Immunity Flashcards
(120 cards)
1
Q
3 things that promote phagocytosis
A
Common bacterial cell wall components (PAMPs)
C3b complement component
Fc region of antibodies
2
Q
3 types of PAMPs
A
Common cell wall structures e.g., LPS and peptidoglycans
Bacterial metabolic processes
Heat-shock proteins (released by stressed cells)
3
Q
Acute phase proteins
A
Produced early in infections and tissue injury in response to early alarm mediators
Act to enhance host resistance, minimise tissue injury and promote resolution and repair of inflammatory lesions
4
Q
Effector cells
A
B cells
CD8 cells
Natural Killer cells
5
Q
Regulator cells
A
CD4 cells
Th1, Th2, Treg + T17
6
Q
Specialised APCs of the: Skin Lungs Blood Liver Gut
A
Skin – Langerhans cells (transport to regional nodes)
Lungs – Alveolar macrophages (transport to spleen or regional nodes)
Blood – Blood monocytes (transport to spleen)
Liver – Kupffer cells (transport to spleen or regional nodes)
Gut – Epithelial M cells (transport to Peyer’s patches)
7
Q
Process of antigen presentation by APC e.g., skin wound
A
Multiplying bacteria uptaken into Langerhans cells of skin
Dendritic cells bind bacteria and transport it through lymphatics
Antigen enters lymph node, followed by small naive lymphocytes from the bloodstream
T cells migrate to paracortical areas of nodes and B cells migrate to follicles
Lymphocytes that recognise the antigen are activated and stop recirculating
Lymphocytes that do not recognise the antigen leave via afferent lymphatic vessels
After several days activated lymphocytes leave the efferent lymphatic vessel as effectors
Meanwhile, antigen is held in lymph node and antigen-specific cells are recruited
8
Q
Endogenous pathway of antigen processing
A
Used for peptides derived from cytoplasmic proteins, like in viral infections Cytosolic proteins degraded into peptide fragments by proteasomes Peptides produced are unaccessible to class I MHC molecules, which are bound to the TAP-1 transporter complex on the ER membrane Peptides transported into ER lumen by TAP-1 transporter and inspected by TAP-1-bound class I MHC When a peptide binds to class I MHC, the MHC molecule folds around the peptide and is released from TAP-1 to be transported to the cell membrane
9
Q
Exogenous pathway of antigen processing
A
Used for peptides derived from ingested material Antigen is taken up from outside the APC into intracellular vesicles Acidification of vesicles activates proteases to degrade antigen into peptide fragments Vesicles containing peptide fragments fuse with vesicles containing class II MHC and peptides with affinity for antigen-binding groove of class II MHC bind to it Bound peptide transported by class II MHC to cell surface
10
Q
Where are class I MHC molecules expressed?
A
Virtually all nucleated cells in the body
Therefore most cells can present peptide fragments derived from metabolic breakdown of intracellular infectious processes
11
Q
Where are class II MHC molecules expressed?
A
Only on B cells and professional APCs
Therefore only these cells can present peptide fragments of ingested material
12
Q
Th1 cells have activity against:
A
Viruses, bacteria and intracellular agents
13
Q
Th2 cells have activity against:
A
Parasites, allergies and multicellular agents
14
Q
The main role of Treg cells is to:
A
Downregulate other responses/suppress antigen-specific
15
Q
The main role of Th17 cells is:
A
Inflammation and mucosa maintenance
16
Q
4 types of immune conversations
A
Adhesion molecules
Co-stimulator molecules
Cytokines
Hormones
17
Q
3 types of adhesion molecules
A
Selectins
Integrins
Cadherins
18
Q
Co-stimulators
A
Surface molecules induced on antigen-presenting cells and lymphocytes
Involved in modulating lymphocyte activation and function
19
Q
Example of co-stimulators found on B cells
A
CD40 (which binds to CD40-L on CD4 T cell)
CD40 then upregulates B7 which binds CD28 on the T cell which then releases cytokines
20
Q
Type I interferons
A
IFN-a and IFN-B
21
Q
Proinflammatory cytokines
A
IL-1, IL-6 and TNF-a
22
Q
Adaptive immune response cytokines
A
Il-1, Il-2, IFN-y and IL-4–6
23
Q
Chemokines
A
IL-8, MCP-1 and MIP-1a
24
Q
Haematopoietic cytokines
A
IL-3, G-CSF, M-CSF, GM-CSF, IL-5 and IL-7
25
IL-1
Second messenger to activate T cells following contact with antigen
26
IL-2
Stimulates clonal proliferation of antigen-specific T cells
27
IFN-y
Causes activation of macrophages, promotes HLA expression and activates NK cells
28
IL4–6
Important in stimulating growth and differentiation of B cells
29
IL-8
Influences neutrophil chemotaxis and activation
30
CSF cytokines
Stimulate proliferation of granulocytes (G) and monocytes (M)
31
IL-3
Promotes proliferation of all lineages of haematopoietic cells
32
IL-5
Stimulates eosinophil growth and activation. Also important in allergic responses
33
IL-7
Stimulates erythroblast and megakaryocyte growth and involved in B cell development
34
MCP-1 and MIP-1a chemokines
Important in allergic inflammation by stimulating basophils to release histamine
35
Adhesion molecules
Link cells to other cells
Important in binding lymphocytes to antigen-presenting cells and also in directing lymphocytes and phagocytic cells to parts of the body where they are needed
36
Co-stimulator molecules
Pass signals between linked cells through surface–surface interactions to trigger or inhibit antigen-specific effects
37
Cytokines
Soluble glycoproteins that signal cells expressing specific cytokine receptors e.g., lymphocytes following antigen activation
38
Hormones
Soluble molecules produced by neuroendocrine hormones that modulate the response of antigen-activated cells
39
3 types of selectins
L-selectin (lymphocytes)
P-selectin (platelets)
E-selectin (endothelial cells)
40
Integrins
Important in cell–cell adhesion and cell–ECM adhesion
| Hold lymphocytes together for activation and hold lymphocytes on capillary wall
41
Leukocyte adhesion deficiency
Hereditary deficiency of some integrins
| Leukocyte trafficking impaired and patients are susceptible to recurrent pyogenic infections
42
Anergy
Fail-safe mechanism that prevents T cells from responding to self-antigens
Occurs when an antigen is presented to a T helper cell without the required co-stimulator molecule being presented on the APC causing the T cell to become paralysed
43
Properties of IgM
Large pentamer, confined to bloodstream, does not cross placenta, 3rd most common
Produced early in primary antibody response, good defence against bacterial spread
Efficient agglutinator and complement activator
44
Properties of IgG
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Small monomer, diffuses easily out of blood, crosses placenta, by far the most common
Major class in secondary responses
Good complement activator, opsonin and Fc receptor-mediated effector mechanisms
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45
Properties of IgA
Defends exterior surfaces
| 2nd most common
46
Properties of IgD
Trace amounts
HIghly sensitive to proteolysis
Receptor on virgin, antigen-sensisitve B lymphocytes
47
Properties of IgE
Trace amounts unless allergy or parasite infection
| High affinity Fc receptor on mast cells and basophils
48
Antibody structure
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Four polypeptide chains held together by disulphide bonds and non-covalent interactions
Light chains and either kappa or lambda
Heavy chains can be one of 5 types with each giving rise to the class of antibody
Variable and constant regions on the top of the Y
Also an Fc region on the bottom of the Y containing the bottoms of the heavy chains, which are constant regions, a complement-binding region and a hinge region
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49
Antibody class switching
IgM is the first class of antibodies to be synthesised in a primary antibody response
After some time, IgM synthesis begins to decrease and is replaced by IgG production
Individual activated B cell clones begin by producing IgM, but then switch to IgG
IgG synthesis is dramatically increased in secondary responses because memory cells preferable make IgG over IgM. IgM mostly due to activation of new naive antigen-sensitive B cells seeded to secondary organs from bones marrow after initial antigen contact
50
Properties of antibodies
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Direct neutralisation
Agglutination
Opsonisation
Antibody-dependent cell-mediated cytotoxicity
Activation of complement cascade
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51
Direct neutralisation
Blocks attachment and entry to host cells by physically preventing adsorption of viral/bacterial particles
Immobilises bacterial flagella
52
Agglutination
Antibodies clump small particles into larger complexes which are easier to ingest and phagocytose
However, too much can be dangerous – agglutination must be moderated
53
Opsonisation
Granulocytes and macrophages have surface receptors for the Fc region of Igs and C3b. Phagocytes can bind these cells using antigen–antibody complexes with high affinity to enhance phagocytosis.
54
Antibody-dependent cell-mediated cytotoxicity
NK cells have Fc and C3b receptors on their surface
Not phagocytic but kill cell material that they bind to through antibody or C3b mediators by delivering short-range cytotoxicity factors
55
Properties of C3a
Anaphylotoxin i..e, stimulate mast cells to release histamine which causes increased vascular permeability and vasodilation
Chemotaxis
56
Properties of C3b
Opsonisatation
Very reactive and has a short half-life
Binds C3 convertase to make C5 convertase
57
Properties of C5a
Chemotaxis
58
Properties of C5b
Makes up part of the complex membrane attack system
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Autologous
Donor tissue from recipient
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Syngeneic
Genetically identical donor and recipient
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Allogeneic
Genetically non-identical donor and recipient from same species
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Xenogeneic
Donor species different from recipient
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B cell ontogeny and self-tolerance
B cells mature in bone marrow through pre-B cell stage where only the heavy chain is rearranged, and immature B cell stage where both heavy and light chains are rearranged
This produces sIgM and sIgD
Potentially self-reactive B cells censored at immature B cell stage
Mature B cells can switch Ig classes while retaining same antigen-binding specificity
64
T cell ontogeny and TCR genes
Undergo rearrangement during T cell development
T cells develop in thymus from immature stem cells into mature, antigen-sensitive T cells by TCR gene rearrangement, positive selection for self-MHC recognition, negative selection to eliminate strongly auto-reactive cells, and CD4/CD8 differentiation
65
Sources of diversity in B and T cell repertoires
Multiple V, D and J exon segments
Combinatorial diversity among exons
Base substitutions at V-J and V-D-J joining boundaries
Somatic mutations within hypervariable regions
66
Adoptive transfer
Transfer of immunity from one animal to another by transfer of cells or antibodies
Can result in graft rejection due to T lymphocyte activity mostly
67
Cytotoxic T cell activation
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Secondary lymphoid organs contain cytotoxic T cell precursors: antigen-sensitive CD8 T cells, which each have a set of TCRaB receptors
Foreign antigens come into contact with these precursors
T cells with TCR receptors that bind most strongly to the antigen presented by class I MHC are selected and activated via signal 1
Further activation signals provided by costimulator interactions and cytokines from TH cells
Cytotoxic precursors proliferate and differentiate into cytotoxic effector cells and the memory population
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68
Cross-priming
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CD8 T cells recognise antigens presented by class I MHC (endogenous pathway) but also require activation signals from CD4 helper T cells, which recognise antigens presented by class II MHC (exogenous pathway)
Therefore dendritic cells present exogenous antigens to CD4 cells and receive signals back from these activated helper cells to license the dendritic cells to present some exogenously-acquired antigens through the endogenous class I MHC pathway to present to CD8 cells to activate them
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69
3 mechanism through which cytotoxic T cells kill their targets
Insert perforin into the target cell membrane which assemble into donut-shaped holes in the membrane
Release enzymes that digest the membrane
Release cytokines that bind to receptors on target cells to induce apoptosis
70
Ig gene rearrangement process in bone marrow
1) Heavy chain rearrangement at pre-B cell stage (V–D–J)
2) Light chain rearrangement (kappa then lambda if kappa rearrangement fails)
3) Splicing
4) Expression of surface IgM (immature B cell)
5) Test for sIgM receptor binding to self-antigens in the bone marrow
6) If no self-recognition then expression of surface IgD and export to secondary lymphoid organs (mature B cell)
71
Central tolerance
Some receptors may be able to recognise self-antigens due to random, antigen-independent Ig gene rearrangement, therefore immature B cell receptors are tested for self-antigen binding in the bone marrow. If the receptors bind with high infinity, the cell is deleted.
72
TCR gene rearrangement in the thymus
1) Heavy chain (B or y) rearrangement (V–D–J–C)
2) Light chain (a or d) rearrangement (V–J–C)
3) Splicing
73
Where are TCRyd-bearing cells found?
Mostly in the mucosa of the gut and the skin
May play a role in early defence against pathogens – known to respond to heat shock proteins expressed by invading micro-organisms in response to stress
74
T cell positive selection
Recognition of self-MHC – if T cell responds, it survives
75
T cell negative selection
T cells that respond to self-MHC PLUS self-peptide so strongly that they are self-reactive in the absence of foreign antigen are killed
76
Double positive CD4/CD8 T cells
Cortical thymocytes express both receptors before they down-regulate one to be single positive via differentiation
Positive selection occurs when they are double positive, negative selection occurs after T cells become single positive
77
4 factors relating to the micro-organism regarding infection
Type of micro-organism
Degree of exposure
Virulence
Route of entry
78
5 factors relating to the host regarding infection
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Integrity of non-specific defences
Competence of specific immune system
Genetic capacity to respond normally to a specific organism
Evidence of previous exposure
Co-infection
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79
6 specific immune factors regarding infection
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Direct neutralisation by antibodies
Opsonisation and phagocytosis
Complement-mediated effects
T cell cytotoxicity
Inflammatory and immunoregulatory cytokines
Anti-viral cytokines (interferons)
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80
2 reasons that antibodies are important in infection
Recovery from extracellular infection
| Protection of mucosal surfaces
81
Antibodies active against virus particles
A, G and M
82
Antibodies active against toxins
G and M
83
Antibodies active against extracellular bacteria
A, G and M
84
Antibodies active against parasites
E and M
85
Describe antibody concentrations across the life-span
In utero, maternal IgG is present from 3 months, increasing rapidly until birth.
After birth, maternal IgG decreases rapidly, levelling off around 2–3 months. Completely disappears by 8 months
Baby's own IgG begins to be made after one month and shoots up. More prominent than maternal IgG at 2 months and levels off at 3 months, but continues to increase. 80% of adult IgG levels at 12 months.
IgM starts to be produced at 7 months in utero, but is slow and gradual. At 12 months after birth, IgM at 75% adult levels.
IgA starts to be produced at 2–3 months after birth, but is slow and gradual. At 12 months after birth, IgA at 20% adult levels. IgA also passed through breast milk.
86
What are cytotoxic T cells effective against?
Viruses (cytoplasmic peptides), tumours and transplanted organs
87
Surface IgA
IgA gives protection in external body fluids, tears, saliva, nasal secretions, and intestine/lung surface fluids
If an infectious agent penetrates the IgA barrier, it will come up against the IgE facet of the secretory system (mast cells)
88
NK cells key points
Large, granular leukocytes in the blood, spleen and peritoneal exudate
Identified by presence of CD16 Fcy receptor and CD56 surface marker
Do not have rearranged Ig (like B cells) or TCR (like T cell) genes
Activated to kill cells that have down-regulated class I MHC expression – these cells are often virus-infected or tumour cells
Activity can be enhanced by CD4 T cell-produced cytokines
89
Role of CD16 receptor in NK cells
Bind antibodies attached to target cells and exhibit antibody-dependent cell-mediated cytotoxicity
90
What determines viral infection recovery?
Cytotoxic T cells and IFNs, rather than antibodies
91
Antibodies associated with Th1 CD4 T cells
IgM and IgG
| virus and acute bacterial infections
92
Antibodies associated with Th2 CD4 T cells
IgG and IgE
| chronic infections, especially parasites
93
Balance of Treg and Th cells
The balance between the four subsets of CD4 T cells has evolved due to a diverse variety of antigens that humans have been exposed to. Due to a revolution in technology and cleanliness, humans are exposed to much fewer antigens and barely any parasites. As a consequence of this, without the time to evolve and recalibrate the balance of these different subpopulations, it seems that Th17 cells, which are now more used in an age where inflammatory diseases are much more common than parasitic infections, are massively upregulated, bringing with it a new wave of autoimmunity and allergies.
94
4 types of hypersensitivity
Type I IgE: IgE-mediated/allergic/anaphylactic
Type II IgG: Antibody-mediated/cytotoxic
Type III IgG: Immune complex-mediated
Type IV Th cells: T cell-mediated/delayed-type hypersensitivity
95
Type I hypersensitivity
Occurs when a divalent allergen cross-links two IgE molecules which were previously passively bound to high affinity Fce receptors. Mast cell mediators are released.
96
2 types of mast cell mediators
1) Granule-associated performed mediators
| 2) Newly formed mediators
97
Examples of granule-associated mediators
Histamine
Heparin
Enzymes
Chemotactic and activating factors e.g., eosinophil chemotactic factor, neutrophil chemotactic factor, platelet activating factor
98
Examples of newly formed mediators
Lipoxygenase pathway products e.g., leukotrienes
| Cyclooxygenase pathway products e.g., prostaglandins, thromboxanes
99
Main effects of mediators released in type I hypersensitivity
Vasodilation
Vascular leakiness
Pruritis
Smooth muscle contraction
100
Treatment of Type I hypersensitivity
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Avoidance
Antihistamines
Corticosteroids
Sodium cromoglycase
Sympathomimetics e.g., epi-pen
Desensitisation
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101
Desensitisation
Theory revolves around slowly exposing a person to their allergen in the hopes of replacing the IgE binding to the Fce receptors with IgG binding, which does not produce an allergic reaction
102
Atopic patients
Patients with a tendency to make IgE antibodies to multiple allergens
103
Bronchial reactions to allergens
Immediate phase due to IgE reaction late phase due to IgG reaction
104
Type II hypersensitivity
Mediated by IgG targeting membrane-associated antigens. Involves a sensitization phase leading to antibody production to recognize substances or metabolites that accumulate in cellular membrane structures. In the effector phase, target cells become coated with antibodies (opsonisation) which leads to cellular destruction by frustrated phagocytosis, complement-dependent cytotoxicity and ADCC.
105
Frustrated phagocytosis
Phagocyte unable to engulf whole target, therefore releases vacuole contents to break it down into smaller parts ready for ingestion. When this happens in type II hypersensitivity, it damages host cells too.
106
Type II hypersensitivity: Frustrated phagocytosis
IgG coat target cells and bind to Fc receptors present on cells such as macrophages and neutrophils and mediate phagocytosis and activate complement via the classical pathway. This leads to C3b deposition which mediates phagocytosis.
107
Type II hypersensitivity: CDC
Complement activation leads to production of the MAC, which forms pores in the cellular membrane resulting in cytolysis (complement-dependent cytotoxicity).
108
Type II hypersensitivity: ADCC
IgG antibodies bind NK cells and macrophages and cause granzyme and perforin release resulting in cell death by apoptosis (ADCC).
109
Type III hypersensitivity
Binding of antigen and complementary antigen and recruitment of other inflammatory cells by soluble mediators. Large immune complexes are formed by cross-linking and get lodged in small vessels, activating immune processes and damaging the vessels. Can be systemic or localised.
110
Systemic type III hypersensitivity
Complexes deposit around the body, commonly the skin, resulting in a rash, the joints, resulting in arthritis and the kidneys, resulting in nephritis. Common example is serum sickness and non-human monoclonal antibodies.
111
Localised type III hypersensitivity
Occurs in tissues. IgG antibodies from the circulation meet antigens and activate complement and recruit inflammatory cells. Common example if Farmer's lung, where actinomycete fungi grow in hay and are inhaled, causing extrinsic allergic alveolitis.
112
Type IV hypersensitivity
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Initial phase involves uptake, processing and presentation by dendritic cells in the skin and then presentation of antigen to T cells in nearby lymph nodes
T cells (mainly Th1) secrete cytokines to recruit and activate macrophages. Also causes upregulation of adhesion molecules and MHC expression on keratinocytes.
Normal proteins act as carriers for small molecules, which are transported to lymph nodes, causing T cell stimulation. Then memory Th1 cells return to the site and provoke inflammation.
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113
Mantoux reaction
Classic example of type IV hypersensitivity which is utilised to test for memory against Tb antigens
114
4 mechanisms of tolerance
Clonal deletion
Clonal anergy
Immunological ignorance
Suppression
115
Clonal deletion
AKA central tolerance
| Complete removal of self-reacting cells
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Clonal anergy
AKA peripheral tolerance
| Self-reacting lymphocytes exist but are resistant to stimulation. Important for antigens only found in the periphery
117
Immunological ignorance
Self-reactive cells present but do not mount a pathological response because the antigens are sequestered in immunologically privileged sites or require T cell help
118
Suppression
Self-reactive B and T lymphocytes are present and potentially active but are kept in check by Treg cells
119
Molecular mimicry
Past infection presented in a similar way to a self-peptide which causes cross-reactivity
120
Natural autoantibodies
Some B cells in the healthy immune repertoire have the potential to produce autoantibodies
Usually IgM, low titre and low affinity
Thought to have a regulatory role or help dispose of breakdown products
