IgA with a longer half life to neutralise pathogens in lumen upon release
112
Q

Describe the IgA class of antibodies:

A
  • Forms pentamers: 5 monomers joined by J chains
  • Mainly in blood
  • 1st Ig synthesised after exposure
  • Multiple binding sites compensate for low affinity
  • Efficient for agglutination and activating complement
113
Q

Describe the IgD class of antibodies:

A
  • Extremely low serum concentrations
  • Surface IgD expressed in early B cell development
  • Involved in development and activation
114
Q

Describe the IgE class of antibodies:

A
  • Present at low levels
  • Prod. against parasites and in allergy
  • Binds to high affinity Fc receptors of mast cells and basophils
  • Cross-linking by antigen triggers mast cell activation and histamine release (hence allergic reaction)
  • When IgEs linked by allergen causes degranulation
115
Q 
What type of heavy chain do the following classes of antibodies have:
IgG
IgA
IgM
IgE
IgD
A 
Gamma
Alpha
Upsilon
Epsilon
Sigma
116
Q

Where are the immunoglobulins (Igs) distributed?

A

IgG and IgM in blood
IgG in ECF
Dimeric IgA in epithelia & breast milk

117
Q

What are 5 consequences of antibody binding to antigen

A 
Neutralisation
Agglutination
Opsonisation
Complement activation
Bound by cells w Fc receptors
118
Q

What is the main driver of adaptive/memory immune response

A

Lymphocytes

119
Q

What are SCID babies?

A

Severe Combined ImmunoDeficient kids

- cannot fight infections as no T and B cells §die

120
Q

Define innate immunity

A

Generic & early response

- CONTROLS INFECTION

121
Q

Define adaptive immunity

A

Improves efficacy of innate immune response, focussing on site and organism, has memory and needs time to develop
- CLEARS INFECTION
2ndary response, stronger and faster

122
Q

Define antigens

A

Proteins/mols that induce adaptive immune response

123
Q

Difference btwn linear and structural epitopes?

A

Linear = recognised by T-cells; recognise sequence

Structural = recognised by antibodies; recognise structure

124
Q

What 2 cell types are involved in a humoral response

A

B-cells and antibodies

125
Q

What cells are involved in cell-mediated response

A

T-cells w cytokines and killing

126
Q

Define what B-lymphocytes are

A

WBCs derived from haematopoietic stem cells that are effector cells of humoral immune system, secreting ABs & becoming memory cells

127
Q

Describe the 4 steps of clonal selection

A 
#1 Each lymphocyte bears single, unique receptor 
#2 Develop panel of T/B-cells when growing
#3 Interaction btwn foreign antigen & receptor on naïve cell leads to activation
#4 Activation leads to transition to effector state (and later memory state) & clonal selection
128
Q

In natural recombination to prod. lymphocytes, some will be produced against self antigens that would lead to an autoimmune response. How is this controlled?

A

Selection pathway destroys those reacting w self

129
Q

B-cell receptors are ______ and have unique binding sites where ___________

They are attached to _________ that can transduce signals to cascade mols

A

ABs
Antigenic determinant/epitope can bind
Transmembrane domains

130
Q

B-cell receptors are a transmembrane protein complex composed of ….

A

Monomeric immunoglobulin and di-sulfate linked heterodimers of IgA and IgB on either side for signalling

131
Q

B-Cell Receptors-

Cytoplasmic tails of IgA and IgB contain_______ that allow for intracellular signalling

A

ITAM domains

132
Q

On B-cell receptor binding to antigen, structural changes occurs that leads to …..

A

IgA and IgB signalling into cytoplasm

133
Q

Each BCR chain (kappa, lambda and heavy chains) encoded by separate multigene families on _______, and these are rearranged during maturation to form unique BCRs

A

different chromosomes

134
Q

WHat do T-cells do?

A

Detect and combat INTRACELLULAR pathogens - as antigens can only destroy extracellular pathogens

135
Q

What is the only sub able to destroy extracellular pathogens

A

Antigens

136
Q

T-cell receptor is used to detect infected cells.

How do they do this>

A

Antigen presented on MHC molecule of host infected cell

analogous in struct to Fab region of antigen

137
Q

What allows for association w CD3 polypeptides (expressed by all T-cells) for signalling

A

Charged residues in membrane

138
Q

What is a CD4 receptor

A

Co-receptor that recognises antigens on MHC Class II molecules (class II restricted)

139
Q

WHat is a CD8 receptor

A

Co-receptor that recognises antigens on MHC Class I molecules (class I restricted)

140
Q

What do co-receptors bind to? What effect does this have?

A

Bind to invariant region of MHC;

INC avidity of T cell-target interaction and for signalling

141
Q

CD4 cells (Th cells) secrete….

A

Cytokines to recruit effector cells and activate macrophages

142
Q

CD8 cells (Tc cells) are cytotoxic and there function is to…

A

Kill target cells by secreting cytokines to induce apoptosis

143
Q

What does the Major Histocompatibility Complex do?

A

Displays sample of internal cell contents @ cell surface for immune cell recognition
-> Markers of self/health & continuously present peptides even when not infected

144
Q

MHC are a group of tightly linked genes for immune responses, molecules present antigens to….

A

T-CELLS

145
Q

MHC Class I has ____ transmembrane and ____ cytoplasmic region. They also have immunoglobulin-like regions with…..

A

one
one
a single beta chain that is non-covalently bonded

146
Q

MHC Class II has ____ transmembrane and ____ cytoplasmic region. Both polypeptides are same size, larger than the ones in MHC I with peptides spanning length of whole MHC being ___ AAs

A

Two
Two
>13

147
Q

Where are the two types of MHC genes expressed?

A
  • MHC Class I: all nucleated cells, though levels may be altered during infection or by cytokines
    • MHC Class II: normally only on professional antigen presenting cells and may be regulated by cytokines - activated naïve T-Cells
148
Q

What do antigen presenting cells do?

A

Present processed antigens to T-cells to initiate adaptive immune response, including dendritic cells, B cells and macrophages

149
Q

Where do endogenous antigens come from?

A

Inside cells

eg. virus infected cells- use CD8 Class I restricted T-cells

150
Q

Where do exogenous antigens come from?

A

Outside cells

eg. phagocytic and antigens captured and presented on B-cells- use CD4 Class II restricted T-cells

MY MCD (2 decks)

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