Immune Response and Hypersensitivity Flashcards
1
Q
What are the 2 main subdivisions of the immune system?
A
Innate and adaptive.
2
Q
What is innate immunity?
A
Non-specific defence mechanisms (e.g. skin, chemicals, immune cells).
-fast action
3
Q
What are the main subdivisions of the innate immune system? (3)
A
- Barrier and chemical mechanisms (e.g. skin)
- Pattern recognition receptor (PRR)
- Cellular (phagocytes, NK cells)
4
Q
What is adaptive immunity?
A
Antigen-specific immune response.
-slower repsonse
5
Q
What are the main subdivisions of the adaptive immune system? (2)
A
- Humoral
- Cellular
6
Q
What is humoral immunity?
A
Immunity mediated by macromolecules ( not cells) found in ECF such as secreted antibodies and complement proteins.
7
Q
What are the main components of the innate immune system? (5)
A
- PRR
- Antimicrobial peptides
- Cells
- Complement components
- Cytokines
8
Q
What are pattern recognition receptors (PRR)?
A
Antigen recognition receptors in the innate system.
9
Q
Are PRRs identical?
A
No, there’s a diversity of type, but each cell carries identical receptors of a given type.
10
Q
What do PRRs commonly recognise? (2)
A
- Pathogen-associated molecular patterns (PAMPs)
- Danger associated molecular patterns (DAMPs)
11
Q
What are the 2 groups of PRRs?
A
- Transmembrane (cell suraface) and intracellular
- Fluid-phase soluble molecules
12
Q
Pattern recognition receptors:
What molecule does TLR4 recognise?
A
LPS.
13
Q
Pattern recognition receptors:
What molecule does TLR5 recognise?
A
Flagellin.
14
Q
Pattern recognition receptors:
What molecule does TLR9 (intracellular) recognise?
A
MyD88.
15
Q
What are antimicrobial peptides (AMPs)?
A
Proteins produced in secretions»_space; break down proteins in microbes.
16
Q
Give some examples of antimicrobial peptides.
A
Defensins
Protegrin
Granulysin
Histatin
17
Q
Give some examples of cells that play a role in the innate immune system.
A
Macrophages Dendritic cells NK cells Neutrophils Eosinophils
18
Q
What are the complement components of the innate immune system?
A
- Classic and alternative complement pathway.
- Proteins that bind components
19
Q
What are cytokines?
A
Molecules that mediate host defence and inflammation, and regulate the adaptive immune response.
-autocrine/paracrine/endocrine
20
Q
What does autocrine mean?
A
Relating to a cell-produced substance that has an effect on the cell by which it is secreted.
21
Q
What does paracrine mean?
A
Relating to a hormone which has effect only in the vicinity of the gland secreting it.
22
Q
What does endocrine mean?
A
Relating to glands which secrete hormones or other products directly into the blood.
23
Q
What is a fluid-phase recognition molecule?
A
Collectins.
- C-type lectin family
- Mannan-bindng lectin
- Surfactant protein A / D
24
Q
What is the function of fluid-phase recognition molecules? (3)
A
- Recognise carbohydrates
- Neutralisation of pathogens
- Recruitment of adaptive response
25
What do fluid-phase recognition molecules bind via?
Carbohydrate-recognition domains (CRDs).
26
How many carbohydrate-recognition domains does mannose-binding lectin have?
2-6 clusters.
27
What are the main innate immune pathways? (3)
- Classical
- Mannose-binding lectin
- Alternative
28
What is the role of IL1?
Initial cytokine >> unwell, muscle ache, etc.
29
What does IL1 target? (3)
- Endothelia
- Hepatocytes
- Hypothalamus
30
When are TNF and IL6 produced?
Early infection.
31
What does TNF target? (4)
- Endothelia
- Hepatocytes
- Hypothalamus
- Neutrophils
32
Adaptive immune response; what happens when a lymphocyte comes into contact with its specific antigen?
Clonal expansion.
33
What happens in primary lymphoid organs?
Lymphocytes develop and mature.
34
What are the primary lymphoid organs? (2)
- Bone marrow (B cells)
| - Thymus (T cells)
35
What happens in secondary lymphoid organs?
Initiate adaptive immune response and lymphocyte activation.
36
What are the secondary lymphoid organs? (3)
- Spleen
- Lymph nodes
- Mucosal surfaces
37
What is the range of antigenic variability?
10^9.
38
How many genes does the human genome contain?
30,000.
39
How is diversity increased in human antigen receptors?
VDJ recombination.
40
What is the mechanism of antigen presentation?
```
Antigens are internalised
>> broken down into peptides
>> peptides associated with class 2 molecules
>> brought to cell surface
>> activate helper T cells
>> these produce cytokines
>> B cells, T cells, etc.
```
41
What are histocompatibility antigens?
Glycoproteins on mammalian cell surfaces.
| -make us unique
42
Where were histocompatibility antigens first found?
WBCs.
| -ABO blood groups on RBCs
43
What is another name for histocompatibility antigens?
Human leucocyte antigens (HLA).
- determine blood group
- used to match donors
44
How many classes of histocompatibility antigens are there?
TWO;
- class 1
- class 2
45
Name the class 1 histocompatibility antigens. (3)
HLA-A
HLA-B
HLA-C
46
Name the class 2 histocompatibility antigens. (3)
HLA-DP
HLA-DQ
HLA-DR
47
What are MHC proteins?
Cell surface proteins that present antigenic peptides to T cells.
48
What type of T cell do MHC class 1 proteins present peptide to?
Cytotoxic T cells.
49
What type of T cell do MHC class 2 proteins present peptide to?
Helper T cells.
50
What is the function of B lymphocytes?
Produce and secrete antibodies.
| -humoral immunity
51
What is the function of cytotoxic T lymphocytes?
Kills infected/damaged cells.
| -cellular immunity
52
What is the function of helper T lymphocytes?
Secrete cytokines >> control immune response.
| -help B and T lymphocytes
53
What is the function of suppressor T lymphocytes?
Dampen down the immune repsonse.
54
How does binding of antibodies to antigens inactivate them? (4)
-Neutralisation
-Agglutination of microbes
-Precipitation of antigens
(these 3 >> PHAGOCYTOSIS)
-Activation of complement system
(>>cell lysis)
55
What is agglutination?
Clumping of particles.
56
What protein secreted by cytotoxic T cells makes holes in the infected cell's membrane.
Perforin.
57
What is immunosuppression?
Reduced activation or efficacy of the immune system.
| -can result in immunodeficiency
58
What is immunodeficiency?
Lack of an efficient immune system-susceptibility to infections.
59
What are the main uses of immunosupression? (3)
- Transplant rejection
- Autoimmune disease
- Lymphoproliferative diseases
60
What is hypersensitivity?
Undesirable, sometime fatal, reactions produced by normal immune system against innocuous antigens in a pre-sensitised host.
61
What does innocuous mean?
Not harmful/offensive.
62
What are the 4 types of hypersensitivity reactions?
I - IgE mediated
II - cytotoxic
III - immune complex
IV - cell mediated
63
What is another name for a severe type 1 (IgE mediated) reaction?
Anaphylactic.
64
What is the general process of a type I hypersensitivity reaction?
IgE mediated mast cell and basophil degranulation
>> release of inflammatory mediators (e.g. histamine)
>> and synthesis of lipid mediators (e.g. leukotrienes)
65
What are the main clinical features of a Type I hypersensitivity reaction? (3)
- Fast onset (15-30 mins)
- Weal and flare
- Can have 2nd phase response
66
What are the common antigens associated with a Type I hypersensitivity reaction?
- Pollen
- Bee venom
- Animal fur
67
What common diseases are associated with Type I hypersensitivity reaction?
- Hay fever
- Allergic asthma
- Dermatitis
- Food allergies
68
How is IgE produced?
By plasma cells under the control of IL-4 and CD40L-CD40 interaction.
69
How high are IgE serum levels?
Extremely low.
| -but high affinity receptor (FcR1) on mast cells and basophils
70
What are the 2 types of response associated with Type I hypersensitivity reactions?
- Early phase response
| - Late phase response
71
What is the general process of the early phase response?
Mast cell activation (FcR1)
| >> degranulation (release of pre-formed mediators) and synthesis of lipid mediators.
72
How are mast cells activated in Type I hypersensitivity reactions?
Cross-linking of FcR1 by allergen >> activation.
73
Name 3 common pre-formed mediators involved in Type I hypersensitivity reactions.
- Histamine
- Kallikrein
- Tryptase
74
What is the main action of histamine? (2)
- Smooth muscle contraction
| - Increased vascular permeability
75
What is the main action of kallikrein?
Activate bradykinin.
| -similar actions to histamine
76
What lipid mediators are synthesised from arachidonic acid? (2)
- Leukotrienes
| - Prostaglandins (e.g. thromboxane)
77
What are the main cells involved in the late phase response? (3)
- Basophils
- Eosinophils
- T cells
78
What is the role of basophils in the late phase response?
Similar to mast cells but over a longer time period.
| -release of mediators
79
What is the role of eosinophils in the late phase response?
Attracted to sites of allergic inflammation by chemokines
>> release contents of granules (cytotoxic proteins)
>> tissue damage
80
What is the role of T cells in Type I hypersensitivity reactions?
Produce cytokines once activated.
| -involved in both early and late phase responses
81
What is a major source of pathogenesis in allergic responses?
Cytokine-driven activity.
82
What type of reaction are Type II hypersensitivity reactions?
Antibody-mediated cytotoxic reactions.
83
What is the process of Type II hypersensitivity reactions?
Antibodies bind to antigen on cell membrane;
- activation of complement cascade >> cell lysis
- Aggregation of Fc portions >> opsonisation/phagocytosis/destruction
84
What are Type II hypersensitivity reactions initiated by? (2)
- IgM
| - complement-binding IgG
85
Which is more efficient; IgM or IgG?
IgM.
| -pentavalent
86
Which requires multiple binding; IgM or IgG?
IgG.
87
What sort of cells are normally affected by Type II hypersensitivity reactions?
Haematopoietic cells.
88
What common disorders are associated with Type II hypersensitivity reactions?
- Blood group incompatibility
- Autoimmune haemolytic anaemias
- Affects neutrophils and platelets
89
What sort of reactions are Type III hypersensitivity reactions?
Immune complex reactions.
90
What is the general process of Type III hypersensitivity reactions?
```
Ig + Ab = AgAb complex
>> FcR bind C1q
>> complement activation
>> C5a attracts neutrophils
>> C3b opsonin
>> phagocytosis of complexes (enzymes released)
>> TISSUE DAMAGE.
```
91
What are the types of inactivation caused by antibody-mediated immunopathology? (3)
- DIRECT (e.g. B12 deficiency)
- INDIRECT (e.g. binding to hormones >> AgAb complex clearance)
- RECEPTOR BLOCKADE
92
What sort of reactions are Type IV hypersensitivity reactions?
T cell mediated reactions.
93
What is the general process of Type IV hypersensitivity reactions?
Initial perivascular infiltration of lymphocytes and monocytes
>> Langerhan's cells present antigen to T cells
>> T cells release cytokines
>> recruit macrophages
>> TISSUE DAMAGE
94
What do Type IV hypersensitivity reactions require?
Previous exposure to the antigen.
95
Give an example of a skin condition caused by T cell mediated cytotoxicity (Type IV).
Contact dermatitis.
-Nickel, poison ivy
>> DTH and cytotoxic reaction
96
What type of hypersensitivity reaction causes granulomatous reactions?
Type IV hypersensitivity reactions.
97
What are granulomas?
Collections of inflammatory cells (macrophages/lymphocytes) in tissues.
-IL2 release critical in initation of response
98
What causes granulomatous diseases?
- INFECTIONS (e.g. TB, leprosy)
| - UNKNOWN (e.g. sarcoidosis, Crohn's)
