Immunology Flashcards
What is the role of the macrophage:
a) at rest?
b) when primed?
a) Processes cellular debris
b) Phagocytosis of invading microorganisms (hyper activation)
Presentation of antigen at the lymph node
What happens when the macrophage is ‘primed’ in response to IFNgamma?
It expresses more MHCII so that it can become an antigen presenting cell
What is ‘hyper activation’?
Component of the innate response:
- Toll like receptor recognises PAMP on pathogen
- Macrophage has increased numbers of reactive oxygen molecules and lysosomes
- Macrophages ingest and kill pathogens (phagocytosis)
What chemicals does the activated macrophage release?
IL1B TNFa IL6 CXCL8 IL12
What does IL1B do?
Local - activates vascular endothelium and lymphocytes
Systemic - fever, activates IL-6 production
What does TNFa do?
Local - activates vascular endothelium and increases its permeability so that more IgG, complement and cells go into the tissue and more fluid is drained to the lymph nodes
Systemic - fever, shock
What does IL-6 do?
Local - activates lymphocytes and increases antibody production by plasma cells
Systemic - fever, acute phase protein production
What does CXCL8 do?
Local - recruits neutrophils, basophils and T cells to the site of infection
What does IL12 do?
Activates NK cells and induces CD4 T cells to become Th1 cells
How does a natural killer cell work?
- Recognises infected cells in the absence of antibodies or MHC molecules
- Forms a pore in the cell membrane of the target cell so that granzymes can enter and induce apoptosis
How does a neutrophil work?
Ingests and kills microbes by phagocytosis, hallmark of acute inflammation
THEY ARE NOT APCs
What chemokines often attract immune cells to the site of infection?
IFNgamma, IL8
What is the role of dendritic cells?
At rest - sample the environment
Primed - Phagocytosis of pathogens and APC, travels to local lymph node to await T cell sampling and then activation. Also secretes monocytes to the site of infection
How long do dendritic cells live?
They die after 1 week at the LN, to prevent T cell activation in absence of infection
What do dendritic cells make when there is no infection, and what is the purpose of this?
TGFb and IL6 (in v small amounts)
This activates CD4T cells to express FOXP3 and become Tregs
What do dendritic cells produce when there is an infection?
IL6, IL12, IL4
These chemicals cause naive CD4 t cells to become T helper cells
What are the different types of B cells and what do they do?
Plasma cells - antibody production
Memory cells - enable faster antibody production in future infections
Follicular cells - reside in the lymph nodes
What is the role of a B cell in the early stage of an infection?
They can act as a APC as they have a very high affinity for the antigen
They need to be activated by an activated T cell
What happens once a B cell has been activated?
a) form a primary focus in nearby medullary cords
a) forms a germinal centre in a nearby follicle
What is the purpose of a germinal centre?
Some cells will leave the primary focus to form a germinal centre.
It is a site where mature B cells:
- differentiate
- proliferate
- mutate their antibody genes (somatic mutation)
- class switch their antibodies (Igm - Igg)
At the end of this process, B cells will leave as a memory cell, plasma cell, or they may have to restart the process again
What are the different types of T cells and what do they do?
CD4 T helper - assist in B cell maturation and activation of cytotoxic T cells and B cells and macrophages
CD8 T killer - destroy virus infected cells
T regulatory (FOXP3) - shut down T cell mediated immunity towards the end of a reaction and prevent autoimmunity
What activates CD4 T helper cells?
MHCII molecules on APCs
What activates CD8 T killer cells?
- MHCI molecules on all nucleated cells
- Activation by CD40L from cytokine secretion by the CD4 cell
What are the three APCs?
Dendritic cells
Macrophages
B cells
Describe the two pathways that stop the immune system
Intrinsic - lack of survival sign prompts release of cytochrome c from the mitochondria causing apoptosis
Extrinsic - Fas causes activation of death domains with FADD
Both pathways involve recruitment of PROCASPASE, which induces APOPTOSIS
What is an immune privileged site?
Somewhere where there are no immune cells eg. eyes, brain, testes
What is the definition of auto reactivity?
The presence of immune response reactive with self antigens, which is often harmless
What is autoimmunity?
A disease process resulting from auto reactivity
What is central tolerance?
- In the thymus and bone marrow, maturing lymphocytes are exposed to self-antigens from MHCII molecules
- Lymphocytes that bind strongly to self-antigen are deleted by apoptosis
- Those that are weakly auto reactive may become Tregs, which go on to regulate peripheral tolerance
This process is known as negative selection
What is peripheral tolerance?
- Tregs, DCs and other regulatory cells recognise self-reactive T/B cells in the periphery
- These cells are either inactivated or deleted
What is a type I hypersensitivity reaction?
An IgE mediated response in which:
- Antigen induces cross linking of IgE bound to mast cells and basophils
- When antigen is reintroduces, vasoreactive markers are released from degranulation of the mast cell
What is an example of a type 1 reaction?
Anaphylaxis
Allergy
What is a type 2 hypersensitivity reaction?
An IgM/IgG/complement mediated response in which:
- There is a cytotoxic reaction against a harmless antigen
- Antibody-mediated
What in an example of a type 2 reaction?
Blood transfusion reaction
Myasthenia Gravis
Graves Disease
Goodpastures
What is a type 3 hypersensitivity reaction?
An IgM/IgG/Neutrophil mediated reaction in which:
- An immune complex is formed, which is deposited in various tissues causing massive neutrophil infiltration
What is an example of a type 3 reaction?
Vasculitis
Rheumatoid arthritis
SLE