ICS - IMMUNOLOGY Flashcards
1
Q
What is haematopoiesis?
A
Formation of red and white blood cells
2
Q
What types of barriers make up the innate immune response - give examples of this
A
Physical barriers - Skin, gut lining, Ciliated Epithelia of airways
Chemical - Stomach and Vaginal low pH, and lysozymes in tears - break down bacteria cell walls
3
Q
What are the 2 branches of the immune system?
A
Innate and adaptive
4
Q
Give some features of the innate immune system
A
- Non - specific
- Resistance is not improved by repeat infections
- Instinctive
- Short lasted (days)
- No memory
- Involves Myeloblasts (Basophil Neutrophil and Eosinophil) and Macrophages
- Present from birth
5
Q
Give some features of the adaptive immune system
A
Specific ‘Acquired’ immunity
* Requires lymphocytes
* Antibodies involved
* Resistance is improved by repeat infection
* Slower response (days-weeks)
* B lymphocytes & T lymphocytes
6
Q
What is the cell from which all WBCs and RBCs are made from?
A
Haematocytoblast
7
Q
What is the function of lysozyme?
A
It destroys bacterial cell walls.
8
Q
Give examples of 3 polymorphonuclear leukocytes.
A
- Neutrophils.
- Basophils.
- Eosinophils.
9
Q
Give examples of 3 mononuclear leukocytes.
A
- Monocytes.
- B lymphocytes.
- T lymphocytes.
10
Q
What are the two cells that a Haematocytoblast gives rise to?
A
Common Myeloid Progenitor
Common Lymphoid Progenitor
11
Q
What cells do Common Myeloid Progenitors give rise to?
A
Erythrocyte (RBC)
Mast Cell
Megakaryocyte
Myeloblast
EMMM
12
Q
What cells do Myeloblasts give rise to?
A
- Neutrophil
- Basophil
- Eoisinophil
- Monocytes
13
Q
What do Monocytes give rise to?
A
Macrophages and Dendritic cells
14
Q
What cells do common lymphoid progenitor cells give rise to?
A
Natural killer cells
B Lymphocyte
T Lymphocyte
15
Q
What cell does a B lymphocyte give rise to? What does this cell do?
A
Plasma cells, that release antibodies
16
Q
In which primary lymphoid tissue do T cells mature?
A
Thymus.
17
Q
In which primary lymphoid tissue do B cells mature?
A
Bone marrow.
18
Q
What do neutrophils do in innate immunity
A
They Phagocytose
Can either use cytoplasmic granules, or
Oxidative Burst, where Neutrophil produces lots of ROS - Destroy themselves and engulfed pathogens
Make up 70% of WBC
19
Q
What is serum?
A
The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed.
20
Q
Describe the role of eosinophils
A
Make up 5% of blood
Lifespan: 8-12 days
Stain Pink with Eosin
Phagocytic
Known for fighting Parasites
Larger than neutrophils
21
Q
What is the difference between a macrophage and a monocyte?
A
Monocytes are found in the blood and then differentiate into macrophages or dendritic cells in tissue
22
Q
Describe the neutrophil innate immune response
A
Engulf pathogens using phagocytosis, FORMING PHAGOSOME
Granules in neutrophil FUSE TO FORM PHAGOLYSOSOME, causes it to become acidic (kills 2% of pathogens)
Neutrophil continues to engulf more pathogens
Once neutrophil is full, an oxidative burst occurs
These highly reactive oxygen species kill neutrophil but also the pathogens engulfed
23
Q
Describe the role of basophils
A
Make up 2% of blood
Lifespan: 2 days
Similar to mast cells involved in allergic reactions
High affinity for IgE, when IgE binds, they DEGRANULATE, RELEASSING HISTAMINE
24
Q
How are basophils involved in allergic reactions?
A
They have high affinity IgE receptors
Binding of IgE to receptor results in de-granulation releasing histamine
25
What is the difference between mast cells and basophils?
Mast cells are in fixed tissue, whereas basophils are able to circulate around the body
26
What are the 3 categories of Soluble factors
Complement factors
Antibodies
Cytokines, Chemokines
27
What are complement factors? What do they do?
Group of ~20 serum proteins secreted by the liver that need to be activated to be functional.
They are activated only as part of the immune response – 3 activation pathways
Modes of action:
- Direct lysis - via MACs
- Attract more Leukocytes to site of infection (C3a and C5a, chemotaxis)
- Coat invading organism (make them easier to eat by phagocytes, C3b) ==> opsonization
28
Where do antibodies come from? What are they, effectively?
Antibodies - Immunoglobulins, **act as adapter that links a microbe to a phagocyte.** - or , A **blood protein produced in response** to and counteracting a specific antigen
Antigen is presented to them, often by T Helper cell, links to a B cell receptor - this turns into a plasma cell, that secrete antibodies, which can bind to the specific antigen it was presented with
***Basically just B cell receptor in secreted form***
29
What do antibodies do?
Circulate in the serum (noncellular part of the blood) and MARK PATHOGENS FOR DESTRUCTION
They act as an adapter that links a microbe to a phagocyte
SO ANTIBODIES AREN'T BOUND TO CELLS AND FLOAT FREELY IN THE BLOOD
30
What are cytokines? What do they do? Name some key ones
Cytokines - proteins secreted by immune and non-immune cells, signal immune cells to move to the site of inflammation
Interferons
Interleukins
Colony Stimulating factors
Tumour Necrosis Factors
Chemoknies
31
specific cytokines: What do interferons do?
Inducer a state of antiviral resistance in uninfected cells
32
What do colony stimulating factors do?
Involved in directing the division and differentiation of bone marrow stem cells – precursors of leukocytes
aka specific CSF will stimulate/signal the growth of specific leukocytes
33
What do chemokines do?
attract Leukocytes, that travel along chemokine concentration gradient
34
What are interleukins
Can cause cells to divide, to differentiate and to secrete factors
Can be pro-inflammatory (eg. IL1) or anti-inflammatory (eg. IL-10)
DDS - Divide, Differentiate, Secrete
35
What substance causes endothelial cells to become sticky? What secretes this substance?
TNFa, secreted by macrophages in the infected tissue.
36
How does the body recognise bacteria that is foreign?
PAMPs = Pathogenic Assocaited Molecular Patterns - Patterns on microbes that are different to ours
37
What senses microbes in
a) Blood
b) Tissues?
In blood – Monocytes, Neutrophils
In tissues – Macrophages, Dendritic cells
38
What links the innate and adpative immune systems together?
The displaying of antigens by phagosomes on MHCs, can then present the antigen to the lymphocytes
39
Name the 3 antigen presenting cells
Macrophages
Dendritic Cell
B cells
40
Why can't T cells recognise your own cells?
T cells that recognise self are killed in the foetal thymus as they mature (called T cell selection)
41
What are the 2 types of antigens?
Intrinsic/Intracellular (in the cells eg Virus)
or
Extrinsic/Extracellular
42
For extrinsic antigens, what is do they use class I or II MHC? Do they need Antigen Presenting cells or can they use any? What T Cells do they use?
Class II MHC, Uses APCs only. Uses T helper cell (CD4)
43
For intrinsic antigens, do they use class I or II MHC? Do they need Antigen Presenting cells or can they use any? What T Cells do they use?
Class I MHC, presented on all cells. Uses T Cytotoxic CD8 Cells
44
Describe the role of T lymphocytes
Can they recognise soluble antigens?
Make up 10% of blood
Lifespan: hours-years
In charge of cell mediated immunity - antigen specific
**Can’t recognise soluable antigens**
45
Where do T lymphocytes originate and mature
They originate in bone marrow and mature in the thymus
46
What are B cells?
What do they do?
What MHC do they contain?
Do they need an MHC?
Have receptors on surface but **don’t need MHC**
Can bind to any antigen that has shape specific to their receptors
**Contain MHC II**
Can also:
- Perform phagocytosis
- Can be an antigen presenting cell
47
What happens when a T cell gets activated
It helps a B cell to transform into a plasma cell
48
How do T cells recognise antigens?
For T cells to recognise antigens they must be displayed by an antigen presenting cell and bound to MHC1/2.
**T cells can’t recognise soluble antigens.**
49
What is the function of T helper 1 (CD4)?
It helps the immune response against **intracellular pathogens.**
Secretes cytokines.
50
What is the function of T helper 2 (CD4)?
It helps produce antibodies against extracellular pathogens. Secretes cytokines.
51
What is the function of Cytotoxic T cell (CD8)?
It can kill cells directly by binding to antigens; they induce apoptosis.
52
What is the function of T reg (FoxP3)?
They regulate the immune response.
53
Which cells express MHC1?
All nucleated cells express MHC1. e.g. a virus infected or cancer cell would express MHC1.
54
Which cells express MHC2?
Antigen presenting cells ONLY e.g. macrophages, B cells, dendritic cells.
55
Which MHC would an extracellular antigen (exogenous) lead to the expression of?
MHC2.
56
Which MHC would an intracellular antigen (endogenous) lead to the expression of?
MHC1.
57
What does a helper T cell bind to?
The T cell receptor binds to **an antigen epitope which is bound to MHC2** on an APC.
See left hand picture
58
Which interleukin is secreted when a helper T cell is bound to a T cell receptor?
IL-2. This then binds to an IL-2 receptor on the T cell and produces a positive feedback mechanism leading to division and differentiation.
59
Describe the process of a T helper cell binding to a B cell.
So B cells - pick up an antigen form a pathogen and display it on **MHC 2** ===> T helper 2 cells bind to the B - cells via this, and **release cytokines that induces B cell Clonal expansion**
- so they differentiate into plasma cells and memory B cells
60
What do plasma cells secrete
Antibodies
61
Give 3 functions of antibodies.
Neutralise toxins.
Opsonisation.
Activate classical complement system.
62
What are the two main types of T cell
CD4+ (Helper)
CD8+ (Cytotoxic)
63
What CD are all T cells positive for?
CD3
64
What are CD4+ cells called and what do they do?
What MHC do they see
-They are called helper T cells
- They secrete cytokines that coordinate immune response
- Can only see antigens presented on an MHC II molecule
65
What are CD8+ cells called and what do they do?
They are called cytotoxic T cells
They kill target cells
Very specific killing (only kill cells with antigen presented on MHC I molecule)
66
What do antibodies consist of?
Two heavy chains, and two light chains
These form two regions that are joined together by a **disulphide bond**
see picture
67
What are the two different regions of an antibody?
Fragment antigen binding (Fab) (A variable region)
Constant fragment (fc) (stays the same)
68
What makes up the two different regions on an antibody?
The fab regions is made up of 1 of the light chains, and a part of one of the heavy chains.
The Constant fragment is made of the remainder of the heavy chain
There are two fab regions and two constant fragments
69
What chains determine the class of antibody?
Heavy chain
70
What are the 5 classes of antibodies?
IgG
IgA
IgM
IgE
IgD
GAMED
71
What are Natural Killer Cells? What do they do?
Large lymphocytes with granules
They target cells infected with intracellular organisms e.g., virus
They also target cancer cells
72
Describe how dendritic cells are involved in the immune response to a pathogen
They are excellent at phagocytosis
Once they are mature, they break up pathogens into small amino acid chains
Will move through lymph to nearest node and perform antigen presentation to T cells - they are the best at this
73
How do NKC’s kill target cells?
They punch holes in cell membranes creating pores or they enter cells and cause apoptosis
74
What is the only way that CD4+ Helper T Cell see antigens?
Only if the antigen is presented on MHC II
75
What is the only way that CD8+ Cytotoxic T Cell KILL antigens?
It can only KILLs cells with anitgen presented on MHC I
76
Name 3 receptors that make up the PRR family
Toll-like receptors (TLR).
2. Nod-like receptors (NLR).
3. Rig-like receptors (RLR)
TLRs are the main ones
77
What is the main function of TLR's?
TLR's send signals to the nucleus to **secrete cytokines and interferons.**
These signals initiate tissue repair. Enhanced TLR signalling = improved immune response
78
What are PRR's a receptor for?
PAMPs
79
TLR's are adapted to recognise damaged molecules. What characteristic do these damaged molecules often have in common?
They are often hydrophobic
80
Where are circulating PRR secreted from?
Epithelia, phagocytes and the liver. They can activate the complement cascade and induce phagocytosis
81
What happens when a PAMP binds to a PRR?
The innate immune response and inflammatory response is triggered.
82
What is extravasation? What causes it?
Leukocyte (WBC) migration across the endothelium.
It is caused by the secretion of TNF alpha, from the macrophages ast tissues
83
Describe the process of extravasation
1. Macrophages at tissues release TNF alpha.
2. The endothelium is stimulated to express **adhesion molecules and to stimulate chemokines.**
3. Neutrophils bind to adhesion molecules; they **roll, slow down and become stuck** to the endothelium.
4. Neutrophils are **activated by chemokines.**
5. Neutrophils pass through the endothelium to the tissue to help fight infection.
84
What are TLRs? Where are they found?
Found on macrophages, dendritic cells & neutrophils
- They are proteins that recognise and bind to PAMPs; eg lipopolysaccharide, viral and bacterial nucleic acids
When binding happens, second messengers are
generated within the immune cell which lead to the
secretion of inflammatory mediators such as IL-1, IL-12
& TNF-alpha
They are PLASMA MEMBRANE BOUND AND BIND TO EXTRACELLULAR LIGAND
85
Specific TLRs: What does TLR 2 bind to?
Gram Positive Bacteria
Fungi
Specifically - **binds lipoteichoic acid,** part of peptidoglycan on gram positive bacteria (note there is a thin peptidoglycan cell wall on gram negative bacteria)
86
Specific TLRs: What does TLR 5 bind to?
Flagellin is detected by TLR5, 5 begins with F as does flagellin is a good
way to remember
Eg E.Coli flagellated, so TLR 5 can detect it
87
Specific TLRs: What does TLR 4 bind to?
Gram Negative Bacteria
Specifically - lipopolysaccharide, part of the bacterial cell wal
88
Describe the role monocytes
Make up 5% of blood
Lifespan: months
Play an important role in innate (phagocytosis) and adaptive (antigen presentation) immunity
89
What role do macrophages play in the immune response?
3 THINGS
The first line of non-self-recognition
Main role is to remove foreign (microbes) and self (dead/tumour cells)
Present antigens to T cells
Release cytokines to attract other immune cells
90
What do eosinophil granules contain? What does this do?
Contains Major Basic Protein, which
Activates neutrophils
Induces histamine release from mast cells
Provokes bronchospasm
91
What cells is known as the professional antigen presenting cells
Dendritic cells
92
What is IgM
Makes up 4% of antibody population
1st antibody response made
Can be made without T cell response
Most effective at activating complement pathway
93
What is IgG?
Most abundant antibody in serum makes up 75%
Serves as an opsonin: helps phagocytes bind to pathogen and makes it easier for phagocytosis to occur
Activates the common complement pathway
Helps NKC’s to kill viruses
94
What is IgA?
Makes up 20% of antibody population in serum
Serves as an opsonin
Main antibody found in mucosal sites and prevents pathogens entering the body
Forms IgA1 and IgA2
Babies receive lots if IgA in breastmilk
95
What is IgE?
Makes up 0.004% of antibody population in serum
Associated with allergic and **anti-parasitic responses**
Triggers granule release when binding to basophils, Eosinophils and mast cells
Triggers inappropriate release of histamine granules in allergic reactions
96
What is IgD?
Makes up 1% of the serum antibody population
Found with IgM
Helps mature B cells leave the Bone marrow
97
Specific TLRs: What does TLR 7 and 8 bind to?
Viruses
98
Specific TLRs: What does TLR 9 bind to?
Bacteria and DNA viruses
TLR 9 is an intracellular PAMPS
99
What are the 5 main classes of antibody?
What is the main type? What one is made first?
5 distinct classes
IgG
IgA
IgM
IgD
IgE
But IgG is the main type
IgM is made first
100
What is the basic structure of antibodies?
Has a four-chain structure; two identical heavy (H) chains and two
identical light (L) chains
101
Where are the complement proteins produced?
The Liver
102
What are the 3 complement pathways:
The classical pathway (discovered first)
The alternative pathway (always at work)
Lectin Binding pathway
103
What does C1 do? (Classical pathway)
C1 proteins bind two or more antibodies, leading to activation
.
Activated C1 then cleaves C4 and C2, which combine to from **C3 Convertase**, on the surface of the Pathogen
C3 convertase activates C3, making C3a and C3b
104
The classical pathway: What does C3b do?
**C3b is an opsonin** - They bind to the **antiphagocytic capsule** around the pathogen, **making it easier and quicker to be phagocytosed**
It also cleaves and activate C5, producing C5b
105
The classical pathway: What does C5b do?
Reacts with C6,7,8,9 to form the membrane attack complex (MAC)
106
Lectin Binding pathway: How is it triggered? What is mannose
By Mannose binding lectin protein
Mannose is a sugar that is very commonly found in the cell walls of pathogens
107
Lectin Binding pathway: What does Mannose binding protein do?
**It activates C2 and C4 into C3 convertase,** like C1 does in the classical pathway.
108
Outline how the alternative pathway is activated, and what happens in it
**Usually activated by bacterial endotoxin**, a **lipopolysaccharide present on the outer membrane of gram negative** bacteria.
This results in **spontaneous hydrolysis of C3 into small amounts of factor C3b,** which combines with other factors to produce C3 convertase.
C1 inhibits it
109
Outline the two main roles of
C3a, C4a, and C5a
1. promote synthesis of **pro-inflammatory cytokines.**
2. They bind to mast cells and basophils to cause degranulation, and **The histamine and serotonin released increase vascular permeability**
They are complement components responsible for causing inflammation
110
What are the 3 main outcomes that can be brought about by the complement pathway?
1. Formation of MACs - (C5b - activating MACS with C6 C7, C8, C9)
2. Opsonisation of pathogens - (C3b)
3. Lead to the Formation of chemokines, for Chemotaxis (C3a, C4a, C5a,)
111
What are MACs? How are they harmful to bacteria
Membrane attack complex, formed by the joining of C5-9 on the cell membrane of bacteria
MAC is a leaky pore like channel. Ions and water pass through the channel and disrupt the intracellular microbe environment -> microbe lysis.
112
Which complement plasma proteins are pro-inflammatory and cause chemotaxis and activation of neutrophils and monocytes etc?
C3a and C5a.
113
Which complement plasma proteins have opsonic properties when bound to a pathogen?
C3b
114
Outline the main complement proteins - what activates what?
C1 --> C2 +C4 --> C3 CONVERTASE -- C3A (CHEMOTAXIS) AND C3B (OPSONIN)
C3B OPSONISATION, AND CLEAVES C5 ----> C5A AND C5B C5A (CHEMOTAXIS) C5B ---. REACTS WITH C6,7,8,9 TO FORM MACS
115
Define Opsonisation
Opsonisation - the process where molecules bind to a pathogen, making it more palatable to the phagocyte, for easier phagocytosis
C3b binds to the pathogen, easier for phagocytes to grab
116
Outline what hypersensitivity is
The over-reaction by the immune system to things you don't need to react to
* Refers to diseases in which immune responses to the environmental antigens
cause inflammation and damage to the body itself
117
What is a cytokine?
Soluble proteins secreted by lymphocytes or macrophages/monocytes
that act as stimulatory or inhibitory signals between cells
118
Give some specific examples of PAMPs that macrophages may recognise
- Peptidoglycan
- Lipopolysaccharide
- Lipoteichoic Acid
^^^ All in bacteria cell walls
or
- Flagella proteins
- Mannan
^^ in Fungal wall
- Viral RNA or DNA
119
Name some cells with PRRs
(5)
Macrophages
Neutrophils
Eosinophils
Basophils
Mast Cells
120
What are the two types of PRRs
Phagocytic PRRs - Bind and eat pathogen (do not release cytokines)
Signalling PRRs - Release Cytokines - to send reinforcements, but don't phagocytose
121
Where are TLRs found?
Found on all Leukocytes, as well as Endothelial cells and epithelial cells
*They pick up PAMPs and DAMPs*
122
Where would you find TLRs 1,2,4,5 and 6? What do they bind to?
What do they lead to the release of?
Find them on the cell surface - Bind to PAMPs such as
- Peptidoglycan
- Lipopolysaccharide
- Flagella proteins
**PLF**
Secrete Interferon alpha and beta ===> Viral resistance
123
Where would you find TLRs 3,7,8 and 9? What do they bind to?
What do they lead to the release of?
In the cell - bind to intracellular PAMPs - eg Viral RNA
secrete chemokines, to attract immune cells, eg TNF-a
124
What happens when the TLRs within the cell get activated?
When activated they lead to the stimulation of pro inflammatory cytokines such as
TNF-a
Il-1b and IL-6
Which leads to Vasodilation, more leukocytes to the site and fever
125
What happens with TLRs get activated? (Intracellular)
activate chemokines eg TNF-a
126
What antibody is involved in a type 1 hypersensitivity reaction?
IgE
127
In an allergic reaction what do the T-helper cells differentiate in to?
Th2 cells
128
What does interleukin 1 do?
What about Interleukin 2?
IL-1 is mainly involved in acute inflammation and inducing fever, vasodilation, hypotension - (mainly comes from macrophages)
IL-2 - main functions include: stimulates **growth and differentiation of T cell response** (so would be decreased in HHIV/AIDS)
129
What helps a T-helper cell to differentiate into a Th2 cell
interleukins: IL-4, IL5, IL-10
130
What interleukin released by TH2 cells causes B-cells to release IgE antibodies?
IL-4
131
What interleukin released by TH2 cells stimulates production of eoisnophils In a Type I hypersensitivity reaction?
IL-5
132
What receptors do IgE antibodies bind to on mast cells?
Fc receptor
Its name is derived from its binding specificity for a part of an antibody known as the Fc (fragment crystallizable) region.
Fc receptors bind to antibodies that are attached to infected cells or invading pathogens.
133
What happens when a sensitised mast cell (one that's binded with IgE) binds to a previously seen antigen e.g., pollen
It degranulates and releases pro-inflammatory molecules e.g, histamine
134
What receptors does histamine bind to? What does this lead to?
H1.
Bronchoconstriction
- Vasodilation
- Increased vascular permeability (which causes swelling and hives and redness)
135
What happens 8-12 hours after an allergic reaction?
Leukotrienes LTB3, LTB4 are secreted by immune cells
Cause smooth muscle contraction
Causes signalling to other immune cells to aggregate in the area
136
What cells are the primary cause of a type II hypersensitivity reaction?
B-cells
137
What antibodies are secreted in type II hypersensitivity reaction?
IgG, IgM
138
What are the two types of antigens attacked on cells by antibodies in a type II hypersensitivity?
Intrinsic (antigens normally produced)
## Extrinsic (things that have become attached to cells e.g., drugs)
139
What is it called when an antibody binds to an antigen? When is this a problem?
Antigen-antibody complex, is an issue when this happens to host tissue
140
Type I - what Interleukins are involved, and what do they do? What does IL-4 and IL-5 do, specifically?
IL-4, IL-5, IL-10, prime the niave T cells into becoming TH2 cells
IL-4 causes B cells to switch from making IgM to making IgE antibodies, that are specific to the antigen that triggered the reaction
IL-5 causes the activation and degranulation of Eosinophils
141
Type I hypersensitivity - what does the secreted IgE do?
Binds of FCe receptors on mast cells activating them so they can recognise the allergen again next time it comes in, and degranulate
142
Type I hypersensitivity - When mast cells degranulate and release proinflammatory mediators, what does this cause?
What do Leukotrienes do?
The release of Histamine that binds to H1 receptor leads to:
- Bronchi Smooth muscle contraction ==> Leads to difficulty breathing
-Blood vessel dilation => Leads to more vasclar perembaility, so oedma and hives
Leukotrienes (specifically LTB4 and LTC4) facilitate communication that causes smooth muscle contraction and attracts more immune cells
143
What is a feature of type II hypersensitivity?
Tissue specific antibodies lead to the destruction of SPECIFIC ORGANS
In General it is Cytotoxic
Antibody mediated
144
Type II Hypersensitivity: What is central tolerance?
When immune cells that are self-reactive to your body cells get destroyed
145
Type II Hypersensitivity: What happens, because central tolerance isnt perfect?
Imperfect central tolerance means that escpated self reactve B cells become activated and secrete IgM or (with the help of T helper cells) secrete IgG
146
Type II Hypersensitivity: What does the IgM and IgG do when it is released from self reactive immune cells? What does it go on to form?
Binds to antigens on your own normal cells, Either on:
Intrinsic Antigens: Antigens normally made by host
Extrinsici Antigens: Antigens that are attached on self-cells from outside the body (eg penicillin medication that binds to the surface of a RBC)
Which creates a Antigen-Antibody Complex. This is normal in infection , but problematic when this happens on a host tissue, like in Type II reactions
147
What specific disease can occur when specific cells are targeted in type II hypersensitivity?
==> The attacking of certain cells can lead to Haemolytic Anaemia, Thrombocytopaenia, or Neutropoenia. Or, antibodies binding to basement membrane can lead to Goodpasture's Syndrome , seen in the Kidney or Lung
148
Type II Hypersensitivity: Now a Antigen-Antibody Complex has formed on a host tissue, cytotoxic mechanisms become activated - What will the complement pathway cause?
The 3 Complement things
Complement System C1 binds to the Fc portion of the antibody. The 3 outcomes of Compliment system happens
149
Type II Hypersensitivity: If you suspect Haemolytic anaemia, what test can you use?
Coombs test: RBCs are mixed with Coombs reagent.
If Agglutinates, then antibodies are present
(Agglutinates - the formation of clumps of cells)
150
Type II Hypersensitivity: What do Natural killer cells do?
They recognise the Fc tail of the antibodies that have tagged the bodies own cell, and destroy this cell by punching holes in it and releasing granzymes
151
Type III Hypersensitivity: What are Immune complexes
They are a molecule formed from the binding of multiple SOLUBALE antigens to antibodies.[1]
The bound antigen and antibody act as a unitary object
152
Type III Hypersensitivity: Using Lupus as an example, what happens to the DNA, and what forms?
Escaped Self B cells take DNA that has come from an old body cell, and takes a bit of it, forming an AUTOANTIGEN (an antigen that has come from the body)
Triggers B cells to make specific IgG autoantigen to the DNA
153
Type III Hypersensitivity: Because the autoantigens are small and soluble in the blood, what do they end up doing?
They float and get stuck in the basement membrane of vessels, which activates the compliment system.
Leads to increased Vascular permeability, leading to oedema
C5a,4a,3a cause chemotaxis, causing macrophages to try and phagocytose vessel wall with autoantigen - LEADING TO VASCULITIS, leading to more leakage of DNA for example, so the process starts again
154
Type III Hypersensitivity: Where in the body does Vasculitis seen in Type III Hypersensitivity most often occur?
Basement membranes in the Kidney - Glomerulonephritis
Joints, in synovial fluid - Arthritis
155
What makes a T cell naive?
The fact that their T cell receptor hasn't bound to a specific antigen yet.
156
Type IV Hypersensitivity: What do T helpers do when they become activated?
T Helper cells become activated by an antigen (eg poison ivy molecule)
Th1 cells release IL-2 which proliferate/duplicate, and then release interferons that lead to macrophages that:
release proinflammatory cytokines, (TNF, IL-1, IL-6) leading to leaky endothelial membranes --> More immune cells at the site ==> oedema, redness, fever
ROS, lysosomes that attack the site
Th17 cells triggered neutrophil recruitment
157
Type IV Hypersensitivity: What do T Cytotoxic do when they become activated?
Attack the target self cells that present the specific antigen - eg in Type 1 diabetes, where immune cells attack islet cells in the pancreas
158
Outline Type I Hypersensitivity, in an essence. Give an example of it and the reactant involved.
Mast-cell activation releases histamines and other mediators, IgE,
Anaphylaxis
159
Outline Type II Hypersensitivity, in an essence. Give an example of it and the reactant involved.
Antigen EMBEDDED IN HOST CELLS cause complement activation and destruction by MAC.
IgG,
Acute Transfusion reactions
160
Outline Type III Hypersensitivity, in an essence. Give an example of it and the reactant involved.
Antibody BINDS TO SOLUABLE ANTIGEN, forming a circulating immune complex lodges in a vessel wall and causes a local inflammatory response.
IgG,
Rheumatoid Arthritis, Vasculitis, Glomerulonephritis
161
Outline Type IV Hypersensitivity, in an essence. Give an example of it and the reactant involved.
Antigen presenting cells activates Th1/Cytoxic T cells. T cells activation macrophages and cause an inflammatory response.
T Cells
Contact Dermatitis (to Nickel/Poison Ivy), Mantoux tuberculin test, T1DM, Hashimotos Thyroiditis
162
What test can diagnose contact delayed Type IV hypersensitivity reactions, to things such Nickel??
The patch test
163
Talk through the Pathophysiology of immune anaphylaxis, 1st exposure
1st exposure to allergen: Th2 cells are primed, and the release of IL-4 causes B cells to switch their production of IgM to IgE antibodies.
IgE antibodies bind to mast cells and basophils. The cells are now sensitised to the allergen.
164
Talk through the Pathophysiology of immune anaphylaxis, 2nd exposure
On the Second exposure, : Cross linkage of the antigen-specific IgE antibody bound to the sensitised cells causes mast cell degranulation and release of various mediators (leukotrienes, histamine and prostaglandins).
This causes widespread vasodilation, bronchoconstriction and increased permeability of vascular endothelium
165
What happens in non immune anaphylaxis?
Not caused by any IgE antibodies
* Due to direct mast cell degranulation
* Some drugs/food are recognised to cause this
* No prior exposure needed
* Clinically identical to immune anaphylaxis
166
Anaphylaxis - how do you treat it?
Commence basic life support ; A (airway), B (breathing), C (circulation)
Specific treatment:
- STOP DRUG if infusion
- Adrenaline 1mg (10mls of 1:10,000 (IV)) 1ml IV increments -
note: if cardiac arrest then may need to give cardiac massage in
order to get drugs circulating
- IV Anti histamine (Chlorphenamine 10mg)
- IV Hydrocortisone (100 to 200mg) - note: unlikely to cause harm
in excess so can’t really give too much
* Effect of adrenaline:
- Vasoconstriction, bronchodilation & increased cardiac output
167
What is the precise dose of adrenaline that you give in anaphylaxis?
What is the MOA of adrenaline here?
Adrenaline IM / 0.5mg / 1 in 1,000
Stimulation / agonist of beta adrenergic receptors
168
Name some physiological responses in the body to the mediators of anaphylaxis
Vasodilation,
Increased vascular
permeability
tachycardia
hypotension
maximise blood glucose levels in brain
All of these responses occur due to stimulation of beta-adrenergic receptors
169
What are some risk factor for anaphylaxis?
<30 years old
Having a history of anaphylaxis
Having allergies/asthma
Atopy - the genetic tendency to develop allergies
Being female
170
What blood test would you use to look for anaphylaxis?
**Serum mast-cell tryptase**
Tryptase - can show mast-cell degranulation (histamine elevation, only lasts a short amount of time).
Levels of serum tryptase, ***which is a mast-cell specific protease***, peak at one hour after an anaphylactic reaction, remaining elevated for approximately six hours.
Elevated serum tryptase levels imply either massive mast-cell degranulation, as occurs in anaphylaxis, or a condition such as mastocytosis.
However, not every case of anaphylaxis causes a rise in tryptase - both the sensitivity and specificity are around 95%.
171
Recap - name the toll like receptors that are found on the cell surface.
TLRs 1,2,4,5,6
172
Recap - name the toll like receptors that are intracellular
TLRs 3,7,8,9
