Lecture Eighteen - Immunology Flashcards
What proof is there that the immune system exists?
SCID = Severe combined immunodeficiency Disease:
Children that lack ability to generate key aspects of immune system.
Need sterile environment to survive.
Fatal if not treated.
AIDS = Acquired Immunodeficiency syndrome:
Cells of the Immune system are target of the human immunodeficiency virus.
Reduced immune defense allows opportunistic infections and uncommon diseases to become life threatening.
Diseases that are rarely seen in population are killers here.
What are the ‘layers’ of the immune system?
What are the different cells of the immune system?
What processes and mechanisms come into play when a pathogen enters the body?
Recognition of a pathogen invasion.
Response to that invasion.
Send out signals to recruit further asistance to deal with invasion.
Deal with invasion.
What structures can the innate immune system recognise?
Pathogen Associated Molecular Patterns (PAMPs) are structures which are only present on pathogens, and not self cells.
E.g. Flagellin, lipopolysaccharides and dsRNA.
Pattern Recognition Receptors (PRRs) are a group of innate receptors which can reognise pathogen structures.
A type of PRR’s are the **Toll Like Receptors. **
They are similar in structure but have some speicificity.
- TLR4 binds to LPS.
- TLR5 binds flagellin.
- TLR3 binds dsRNA.
They can be located within, or outside the cell.
- TLR4 and 5 on the outside.
- TLR3 on the inside.
What is phagocytosis and how does it work?
A consequence of bindsing Pathogen Associated Molecular Patterns (PAMPs) and Pattern Recognition Receptors (PRRs) is phagocytosis.
This is accomplished by cells that can act as phagocytes = macrophages and neutrophils.
Phagocytosis:
Internalisation of large particle (pathogen) into specialised compartement.
Release of mediators to cause injury to the pathogen molecule.
- Enzymes, free redicals and peroxides.
What is the approximate number of the different cell types in the body at any one time?
What is an simple over view of a generic adaptive immune response?
- Antigen exposure and presentation
- Antigen: structure that can induce immune response. - T cell activation
- Finding the right T cell from cells available. - Bcellactivation
- Finding the right B cell from cells available. - T and B cell effector functions
- T and B cells help clear the pathogen.
What are MHCs?
MHC = Major histocompatibility complex.
• There are two types of MHC.
- MHC class I and MHC class II.
- They can both present peptides.
- MHC class I is expressed on all cells of the body (except red blood cells, which lack a nucleus).
- MHC class II are expressed on only few types of immune cells.
- Dendritic cells as main cells that initiate adaptive immunity (and are also part of innate immunity).
- B cells (These also make the antibodies).
- Macrophages (These were mentioned as
innate cells).
SO, antigen presenting cells can express peptides on surface MHC and this is the key way that T cells interact with cells expressing MHC.
T-cell receptor (TCR), is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex (MHC) molecule
What are dendritic cells?
Dendritic cells (DCs) are antigen-presenting cells, (also known asaccessory cells) of the mammalian immune system. Their mainfunction is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and theadaptive immune systems.
Explain a generic adaptive immune response.
Dendritic cell moves to a near by lymph node.
Lymph nodes (including spleen) are packed full of T and B cells.
Dendritic cell which has picked pathogen at the site of infection migrates to the nearest (draining) lymph node.
Goal 1 is hopefully find a T cell that will recognise the processed antigen presented its surface MHC molecules.
Goal2 is to also find a B cells that is specific for pathogen.
What defines the specificity of B and T cells?
- T cells and B cells express receptors on their surface called antigen receptors.
- On T cells are are called T cell receptors (TCR).
- Each T cell has a unique receptor.
- Each TCR on anyone T cell is the same.
• On B cell they are called B cell receptor (BCR).
- Each B cell has a unique receptor.
- Each B CR on any one B cell is the same.
- Once B cells are activated, they secrete the receptor, this is called antibody or immunoglobulin.
–> T cells DO NOT do this.
T cell receptors:
- Composed of 2 different chains.
- (α and β).
Regions classified as:
• Constant- similar across all TCR.
- Variable.
- Specific to each TCR.
- TCR binds to “sees” MHC plus peptide.
Note how the TCR “docks” down on the MHC+ peptide.
B cell receptors:
- Composed of 4 chains.
- 2 x 2 pairs (heavy and light chains).
Regions also classified as:
- Constant- similar across BCR.
- Variable.
- Specific to each BCR/antibody.
- BCR/antibody binds to “sees” structures as they exist in nature.
I.e. not processed or broken down.
- T and B cell receptors are not the same.
- Different structures and behave differently.
- Each individual T and B cell has a slightly different receptor specificity.
- What it can bind to or recognise.
- This is called diversity and what enable us to respond to anything.
- This diversity is generated through processed called somatic recombination.
- It affects the “tips” of the receptors.
How is receptor diversity achieved?
Problem:
- For our species to survive immune system has to be able to respond to a vast number of foreign and unknown pathogens.
- The innate system with its receptors can help to some extent but not that many receptors => limited scope.
- Innate receptors (eg TLRS) are germline encoded and can be inherited.
- Having encoded in our genome a receptor that could potentially bind to any pathogen now and into the future is unthinkable => need thousands/millions??
- Genome not big enough to encode (30,000 genes now).
- Immune system has gotten around this by mixing and matching little bits of genome in each cell as it develops to generate receptors that look the same but have subtle differences.
Solution:
• Variable regions (of heavy and light chains) are generated from gene segments called V(D)J (depending on whether heavy or light chain).
- V stands for variable, D stands for diversity and J stands for joining.
- There are sets of variations of these encoded in the genome and so found in all cells of the body and also germ cells.
For heavy chains- there are:
44 individual V segments.
4 individual D segments.
6 individual J segments.
For the light chain- there are:
31 individual V segments.
No D segments for light chain.
5 individual J segments.
The variable region of the heavy chain will have 1 of each VDJ segment.
The variable region of the light chain will have 1 of each VJ segment.
Each binding pocket is made from heavy and light chain so total combinations possible from just recombination of segments is 1056 x 155 = 163,680.
This process happens in each T and B cells as it develops, independently and randomly.
Germline cells are not processed- that is why we can inherit the ability to generate an adaptive immune response but not a generated one.
This is why vaccination cannot be inherited and each generation needs to be immunised in its own right.
Describe the basics of a viral infection - from the viruses perspecive.
Infected cells producing new viral particles.
Release viral particles capable of infecting adjacent cells.
All cells express MHC class I and this in virally infected cell, viral peptides will also be presented on the surface of that cell in MHC.
Note - in non-infected cell these peptides are self peptides.
New viruses released from cell are bound by the antibody and prevented from infecting a new cell- thus stopping the spread of virus- blocking further infection.
The cytotoxic T cells activated in lymph node will then search for cells expressing the same peptide in MHC (ie viral peptide) and kill that cell via apoptosis.
This eliminates the capacity to make new viruses.
Antibodies mop up free virus.
- Via natural shape/structure of virus.
T cells kill virus infected cells.
T cells do not bind directly to virus.
What are the five phases of adaptive immune response?
Recognition, Activation, Effector, Decline, Memory.
It is the ability to generate memory cells that enables vaccination to work.
One subsequent exposure to the same pathogen, immune respinse is much faster and stronger in response.
