immunology Flashcards
(302 cards)
1
Q
What are the 2 types of immunity?
A
- Innate (natural) immunity
- Acquired (adaptive) immunity
2
Q
What is innate immunity?
A
Innate immunity is present continuously, it is a defence mechanism that is present from birth and is generally non-specific (i.e. the same generic response occurs towards many different types of material).
3
Q
What is acquired immunity?
A
Acquired immunity is induced by the presence of ‘foreign’ or ‘non-self’ material (including infectious microorrganisms). The response that occurs is (usually) unique to the specific substance or pathogen that induced the response.
4
Q
Do the innate and acquired immune systems work separately?
A
No. Both innate and acquired immune systems work closely together to eliminate disease-causing micro-organisms.
5
Q
What are the 3 types of innate(natural) immunity?
A
- Natural/physical barriers
- soluble factors
- immune cells
6
Q
What are the two types of adaptive (acquired) immunity?
A
- soluble factors
- immune cells
7
Q
What are the 4 types of soluble factors involved in innate (natural) immunity
A
- cytokines
- acute phase proteins
- inflammatory mediators
- complement proteins
8
Q
What are the 4 types of immune cells involved in innate (natural) immunity?
A
- macrophages
- mast cells
- natural killer cells
- neutrophils
9
Q
What are the 2 types of soluble factors involved in acquired (adaptive) immunity?
A
- Cytokines
- Antibodies
10
Q
What are the 2 types of immune cells involved in acquired (adaptive) immunity?
A
- B cells
- T cells
11
Q
What are the two types of intrinsic epithelial barriers to infection?
A
- skin
- mucous membranes
- respiratory tract
- Gastrointestinal tract
- Urogenital tract
12
Q
___________ barriers are highly effective at preventing infectious disease. If these defences are _________(e.g. by a wound, a foreign object, a medical device, etc.), __________ diseases can arise. These diseases can be caused by over growth of commensal micro-organisms in an undesireable anatomical location OR by the invasion of pathogenic microorganisms.
A
- constitutive
- breached
- infectious
13
Q
What are primary lymphoid tissues?
A
Anatomical sites where white blood cells (leukocytes) are produced.
14
Q
What are primary lymphatic organs?
A
Primary lymphatic organs are where lymphocytes are formed and mature. They provide an environment for haematopoietic stem cells to divide, differentiate and mature into red blood cells (leukocytes) and platelets.
15
Q
Name the 2 primary lymphatic organs
A
- red bone marrow
- thymus gland
16
Q
What is the lymphatic system?
A
A secondary transport system that protects and maintains the body by producing and filtering lymph. system present throughout the body except cartillage and epidermis.
17
Q
What is lymph?
A
A clear fluid that contains white blood cells (also known as leukocytes) and arises from the drainage of fluid from the blood and surrounding tissues.
18
Q
Where is lymph filtered?
A
Lymph is filtered at points called lymph nodes, where pathogens are removed before the fluid is returned to venus circultation.
19
Q
What do lymph nodes do?
A
Lymph nodes help filter bacteria and other toxins from your body by trapping harmful organisms and using specialized white blood cells (leukocytes) to destroy them.
20
Q
Lymph vessels are equipped with valves that make sure fluid can be easily transported. How else is lymph fluid transport aided (4 ways)?
A
- breathing
- muscle contraction
- pulsation in the arteries
- external compression including
- manual lymphatic drainage
- short stretch bandages
- gradient compression garments
21
Q
What do secondary lymphoid tissues do?
A
They are arranged as a series of filters monitoring the contents of the extracellular fluids, i.e. lymph, tissue fluid and blood.
- lymphoid tissue filtering each of these fluids is arranged in a different way
- these tissues include: lymph nodes, tonsils, spleen, Peyer’s patches and mucosa associated lymphoid tissue (MALT)
Secondary lymphoid tissues are also where lymphocytes are activated during adaptive immune responses.
- these tissues all share a common feature-distinct zones for different types of lymphocytes (T cells versus B cells)
22
Q
What do the lymph nodes do in their role as secondary lymphoid tissues?
A
- small organs that filter for lymph
- removes dead cells, pathogens and antigens uses them to activate adaptive immune responses.
23
Q
What does the spleen do as a secondary lymphoid tissue?
A
- serves as a filter for blood
- removes old and damaged RBCs
- removes infectious pathogens and uses them to activate adaptive immune responses.
24
Q
Name 5 of the secondary lymphoid tissues
A
- lymph nodes
- tonsils
- spleen
- Peyer’s patches
- mucosa associated lymphoid tissue (MALT)
25
What is the common feature of all secondary lymphoid tissues?
They have distinct zones for different types of **lymphocytes (T cells versus B cells)**
26
Which 3 components of the immune system are found in the blood and recruited into inflamed tissues?
* neutrophils
* eosinophils
* basophils
27
Which 3 cellular components of the immune system are found in the blood and seconday lymphoid tissues?
* Natural killer cells
* T cells
* B cells
28
Which cellular comoponent of the immune system is found in the blood and recruited into normal and inflamed tissues?
Monocyte
29
Name the three tissue resident cellular components of the immune system
* Mast cells
* macrophage
* dendritic cells
30
What type of stem cell do all cellular components of the immune system develop from in the bone marrow and foetal liver?
**Pluripotent haemotopoietic stem cells**
31
Pluripotent haematopoietic stem cells give rise to cells with progressively more and more limited ______________ potential.
Differentiation
32
During their first division what are the two potentials of pluripotent haemoptoetic stem cells?
* Myloid/erythroid
* lymphoid potential
33
Myleoid progenitors give rise to all non-lymphoid lineages, name the two kinds
* **Monocytes**- which give rise to **dendritic cells** (DC) and **macrophages**
* Granulocytes (**neutrophils, eosinophils** and **basophils**)
34
lymphoid progenitors give rise to which 3 types of cells
* T cells
* B cells
* Natural killer (NK) cells
35
What are the major functions of natural killer cells?
NK cells are large granular lymphocytes that can detect and kill tumour cells and virally infected cells ; they can also kill antibody-bound cells/pathogens
36
What are the functions of mast cells, eosinophils and basophils?
* pro-inflammatory
* parasitic killing mechanisms
* linked to allergy and asthma
* important in defence against large antibody-coated pathogens that cannot be phagocytosed (e.g. parasites)
37
What are the functions of monocytes, macrophages and neutrophils?
* **phagocytosis**- ingest and kill extracellular pathogens as well as dead/dying apoptotic cells and small immune complexes (antigen/antibody complexes)
* important source of **cytokines** which regulate **acute inflammatory responses**
* particularly important at sites exposed to the external environment
Monocytes circulate in the blood; some migrate into peripheral tissues where they can differentiate into tissue-resident macrophages. Macrophages have additional functions, including promoting tissue repair and limiting acute inflammatory responses after the invading pathogen has been eliminated from the body.
Neutrophils circulate in the blood but are rapidly recruited into inflamed, damaged and infected tissues.
38
What is the function of dendritic cells (DC)
* antigen uptake in peripheral sites
* antigen presentation
* Naive T cell activation
* function to phagocytes, **process and present** antigens on their cell surface to help activate T cells
* present in large no.s in tissues that are in contact with the external environment
39
Mature T cells and B cells constantly circulate through the blood, _______ and secondary lymphoid tissues; they are inactive until meet a pathogen/\_\_\_\_\_\_\_\_ that they can recognise and respond to; some are very _____ \_\_\_\_\_\_\_ (e.g. memory T cells and memory B cells)
* lymph
* antigen
* long-lived
40
What do B cells do?
They are responsible for the production and secretion of circulating antibodies
41
What do CD4+T cells (helper T cells, TH cells) do?
Secrete cytokines that regulate innate and acquired immune responses
42
What do CD8+T cells (cytotoxic T lymphocytesm CTLs) do?
Kill tumour cells and virally-infected cells.
43
Name the 3 types of soluble (humoral) components of the immune system
* antigens and antibodies
* complement system proteins
* cytokines
44
Adaptive immune responses are induced by which specific structures?
Antigens
45
What is an antigen?
Any substance which can cause an adaptive immune response by activating B cells and T cells.
46
What is an antibody?
An antibody (also known as an **immunoglobulin**) is a protein that binds to one specific antigenic epitope.
47
Why is an antibody produced during acquired immune responses?
It is produced in response to a specific antigen
48
True or false, Individual antigens do NOT contain many different antigenic epitopes.
False, individual antigens contain many different antigenic epitopes
49
Are antibodies unique?
Yes, they can only bind to one specific antigenic epitope.
50
Do different microbial species contain unique or similar sets of antigens.
Unique.
Individual cells/microorganisms contain many different antigens but different microbial species will express a unique set of antigens.
51
What three things do viruses provide protection against?
* extracellular pathogens
* viruses
* toxins
52
Can antibody-deficiency diseases be life threatening?
Yes
53
Describe compliment proteins
* family of approx 30 different proteins
* produced in the liver
* circulate in the blood/tissues as inactive precursor proteins (constitute ~ 10% of serum proteins)
54
How can compliment proteins be activated?
Directly or indirectly by invading micro-organisms
55
Compliment proteins can enzymatically cleave and activate other downstream compliment proteins in a __________ \_\_\_\_\_\_\_\_\_\_\_\_.
Biological cascade
56
What are two critical roles of compliment system proteins
* Promoting inflammation
* defense against extracellular bacterial species
57
What are cytokines?
A diverse collection of small proteins and peptides
58
when are cytokines produced?
In response to infection, inflammation and tissue damage.
59
describe the function of cytokines
* modulate behaviour of cells and so play a key role in co-ordinating the immune system
* many have multiple functions
* different cytokines may have overlapping functions
* short half-life
* can act locally and/or systemically
60
Name 4 cytokines and their functions
1. interferons- anti-viral activity
2. Tumour necrosis factor alpha (TNFalpha)- a pro-inflammatory cytokine
3. chemokines- control and direct cell migration
4. interleukins- various functions
61
Give 2 examples of the various types of signals through which cells communicate
cells communicate via various types of signal (e.g. cytokines or hormones) that travel to target sites (cells) in order to elicit a specific biological response.
62
cytokines may act on the cells that produce them; on nearby cells or on distant cells. Name and describe these three types of signalling
* **autocrine signals** are produced by signalling cells that can also bind to the ligand what is released, which means the signalling cell and the target cell can be the same or similar cells.
* **Paracrine signalling** occurs between local cells where the signals elicit quick responses and last only a short amount of time due to the degradation of the paracrine ligands.
* **Endocrine signalling** occurs between distant cells and is mediated by hormones and cytokines released from specific cells that travel to target cells, producing a slower, long-lasting response.
63
Give an overview of the innate immune response
* Inflammation,complement activation, phagocytsosis and destruction of pathogen
* Typical time after infection to start response- minutes
* duration of response- days
64
Give an overview of the adaptive immune response
* interaction between antigen presenting dendritic cells and antigen specific t cells: recognition of antigen, adhesion, co-stimulation, T-cell proliferation and differentiation.
* activation of antigen-specific B cells
* Formation of effector and memory T cells
* Interaction of T cells with B cells, formation of germinal centres. Formation of effector B cells (plasma cells) and memory B cells. Production of antibody.
* Emigration of effector lymphocytes from peripheral lymphoid organs.
* elimination of pathogen by effector cells and antibody.
65
Describe the immunological memory
* maintenance of memory B cells and T cells and high serum or mucosal antibody levels. Protection against re-infection
* Typical time after infection to start of response= days to weeks
* duration of response= can be lifelong
66
List the 6 innate immune system responses
* acute inflammation
* macrophages
* mast cells
* natural killer cells
* neutrophils
* complement
67
What are the 2 acquired immune system responses?
* B cells, antibodies
* T cells
68
What does the immune system do?
Identifies and eliminates microorganisms and other harmful substances as well as abnormal cancer cells.
69
How does the immune system identify and eliminate microorganisms and other harmful substances as well as abnormal cancer cells?
* by distinguishing 'self' molecules from 'non-self' molecules
* by identifying 'danger' signals (e.g. from acute inflammation)
* or via a combination of the two
70
A balanced immune system provides optimal effectiveness, What are the two components of a balanced immune system?
* protection from pathogens
* rejection of donor tissues
71
In organ transplantation the new tissue would be recognised as foreign and initiate an immune response. How can this be prevented?
With anti-inflammatory and immunosuppressive drugs to prevent rejection of the tissue
72
What are the two possibilities if the immune system goes wrong?
* Immune over-reaction
* Immune under-reaction
73
What are the two ways the immune system can over-react
* Reaction to 'self'=autoimmunity
* reaction to innocuous substances= allergies
74
What are the two ways the immune system can under-react?
* Recurrent infections
* Cancer
75
Which 3 ways can we manipulate the immune system to prevent or treat human diseases?
1. **Immunization**
2. **anti-inflammatory and immunosuppressive drugs**
3. **Cancer immunotherapy**- immunotherapy enables the immune system to recognize, target and eliminate cancer cells, making it a potential 'universal answer' to cancer.
76
What is the first line of defenc against infection?
Natural/physical barriers
77
What are the 4 points of energy where pathogens can infect the body?
* digestive system
* respiratory system
* urogenital system
* skin damage
78
What are the two routes of attack for pathogens?
* circulatory system
* lymphatic system
79
what is the most important barrier to infection?
The skin
80
How does the skin act as a barrier to infection?
* **Physical barrier**
* composed of tightly packed, highly keratinized, multi-layered cells
* constantly undergo renewal and replacement
* **Physiological factors**
* Low pH 5.5 (acidic)-most pathogens are intolerant to acidic environments
* low oxygen tension
* **Sebaceous glands**
* secrete hydrophobic oils- slippery surface limits physical colonization by pathogens and microorganisms
* lysozyme- destroy the integrity of bacterial cell walls.
* ammonia - "
* antimicrobial proteins
81
How does secreted mucous act as a constitutive barrier to infection?
Mucous membranes line all body cavities that come into contact with the environment.
* respiratory
* Gastrointestinal
* Urogenital tract
The mucous traps bacteria which are subsequently removed by ciliated cells.
Mucous also contain specialised chemicals that can have anti-microbial properties.
82
How do commensal bacteria act as a constitutive barrier to infection?
* "friendly" bacteria which exists in the gut, skin, etc
* either have no deleterious effect on the host or sometimes live symbiotically
* can compete with bad bacteria
* can contain chemicals which kill pathogenic microorganisms
* 100 trillion bacteria normally reside at epithelial surfaces amongst mucus and epithelial cells
* \> 500 different microbial species
* symbiotic relationship with the host
83
Provide a brief summary on the 5 natural barriers to infection
1. **Physical barrier**- skin & mucous membranes lining digestive, urinary, respiratory & reproductive systems
2. **Traps** - mucous, cilia (in nose & trachea), hair (covering body & in nose/ears), earwax
3. **Elimination**- coughing, sneezing, urination, diarrhea
4. **unfavourable pH**- stomach acid, sweat, saliva, urine
5. **Lysozyme enzyme**-in tears, sweat; digests bacterial cell walls
84
What are the fundemental properties of adaptive (acquired) immunity?
* specificity
* adaptiveness
* discrimination between self and non-self
* memory
85
Describe innate immunity
* innate immunity is present continuously, it is a defence mechanism that is present from birth
* the same generic response occurs to many different microbial species
* rapid response (mins-hours)
* NO immunological memory
* non-specific
* can distinguish SELF from NON-SELF ad should only react against non-self
86
Decribe acquired (adaptive) immunity
* acquired (adaptive) immunity is induced by the presence of foreign materials
* a unique response is generated to each individual pathogen
* slow response (days), lag time from exposure to the response
* Immunological memory thus subsequent responses are faster and more powerful; basis for protective vaccination against infectious disease
* specific for each antigen encountered
* self-regulating through regulatory T cells
* can distinguish SELF from NON-SELF and should only react against non-self
87
What do tissue-resident innate immune cells such as macrophages and mast cells, and the complement system lead to?
* Pathogen killing
* acute, local inflammation
88
What happens when physical (natural) barriers are breached?
* pathogens invade
* innate immune responses initiated
89
Which tissue-resident innate immune cells recognise pathogens as 'non-self' and dangerous?
* Phagocytic ('eating' cells) - macrophages and dendritic cells (DCs)
* other cells- mast cells
90
What are the 3 modes of ingestion by macrophages?
* Pinocytosis
* Receptor-mediated endocytosis
* Phagocytosis
91
What is pinocytosis?
Ingestion of the fluid surrounding cells
92
What is receptor-mediated endocytosis?
* molecules bound to membrane receptors is internalized
* an important step in the generation of adaptive immunity
93
What is phagocytosis?
* intact particles (e.g. bacteria) are internalized whole
* these are facilitated by **opsonisation**
94
What are the 7 steps of phagocytosis?
1. macrophages express a set of '**PRR's**'
2. Receptor binding to '**PAMPs**' signals the formation of a phagocytic cup.
3. cup extends around the target and pinches off, forming a **phagosome**.
4. fusion with lysosomes to form a **phagolysosome**- killing of pathogens and degradation of contents (acidification, lysosomal hydrolases)
5. debris (including **antigens**) is released into extracellular fluid.
6. pathogen-derived peptides are expressed on special cell surface receptors (**MHC-II molecules**)
7. **Pro-inflammatory mediators** are released (e.g. **TNF*a***)
95
Phagocytosis is a specific form of _____________ by which cells internalise solid matter, including apoptotic cells and microbial pathogens.
While most cells are capable of phagocytosis, it is the professional phagocytes of the immune system, including \_\_\_\_\_\_\_\_\_\_\_\_, neutrophils and immature __________ cells, that truly excell in this process.
* endocytosis
* macrophages
* dendritic
96
What does the phagolysosome contain and what are their roles?
* Highly acidic pH- has bacteriostatic or bactericidal effects
* lactoferrin- prevents further microbial proliferation in the phagolysosome
97
What is the definition of opsonisation?
The coating of pathogens by soluble factors (opsonins) to enhance phagocytosis.
98
What are opsonins?
Soluble factors that bind to pathogens and enhance phagocytosis, they allow faster and better recognition.
99
Provide 3 examples of opsonins
* C3b
* C-reactive protein (CRP)
* IgG/IgM
100
Can largeextracellular parasites be phagocytosed?
No, extracellular bacterial pathogens do not invade cells and proliferate instead in the extracellular environment which is enriched with body fluids.
101
What happens when parasites are too large to be phagocytosed?
Mast cells step in...
* resident all the time in tissues
* very rapid resonse
* second wave of mast cell responses is due to gene expression
102
Describe the mode of action of mast cells
* Mast cells contain granules
* Danger signals from damaged cells reach the mast cells
* mast cells become activated by binding of a pathogen to PRRs on their surface and degranulate
* degranulation is the release of pre-formed pro- inflammatory substances
* the mast cells express genes which lead to the production of new pro-inflammatory substances.
103
Name 4 pro-inflammatory mediators released in the innate immune response
1. nitric oxide
2. prostaglandins/leukotrienes
3. histamines
4. pro-inflammatory cytokines (TNF*a*)
104
Provide a brief summary of the early innate immune response
* pathogens which display PAMPs and injured tissue cells which produce 'danger' signals activate macrophages and mast cells
* pathogens and infected cells are killed
* pro-inflammatory mediators are produced
* leads to localised, acute inflammation
105
Why is acute inflammation an important response to cellular injury or infection?
* it has both a rapid innate phase as well as a prolonged phase that is an important component of acquired immunity.
* immediately after injury or infection a number of proteins are released. These lead to the physiological characteristics of inflammation: swelling, redness, heat and pain.
106
What are the local physiological signs of acute inflammation caused by TNF*a*, histamine, C3a and C5a and their symptoms?
* dilation of small blood vessels; increased blood flow; cell accumulation; increased cell metabolism- redness(rubor) and heat (calor)
* increased permeability of post-capillary venules; fluid accumulates in extra-vascular spaces- swelling (tumour)
* stimulation of nerve endings- pain (dolor)
* swelling/pain- loss of function (functio laesa)
107
Name the 5 natural (anatomical/chemical) barriers
* **Physical barrier**: skin and mucous membranes lining digestive, respiratory and reproductive systems
* **Tranps**: mucous, cilia (in nose and trachea), hair (covering body and in nose/ears), earwax
* **Elimination**: coughing, sneezing, urination, diarrhea
* **Unfavourable pH**: stomach acid, sweat, saliva, urine
* **lysozyme enzyme**: in tears, sweat, digests bacterial cell walls
108
Which tissue-resident innate immune cells recognise invading pathogens as 'non-self' and dangerous
* phagocytic ('eating') cells
* macrophages and dendritic cells (DCs)
* Other cells- mast cells
109
Pathogens express 'signature' not found on/in human cells, what are these called?
**Pathogen associated molecular patterns (PAMPs)**
common to many different pathogenic species
110
Innate immune cells (and some other cell types) express partner receptors for PAMPs, what are these called?
Pattern Recognition Receptors (PRRs)
Found on the cell surface and in the cytosol for detection of extracellular and intracellular pathogens, respectively.
111
Which 2 types of cells express pattern recognition receptors?
* Mast cells
* macrophages
112
Non-immune cells also express _______________ PRRs in order to recognise that they have been infected by intracellular pathogens such as viruses.
Intracellular
113
Low levels of ___________ complement system proteins are found in extracellular fluids normally.
inactive
114
The complement system, when activated, creates a cascade of chemical reactions which promotes which 4 things?
* opsonization of pathogens
* direct pathogen killing
* acute inflammation
* leukocyte recruitment
115
Name the 3 pathways for the complement system
* Classical pathway
* Mannose-binding lectin pathway
* Alternative pathway
116
What do all 3 pathways which activate the complement system lead to?
Activation of downstream complement proteins
117
What does healthy tissue look like in relation to inflammatory mediators and immune cells/vasculature?
* no inflammatory mediators
* normal vasculature
* circulating neutrophils
118
What two things does inflammation promote?
* vascular changes
* rectruitment and activation of neutrophils (transendothelial migration)
119
What 3 things does changes in the local vasculature due to pro-inflammatory mediators and chemokines in infected and damaged tissue lead to?
* vasodilation and increased blood flow (redness)
* increased vascular permeability (swelling/oedema)
* expression of specific adhesion molecules on the surface of the endothelial cells and activation of adhesion molecule receptors on circulating neutrophils
* can include selectins or interleukins
120
what are the 5 steps of transendothelial migration?
1. Margination of neutrophils to the endothelium near sites of tissue damage/infection
2. binding of neutrophils to adhesion molecules (selectins, ICAM-1) on the endothelial cells
3. Migration of neutrophils across the epithelium, via the process of diapedesis
4. movement of neutrophils within the tissue via chemotaxis
5. activation of neutrophil by PAMPs and TNF*a*
121
Why do normal, non-infected cells express a ligand for the NK cell inhibitory receptor (MHC-I) all the time?
So that they can actively prevent the NK cell which express the inhibitory receptor continuously and migrate around tissues scanning cells constantly, from killing them.
122
What are the three killing mechanisms of neutrophils?
* Phagocytosis
* degranulation
* NETs
much better killers than macrophages
123
In infected tissues, pathogens release chemical signals that attract \_\_\_\_\_\_\_\_\_\_. These use ________ \_\_\_\_\_\_\_\_\_ _________ to bind to and phagocytose these pathogens.
neutrophils
pattern recognition receptors
124
What are the 2 ways neutrophils can kill internalised pathogens?
* Phagolysosomal killing
* ROS-dependent killing
125
Describe phagolysosomal killing in 4 steps
1. bacterium is phagocytosed by neutrophil
2. phagosome fuses with azurophilic and specific granules
3. pH of phagosome rises, antimicrobial response is activated, and bacterium is killed.
4. pH of phagosome decreases, fusion with lysosomes allows acid hydrolases to degrade the bacterium completely
126
Describe in 3 steps, ROS-dependent killing
NADPH oxygenase-dependent mechanisms (the '**respiratory burst'**) -\> production of toxic **reactive oxygen species (ROS)**
1. **neutrophil activation** (PAMPs, pro-inflammatory cytokines)
2. **Assembly of the NADPH oxidase complex**
3. **Production and release of ROS into phagolysosome**
127
What happens when neutrophils kill via the mechanism of degranulation?
**Release of anti-bacterial proteins from neutrophil granules into the extracellular milieu** leads to direct killing of extracellular pathogens,bacteria and fungi.
128
Why is degranulation not always an ideal mechanism of killing?
Can lead to tissue damage and (potentially) systemic inflammation.
129
How do NETs (neutrophil extracellular traps) work?
Neutrophils release the contents of their nuclei which kills the cells extracellularly. Other phagocytes come and mop up the debris.
130
Why are neutrophils better killers than macrophages?
As they have a second way to kill internalised pathogens via a ROS-dependent mechanism
131
What happens in the liver during acute phase inflammation?
Increased synthesis of acute phase proteins.
132
What happens in the bone marrow during acute inflammation?
increased production and mobilisation of neutrophils
133
What does the acute phase response broadly involve?
Changes in the plasma concentrations of specific proteins in response to inflammation.
134
What are the changes in plasma concentrations of specific proteins in response to inflammation driven by?
Pro-inflammatory mediators released by activated macrophages.
135
How is the acute phase response mediated?
By liver hepatocytes which produce a variety of acute phase proteins.
136
Name the 3 types of acute phase proteins produced by liver hepatocytes
* **C3 and MBL** (complement system proteins)
* **C reactive protein (CRP)**
137
Describe the role of C reactive protein (CRP) and how it can be used
* Primes bacteria for destruction by the complement system
* Has a prognostic role (severity, duration of inflammation)
* So it is a very good biomarker of acute inflammation
* short half-life but rapidly generated during inflammation.
138
Are interferons specific to individual viruses?
No, interferons are not specific to any one virus.
139
Virally infected cells produce and release small proteins called ___________ (IFN*a*/ß)
Interferons
140
In what 3 ways can interferons attack virally infected cells?
* signals neighbouring uninfected cells to destroy RNA and reduce protein synthesis
* signals neighbouring infected cell to undergo apoptosis and produce anti-viral factors
* activates immune cells e.g. NK cells
They can directly interfere with the ability of infected cells to serve as a factory for making viral particles. So they can help prevent or slow down viral replication.
141
What do natural killer cells do?
* Specifically kill infected cells and abnormal cancer cells.
* They ignore normal healthy tissues and cells.
* Amplify acute inflammation by secreting the pro-inflammatory mediators.
142
Low levels of ________ complement system proteins are normally found in plasma and extracellular fluids.
inactive
143
The complement system when activated creates a cascade of chemical reactions that promotes which 4 things
* opsonisation of pathogens
* direct pathogen killing
* acute inflammation
* leukocyte recruitment
144
In response to hydrostatic pressure complement molecules can leak out from capillary beds into extracellular fluid. Are they active or inactive at this point?
Inactive, if there is a pathogen present in that compartment they become activated.
145
Which system generates proteins to sustain vasodilation?
Kinin
146
What happens when any of the 3 complement system pathways activate C3?
* C3 cleaves into two active components C3b and C3a
* if the pathogen is present C3b binds to the protein or carbohydrate components on the surface of the pathogen and become stabilised.
* C3b can then activate the cascade but can also feedback and trigger the alternative pathway
147
What do all three pathways which activate the complement system have in common?
All end in a terminal event that generates an active enzyme that can cleave C3 into its active components C3b and C3a.
148
What does the alternative pathway do?
* alternative pathway generates the enzyme complex C3 convertase which can convert more and more C3 into active components
* this is called an amplification loop and is great if the pathogen is present.
149
What happens if C3 is broken down and the environment is sterile?
* host tissue cells also have some of the protein ligands that C3b could bind to.
* it does not activate as human cells express special inhibitory proteins that prevent bound C3 from activating downstream compliment pathway events and ensures the alternate pathway is only activated in the presence of a pathogen.
150
does spontaneous cleavage of C3 occur and if so how is it resolved?
* very little spontaneous cleavage but it does happen.
* C3b is a very unstable protein so when this happens can be rapidly degraded.
* Pathogen induced acute inflammation increases C and helps stabilise any C3b generated through spontaneous cleavage.
151
Mannose binding lectin is also an acute phase protein, where is it produced in response to acute inflammation?
The liver
152
How does the Mannose binding lectin pathway work?
* Mannose binding lectin binds very specifically to certain sugars uniquely expressed by certain bacterial species.
* these include mannose which is not a sugar expressed on human cells.
* so there is selective activation of the complement cascade in the presence of a pathogen
* when bound, mannose binding lectin activates a downstream series of events
* eventually leads to the formation of an enzyme which can cleave C3 into its active components
* strong and rapid response when the compliment system gets going.
153
What happens within the downstream compliment pathway when C3b becomes stabilised on the surface of pathogens?
* when stabilised it can interact with inactive components of the compliment system that can generate an enzyme complex
* Enzyme complex can cleave inactive C3 into components
* strong and rapid response when the complement system gets going
154
What are C3 and mannose binding lectins?
Acute phase proteins
155
What happens to C3 when there is spontaneous cleavage and a pathogen is present?
* it binds to the protein or carbohydrates on the surface of the pathogen and becomes stabilised
* C3b can then activate the cascade but can also feedback and trigger the alternative pathway.
156
What is the alternative pathway termed?
An amplification loop
157
Levels of C3 produced in the liver increase dramatically as a result of what?
Pro-inflammatory mediators such as TNF*a*
158
What happens when C3b becomes stabilised on the surface of pathogens?
When it is stabilised it can interact with other inactive components of the compliment system that can generate an enzyme complex.
159
When C3b becomes stabilised, what can the generated enzyme complex then do?
Cleave inactive C5 into 2 active components.
160
which 2 active components can C5 be cleaved into?
C5a which is soluble and C5b which remains on the surface of the protein.
161
What does C3b do?
Interacts with a large number of other complement cascade proteins and these together generate a complex that forms a pore in the membrane of the pathogen.
162
What is the name of the pore produced by C5b and what does it do?
The membrane attack complex (MAC) which allows salts and extracellular fluid to enter the pathogen at osmotic pressure causing it to swell and burst.
163
C3b leads to the breakdown of C5 and what else?
Opsonisation of pathogens which are responsible for phagocytosis and killing.
164
What do C3a and C5a both do?
* Very much involved in amplifying an acute inflammation by producing a positive feedback loop.
* Can directly promote changes in the local vasculature, mimicking actions of of histamine and and TNF*a:* For example, increased vasodilation, increased vascular permeability
* Regulate expression of adhesion molecules on the endothelial cells that allow circulating neutrophils to attach and undergo transendothelial migration.
165
What is the effect of C3a and C3b on mast cells?
Degranulate and release histamine and more pro-inflammatory mediators.
166
What happens when the innate immune system responds to a pathogen?
* acute inflammation
* macrophages
* mast cells
* natural killer cells
* neutrophils
* complement
* Dendritic cells stimulated
167
Which cells link the two arms of our immune system?
Dendritic
168
What stimulates B cells and T cells?
Antigens
169
What is the main function of dendritic cells in linking the two arms of the immune system?
To process and present antigens to activate T cells.
170
What are the 3 roles of B cells?
* responsible for hummoral immune responses
* produce antibodies that attack pathogens circulating in the blood and lymph
* key role in defence against extracellular pathogens
171
Where do B cells mature?
In the bone marrow
172
Where do T cells mature?
In the thymus
173
What are the 2 key roles of T cells?
* responsible for cellular immune responses
* key role in defence against intracellular pathogens
174
What are the two types of T cells?
CD4+T cells
CD8+T cells
175
What is the key function of CD4+T cells?
Key regulators of the entire immune system
* known as helper T cells as they produce cytokines which regulate innate and adaptive immune systems, key regulators
176
What is the key function of CD8+T cells?
They kill virally infected body cells
177
What happens to both B cells and T cells as they develop?
They learn to distinguish self from non-self.
178
What do pathogens display and which are detected by Pathogen associated molecular patterns (PAMPs) on the innate immune cells?
Pattern recognition receptors (PRRs)
179
What do acquired immune cells contain which recognise antigens displayed on pathogens?
Antigen receptors
180
Why do innate immune cells show non-specific recognition?
* Limited numbers of PAMPs, which are common to many different pathogens
* only a small no. of different PRRs are required to stimulate innate immune cells
181
Why do acquired immune cells show specific recognition to pathogens?
* millions of different antigens- unique to individual pathogenic species
* Individual T cells and B cells only express one specific antigen receptor, which binds to only one specific antigenic epitope.
182
What is the B cell receptor?
An antibody
183
What are antibodies?
Proteins that bind to one specific antigen.
184
Describe the form of antibodies?
* complex of 4 polypeptide chains
* 2 x light chain and 2 x heavy chain
* each antibody has a **unique variable region** that binds to **one specific antigen**.
185
How many antibodies are present in our bodies?
Millions of different antibodies which are able to respond to millions of different antigens.
186
What do B cells use as a receptor to recognise and bind to membrane associated or soluble antigens?
Membrane-bound antibodies
* Each B cell expresses ~50,000 copies of one specific BCR antibody
* different B cells express different antibodies
187
What are the two forms in which antibodies are expressed?
* Membrane bound
* soluble
188
Any specific structure can be an antigen for B cells, name some antigens they can respond to...
* lipids
* nucleic acids
* proteins
* sugars
* metals
* etc
189
What is the only type of antigen which can be recognised by T cells?
Peptide antigens
190
True or false: A single T cell expresses thousands of copies of many different antigen receptors?
False
A single T cell expresses thousands of copies of a single antigen receptor.
191
How is the unique antigen binding of each individual T cell created?
A hypervariable region formed by the tips of the *a*/ß TCR chains forms the antigen binding and is unique to each individual T cell.
192
Each T cell expresses a _______ TCR that can bind to only one specific peptide antigen.
unique
193
Can T cells bind to long or shory peptides only?
Can only bind to short peptides
194
T cells can only recognise peptide antigens presented to their TCRs by which type of molecules?
MHC molecules
195
Protein antigens can become broken down by proteases into short peptide fragments which can be loaded onto MHC molecules to form a \_\_\_\_\_\_\_\_\_\_.
Complex
196
What are the major roles of Major Histocompatibility Complex (MHC) molecules?
Also known as HLA (human leukocyte antigens)
* Display specific peptide antigens to T cells
* MHC/HLA molecules can present many different peptides to T cells.
* not involved in regulating antigen responses by B cells.
197
Name the 2 major classes of MHC molecules
Class I MHC and Class II MHC
198
Name the most professional antigen presenting cells of the immune system
Dendritic cells
199
Where are class I MHC molecules expressed?
On all nucleated cells
200
What do class I MHC molecules do?
Present peptide antigens to CD8 +T cells
201
Where is the _only_ place class II MHC molecules are expressed?
On professional antigen presenting cells (APCs)
202
Name three types of professional antigen presenting cells
* **Dendritic cells**
* Macrophages
* B cells
203
What do class II MHC molecules do?
Present the peptide antigen to CD4+T cells
204
What are the thymus and bone marrow?
Primary lymphoid tissues
205
Where do adaptive immune responses occur?
In secondary lymphoid tissues
206
Mature, quiescent (resting), antigen ________ T cells and B cells constantly re-circulate between the blood, _____________ lymphoid tissues (such as the spleen) and lymphatic vessels.
* specific
* secondary
207
Do naive T cells and B cells remain in the same area within secondary lymphoid tissues?
No, they segregate into different areas
208
What is unique about secondary lymphoid tissues?
They are fed by specialised blood regulatory vessels called high endothelial venules. These constantly express specialised adhesion molecules that allow T cells and B cells to arrest on the endothelial cells and undergo transendothelial migration to enter the lymph node.
209
How do antigens get into secondary lymphoid tissues?
Via the afferent lymphatics
210
How do B cells encounter antigens?
* phagocytes release pathogenic debris which contains membrane associated and soluble pathogenic antigens which are derived from that antigen, these can become opsonised
* these then migrate through the afferent lymphatics with the lymph fluid and become trapped within B cell follicles within the lymph node
211
How do T cells encounter antigens?
1. dendritic cells phagocytose pathogen-derived particles and antigens
2. Pro-inflammatory TNF*a* stimulates immature tissue-resident dendritic cells to increase expression of co-stimulatory molecules.
3. dendritic cells digest ingested proteins and display small peptides derived from these on their cell surface in complex with co-stimulatory molecules.
212
Which zone of the lymph node do dendritic cells enter?
The T cell zone
213
Is binding to an antigen alone sufficient to activate a B cell?
no
214
What are the 2 signals which B cells need to become fully activated and clonally proliferate in response to protein antigens?
1. Antigen
2. 'Helping' cells
215
What happens when B cells become fully activated?
B cell enters the cell division cycle and divides many times to produce clones.
the clonal cells differentiate into plasma cells.
216
What is different about plasma cells in comparison to B cells?
Specialised cells which are much larger than B cells
217
What do plasma cells do?
Produce many antigen specific antibodies which disseminate throughout the body in the blood, lymph and extracellular fluid to help defend from the pathogen.
218
Which type of antibodies are initially secreted by short-lived plasma cells?
Low affinity antigen-specific IgM antibodies
219
Why is there a lag period (about a week) before there is a high level of antibodies in the serum?
It takes time for the cells to clonally expand
220
Which antibody is better, the initial IgM or later IgG antibodies?
IgG is a much better antibody.
221
What happens during somatic hypermutation?
This selects for antibodies that bind much more tightly to the pathogen.
Later on, some B cells mutate so that they produce and secrete **'better' antibodies**:
Switch from low to **high affinity antibody** production.
Allows much more effective killing and elimination.
222
What does switching antibody isotype from IgM to IgG allow?
Delivery of the pathogens to phagocytes
223
Which chain of the antibody changes when the class switches from IgM to IgG?
Heavy chain
224
Does the antigen binding site change or remain the same when the class of antibody changes?
Remains the same
225
Different antibody classes have the same basic structure and same antigen specificity but different _______ chains.
Heavy
226
What happens after B cells switch the class of antibody that they produce?
B cells differentiate into long-lived plasma cells and long-lived memory B cells (Bm)
227
What can long lived plasma cells do which short-lived ones cannot?
Exit secondary lymphoid tissue and migrate into specialised survival niches in the bone marrow where they can survive for years secreting low levels of highly specific antibodies to the pathogen derived antigen.
228
What are the two activation signals for non-protein antigens?
Signal 1: BCR +antigen
Signal 2: PRR + PAMP
229
What are the two signals to activate B cells for antigens with repetitive antigenic epitopes?
Signal 1+ 2: Multiple BCRs + antigens engaged
230
What are the two activation signals for B cells with protein antigens?
Signal 1: BCR binding to antigen
Signal 2: Help from Th cells
231
What happens when a B cell encounters the correct antigen?
* The protein antigen is internalised by receptor mediated endocytosis.
* Peptides and opsonised antigens taken in are chopped up and peptides derived from them are presented on the B cell surface in complex with MHC II
* MHC II are very good at presenting antigen at CD4+T cells like helper T cells.
* As a consequence of these 2 signals the germinal centre response occurs.
232
What happens in the germinal centre and what does this mean?
Rapid clonal expansion of the B cell population which differentiate into plasma cells and produce high affinity antigen-specific antibodies.
Germinal centre means an active humoral response is happening.
233
What 2 functions do antibodies use to help kill and eliminate antigens/pathogens?
* recognition function
* effector function
234
What is the antibody recognition function?
Binding to antigen mediated by variable region sites.
235
What is the antibody effector function?
Clearance mechanisms mediated interaction of the **heavy chain constant region (Fc region)** with effector molecules.
* complement
* Fc receptors
236
What are the 2 forms in which IgM can be found?
* In membrane-bound monomeric form
* In secreted pentameric form
237
What does IgM fo in membrane-bound form?
Serves as the B cell antigen receptor
238
What does IgM do in its secreted pentameric form?
It is the first Ig type produced during a humoral immune response.
present in plasma and secretory fluids
* agglutination
* complement system activaton
239
Can IgM be found in extracellular fluids in tissues in its pentameric form?
No, due to its very large structure which means it is physically incapable of leaving the blood circulation.
240
Why is it good that the secreted pentameric form of IgM has 10 antigen binding sites?
It is very good at recognising and binding the antigen it is directed against.
241
What is the most abundant antibody in normal human serum? It is monomeric
IgG
242
What is agglutination?
* immune complex formation
* The action of an antibody when it cross-links multiple antigens producing clumps of antigens.
243
How is agglutination mediated?
By specific antigen binding to IgM and IgG antibodies.
244
Name the most effective antibody type
IgG
245
What are the 2 things that agglutination does?
* Agglutination increases the efficacy of pathogen elimination by enhancing phagocytosis (clumping of pathogens increases efficacy as it is easier to much away at one big pathogen)
* Prevents viruses then from binding to and infecting host cells.
246
Which complement pathway does IgM and IgG activate?
The classical pathway
247
Why is the classical pathway of the complement system mediated by IgG and IgM?
Its first system protein can bind to the Fc region of IgG and IgM antibodies when they are bound to the antigen- c1.
248
Describe the complex C1
It is a complex of several proteins with 6 different globular heads.
249
What happens when pentameric antigen bound IgM binds to C1?
Allows the C1 complex to engage with and activate downstream components of the complement system pathway to eventually lead to cleavage of C3 to C5a and C5b which can lead to the killing of the pathogen and inflammation.
250
Name the dominant Ig type produced during a secondary (memory) immune response
IgG
251
Which is the only antibody type that can provide protection to a developing foetus?
IgG
252
What are the 6 functions of IgG?
1. Agglutination
2. complement system activation
3. foetal immune protection
4. neutralisation
5. opsonisation
6. Natural killer cell activation
253
Describe foetal immune protection mentioning the antibody which provides it
* **IgG antibodies are transported across the placenta, directly into the foetal blood circulation.**
* developing foetus doesn't have much of an immune response of its own
* gradual increase in maternally transferred IgG antibodies in developing foetus
* At birth no more source of maternal IgG
* Dramatic decline in maternal IgG antibodies in the neonate just after birth and in 1st few months of life
* only by 3-6 months of age neonates own immune system can start to make antibodies
* Up to 6 months neonate is quite vulnerable
254
How is neutralisation mediated?
By specific antigen binding to high affinity IgG and secretory IgA (sIgA) antibodies.
255
Why are IgG antibodies excellent opsonins?
Phagocytes express an Fc receptor that binds specifically to the constant region of the IgG heavy chain.
256
Why is the opsonisation function of IgG antibodies really important?
Really important in protection against encapsulated bacteria as they have slippy polysaccharide coats.
Good opsonisation needed for neutrophils to bind and eat them.
257
What is the IgM heavy chain?
Igu (micro)
258
What is the IgG heavy chain?
Ig*y* (gamma)
259
What is the IgD heavy chain?
Ig*S*
260
Some B cells may switch from IgM to IgD. In membrane-bound monomeric form, IgD serves as a B cell antigen receptor, what does this do?
Mediates B cell activation
261
What is the function of the secreted form of IgD?
It is not well understood
Found at extremely low concentrations in the blood
262
Name the second most abundant Ig type
IgA
263
What is the heavy chain of IgA?
Ig*a* (alpha)
264
How is IgA present in serum and what is its function?
* In a monomeric form
* Functions: neutralisation
265
How is IgA present in secretory fluids and what is its function?
* In a dimeric form (secretory IgA, sIgA)
* Functions:
* neonatal defence
* neutralisation (at mucosal sitess)
* Actively transported across mucosal surfaces
266
Why is secreted IgA important in neonatal defence?
sIgA antibodies are transported into colustrum and breast milk in order to protect the GI tract of neonates.
267
What do IgE antibodies do?
Can trigger allergic responses
* allergy
* asthma
* anaphylaxis
268
Which lymphocytes are involved in acquired (adaptive) immune responses?
T cells
269
Describe the role of dendritic cells
* Large phagocytic cells
* present in a large no. of tissues in contact with the external environment e.g. skin, epithelium in RT
* in infected, inflamed tissues recognise and phagocytose antigenic debris released from neutrophils and macrophages
* Express PRRs which combine with PAMPs on debris
* Migrate and enter T cell areas of the lymph node where they can potentially engage with and activate any antigen specific T cells with specific receptors
270
Pro-inflammatory mediators such as TNF*a* stimulate the dendritic cells to do what?
To express co-stimulatory molecules
271
Where are MHC molecules displayed?
On dedritic cells which are professional antigen presenting cells that can display both classes.
272
MHC I molecules present to \_\_\_\_\_\_\_\_\_\_\_
and
MHC II molecules present to \_\_\_\_\_\_\_\_\_\_\_\_
CD8+T cells
CD4+T cells
273
Which 2 signals are needed to activate dendritic cells?
* specific antigen receptor
* costimulatory molecules which were induced on the dendritic cell back when it was in the peripheral tissues because of the expression of pro-inflammatory mediators also produce a signal
274
One in every million T cells expresses _________ receptor specific for one particular peptide.
Antigen activated T cell _____________ and undergoes _________ proliferation.
* antigen
* differentiates
* clonal
275
What is the minimum length of time needed post-infection for an effective T resposne?
1 week
276
Which type of T cells mediate cellular immune responses?
CD4+T cells
277
Describe the possible pathways of Naive CD4+T cells
* Naive cells spend their life circulating looking for the antigen carrying the specific receptor complimentary to them.
* if they find them they become activated into TH0 cells and proliferate
* differentiation occurs
* fate of TH0 cells and its differentiation path is effected by what cytokines are present in the lymph node at the time of activation.
278
Name the 4 types of CD4+ effector TH cells
* TH1 cells
* TH2 cells
* TFH cells
* Regulatory T cells
279
What happens in the T cell zone of draining lymph nodes?
* CD4+T cells start to produce and secrete a special cytokine called IL2
* IL2 mediates growth, proliferation and cell division in activated T cell in an autocrine manner.
* so the activated T cell secretes the growth factor which stimulates its own proliferation
* T cell also starts to express the receptor for IL2
* eventually get an expanding population of your activated TH0 cells secreting loads and loads of key growth factor IL2
280
True or false: CD8+T cells are just as good at making IL2 as CD4+T cells
False, they are not great at making IL2
281
What do TH1 cells do after differentiation?
* clonally expanded population of these effector cells can actively migrate out of the lymph node and enter the circulatory system where they are attracted to sites of infection and acute inflammation.
* once they've arrived TH1 cells help macrophages kill internalised pathogens.
282
Describe the interaction between TH1 cells and macrophages
* Activated macrophages secrete inflammatory cytokines which allow activated TH1 cells to enter into the infected tissue.
* Macrophage also starts to degrade and break down proteins derived from the pathogen and expresses them on its surface in complex with MHC II molecules.
* so activated macrophages also express MHC II
* If MHC II molecules are expressing the precise peptide TH1 cells can respond so they can actively bind to that peptide MHC complex and provide co-stimulation for the infected macrophage (pro-inflammatory signals that make the macrophage a better killer)
283
Give 4 examples of some pathogens which can escape phagolysosomal killing by macrophages
1. listeria
2. Shigella
3. Mycobacteria
4. Legionella
284
How do some pathogens evade phagolysosomal killing by macrophages?
Infect and propagate in macrophages by escaping from the phagosome into the cytosol.
285
How do TH1 cells 'help' macrophages become super killers?
**Switch on expression of NADPH oxidase genes.**
NADPH oxygenase-dependent mechanisms (the '**respiratory burst**')
\> production of toxic **reactive oxygen species (ROS)**
1. Neutrophil activation (PAMPs, pro-inflammatory cytokines)
2. Assembly of the NADPH oxidase complex.
3. Production and release of ROS into phagolysosome.
286
What do TFH cells do?
Stimulate B cells to develop into long-lived plasma cells which produce high affinity, antigen-specific antibodies.
287
How do CD8+T cells mediate immune responses?
* With help from IL2 released from TH0 cells CD8 helper T cells will proliferate and differentiate into cytotoxic T lymphocytes which are quite small but powerful killers.
* Antigen-activated CD8+ cells proliferate and differentiate into 'killer' cells.
288
What do cytotoxic T lymphocytes (CTLs or Tc cells) do?
* induce apoptosis
* these CTLs migrate out of the lymph node and enter sites of infection in order to kill infected host cells.
289
Why are cytotoxic T cells very good killers of abnormal or virally infected cells
As they can recognise MHC I molecules expressed by all nucleated cells in the body.
In normal cells or uninfected, the only source of these proteins are self peptides which cytotoxic T cells are trained to ignore in normal circumastances.
290
How are any infected/cancer cells killed by cytotoxic T cells?
1. CTL recognises and binds virus-infected cell
2. CTL programmes target for death. inducing DNA fragmentation
3. CTL migrates to new target
4. Target cell dies by apoptosis
291
MHC I molecules constantly sample the internal environment of the cell and select __________ from any proteins present in the cell and display them on their surface.
Peptides
292
Name the 3 types of protein in lytic granules of cytotoxic T cells
1. Perforin
2. Granzymes
3. Granulysin
293
What is the action of the lytic protein perforin on target cells?
polymerizes to form a pore in the target membrane
294
What is the action of the lytic protein granzymes on target cells?
These are serine proteases, which activate apoptosis once in the cytoplasm of the target cell.
295
What is the action of the lytic protein granulysin on target cells?
Induces apoptosis
296
Toxins released from the cytotoxic T cells enter the target cells through the _________ pore.
Perforin
297
Does apoptosis promote further inflammation?
No, apoptosis is a form of cell suicide which does not promote further inflammation.
298
How do viruses try to defend their host cell from cytotoxic T cells?
By sending out signals which downplay MHC I molecules on their surface so they can try to hide.
299
Why does it not allow virus' to defend their host cell by downplaying MHC I molecules?
NK cells actively ignore host cells expressing MHC I, so if they downplay to try hide from cytotoxic T cells then NK cells end up attacking them instead.
300
There is a lot of tissue damage, debris, rubbish, unjury to cells, etc that has to be cleared at the end of an immun response. How is an immune response resolved?
* a lot of pro-inflammatory mediators have a very short half like antibodies and levels of these will die off/decline.
* So there are no problems with chronic inflammation except when you cannot get rid of a pathogen
* all of the debris is mopped up by macrophages
* IL1 become anti-inflammatory cytokines
* at the end of an immune response in the absence of any pathogen or activating antigens macrophages switch character and become anti-inflammatory.
301
Why do we need memory cells?
If we eliminate the pathogen, there is no longer material to initiate further immune response or inflammation which is why they are needed/generated.
302
