ICS - Immunology Flashcards
1
Q
Innate immunity characteristics
A
- Non-specific
- Rapid response
- No memory
- Phagocytic cells (neutrophils, macrophages)
- Complement system
2
Q
Adaptive immunity characteristics
A
- Specific
- Slower response
- Immunological memory
- B and T cells
- Antibodies involved
3
Q
Neutrophils
A
- 65% of WBC
- Life-span 6hrs - 12 days
- Intracellular granules - primary lysosomes and secondary granules
4
Q
What do the two types of granules in neutrophils contain?
A
- Primary lysosomes - myeloperoxidase, etc., combine with phagosomes containing microbes to digest them
- Secondary granules - lactoferrin and lysozymes
5
Q
Monocytes
A
- 5% of blood
- Lifespan - months
- Differentiate –> macrophages in tissue
- Role - remove anything foreign
- Have lysosomes containing peroxidase that can kill microbes
6
Q
Macrophages
A
- Lifespan - months/years
- e.g. Kupffer cells, microglia
- Role - remove foreign microbes
- Have lysosomes that contain peroxidase and can kill microbes
7
Q
Eosinophils
A
- Make up 5% of the blood
- Lifespan - 8-12 days
- Associated with parasitic infections
8
Q
Basophils
A
- 2% of WBC
- Lifespan - 2 days
- Express high affinity IgE receptors, binding to which results in de-granulation, releasing histamine, involved in allergic phenomena
9
Q
Mast cells
A
- Only in tissues, v. similar to basophils
- Express high affinity IgE receptors
10
Q
T lymphocytes - types
A
- T helper - CD4+, help B cells produce antibodies, activate macrophages, help development of T cytotoxic cells
- T cytotoxic - CD8+, kill cells directly
- T regulatory - regulates immune response, dampens
11
Q
B lymphocytes
A
- Originate and mature in bone marrow
- Express membrane bound antibody on cell surface
- Differentiates into plasma cell that can make antibodies
12
Q
Natural killer cells
A
- Express CD56
- Found in spleen and tissues
- Kill virus infected cells adn tumour cells by apoptosis
13
Q
Dendritic cells
A
- Detect foreign pathogens, ingest and display piece of pathogen on surface
- Induce immune response in the inactive/ resting T cells
- Produce cytokines, etc. to induce B cells
- Found in tissue that has contact with the outside environment, e.g. skin, stomach, intestines
14
Q
Complement
A
complex series of interacting plasma proteins which form a major effector system for antibody-mediated immune reactions
15
Q
Which organ produces the proteins in the complement cascade?
A
Liver
16
Q
Opsonisation
A
Identifying the invading particle to the phagocyte
17
Q
Purpose of the complement cascade?
A
To remove/ destroy an antigen either directly by lysis or by opsonisation, increase chemotaxis
18
Q
3 complement activation pathways
A
- Classical
- Alternative
- Lectin
19
Q
Classical complement pathway
A
Antigen-antibody immune complexes. When IgM or IgG binds to antigen, causes shape change and allows to bind with first component of the pathways (C1)
20
Q
Alternative complement pathway
A
Complement binds directly to microbe
21
Q
Lectin complement pathway
A
Initiated by mannose-binding lectin (MBL) binds to mannose on the pathogen
22
Q
Pattern recognition receptors (PRR)
A
Proteins capable of recognising molecules frequently found in pathogens, two types:
- Secreted and circulating, e.g. lectins
- Cell bound
23
Q
What do PRRs recgonise?
A
PAMPs and DAMPs (pathogen/damage associated molecular patterns) that are found on microbes
24
Q
Role of MHC (major histocompatibility complex)
A
Bind peptide fragments derived from pathogens and display them on the cell surface for recognition by appropriate T cells
25
Antibody
protein produced in response to an antigen, only binds with the antigen that induced its formation
26
Antigen
A molecule that reacts with preformed antibody and specific receptors on T or B cells
27
Epitope
Part of the antigen that binds to the antibody/receptor binding site
28
Affinity
Measure of the binding strength between an epitope and an antibody binding site
29
Soluble antibodies =
Immunoglobulins
30
5 classes of Ig
IgG, IgA, IgM, IgD, IgE
31
IgG
- Majority of immunoglobulins (70-75%)
- Penetrates tissue easily
- Only Ig to cross the placenta and provide immune protection to the neonate
- Important in secondary/memory responses
32
IgA
- 15% of Ig
| - Predominant Ig in mucous secretions such as saliva, colostrum, milk, bronchiolar and GU secretions
33
IgM
- 10% of Ig
- Mainly found in the blood (large, difficult to cross endothelium)
- Involved in primary response, inital contact with antigen
34
IgE
- Basophils and mast cells express IgE receptors
- Binding antigen triggers release of histamine
- Associated with allergic response and defence against parasitic infections
35
IgD
- Expressed on naive B cells, acts as a B cell antigen receptor
36
Cytokines
Soluble proteins secreted by lymphocytes or macrophages/monocytes that act as stimulatory or inhibitory signals between cells
37
Cytokines that act between cells of the IMMUNE SYSTEM =
Interleukins
38
Cytokines that induce chemotaxis of leukocytes (WBC) =
chemokines
39
Common features of ALL cytokines?
- Short half-lives
- Rapid degradation
- May affect multiple organs in the body
40
Interferons
Induce a state of antiviral resistance in uninfected cells and limit the spread of viral infection
41
Colony stimulating factor (CSF)
Involved in directing the division and differentiation of bone marrow stem cells (precursors of leukocytes)
42
Physical and chemical barriers of innate immunity
Skin, mucous membranes (saliva, tears, mucous secretions, cilia), pH (gastric acidity kills microbes)
43
MHC I
- Intracellular, i.e. virus
- Found on the surface of virtually ALL cells of the body except RBCs
- Cytotoxic T cells (CD8+) require an antigen to be associate with class I MHC proteins before they kill the cell containing the intracellular pathogen
44
MHC II
- Extracellular, i.e. phagocytosis
- Found mainly on the surface of macrophages, B cells and dendritic cells (antigen presenting cells)
- Helper T cells (CD4+) require MHC II proteins before they help B cells to make antibodies
45
Complement potent in opsonisation?
C3b
46
B cell activation
- Activated upon binding with antigen which is presented on their surface via MHC II
- Activated B cell binds to T helper (CD4) cell via the MHC II complex, inducing the B cell to divide by clonal expansion (occurs in the lymph nodes)
- B cells differentiate then into plasma and memory cells
47
Secreted and circulating PRRs
- Antimicrobial peptides secreted in lining fluids from epithelia
- Lectins and collectins - activate complement, improve phagocytosis
48
Cell-associated PRRs
- Receptors present on cell membranes or in the cytoplasm
| - TLRs (toll-like receptors) are the main family
49
Clinical indications related to allergy?
- epithelial (eczema, itching, etc)
- excessive mucus production
- airway constriction
- abdominal bloating
- anaphylaxis
50
Atopy
Inherited tendency to overproduce IgE antibodies to common environmental antigens
51
High affinity IgE receptor expressing cells
Eosinophils, mast cells (tissue), basophils
52
Type 1 hypersensitivity reaction
anaphylaxis, production of IgE antibodies
53
Type 2 hypersensitivity reaction
antibody binds to antigen on target cell (cytotoxic) --> phagocytosis, e.g. Goodpasture's syndrome
54
Type 3 hypersensitivity reaction
deposition of antibody-antigen complexes e.g. Farmer's lung
55
Type 4 hypersensitivity reaction
Activate T lymphocytes, pronounced secretion of cytokines, delayed, e.g. contact dermatitis
56
Define allergy
abnormal response to harmless foreign material
57
Low affinity IgE receptor expressing cells
B cells, T cells, monocytes, eosinophils, platelets, neutrophils
58
Function of low affinity IgE receptor expressing cells
Regulate IgE synthesis, trigger cytokine release by monocytes
59
Mast cells
- Main effector cells for IgE- mediated immunity
| - Immature mast cells circulate, mature mast cells reside in the tissues
60
Indirect activators of mast cells (via IgE)
- allergens e.g. wasp venom
| - bacterial/viral antigens
61
Direct activators of mast cells
- Aspirin, preservatives
| - Cold/mechanical deformation i.e. asthma
62
Products of mast cells
1. Histamine - arteriolar dilation, capillary leakage, bronchoconstriction
2. Proteases e.g. tryptase
3. Prostaglandin D2 - induces smooth muscle constriction
4. Chemotactic factors
63
What makes an allergen?
Particulate delivery of antigens
64
Hallmarks of cancer
- Growth self-sufficiency
- Escape apoptosis
- Ignore anti-proliferative signals
- Limitless replication potential
- Sustained angiogenesis
- Invade tissues
- Escape immune surveillance
65
Cancer immuno-surverillance
Immune system can recognise and destroy nascent transformed cells, normal control
66
Cancer immunoediting
Tumours tend to be genetically unstable, thus the immune system can kill and also induce changes in the tumour, resulting in tumour escape and recurrence
67
Tumour antigens types
Tumour specific antigens (TSA) and tumour associated antigens (TAA)
68
Tumour specific antigens (TSA)
Peptides on the surface of tumour cells, found ONLY on tumours, due to gene mutations, derived from viral antigens
69
Tumour associated antigens (TAA)
On both normal AND tumour cells, but are OVEREXPRESSED on tumour cells
70
Tumour escape
Immune responses change tumours such that tumours will no longer be seen by the immune system
71
Immune evasion
tumours change the immune responses by promoting immune suppressor cells
72
Cancer immunotherapy
To induce an immune response against the tumour that would discriminate between the tumour can normal cells
73
Active immunotherapy
Vaccinations e.g. killed tumour vaccine, purified tumour antigens, etc.
74
Passive immunotherapy
- Adaptive cellular therapy (e.g. injecting T cells that recognise the tumour specific antigen to destroy the tumour)
- Cell-based therapy (activate the patients immune system to attack the cancer)
75
Tumour hypoxia
- Hypoxia is a prominent feature of malignant tumours
- Inability of the blood supply to keep up with the growing tumour cells
- Hypoxic tumour cells adapt to low oxygen
76
Why does tumour hypoxia = poor patient prognosis? (SSIR)
- Stimulates new vessel growth
- Suppressed immune system
- Increased tumour hypoxia after therapy
- Resistant to radio- and chemotherapy
77
Passive immunisation
Short-term immunity which results from the introduction of antibodies from another person or animal
78
Active immunisation
vaccines - antigenic substance prepared from the causative agent of a disease
79
4 types of vaccine
1. Live-attenuated
2. Inactivated
3. Subunit, recombinant, polysaccharide, conjugate
4. Toxoid
80
Examples of live-attenuated vaccines
MMR, smallpox, chickenpox, yellow fever, rotavirus
81
Examples of inactivated vaccines
Hepatitis A, polio, rabies, flu
82
Examples of subunit, recombinant, polysaccharide and conjugate vaccines (parts of the germ)
Hepatitis B, HPV, pneumococcal, meningococcal, shingles
83
Examples of toxoid vaccines (respond to the toxins produced by the germs)
Diptheria, tetanus
84
The complement pathway consists of proteins which conduct...
opsonisation, membrane attack complex (lysing microbes directly), enhancement of inflammation
85
C3 is cleaved into
C3a and C3b
86
C3b is potent in
opsonisation
87
The different pathways in the complement system ultimately lead to the formation of
C3 convertase
88
2 main intracellular granules in neutrophils?
- Primary lysozymes (myeloperoxidase)
| - Secondary lysozymes (lactoferrin and respiratory burst components)
89
Function of macrophages
To remove anything foreign / dead
90
Macrophages have lysosomes containing?
peroxidases
91
What are dendritic cells?
Antigen-processing cells, act as messengers between the innate and adaptive immune system
92
Two types of pattern recognition receptors (PRRs)
1. Secreted and circulating
| 2. Cell associated
93
PRRs recognise
PAMPs or DAMPs (pathogen/damage associated molecular patterns)
94
Secreted and circulating PRRs
1. Antimicrobial peptides secreted in lining fluid of epithelia
2. Lectins and collectins (carbohydrate containing proteins that bind to carbs/lipids in wall)
95
Activate of toll-like receptors drive production of ?
Cytokines by antigen presenting cells (increasing likelihood of successful T cell activation)
96
Where are TLRs found?
on macrophages, dendritic cells and neutrophils
97
Main family of cell-associated PRRs?
Toll-like receptors (TLRs)
98
Stages of vaccination
1. Engage the innate immune system
2. Danger signals that activate the immune system, triggers such as PAMPs
3. Engage TLR receptors
4. Activate specialist APC
5. Engage the adaptive immune system (generate memory T and B cells, activate T cell help)
99
What is an adjuvant?
Any substance added to a vaccine to stimulate the immune system (ensuring a powerful immune response)
100
Examples of adjuvants
Whole killed organism, toxoids, proteins, chemicals
101
Why do transplant organs pose a threat to the host immune system of the patient?
Presence of different major histocompatability antigens (MHA) on the surface of organs
102
3 types of clinical organ transplant rejection
hyperacute, acute, chronic
103
Which type of T cells are key to organ transplant rejection?
CD4+
104
Two phases of the rejection process?
afferent phase, efferent phase
105
Afferent phase of graft rejection
donor MHC molecules within the graft (organ) are recognised by the recipient CD4+ T cells
106
Efferent phase of graft rejection
CD4+ T cells enter the graft and recruit effector cells responsible for the tissue damage of rejection - macrophages, CD8+ T cells, natural killer cells, B lymphocytes
107
Most importnat cytokines in graft rejection?
interleukin-2 and interferon-gamma
108
Not all parts of the graft need to be attacked for rejection to occur - critical targets are:
microvasculature, specialised parenchymal cells of the organ
109
Preventing graft rejection
immunosuppresive drugs
110
Immunosuppressive drugs
1. Ciclosporin
2. Azathioprine - inactive until metabolised by the liver, but then effects all dividing cells including lymphocytes by inhibiting their DNA synthesis
