Immunology Flashcards
1
Q
What physical barriers does the body have to keep out infecting organisms?
A
Skin
Mucociliary escalator (upward flow of mucus in bronchi)
Complete emptying of bladder
2
Q
What simple chemical and biological barriers help the body prevent invasion from infecting organisms?
A
Low pH in stomach and vagina
Sebum on skin
Normal flora on skin, in bowel and in vagina
3
Q
What cells and molecules form immunological defence mechanisms?
A
Lymphocytes, macrophages, antibodies and complement
4
Q
Why is it important for immunological agents to have recognition capabilities?
A
To distinguish from self and non-self and tell the difference between damaged and healthy tissues.
Prevent autoimmunity
5
Q
Define ‘immune response’.
A
Activation of the destructive agents that form the body’s immunological defence mechanisms (lymphocytes, macrophages, antibodies and complement)
6
Q
Define ‘immunogen’.
A
Anything that provokes an immune response
7
Q
Define ‘antigen’
A
Anything that is recognised by the cells and molecules of the immune response
8
Q
Define ‘determinant’
A
Agents of the defense system recognise antigens through receptors and recognition sites. The part of the antigen that is recognised is called a determinant.
9
Q
Define ‘receptor’
A
A molecule or complex of molecules which has at least one recognition site (for recognising a determinant on an antigen). Normally present on the surface of cells.
10
Q
Why is recognition important in relation to immune response?
A
The immune system needs:
- to detect the presence of non-self and, usually, to destroy and/or eliminate the invader
- to leave I damaged, as much as possible; the body’s own components (self)
- sometimes to allow toleration of some non-self substances where an aggressive immune response serves no useful purpose
11
Q
How does a receptor bind to the determinant?
A
Complementary shapes and electrostatic forces
12
Q
How do antigen receptors aid immunity?
A
Antigen receptors recognise determinants that are present on non-self substances, but are sparse or absent on self - thus distinguishing self and non-self.
13
Q
How do scavenger receptors aid immunity?
A
Scavenger receptors recognise determinants or features characteristic of dead or denatured material, but scarce or absent on healthy issue - thus distinguishing damaged and healthy tissue
14
Q
Receptors and determinants are used to identify targets of the immune system. How else are they used?
A
Cells and molecules of the immune system also interact and cooperate with each other through specialised receptors and determinants, such as:
- receptors on macrophages for antibodies
- interactions within the complement cascade
15
Q
If a receptor binds only to one particular kind of determinant it is said to be __?__.
A
very specific
16
Q
A receptor may bind to a variety of determinants with a common property (e.g. May bind to all determinants with a strong negative charge, because it has a strong positive charge) in spite of there being differences in their shapes. A receptor of this type is said to be __?__.
A
Non-specific
17
Q
What are antigens usually made of?
A
Antigens are usually polypeptides or polysaccharides, sometimes with other chemical groups attached
18
Q
True or false: each antigen has one determinant
A
False, antigens may have several determinants recognisable by the receptors of the defence system.
19
Q
How can cells that are part of the immune response communicate with each other?
A
Cell surface molecules: cells touching each other may communicate through structures that allow them to fit or bind together to mediate communication.
Secreted molecules, or mediators: such as hormones, cytokines, or lymphokines
20
Q
How do lysosomes assist in the body’s defence?
A
Lysosomes act by damaging bacterial cell walls, but do no harm to eukaryotes, which lack a cell wall
21
Q
How does mannose-binding protein assist in the body’s defence?
A
Mannose-binding protein acts through recognition of particular carbohydrate patterns found on the surface of many pathogenic microorganisms.
22
Q
How does C-reactive protein (CRP) assist in the body’s defence?
A
CRP binds to phosphorylcholine on bacteria, enhancing phagocytosis and assisting in complement binding.
23
Q
What is the complement pathway?
A
A cascade system of enzymes reminiscent of the clotting pathway and is triggered by certain foreign chemical configurations found in endotoxins, and bacterial and fungal cell walls. It culminates in the activation of enzymes destructive to foreign organisms. It also produces chemotactic substances and adherent factors that promote the phagocytosis. It also acts to discriminate self and non-self as it is only stimulated by foreign material.
24
Q
How do chemotactic factors assist in the body’s defence?
A
Chemotactic factors are chemical substances that direct the movement of cells – human or invading – to particular locations.
25
"All body cells play their part in the innate immune system."
In what ways do they do this?
Any cell that is damaged or undergoes necrosis may release mediators, or material such as heat shock proteins that signal the damage to neighbouring cells.
Many cells that are virally infected signal the fact by releasing mediators (interferons (IFNs)).
26
Phagocytes, such as neutrophils, monocytes/macrophages, dendritic cells and eosinophils, play a significant role in the innate immune system, as they can usually kill the microbes they phagocytose.
What methods are used by phagocytes to kill microbes?
Phagocytic destruction mechanisms involve enzymes, free radicals and exclusion of nutrients from the phagosome.
27
Which defence mechanism uses a relatively small number of receptors and recognition sites that detect components common on microorganisms, but not found within the human body?
a) Innate immune system
b) Adaptive immune system
a) Innate immune system
These mechanisms do not recognise all determinants and successful pathogens hide these. The body needs a more sophisticated defence mechanism to deal with these – the adaptive immune system.
28
Which defence mechanism employs the use of lymphocytes?
The adaptive immune system
29
What are the different types of lymphocyte?
- B lymphocytes
- T lymphocytes
- null lymphocytes
30
There are 3 classifications of lymphocyte: B, T, and null.
T lymphocytes can be further divided into what categories?
- CD4-positive (helper T cells)
| - CD8-positive (cytotoxic T cells)
31
Are lymphocyte receptors specific or non-specific?
Specific.
Any one lymphocyte, and its clone from division of a single cell, will have receptors which are specific for an antigen, but different lymphocytes will have different specificities.
32
From where do T lymphocytes originate?
T lymphocytes originate in the bone marrow, but undergo further development in the thymus before they are mature.
33
True or false: Like B lymphocytes, the receptors on the surface of any one T lymphocyte all have the same specificity.
True
34
The receptors on T lymphocytes are known as __1__. Highly variable, these regions interact with an __2__ to activate the lymphocytes.
1) complementarity determining regions (CDRs)
| 2) MHC (major histocompatibility complex)-peptide complex
35
What is CD nomenclature?
CD stands for cluster of differentiation. This is a classification system for the different antigenic determinants found on cells.
The surface molecules are different on different cells and so act as markers of differentiation. The different CD complexes are given a number to differentiate them.
36
What is the 'major histocompatibility complex'?
The MHC region is located on chromosome 6 and consists of about 140 genes, many having immunological functions. Proteins produced from fragmented microorganisms bind to various MHC molecules. The MHC molecule can be divided into three groups: class I, class II and class III.
37
MHC class I
MHC class I molecules are present on the surface of virtually every cell. They present antigen fragments to T lymphocytes and bind to CD8 receptors on cytotoxic T cells.
38
MHC class II
MHC class II molecules are found mainly on macrophages and B cells and present antigen to helper T cells, binding to the CD4 receptor.
39
MHC class III
MHC class III genes encode for other immune components, such as complement, or cytokines such as TNF-α.
40
Human leucocyte antigen (HLA) classifications
HLA antigens are classified into nine divisions:
- HLA-A, HLA-B and HLA-C all belong to MHC class I.
- HLA-D consists of six genes, all belonging to MHC class II.
41
Human leucocyte antigen (HLA) structures
The HLA molecules, class I and II, are both two-chain glycoproteins. Class I molecules have a single transmembrane chain whereas class II molecules have two transmembrane chains. Both classes have an antigen-presenting groove where oligopeptides bind
42
How are T lymphocytes activated?
The interaction of a T cell receptor with an MHC-receptor indicates the presence of a cell with a foreign particle, such as an intracellular microbe.
The binding stimulates the T lymphocytes, which become activated and release various cytokines, depending on what type of lymphocyte has been stimulated.
43
CD4 T lymphocytes (having CD4 receptors, helper T cells) cannot eliminate or kill antigen, so how does their response aid the body's defence?
When a helper T lymphocyte encounters an antigen of the correct specificity, correctly presented, it responds by dividing and secreting cytokines. These lymphocytes cannot eliminate or kill antigen but the secreted cytokines initiate events that do.
44
True or false: CD4 T lymphocytes are cytotoxic.
False. CD4 T lymphocytes are helper T cells. These cannot kill or eliminate antigens.
Most CD8 T lymphocytes are cytotoxic.
45
True or false: T lymphocytes cannot respond to antigen: it has to be presented to them by HLA molecules on antigen-presenting cells (APCs)
True
46
What are the two possible sources for the antigen presented by antigen presenting cells (APCs)?
a) Exogenous antigen – an antigen taken in by the APC. It may be self or non-self.
b) Endogenous antigen – an antigen manufactured within the APC. It may be self (coded for by the APC’s own genes) or non-self (derived from an intracellular pathogen infecting the cell).
47
Where do T cells differentiate into either CD4 or CD8?
In the thymus
48
Where are human leukocyte antigen (HLA) found?
The HLA molecule is on the APC and presents an oligopeptide antigen bound within the groove of the molecule.
49
How do the 2 classes of HLA molecules differ?
- Class I HLA molecules (on most nucleated cells) present endogenous antigen to CD8 cytotoxic T lymphocytes.
- Class II HLA molecules (on B lymphocytes and macrophages) present exogenous antigen to CD4 helper T lymphocytes.
(Extra Help for you too = 'EX'ogenous antigen, 'HELP'er T lymphocytes are CD'4,' and recognise antigen presented on class 'II' HLA molecules.)
50
In what 2 ways can cell killing take place?
- Perforin in the granules produces ion channels in the target cell membrane followed by osmotic lysis.
- Release of tumour necrosis factor (TNF) interacts with receptors on the target cell and initiates programmed cell death (apoptosis).
51
How do you 'switch off' an activated T cell?
Continued antigen presence continues to stimulate the T cells and so when the antigen disappears, the stimulus to release the activating cytokines is ‘switched off’. Other substances appear to assist in this process:
- Transforming growth factor β (TGF-β)
- Hydrocortisone
- T cells might specifically suppress each other, not responding to consumed cytokines.
52
From where do B lymphocytes originate?
Bone marrow
53
Where do B lymphocytes normally 'hang out'?
They leave the bone marrow and circulate through blood and lymph to B cell areas in lymphoid tissues.
54
What are antibodies?
Receptors for antigen on the surface of B lymphocytes.
Antibodies are glycoproteins with a characteristic structure – two heavy chains and two light chains.
Any one B lymphocyte has antibodies all of the same specificity.
55
How do B lymphocytes respond when their antibodies interact with antigen?
The cell responds by dividing.
Some of the progeny change their appearance and become plasma cells, which continually secrete antibody.
Antibodies cannot themselves destroy or eliminate non-self or antigen, but they interact with other agents that do, such as the classical complement pathway, null cells, macrophages, neutrophils, mast cells and eosinophils.
56
How is a B cell activated?
By the binding of an antigen of the correct specificity
57
What are antibodies made of?
Glycoprotein in a Y shape - each with 2 light chains and 2 heavy chains.
58
Which antibody class exists as a pentamer?
IgM
59
Which antibody class exists as a dimer?
IgA
60
Which is the most abundant class of antibody in the body?
IgG
61
Which classes of antibody exist as monomers?
IgD, IgE, IgG
62
Antibodies can be described according to their strength. What do 'affinity' and 'avidity' refer to?
Affinity refers to the strength of the antibody–antigenic determinant bond.
Avidity, in contrast, is the strength of attachment between an antibody and antigen – different because antibodies have at least two antigen-combining sites and antigens may have many different determinants of the relevant specificity.
63
Which antibody class mediates killer activity by null lymphocytes?
IgG
64
Which antibody class opsonises antigen for all phagocytic cells?
IgG
65
Which antibody cell opsonises antigen for phagocytosis only by eosinophils?
IgE
66
Which antibody class can cross the placenta to protect the foetus?
IgG
67
Which antibody class is found in saliva, tears, and breast milk?
IgA
68
Which antibody class mediates mast cell degranulation?
IgE
69
Which antibody class activates the classical complement pathway?
IgM and IgG (subclasses 1,2, and 3)
70
Which antibody class blocks the binding of microbes and toxins to human tissue?
IgG, IgM, IgA.
71
What is the complement system?
The complement system is a triggered enzyme cascade.
The components circulate in inactive forms, the first member of the series, once it is activated, activating the next.
Each molecule can activate several molecules of the next component of the series, so the reaction is amplified.
72
What factors are involved in the complement system?
There is a complex collection of factors and controlling molecules that make up the complement system: C factors (C1 though to C9), factor B, factor D, MCP (membrane cofactor protein), DAF (decay acceleration factor), factor H, factor I, properdin and C1 inhibitor.
73
What is the aim of the complement system?
The aim of the complement cascade is to activate C3 by splitting it into C3a, C3b, C3c and C3d:
- C3a is a chemotactic agent
- C3b initiates the formation of a lytic structure and also binds to C3b receptors on macrophages, aiding phagocytosis.
74
How are the components of the complement system generally activated?
Activation of a component is often achieved by splitting, and the two products that result are labelled with the suffixes a and b: thus C4 is split into C4a and C4b.
The larger fragment generally gets the suffix b and this is also usually the active part.
75
True or false: There are two complement pathways?
True.
The classical pathway and the alternative pathway.
- The classical pathway is triggered by the interaction of an antibody with an antigenic determinant.
- The alternative pathway is triggered by some bacterial cell walls, fungal cell walls and some endotoxins, and does not depend on a pathogen-binding protein.
76
In order to trigger the classic complement pathway, several C1 subunits must bind to IgG antibodies. However, a single IgM can initiate the pathway. Why is this?
This ensures that activation does not simply occur when C1q happens to meet a circulating IgG molecule.
IgM has a pentameric structure and most of its binding-sites must be bound to antigen before the C1q binding-site is revealed. Therefore only 1 IgM is needed.
77
Describe the classical complement cascade from the point at which the C1 complex splits to the point at which the lytic sequence is initiated.
The C1 complex splits C4, and then C2 and the subunits C4b and C2a form a complex, C4b2a.
C4b2a (C3 convertase) cleaves C3 and C3b joins the former to make C5 convertase (C4b2a3b). C3a is chemotactic for leucocytes. The interaction between C5 convertase and C5 initiates the lytic sequence.
78
How is the alternative complement cascade activated?
The alternative pathway is activated when circulating C3 interacts directly with some pathogens or endotoxins.
The activated classical pathway can also activate this pathway, amplifying the response.
79
Describe the alternative complement cascade from the point at which the C3 complex splits to the point at which the lytic sequence is initiated.
C3 is cleaved and C3b combines with factor B to form C3b,B. Factor B is split with factor D and C3b,Bb (C3 convertase Bb). C3 convertase Bb, located on the pathogen surface, activates more circulating C3, leading to more C3b adhering to C3 convertase Bb – positive feedback. The resultant complex on the pathogen, C3b,Bb,3b cleaves C5 to initiate the lytic sequence.
C3b,Bb,3b from the alternative pathway is thus the equivalent of C4b2a3b from the classical pathway.
80
Why is C3 so central to the complement cascade?
Cleavage of C3 results in:
- Activation of lytic sequence
- C3a activates mast cells
- C3a is weakly chemotactic
- Causes the release of C5a, which activates mast cells and is strongly chemotactic
- Opsonisation when C3b binds to microorganisms
81
What is 'bystander lysis'?
In the complement pathway, the lytic sequence can affect innocent cells, causing nearby cells to be destroyed - collateral damage.
82
What is the lytic sequence?
Once C5 is cleaved, C5a leaves the pathway but C5b attaches itself to the target.
It forms a complex with C6 and C7 to form C5b,6,7 and then C8 and multiples of C9 are bound forming the 'membrane attack complex (C5,6,7,8(C9))'.
C8 and C9 have hydrophobic components that incorporate into the membrane lipid but making, at the same time, an ion channel. This channel allows water to move, but not protein. As a result water enters somatically and the cell is lysed.
83
What are basophils and mast cells?
Both cells are derived from pluripotent stem cells in the bone marrow and are rich in granules that contain histamine and other substances that are released by degranulation.
The cells are also involved in the manufacture of leukotrienes, prostaglandins and other substances.
84
How are mast cells activated?
- IgE meeting its antigen and cross-linking with mast cells leads to degranulation.
- C5a and C3a components of complement are chemotactic and cause mast cell degranulation.
- Neurolotransmitter 'substance P' activates mast cells near nerve endings.
- Physical stimuli (heat, cold, pressure etc)
- Certain chemicals (in food, for example)
85
Degranulation of a mast cell causes what to be released?
- Histamine
- Leukotrienes
- Prostaglandins (inflammation)
- Cytokines
86
True or false: Neutrophils cannot present antigen.
True.
On their surface are class I HLA molecules, but not class II, which means that they cannot present antigen.
87
What is the role of neutrophils in inflammation?
- movement to site of damage
- phagocytosis (antibody and C3b receptors)
- release of leukotrienes and prostaglandins
88
What is the role of macrophages in inflammation?
Macrophages are versatile cells and act as the main scavengers of old cells and debris. Producing a wide variety of substances, they are important agents in the inflammatory response and are also the main APCs in the fight against pathogens.
Also release substances to neutralise destructive proteases and promote repair and cell division.
89
What is hypersensitivity?
Hypersensitivity refers to the undesirable side effects of the normal immune response, whether or not that response is directed against self or non-self. There are five types of hypersensitivity (type 1-5)
90
What is type 1 hypersensitivity?
(aka allergic or immediate hypersensitivity)
The interaction between antigen and IgE results in mast cell degranulation and the release of histamines, leukotrienes, prostaglandins and other substances that cause symptoms within minutes.
91
Give examples of type 1 hypersensitivity
Asthma, anaphylaxis, urticaria, hay fever, eczema
92
What is the mediator of type 1 hypersensitivity?
IgE antibody
93
What is type 2 hypersensitivity?
IgM or IgG (and complement) mediated.
This occurs when antibodies attach to determinants on self structures (auto-antibodies). The tissues are damaged by classical complement activation, phagocytosis and/or killer activity.
94
What mediates type 2 hypersensitivity?
IgM or IgG (and complement)
95
What are examples of type 2 hypersensitivity?
Autoimmune haemolytic anaemia (AIHA), idiopathic thrombocytopoenic purpura (ITP), haemolytic disease of the newborn, Goodpasture's syndrome
96
What is type 3 hypersensitivity?
Antigen–antibody immune complexes (with or without complement) cause damage to neighbouring tissue. The antigen may be self, e.g. nuclear constituents as in systemic lupus erythematosus (SLE), or non-self, e.g. streptococci. Effects can be local or systemic.
97
What is type 4 hypersensitivity?
This is damage associated with the interaction between activated helper T cells and activated macrophages, or activated cytotoxic T cells and NK cells (delayed type hypersensitivity).
98
What is type 5 hypersensitivity?
This is a subtype of type 2 hypersensitivity – instead of the antibodies acting against cell surface components, this definition is used to describe situations when the antibodies act against cell receptors.
99
What are examples of type 5 hypersensitivity?
Graves disease, myasthenia gravis
100
What are examples of type 3 hypersensitivity?
Systemic lupus erythematosus (SLE), polyarteritis nodosa
101
What are examples of type 4 hypersensitivity?
BCG vaccinations, transplant organ rejection, contact dermatitis.
102
What is the mediator for type 4 hypersensitivity?
T cells
103
How quickly does each type of hypersensitivity take to have an effect?
Type 1: 30 mins
Type 2: days
Type 3: 6-8 hours
Type 4: 48-72 hours
104
How can you test for type 1 hypersensitivity?
Scratch tests - apply allergen to skin and see if there is a reaction.
ELISA testing tells you how sensitive someone is, not just a binary positive/negative result.
105
What are IgE responses intended for?
Expeling and destroying helminth and protozoa pathogens.
Unfortunately, allergies and other type 1 hypersensitivities have also occurred because of this defence mechanism.
106
What is the difference between type 3 local and type 3 systemic hypersensitivity?
Local is at at particular site - e.g. injection site following vaccination.
Systemic is inflammatory responses across the system.
107
What are the three main cellular mechanisms that lead to toleration?
- Clonal deletion: developing B and T cells that recognise self-antigen are deleted before they can circulate.
- Anergy: Mature T or B cell becomes temporarily frozen when they recognise antigen in certain unfavourable circumstances.
- Acquired tolerance: A specific non-reactivity to an antigen which would normally lead to an immune response. E.g a foetus must be tolerated by the mother.
108
What are interferons (IFNs)?
IFNs are natural proteins or glycoproteins that have non-specific antiviral activity acting through cellular metabolic processes involving synthesis of RNA and protein.
IFNs have an antiviral effect, repress cell growth (of both normal and tumour cells) and regulate the immune system through signals induced when they interact with cell surface receptors. They increase NK activity, increase expression of HLA molecules (synergistically with TNF) and are the main macrophage activator. Binding of IFNs to special receptors on the cell surface induces an antiviral state.
109
What is 'tumour necrosis factor (TNF)'?
TNF is made by macrophages and lymphocytes. It activates and enhances the ability of phagocytes to destroy microbes.
TNF is also involved in the induction of apoptosis of tumour cells and virally infected cells and also interacts with cell surface receptors to elicit an antiviral state. Increased production of TNF has significant side effects. Chronically high levels are seen in malignancy, producing cachexia.
