Immunology Flashcards
(133 cards)
1
Q
Innate immunity
A
Instinctive
Non-specific response
Not dependent on lymphycoytes
Present from birth
2
Q
Adaptive immunity
A
Specific
Acquired/learned
Memory
Requires lymphocytes and ab
3
Q
Blood sample consists of
A
Centrifuge forms 2 layers:
Upper - plasma, straw-coloured
Middle - Leukocytes, White fluffy
4
Q
Leukocytes
A
Lymphocytes
Phagocytes
Auxillary cells
5
Q
Origin of leukocyte cells
A
Multipotent hematopoietic stem cell (haemocytoblast)
6
Q
Leukocyte cell differentiation goes through
A
Bone marrow to thymus to blood
7
Q
Cells of immune system
A
Polymorphonuclear leukocytes (Neutrophil (neutral stain-liking), eosinophil (acidic-stain liking), basophil (basic-stain liking)) Mononuclear leukocytes (Monocyte (kidney shaped nuclei), T-cells, B-cells)
8
Q
When monocytes matures through tissues into blood it becomes
A
Macrophage
9
Q
T cell types
A
T-regs
T-helper
Cytotoxic
Th17
10
Q
B-cells become activated into
A
Plasma cells
11
Q
Other leukocytes
A
Mast cells Natural killer cells |(specialised T cells) Dendritic cell Kupffer cell - liver Langerhans - skin
12
Q
Soluble factors
A
Complement
Antibodies
Cytokines and chemokines
13
Q
Complement
A
Group of 20 serum proteins secreted by liver that need to be activated to be functional
Modes of action - Direct lysis, attract leukocytes to site
14
Q
Antibodies
A
Immunuglobulins
15
Q
IgG
A
Y-shaped
Constant and variable regions
Most predominant Ig in human serum - 70-75%
16
Q
IgM
A
Pentamer-shaped
10% of Ig in serum
Mainly found in blood, too big to cross endothelium
Mainly primary response
17
Q
IgA
A
15% of Ig in serum
Monomer
Mucous secretions such as saliva
Secretory component sticks them together
18
Q
IgE
A
0.05% of Ig in serum
Basophils and mast cells
Allergic reactions
19
Q
Cytokines
A
[roteins secreted by immune and non-immune cells
Interferon - viral infections (alpha, beta and gamma)
alpha and beta - virus infected cells
gamma - activated th1 cells
Interleukins - IL1 (Pro-inflam), IL10 (Anti-inflam)
Colony stimulating factors - stimulate bone marrow to produce leukocyte precursors
TNF alpha and beta - Mediate inflam and cytotoxic reactions
20
Q
Chemokines
A
Chemotactic cytokines Tell leukocytes where to go in body Group of 40 proteins CXCL - Attract neutrophils CCL - Attract monocytes, lymphocytes, eosniphils, basophils CX3CL - attract T and NK cells XCL - attract T cells
21
Q
Innate immunity
A
1st line of defence non-specific barrier to antigen instinctive present from birth slow response no memory
22
Q
adaptive immunity
A
specific to antigen
learnt behaviour
memory to specific antigen
quicker response
23
Q
Innate immunity cells
A
Neutrophils and macrophages
complement
24
Q
Innate immunity physical barriers
A
skin
bronchi - mucus, cilia
gut - acid
25
Inflammatory response
breach of barrier (tissue damage or infection during trauma)
Response - coagulation (stop bleeding), acute inflam (leukocyte recruitment), kill pathogens, neutralise toxins, limit pathogen spread, clear pathogens/dead cells, proliferation of cells to repair damage, remove blood clot (remodel extracellular matrix, re-establish normal structure and function of tissue
26
Inflamamtion
Series of reactions that brings cells and molecules of the immune sytem to sites of infection or damage
Hallmarks - Increased blood supply, increased vascular permeability, increased leukocyte extravasation
27
Acute inflammation
complete elimination of a pathogen followed by resolution of damage, diappearance of leukocytes and full regen of tissue
28
Chronic inflam
persistent, un-resolved inflam
29
Sensing microbes
In blood - monocytes, neutrophils
In tissues - Macrophages, dendritic cells
PRR - Pattern recognition receptors (on cells)
PAMP - Pathogen-assocated molecular patterns (on microbe)
PRR bind to PAMP
TLR - Toll-like receptors
Lectin receptors
Scavenger receptor
30
Complement activation pathways
Classical - Ab bound to microbe
Alternative - C binds to microbe
Lectin - activated by mannose-binding lectin bound to microbe
31
Complement functions
Lysis of bacteria directly by MAC
Bond to bacterial membrane and coat it (opsonization)
Chemotaxis
32
Phagocytosis leukocytes
Macrophages, neutrophils, dendritic cells
33
Mechanisms of microbial killing
Oxygen-dependent - ROI (Reactive oxygen intermediates) - superoxides converted to hydrogen peroxide then OH free radical which kills bacterial DNA
Nitrix oxide - vasodilation (viagra) increase extravasation but also anti-microbial.
Oxygen independent - Lysozymes, proteins (defensins insert temslves into membranes), TNF.
34
Adaptive immunity
Antigen specificity and diversity
Immunological memory
Specific non-self recognition
35
Adaptive immunity
Cell mediated T cells - intracelular microbes
| Humoral B cells (Ab) - extracellular microbes
36
Adaptive immunity
Thymus - primary lymphid tissue (T cells)
Bone marrow - primary lymphoid tissue (B cells and APCs)
Spleen, lymph nodes, MALT - Secondary lymphoid tissue
37
Cell-mediated immunity
Interlay between APCs and T cells
Requires cell-to-cell contact
Also requires MHC (Major histocompatibility complex) and Instrinsic/extrinsic antigens
Recognise self or non self
38
T lymphocytes
Only respond to presented antigens
T cells that recognise self-antigens are killed in the foetal thymus (T cell selection)
TCR (T cell receptor) recognises foreign antigens in association with MHC
39
MHC
Display peptides from self or non-self proteins
40
MHC
Coded for by HLA genes (Human leukocyte antigen)
41
MHC 1 and 2
MHC 1 - Glycoproteins on all nucleated cells, Displays intrinsic antigens, CD8 Tc cells
MHC 2 - Glycoproteins only on APCs, Displays extrinsic antigens, CD4 Th cells
MHC 3 - Code for secreted proteins (complement)
42
Link between innate and adaptive immunity
MHC
43
T cell activation
T cell then: divides (clonal expansion), differentiates (matured/active), effector functions, memory cells
Can become CD4 (Th) or CD8 (Tc)
44
Tc activation
CD8 + MHC1 = Tc
45
Th1 activation
CD4 + MHC2 = Th1
46
Humoral adaptive immunity B cell activation
B cells express membrane-bound Ig (monomeric - IgM or IgD)
47
B cells that recognise self are killed in
Bone marrow
48
B cells present Ag to T cells via MHC
MHC 2
49
B cell division is known as
Clonal expansion
50
B cell differentiates into
```
Plasma cells (AFC - Antibody forming cell)
Memory B cells (Bm)
```
51
Lymphoid tissue of the body
Neck
Armpit
Groin
52
Antibody functions
Neutralise toxin by binding to it
Increase opsonisation - phagocytosis
Activate complement
53
Vaccination
Tetanus vaccination (tetnaus toxoid from clostridium tatni causes muscle spasms/contractions)
54
Handling of pathogens
Bacteria and fungi - phagocytosis and killing
| Viruses - Cellular shutdown, self-sacrifice, cellular resistance
55
Infection is associated with
Damage and injury
56
Patterns
```
Limited characteristics
Gram positive and negative
dsRNA (double stranded)
CpG motifs (DNA nucleotides)
```
57
Most important PRR
Toll-like receptors
58
PRR family
Secreted and circulating PRRs
| Cell-assocated PRRs
59
Secreted and circulating PRRs
Antimicrobial peptides secreted in lining fluids from epithelia and phagocytes (such as defensins and cathelicidins)
Lectins and collectins - carbohydrate-containing proteins that bind carbs or lipids in microbe walls, activate complement and improve phagocytosis
Mannose-binding lectin (deficiency syndromes
Pentraxins - proteins like CRP
60
Cell-associated PRRs
Receptors present on cell membrane
61
TLR 3, 7 and 9 respond to
Viral infections
62
TLR 4
Overactivation can lead to a dangerously high septic response
63
Membrane bound PRRs
Mannose receptor on macrophages (fungi)
64
Not all pathogens are extracellular
Viruses multiply in cytoplasm of cells
65
Nod-like receptors (NLR)
NOD2 - widespread expression, recognises MDP (a breakdown product of peptidoglycan), activates inflammatory signalling pathways. Non-functioning mutation is Crohns disease
66
RLRs
Cytoplasmic based receptor for viruses
| Rig1
67
Pattern recognition
Recognition of microbes and viruses depends on seeing ancient features of them
68
Homeostasis
Blood neutrophl members may be dependentupon TLR4 singalling, inpedendent of LPS in homeostasis
Induction of endotoxin tolerance in newborn gyt
maturation of normal immune system
maintaining a balance with commensal organisms
69
Damage recognition
TLRs recognise range of endogenous damage molecules
| TLR signalling by cellular damage prodcts activates immunity and initate antimocribal signallinh and reapir mechanisms
70
Damage molecules
Extracellular molecules - Fibrinogen
| Intracellular molecules - Heat shock proteins
71
PRRs in adaptive immunity
Activation of TLRs and other PRRs drives cytokine production by APCs that increase likelihood of successful T cell activation
TLR4 agonists used as vaccine adjuvants
72
PRRs and disease
recognition of host molecules in autoimmune disease
73
Translation to therapy
Enhance TLR signaling - improve immunity with adjuvants
| Inhibit TLR signaling - sepsis syndromes, inflammation, arthritis
74
2 greatest public health interventions globally
Vaccines
| Clean water
75
Poliomyelitis
Flu-like symptoms
76
HIV-1 treatment
Antiretrovirals (AZT)
77
Ebola
Highly contagious
New strains emerge at any time
High death rates
Vaccine under approval after phase 3 trial
78
Smallpox
Variolation - scratches on the arm inoculated with pus from a pustule
79
Passive immunisation
Transfer of preformed antibodies
Natural - maternal ab across placenta to developing foetus/breast milk. Provides protection against Diptheria, tetanus, rubella, mumps, poliovirus
Artifical - Pooled normal human IgG or immunoserum against pathogens/toxins
Usually during acute danger or infection that could cause serious complications
80
Passive immunisation disadvantage
Does not provide immunological memory so no long term protection
Possible allergic reactions to antisera (immunoserum)
81
Uses of passive immunisation
Anti-toxins
Prophylaxis
Anti-venins
82
Active immunisation
Manipulating immune system to generate peristent proteticve response against pathogens by safely mimicking natural infection
83
Active immunisation
Engage innate immune system
Elicit dnger signals and activat immune system, triggers such as PAMPs, TLRs
Activate specialist APC - e.g. Langerhans cells
Engage adaptive immune system - Generate memory B and T cells, activate T cell help
84
Influenza
Rapid onset
85
Annual escape variants
Require generation of new vaccines
86
Polio
Slow onset (3 days)
87
Choices of antigens for vaccine designs
```
Whole organism - live attenuated pathogen (BCG - for TB vaccines), killed/inactivated pathogen
Subunit - toxoids (toxins)
Peptides
DNA vaccines
Engineered virus
```
88
Pros and cons for each choice of antigen
Transport
Storage
Stability
Cost
89
Whole organism antigen pros and cons
Ad - Full natural immune response and memory
| Disad - Not advised for immunocompromised patients, ocassionally attenuated organism can revert to viral form also
90
Whole inactivated pathogen pros and cons
Ad - No risk of infection, storage is less critical
| Disad - Weak immune response and so requires repeated booster vaccinations
91
Subunit vaccines pros and cons
Ad - No risk of infection, easy storage
| Disad - Weak immune response, repeated boosters required
92
Toxoid
Heat treated or chemically modified to eliminate toxicity
93
Capsular polysaccharides
Interfere with phagocytes by blocking opsonisation
94
Subunit vaccines
Purified proteins - HepB surface antigen (HBsAg)
| Recombinant proteins
95
Synthetic peptides as vaccines
Peptides can be stimulatory or suppressive
96
DNA vaccines
Express genes from pathogens in host cells to generate immune response similar to natural infection
The expression vector is transfected into muscle cells leading to T and B cells memory responses
97
Recombinant vector vaccines
Initiate effects of transient infections with pathogen but using a non-pathogenic organism
98
Ebola vaccine
Vesicular stomatitis virus relative of rabies virus
99
Adjuvants
Substance added to vaccine to stimulate immune system
TLR agonists
Aluminum salts - form precipitates and potentiate opsonised phagocytosis
100
Ideal vaccine should
Be safe
Induce suitable immune response
Generrate B and T cell memory
Easy to store and transport
101
Virulence
Ability to cause disease once established
102
Invasiveness
Capacity to penetrate mucosal surfaces to reach normally sterile sites
103
Virulence factors
Microbial factors that cause disease
104
Pathogenicity
```
Adherence
Evade host defence
Translocation and invasion
Evade opsonisation and phagocytosis
Microbial and host derived factors, can lead to tissue damage
```
105
Host-pathogen interactions
Commensals
| Resident flora - overgrowth/translocation can cause disease
106
Opportunistic infections only arise if
Immune status becomes altered
107
Microbiome
Genome of all microbes (mostly in gut)
108
IBD (Inflammatory bowel disease)
Causes decreased gut bacterial diversity
Increased numbers of proteobacteria, decreased numbers of firmicutes and bacteroidetes
Faecal transplantation
109
Ebola main symptom
haemorrhagic fevers
110
Viral infections
Rapid cell entry
| Free virus in blood stream easily neutralised
111
Viral infections - blocks
IgA - blocks binding
IgM - agglutinates
Complement - opsonisation and lysis
GAM ab - blocks virus host cell fusion
112
Viral infections - Cell mediated response
Interferon - antiviral action
Cytotoxic T lymphocytes - kill infected cells
Natural killer cells and macrophages - further killing
113
Viral infections - body cells affected due to virus
Influenza virus to resp epithelium
Varicella zoster virus to skin cells
Yellow fever virus to liver cells
114
Viral evasion
Influenza changes coat antigen
HIV and rhinovirus show antigenic variation
Mumps, measles and EBC cause immune suppression
115
Influenza changes in coat antigens reults in
Antigenic drift
| Antigenic shift
116
Influenza
```
Spherical particles surrounded by lipid bilayer acquired from infected host cell
Glycoprotein projections
Haemagglutinin facilitates attachment
Neuraminidase facilitates viral budding
3 Types - A,B,C
```
117
HIV - Viral evasion
Viral infection of lymphocyte
118
EBV - Viral evasion
Cytokine imbalance
119
Adenovirus - Viral evasion
Synthesises proteins which bind to MHC
120
Pus
Dead white blood cells and bacteria
121
Bacterial infection
Enter host via resp, GI, GU tracts and skin breaks
122
Low virulence
Phagocytes
123
High virulence
Immune response stimulated
124
Extracellular bacteria
Antibody response
125
Intracellular bacteria
Cellular response
126
Some bacteria produce bacteriocins (peptides) to
Kill other bacteria
127
Adhesins
Secreted by bacteria to help them bind to mucosal surfaces
128
Biofilms
Bacteria can stick together on a surface by secreting an extracellular substance consisting of protein, polysaccharides, and DNA
Helps protect against antimicrobials
129
In TB there is prolonged DTH
Continuous macrophage activation forms a granuloma, macrophages adhere together, lytic enzyme release, tissue damage
130
PRR and PAMPs
PRR recognise PAMPs but also damage-associated molecular patterns from host cells
131
Bacterial evasion
Neisseria - secrete protease lyses IgA
N. Gonorrhoea - Pilli, antigenic variation
Strep pyogenes - M protein inhibits phagocytosis
Mycobacterium - Escape from the phagolysosome
132
Protozoan infection
Blood stage - humoral immunity
| Tissue stage - cell-mediated immunity
133
Worm infection
Helminths
The immune response is not sufficient enough to kill these worms
Interleukin 5 is main mechanism
