Immunology Flashcards
What is the difference between the innate and adaptive immune response?
Innate immunity is present continuously, it is a defence mechanism that is present from birth. The innate immune response is rapid and attacks microorganisms indiscriminately. Adaptive (acquired) immunity is induced by the presence of foreign material and is usually quite specific. Adaptive immune response mediated by T and B cells.
Explain natural barriers to infection
The skin: This acts as a physical barrier as it is composed of tightly placed, highly keratinized multi layers of cells and constantly undergoes renewal and replacement. Many pathogens also cannot survive on surface of the skin due to the slight acidity and low oxygen tension. There are also sebaceous glands and these can secrete hydrophobic oil, lysozyme, ammonia and antimicrobial peptides.
Mucous Membranes: Line all body cavities that come into contact with the environment. The mucus traps bacteria which are subsequently removed by ciliated cells. Secretory IgA prevents bacteria and viruses attaching to an penetrating epithelial cells. The mucous also contains enzymes such as lysozmes, defensins and antimicrobial peptides.
Commensal Bacteria: Compete with bacteria for scarce resources.
What cells are involved in the innate immune response?
Macrophages, Dendritic Cells, Natural Killer Cells, Mast Cells and Neutrophils
Describe how pathogens are recognised by innate immune cells
Pathogens express signature molecules not found on/in human cell called ‘Pathogen associated molecular patterns’ (PAMPS) that are common to many different pathogens. Innate immune cells express partner receptors for these PAMPS.
What are three neutrophil killing mechanisms?
Phagocytosis, Degranulation and NETs.
How are neutrophils activated and how do they reach the site of injury?
Pro-inflammatory mediators which alter the local vasculature allow neutrophils to exit the blood stream at that site and enter infected tissue. This process of them moving from the blood to the tissues is called transendothelial migration.
What is responsible for inducing fever?
Pro-inflammatory mediators released by activated macrophages
What does the acute phase response involve?
Involves changes in the plasma concentrations of specific proteins in response to inflammation.
What is the role of the C reactive protein (CRP)?
Release in the acute phase response, this protein primes certain bacteria for destruction by the complement system.
What is the complement system?
This is a family of approximately 30 proteins that are produced in liver. They circulate in the blood and constitute 10% of serum proteins. They enter infected and inflamed tissues. The complement system, when activated, creates a cascade of chemical reactions that promotes opsonization, chemotaxis, and agglutination, and produces the MAC.
How do MACs form and what is their function?
Membrane attack complex formed by the last five proteins in the complement system, they insert themselves into pathogen membranes allowing extracellular salts and water to enter, causing the microbe to swell and burst. (OSMOTIC LYSIS)
Describe two ways in which the complement system can be activated
1) Mannose-Binding Lectin Activation Pathway:
Selective activation arises because mannose expression is unique to certain pathogens. It is not expressed on human cells.
2) Alternate Activation Pathway
C3b is unstable and rapidly degraded unless it binds to cell surfaces. Human cells express inhibitory proteins that prevent C3b from activating downstream events. However, pathogens do not express these inhibitory proteins resulting in activation of the pathway.
What is an antigen?
Any substance which can cause an adaptive immune response by activating B cells and T cells
Describe the structure of antibodies
- They are a complex of four polypeptide chains.
- Each antibody has unique variable region that binds to one specific antigen (variable region at the top, constant region at bottom)
What two signals do B cells need to become fully activated?
1) Antigen
2) ‘Helper’ signals from T cells
What two types of cell can B cells differentiate into?
1) Plasma cells- produce and secrete soluble, antigen-specific antibodies.
2) Memory B cells- long lived cells that continue to circulate around the body.
How do antibodies kill or inactivate pathogens?
- Antibodies provide immunological defence against extracellular microbes, they recognise the microbe as foreign and inactivate/eliminate the microbe
- They can bind to soluble antigens or to membrane-bound antigens expressed on the surface of microbes or other immune cells.
- Agglutination is mediated by the antigen binding sites of antibodies. This is the clumping together of particles caused by antibody molecules binding to antigens on the surface of two adjacent particles.
- This increases the efficacy of microbial elimination by phagocytosis as large clumps of bacteria can be eliminated in one pass, versus the elimination of single microbial antigens.
- Different antibodies can work together (recognizing different antigens), causing virus particles to stick together in agglutination.
What is the only type of antibody that can cross the placenta?
IgG
What are the two types of T cell?
- CD4+ T Cells: Key regulators of the entire immune system
* CD8+ T cells: Kill virally infected body cells
What do T cells recognise and how is this different from B cells?
T cells only recognise peptide antigens (B cells recognise appropriate region on full protein)
What must peptide antigens be presented by to T cells
MHC molecules
What is the differences between the two classes of MHC?
1) Class 1: Expressed on all nucleated cells, these present antigens to CD8+ T cells.
2) Class 2: Expressed only on professional antigen presenting cells (dendritic cells, macrophages, B cells). These present peptide antigens to CD4+ T cells
Describe the process of T cell activation
1) Particles and antigens derived from pathogens are released by phagocytes
2) Dendritic cell phagocytose pathogen-derived particles and antigens
3) Pro-inflammatory TNFa stimulates immature tissue-resident dendritic cells to increase expression of co-stimulatory molecules
4) Dendritic cells digest ingested proteins and display small peptides derived from these on their cell surface in complex with MHC proteins.
5) Antigen-activated CD4+ cells regulate innate and adaptive immune responses.
6) Activated cells, proliferate and then differentiate into effector cells and memory cells.
What do CD4 T cells differentiate into?
Helper T cells
1) TH0 cells: produce Interleukin 2 helping to boost CD8+ cells
2) TH1 cells: migrate out of lymph nodes and enter infected/ inflamed tissues
3) TFH cells: these help the B cell response
What do CD8 T cells differentiate into?
Cytotoxic T cells/ CTLs
How do Cytotoxic T cells kill?
- In response to engagement all granules are moved to the front of the cell, accumulating right next to the infected cell.
- The granules contain perforin which makes a pore in target membrane.
- Granzymes and granulysin activate apoptosis once in the cytoplasm of the target cell.
Describe restoration back to homeostasis
- Most of the effector cells are short lived so will die off naturally reducing numbers
- Macrophages release anti-inflammatory cytokines stimulating tissue repair.
What is pinocytosis?
Internalisation of fluids into the cell
C reactive protein is
an acute phase protein that helps activate the complement pathway and is an important mediator of opsonisation of bacteria
What does perforin do?
forms pores in the target cell to allow molecules that induce apoptosis into the infected cell
Which antibody is the first to be made in the immune response?
IgM
Which antibody dominates in second exposure?
IgG
What antibody is present in secretions?
IgA
What antibody is important in allergic reactions?
IgE