Intro to immunology Flashcards
1
Q
Primary function of immune system
A
Eliminate pathogens
Minimise damage they cause
2
Q
How are foreign substances recognised by the immune system
A
Antigens are ANTIbody GENerators
3
Q
Clonal selection
A
Maturation into mature and genetically committed cells in bone marrow
Antigen-dependent proliferation and differentiation into plasma and memory cells in peripheral lymphoid tissue
4
Q
How is the immune response tailored to viruses and intracellular bacteria
A
Identification and killing of infected cells by cytotoxic T cells
5
Q
How is the immune response tailored to extracellular fungi, parasites, bacteria
A
Detection of surface structures by antibodies and destruction by phagocytes
6
Q
How is the immune response tailored to large parasites
A
Deposition of toxic substances or killing by mast cells/eosinophils
7
Q
How is the immune response tailored to immunoprivilged areas
A
No response as infl would be caused, damaging the tissues
8
Q
Immunoprivileged areas
A
CNS
Eyes
Placenta
Reproductive organs
9
Q
Commensal bacteria
A
Bacteria that the body has learnt to tolerate - esp in gut
2 kg in whole body
10
Q
Levels of defence in immune system
A
External defences
Innate immune system - ‘primitive’
Adaptive immune system - highly spp
11
Q
Exterior defences of body
A
Ear Eyes Nasal cavity Skin Urethra Anus Vagina Stomach Trachea and bronchi Mouth cavity
12
Q
Ear as a defence
A
Cerumen inhibits bacterial growth
13
Q
Eyes as a defence
A
Cleansed by tears which also contain antibacterial chemicals
14
Q
Nasal cavity as a defence
A
Hairs and mucus traps organisms
15
Q
Skin as a defence
A
Impervious barrier
16
Q
Urethra as a defence
A
Urine flow prevents bacterial growth
17
Q
Anus as a defence
A
Mucous membrane traps microorganisms
18
Q
Vagina as a defence
A
Acidic secretion inhibits growth of pathogens
19
Q
Stomach as a defence
A
Acidic juices kill many microorganisms
20
Q
Trachea and bronchi as a defence
A
Mucous layer traps microorganisms
21
Q
Mouth cavity as a defence
A
Mucous membrane traps microorganisms and the mouth is cleaned by saliva
22
Q
Innate vs adaptive immune system
A
Non-spp vs spp
Fast response (mins) vs slow (days)
No memory vs memory
23
Q
Immune dysregulation
A
Balance between activation and suppression
24
Q
Types of immune dysregulation
A
Hypersensitivity
Autoimmunity
Immunodeficiency
25
Hypersensitivity
Overaction to benign antigen
| Can be presented as anaphylactic shock
26
Types of hypersensitivity
I - IV
| Type I is allergy e.g. hay fever, asthma, hives, eczema
27
What are allergies mediated by
Particular immunoglobulin, IgE and mast cells
28
Anaphylactic shock
Severe, life-threatening, allergic response
29
Tolerance
Immune system distinguishing between 'self' and 'non-self'
30
What typically happens to self-reactive immune cells
Eliminated by immune system, either in thymus or bone marrow before it reaches the bloodstream
31
What is autoimmunity caused by
Breakdown of tolerance
| Certain genetic and environmental factors can make you predisposed
32
Examples of autoimmunity
Multiple sclerosis - immune system attack against nerve sheaths on brain/CNS leading to neuromuscular dysfunction
Crohn's disease - attack on microbiota/ gut epithelium --> poor food absorption
33
Immunodeficiency
Component of innate/ adaptive immune system absent or defective
34
Primary immunodeficiency
Inherited
35
Most common form of primary immunodeficiency
Severe Combined Immunodeficiency (SCID) - no functional adaptive immunity, has low life expectancy
36
Secondary immunodeficiency
Caused by damage by external agents
37
Most common form of secondary immunodeficiency
Acquired Immune Deficiency Syndrome (AIDS) - Infection w/ HIV, destruction of Thelper cells --> death by opportunistic infections
38
Challenges w/ immune system
Transplantation
| Cancer
39
Why does cancer present as a challenge for the immune system
Cancer cells display self-antigen (tolerated) as they are derived from own body and tumour-spp antigens (recognised)
Cancer cells evade immune response by rapid change (mutations) and active inhibition
Immunotherapies against cancer boost body’s natural defences
40
Primary tissues and organs of the immune system
```
Development and maturation of adaptive immune cells (lymphocytes)
Bone marrow (B cells) and thymus gland (T cells)
```
41
Secondary tissues and organs of the immune system
Mature lymphocytes meet pathogens
| Spleen, adenoids, tonsils, appendix, lymph nodes, Peyer's patches, MALT
42
MALT
Mucosa Associated lymphoid tissue
43
How are lymph nodes placed
Strategically around the body as they act as 'meeting place' for immune cells
44
What happens at lymph nodes
Pathogens from infected tissue sites are picked up by dendritic cells and arrive at closest lymph node
Circulating T and B cells enter and congregate at spp regions in lymphoid follicles
If they encounter a 'matching' dendritic cells, they're activated and proliferate
45
Where do B cells congregate in the lymphoid follicle
Cortex
46
Where to T cells congregate in the lymphoid follicle
Paracortex
47
What changes occur to the lymph node after activation of lymphocytes
Architecture
| Size of the node
48
What other tissues/organs contain organised lymphoid tissues
Spleen and MALT
49
Haemotopoiesis
'Making of blood'
How immune cells are generated
Takes place in the bone marrow after birth
50
What determines what multipotent stem cells in the blood differentiate into
The growth factors received by the myeloid or lymphoid progenitors
51
Where do monocytes differentiate into macrophages
Circulate in blood before migrating to tissues
52
Why do the names of macrophages change
Depending on where they're found
53
Alveolar macrophages
Found in lung
54
Histocytes
Macrophages found in connective tissues
55
Mesangial cells
Macrophages found in the kidneys
56
MIcroglial cells
Macrophages found in the brain
57
Kupffer cells
Macrophages found in the liver
58
Function of macrophages
Phagocytosis
| Antigen presentation
59
Process of phagocytosis
Bacterium becomes attached to pseudopodia
Bacterium is ingested, forming phagosome
Phagosome fuses w/ lysosome
Lysosomal enzymes digest captured material
Digestion products are released from the cell
60
Pseudopodia
Membrane invaginations
61
Endogenous pathway of antigen presenting
```
Ag presentation to cytotoxic T cells via MHC class I
CD8
```
62
Exogenous pathways of antigen presenting
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Ag presentation to helper T cells via MHC class II
CD4
```
63
Why do dendritic cells have lower degradation potential
Better APC's than macrophages
| Leads to antigen preservation
64
Immature dendritic cells
Antigen uptake in peripheral tissues
65
Mature dendritic cells
Migration to lymph nodes and Ag presentation
66
What do dendritic cells activate
Adaptive immune response after finding matching T or B cell
67
Granulocytes
Contain granules and have multi-lobed nucleus
| Neutrophils, basophils, eosinophils
68
Stained eosinophils colour
Appear pink
69
Stained basophils colour
Appear blue
70
Stained neutrophils colour
Appear purple
71
PMN
Polymorphonuclear neutrophils
72
What % of circulating granulocytes is made up by neutrophils
95%
73
How are macrophages similar to neutrophils
Both phagocytose bacteria but much shorter lived (few days - die after phagocytosis)
74
Chemotaxis of neutrophils
Attracted by IL-8
| Follows to site of infection
75
How do neutrophils kill and digest bacteria
Netosis
Release nuclear elastase from granules (antimicrobial)
NE goes to nucleus, chromatin expands and is relegated from the cell to capture bacteria
76
What do eosinophils, basophils and mast cells kill
Larger parasites e.g worms
These are coated by IgE and this allows target recognition - corresponding receptor
Attach to parasite and starts degranulation and release of toxic contents (histamines, proteases)
77
Eosinophils, basophils and mast cells association w/ allergies
IgE
Overreaction to harmless antigens e.g dust mites' compounds
Release cytotoxic compounds, histamine --> infl
78
Abundance of NK cells in the blood lymphocytes
5-10%
79
How do certain viruses and cancer stop Ag presentation
```
Down regulation of MHC class I
Infected cell has lack of MHC class I molecules
NK cell receives only +ve signals --> becomes activated
```
80
Generative lymphoid organs
Bone marrow
| Brain
81
Peripheral lymphoid organs
Lymph nodes
Spleen
Mucosal and cutaneous lymphoid tissues
82
Types of T helper cells
Th1 cells help macrophages digest pathogens
Th2 cells help B cells to produce antibodies
CD4 involved in Class II MHC pathway
83
Class I MHC pathways
CD8 (cytotoxic T cells) kill virus-infected cells
84
Innate barriers to infections
Mucosal surfaces
85
Features of mucosal surfaces
Tight junctions in epithelial layers
| Goblet cells, Paneth cells secrete antimicrobial peptides and enzymes and mucus
86
Cells involved in innate immune system
```
Dendritic cells
Macrophages
Mast cels
NK cells
Granulocytes
```
87
Cells involved in adaptive immune system
B cells
T cells
CD4+ T cell and CD8+ T cell
88
Steps in innate immunity
Recognition
Disposal
Communication
89
Recognition in innate immunity
PAMPs and DAMPs
90
PAMPs
Pathogen Associated Molecular Pathways
| Signal production of cytokines to stimulate immune cells
91
What are PAMPs recognised by
Toll-like receptors on macrophages, neutrophils, epithelial cells of gut and lung
92
Where are PAMPs found
Plasma membrane
| In endosomes/ phagosomes
93
How do we recognise microbes despite their rapid evolution
Using highly conserved and essential features that are different to us e.g cell walls (peptidoglycan), nucleic acids (CpG DNA), sugars (lipopolysaccharides, mannam), flagella
94
DAMP
Damage Associated Molecular Pattern
95
Disposal in innate immune system
Microbes killed by phagocytic cells
| Broken up into common units presented to immune system
96
Recognition by complements
Uses 30 diff proteins
3 main pathways: lectin, classical and alternative
Leads to infl, phagocytosis and MAC (membrane attack complex)
97
Activation of lectin pathways
Microbial sugars (yeasts and bacteria)
98
Activation of classical pathways
Antibodies
99
Acute phase proteins
Produced in liver in response to infl
| Liver is stimulated by IL1, IL6 and TNF
100
Adjuvant
Parts of a pathogen used to activate innate cells in immune systems (macrophages, dendritic cells)
101
Role of IgG
Antibodies bind Fc receptors to activate immune defence
IgG is secreted into blood and removed pathogens from blood and tissues
IgG binds pathogen w/ variable region, leaving Fc domains exposed. Fc domains cluster to generate a recruitment signal
102
What do Fc domains recruit
Complement --> lysis of pathogens (MAC)
103
What does Fc binding to Fc receptors lead to
Binding to Fc receptors on macrophages leads to phagocytosis and killing in lysosomes
Can be helped by complement
104
Opsoninisation and Fc
Phagocytic cells carry Fc receptors and also receptors for complement
Fc domains exposed by antibody on pathogen allows recognition by phagocytic cells
Fc receptors interactions trigger phagocytosis by releasing proteosomes or ROS
105
ROS
Reactive oxygen species
106
What is IgA made and secreted by
B cells in response to infection of mucosal surfaces but doesn't stay in blood
107
Role of IgA
IgA binds an IgA receptor and is secreted across epithelial cells (protects mucosal surfaces)
Tail of IgA binds to an IgA receptor and this complex is then able to bind to pathogens that haven't entered body
108
IgE receptors
Found on mast cells, eosinophils and basophils
109
What does IgE define
The Ag spp of mast cells, eosinophils and basophils, allowing them to recognise Ag
110
Joining chain
Protein linking two IgA molecules
111
Why do mast cells release histamine
To open up the sites of parasite infections to the rest of the immune system
112
What do eosinophils release
```
Peroxidase
Ribonucleases
Deoxyribonuclease
Lipase
Plasminogen
```
113
What is the same for each subtype of antibody
'Variable' region
114
Why do the Fc domains differ
Differences in coding sequences but lies in same Ig gene
115
Which molecules have variable and constant regions
Antibodies
| T-cell receptors
116
What does the constant region bind
Fc receptors
117
T cell receptors
Stay attached to the surface of the T cells
118
Granules in cytotoxic T cells
Contain enzymes e.g perforins are released into the space between the T-cell and infected cells
119
Repeated sequences in Ig genes
Variable region
Diversity region
Joining region
120
What does gene rearrangement allow
One of the duplicated sequences in each region to be used to make the protein
121
1st gene rearrangements
```
Select diversity and joining regions
Constant region (Fc) is constant
```
122
2nd gene rearrangements
Selects the variable region and the constant regions (Fc) is constant
123
VDJ recombination
Brings one of the remaining variable sequences next to the DJ combi, genes within the loop are removed by RAG proteins
124
What does VDJ recombination provide
Antibody and T-cell diversity
125
Rearrangement of T-cell receptors
Creates diversity
| Only rearranges once and only on one chromosome
126
Rearrangement of T and B cells
Rearrange genes at random and each cell can only rearrange genes once
127
What happens to the T-cells that have rearranged the right genes segments
Bind Ag ---> triggers cell division (clonal expansion)
128
What happens to the T-cells that don't rearrange the right gene segments
Can't bind antigen so they die
129
How do B-cells get T-cells help
By becoming APC's
130
What happens when T-cells and B-cells agree on the antigen
The T-cell is activated by the T-cell receptor
The T-cells then express ligands that can bind to B-cells
Co-stimulation
131
What does co-stimulation induce
Cytokine secretion from the T-cell
132
Plasma cells and memory cells
Plasma B cells proliferate to make antibodies secreted into bloodstream – remove the membrane anchor and secrete immunoglobulin
Memory B cells retain the membrane bound receptor and can keep communicating w/ T-cells
Diff cytokines released by T helper cells drives diff types of B-cells
133
What does IL4 drive
Memory B cells
134
What does IL10 drive
Plasma cells
135
When does antibody class switching occur
Once VDJ recombination is complete
136
Features of IgM
Seen in primary immune response
| Low affinity, broad specificity
137
How is IgM produced
Signals for the B-cell receptor and cytokine trigger the removal of the membrane anchor
The mu region is added
138
2nd antibody class switch
Replaces membrane anchor w/ gamma sequence to make IgG
139
Features of IgG
Seen in secondary immune repose
| High affinity, narrow specificity
140
Antibody classes
Mu - IgM
Gamma - IgG
Alpha - IgA
Epsilon - IgE
Followed by membrane anchor
141
How are isotopes generated
Switching of constant domains during recombination
| Uses same variable regions
142
What is isotype switching controlled by
Cytokine secretion from Thelper cells
143
Which interleukins control isotype switching for IgG
IL4
| IL6
144
Which cytokines control isotype switching for IgA
IL5
| TGF beta
145
Which interleukin controls isotype switching for IgE
IL4
