Introduction to the Immune System 2 Flashcards
Where are all our immune effector cells derived from?
From a common pluripotent progenitor cell (Hematopoietic stem cells/0 type in bone marrow
What are all our immune effector cells a part of?
Our Hematopoietic blood system
What are pluripotent progenitor cell?
Hematopoietic stem cells
What are all our white blood cells called?
Leukocytes
Name some white blood cells
Ganulocytes
Megakaryocyte
Following stem cell division what can a daughter cell do?
- Divide
2. Differentiate
Why is it a benefit that some of our daughter cells don’t differentiate but divided into more stem cells?
Means we have stem cells to replenish our blood system as we get older
What is the first step of differentiation a stem cell can take?
Cells can either become:
- A Common lymphoid progenitor
- A common myeloid progenitor
What do Common lymphoid progenitor give rise to?
B cells
T cells
NK cells
What do Common myeloid progenitor give rise to?
Granulocytes and megakaryocytes (White blood cells)
Or dendrites
What happens to a cell as it further differentiates?
They lose the ability to self renew
Name our adaptive effector cells
B cells (which give plasma cells) T cells (which give activated T cells)
Name our innate effector cells
NK cells (which give us activated NK cells) Dendritic cells (both mature and immature) Neutrophils Eosinophils Basophils Monocytes Mast cells Macrophages
What lineage do dendritic cells come from?
Ether a myeloid or lymphoid lineage
Name the only type if lymphocytes that are considered innate
NK cells
natural killer cells
What are monocytes?
The precursor to macrophages
Which is the mature effector: the macrophage or the monocyte?
The macrophage
Where are immature monocytes found?
They circulate the blood
Where are mature macrophages found?
Found in most tissues in sub mucosal layers.
What is the function of monocytes and macrophages
- They are the first responders
- Phagocytic
- Engulf and kill pathogens and infected cells
- Clear dead cells and debris
- Bactericidal
- Present antigen to T cells
- Activate other immune cells
- Induce inflammation
Do macrophages and monocytes have a long or short lifespan?
Long
What does it mean a cell is phagocytic?
They can engulf and kill pathogens and infected cells
They can also clear dead cells and debris
What is another name for granulocytes?
Polymorphonuclear leukocytes
Name the 3 types of granulocytes
- Neutrophils
- Eosinophils
- Basophils
Which of the 3 types of granulocytes has a role in the immune response?
Neutrophils
What is the main role of Eosinophils and Basophils?
Main role is anti parasitic
Where are neutrophils found?
In the blood they migrate to infection sites
What are the functions of granulocytes?
- Phagocytic
2. Bactericidal
Describe the life span of neutrophils
They have a short life span
What is pus made up of?
Dead neutrophils
Describe the morphology of neutrophils
They have lobes nuclei
Their cytoplasms is speckled with cytotoxins
Where are immature dendritic cells found?
Under surface epithelia and in solid organs
They migrate to lymph nodes and mature there
What are the functions of dendritic cells?
- Phagocytic /Macropinocytosis
- Take up antigen to present to adaptive arm
- Activate cells of the adaptive arm
Where are natural killer cells found?
In the blood
They migrate to infected tissues and tumours
What are the functions of natural killer cells?
- Extracellular release of cytotoxic granules
- Anti viral
- Anti tumour
What type of cells are natural killer cells?
They are lymphocytes but are considered within the innate arm of the immune system
How do dendrites mature?
They are immature in the tissues but when they engulf bacteria and migrate they mature
What do dendritic cells do?
Take antigens from the site infection to the lymph nodes and they initiate the adaptive immune response
Describe the morphology of natural killer cells
They have a large single lobed nucleus
Bigger nucleus to cytoplasm
They have cytotoxins
Which cells do our NK cells kill?
Non- self cells
Name some phagocytic cells we have
- Macrophages
- Neutrophils
- Dendritic cells
How to phagocytic cells decide what they want to engulf?
By using different receptors on their cell surface and within the cell
What do Fc receptors look for?
Antibody coated pathogens
What do compliment receptors look for?
Activated compliment molecules like: CRb
What do receptors on phagocytic cells look for?
- Self cells
2. Non-self cells
What does PAMP stand for?
Pathogen associated molecular patterns
What do pattern recognition receptors look for?
Common structures we see in microbes (PAMPs)
What do we call common structures we see in microbes but not in higher organisms?
Pathogen associated molecular patterns (PAMPs)
Name the different types of PAMPS
- Lectin like. Dectin 1
- Scavenger receptors.
- Toll like receptors
Give examples of toll like receptors
TLR4
TLR6
What are toll like receptors always expressed as?
Diamers
Some are homodiamers and some are hetero diamers
Describe how phagocytosis is activated
- Compliment activation leads to deposition of c3b on the bacterial surface
- Compliment receptor 1 (CR!) on macrophage binds to C3b on bacteria
- Endocytosis of the bacterium by the macrophage
- Macrophage membrane fuses creating a membrane- bounded vesicle (Phagosome)
- Lysosomes fuse with the phagosomes forming phagolysosomes
What is a phagosome?
When macrophage membrane fuse creating a membrane-bounded vesicle
What are phagolysosomes?
When lysosomes fuse with phagosomes
How many toll like receptors do humans have?
10
What do TLRs detect?
They each recognise a distinct set of PAMP not found in vertebrates
Name some compounds toll like receptors detect
- LPS of gram negative bacterial outer membranes
- Lipoteichoic acids of gram positive cell walls
- ds RNA
- glucans such as zymosan (fungi)
What is Lipoteichoic acid recognised by?
TLR2 and TLR6
What is LPS recognised by?
TLR4
Where are TLRs expressed
Some are expressed on the cell surface and some inside the cell itself
Some are present on our epithelial cells
What do TLRs expressed inside the cell detect?
They detect molecules that may be present if we are under inter cellular attack like viruses or double stranded RNA
What do TLRs on epithelial cells do?
They trigger the cells to release communicating molecules like inflammatory cytokines and antimicrobial peptides
Name some of the antimicrobial mechanisms phagocytes employ once they have engulfed a pathogen
- Acidification
- Toxic oxygen derived products
- Toxic nitrogen oxides
- Antimicrobial peptides
- Enzymes
- Competiors
What is Acidification?
When a phagosome reduces the ph to around 3.5-4 which can lead to bacteriostatic or bactericidal
What is the respiratory burst?
It is triggered by phagocytes when they engulf a pathogen
It results in the cells producing a lot of toxic oxygen species and nitrogen species
Name some toxic oxygen derived products
- Superoxide O2-
- Hydrogen peroxide H2O2
- Singlet oxygen
- Hydroxyl radical
- Hypo-halite
Name some antimicrobial peptides macrophages produce
Cathelicidin (LL37)
Name some antimicrobial peptides neutrophils produce
Cathelicidin (LL37) Alpha defensins Beta defensives Azurocidin Bacterial permeability inducing protein Lactoferrin
What enzymes do phagocytes produce to break down engulfed pathogens?
Lysozyme
Acid hydrolyses
What does lysozyme do?
It breaks down cell walls of some gram positive bacteria
What do Acid hydrolyses do?
Break down ingested microbes
Name some Acid hydrolyses
Elastase and other proteases
Name some competitor molecules neutrophils produce
Lactoferrin
Vitamin B
How does lactoferrin act as a competitor
It binds to iron ions and locks them up (sequesters iron ions) so that bacteria cannot use them
What are cytokines?
A small protein that affects the behaviour of other cells
They act via a specific cytokine receptor expressed on the surface of the cell type they affect
What are chemokine?
A small chemoattractant protein that stimulates the migration and activation of cells
They act via specific receptors expressed on the surface of the cell type they affect
Cytokines produced by lymphocytes are called what?
Interleukins
Macrophages have an important role in what?
Co ordination of the immune response
What stimulates the macrophages to release cytokines?
Engulfing a pathogen
What do macrophages release?
Cytokines
Chemokines
What do cytokines have a profound effect on?
Cells lining the blood vessels (our vascular endothelial)
This makes the blood vessels to be more permeable (Leaky)
What is an advantage of cytokines making our blood vessels leakier?
Allows neutrophils to crawl out through the blood vessels near the infection site
Allows more plasma fluid to get to the infection site
What do chemokine cells do during an infection?
They draw the neutrophils to them telling them were to go
How does the compliment system help when they body suffers from an infection?
The formation of the membrane attack complex will allow for cell lysis to occur
Describe what steps the body takes initially when it is infected
- Increased permeability which increases flow of plasma proteins (eg compliment) to site
- Diameter of blood vessels increases this slows down blood flow
- Clotting of some local micro vessels to inhibit infection spread
- Endothelium now promotes leukocyte binding, increasing extravasion.
Describe the innate defence system
Eg response time, cel recognition, memory
- Responds on minutes-hours
- Is always presnt
- Has a limited range of antigen detection receptors
- It is unchanged during the response
- Genome encoded receptors
- No memory
Describe the adaptive defence system
Eg response time, cel recognition, memory
- Take days-weals to response
- Is usually silent till activated
- Has a vast range of antigen receptors
- Receptor recognition improves during the response
- Receptors are not genome encoded
- Has memory cells
What initiates the adaptive immune response?
Dendritic cells
What happens to innate response when the adaptive immune response is initiated?
Increases the efficiency of our innate response
Define antigen
Any molecule or fragment of molecule that is recognised by the specific receptors found on B and T lymphocytes
Define specificity
The ability of an antibody/ antigen receptor to distinguish a particular antigen from other antigens
What does adaptive immunity generate?
Vast range of recognition specificity
Random generation of specificity
How are effector cells made?
- A single progenitor cell gives rise to a large number of lymphocytes each with a different specificity
- Removal of potentially self-reactive immature lymphocytes by clone deletion
- Pool of mature naive lymphocytes forms
- Proliferation and differential of activated specific lymphocytes to form a clone of effector cells
What does each immature B cell have>
A single and unique specificity for antigen
We need more than one individual cell of each specificity to combat an infection, how is there space in the haematopoietic system?
A particular cel encounters its complimentary antigen
This causes the cell to proliferate and form a clonal army
How can Random receptor generation cause problems with recognising self and non self
As we produce self antigen receptors which have to be removed by clonal deletion when the cells are still immature in the bone marrow or thymus
Cells under apoptosis
What problems can occur if our body can’t distinguish between self and non self
Our body will start attacking its own cells-> auto immune disease
What is clonal deletion?
Apoptosis of lymphocytes that have antigens complimentary to self cells
How is there enough space in the genome to encode all these receptors
The DNA sequences encoding antigen receptors in mature effector cells is different in progenitor / stem cells
What happens after clonal expansion?
Cells further differentiate to generate effector cells, plasma cells, memory cells and effector T cells as
What cells do B cells further differentiate into?
Memory cells and plasma cells
What cells do T cells further differentiate into?
Effector T cells and memory cells
What Is our B cell antigen receptor?
A membrane bound antibody molecule (immunoglobulin )
Name our B cell antigen receptor
mIg (membrane immunoglobulins)
It binds ti antigen alone
What Is our T cell antigen receptor?
The T cell receptor can’t recognise antigen on its own it can only see it is antigen if the antigen is complexed with another molecule called Major Histocompatibility Complex
What does MHC stand for?
Major Histocompatibility Complex
Define epitope
A site on an antigen that is recognised by specific lymphocyte receptors.
What are epitopes made of?
Carbohydrates, proteins or both:
Name the 2 types of epitopes
- Continuous/Linear
2. Conformational / discontinuous
Describe continuous/ linear epitopes
They are a single fragment of polypeptide chain
Describe Conformational / discontinuous epitopes
amino acids that are not continuous in the polypeptide sequence but are brought together in 3D structure.
Where do B cell recognise epitopes?
Epitopes found on surface of antigen structure.
Where do T cell recognise epitopes?
more likely to recognise linear short peptide (often buried within antigen structure) presented by an MHC molecule. Continuous.
What are multivalent antigens?
One antigen that contains many epitopes
Describe multivalent antigens
Can be all the same (repeated sequence) but more commonly are chemically distinct.
Epitopes within folded myoglobin chain.
Which innate cell would you find in most tissues in the sub mucosal layer?
Mature macrophages
Which innate cell would you find circuiting the blood?
Immature monocytes
Neutrophils are what?
Granulocytes (Polymorphonuclear leukocytes)
Which receptor looks for antibody coated pathogens?
Fc receptors
Which receptors look for Activated compliment molecules like: CRb?
Complement receptors
Which receptors look and target non self cells?
Pattern recognition receptors
What are pathogen associated molecular patterns?
They are common structures we see in microbes that are detected by pathogen recognition receptors
What does TLR4 recognise?
LPS
What are Interleukins?
Cytokines produced by lymphocytes
How do cytokines act?
via a specific cytokine receptor expressed on the surface of the cell type they effect
What do TLR2 and TLR6 recognise?
Lipoteichoic acids
What does PRR stand for?
Pattern recognition receptors
What does PAMPs stand for?
Pathogen associated molecular patterns
What does TLR stand for?
Toll like receptors
What makes up 90% of our lymphocytes?
B and T cells
What is the name of an antigen that contains many epitopes?
Multivalent antigens
B and T cells make up what?
90% of our lymphocytes
