Lecture 1 (Week 1A) - Introduction Flashcards
Why is immunology important and interesting?
- it is of fundamental importance for life
- immunology underpins vaccination
- immunological techniques underpin many diagnostic technologies
- many of the diseases of the modern world are caused by the immune system going wrong
The answer to most immunology questions is
“it depends”
• context is everything!!!
Important features of the immune system
• complexity
• redundancy
• its basic function is to distinguish between
SELF vs NON-SELF
The basic function of the immune system is
to distinguish between SELF and NON-SELF
Even low-grade pathogens find us nourishing
- bacteria in the gut (10,000 species)
- Staphlycocci on skin
- Klebsiella/Neisseria/Pneumococci in throat
• when they get into the wrong place, without an immune system, we die
• even with an immune system they can still kill us
HIV kills
immune cells (T-cells)
• patients die of opportunistic infections
(Pneumocystis carinii, Cryptosporidium, atypical Mycobacteria_
The immune system is very complex, with lots of different potential problems, but the most extreme phenotype is
lack of lymphocytes
SCID
severe combined immune deficiency
• lack of lymphocytes
• lots of causes
A baby with SCID may have
recurrent bacterial, viral, or fungal infections that are much more serious and less responsive to treatment than would normally be expected. These can include • ear infections (acute otitis media) • sinus infections (sinusitis) • oral thrush (a type of yeast infection in the mouth) • skin infections • meningitis • pneumonia • infants with SCID may also have chronic diarrhea
The cells of the immune system come from
a stem cell in the marrow
T cells mature in the
thymus (hence T)
B cells are so-called because
they were identified in the chicken Bursa
In mammals, most b cells are made in
bone barrow
Primary lymphoid tissues
Bursa
Thymus • capsule • thymic corpuscle • thymic lobule • cortex • medulla • interlobular septum
(ask about bone marrow)
Secondary lymphoid tissue
- tonsils
- lymph nodes
- lymphatic vessels
- liver
- spleen
- Peyer’s patch on small intestine
- appendix
Key basic concepts in immunology
- the immune system recognizes pathogens by responding to non-self
- an antigen is anything which elicits an adaptive immune response
• self antigen
• foreign antigen - the adaptive immune system shows exquisite specificity
- like the brain, the immune system has memory
The immune system recognizes pathogens by
responding to non-self
• self vs non-self
An antigen is
anything which elicits an adaptive immune response
• self antigen - when the immune system goes awry and starts responding to self
• foreign antigen - when the antigen comes from outside you
Self antigen
when the immune system goes awry and starts responding to self
Foreign antigen
when the antigen comes from outside you
Immune cells need to respond to foreign molecules (pathogens) - they use
surface receptors
Lymphocyte (T or B) • antigen specific T cell receptor • antigen specific B cell receptor --> massive cell division then effector function (adaptive immunity)
Phagocyte • pattern recognition receptors • Fc receptors --> do their business immediately (innate immunity)
Surface receptors - Lymphocyte
Lymphocyte (T or B) • antigen specific T cell receptor • antigen specific B cell receptor --> massive cell division then effector function (adaptive immunity)
Surface receptors - Phagocyte
Phagocyte • pattern recognition receptors • Fc receptors --> do their business immediately (innate immunity)
In health, white cells are
- in blood and lymph nodes
* not in tissues
Innate immunity eg step on nail
normally, neurophil in blood remains in vessel
step on a rusty nail (how does the host know the infection is there?) • neurophil in blood leaves vessel --> bacteria phagocytosed and killed • endothelial cells cytkines increase adhesion molecules • vessel becomes sticky
Pathogen-associated molecular patterns
- gram + and gram - bacterial cell wall
- virus
- bacterial flagella
- eukaryotes (us)
The Toll-like receptors
molecules on the surface of mammalian cells which recognize components of bacteria and viruses to alert the immune system
• 10 of them
–> cell becomes activated and starts to make pro-inflammatory cytokines
A spot is
inflammation and tissue injury caused by white cells leaving the blood and going into a follicle to kill skin bacteria growing in the wrong place
Acne
inflammation is when white cells leave the blood and move into the tissues - and in the process of getting rid of the bugs, kill normal tissue as well
• neutrophils produce, and are full of, dangerous molecules and die in tissues
–> destroys normal tissue as well
Ulcerative colitis
- neutrophils
- crypt abcesses
- usually superficial
- organ specific
Adaptive immunity
- at birth we already have T and B cells which can recognize billions of different foreing antigens, wo we are ready for any infections
- but as there are 10^13 cells in our body, we cannot devote them all to the immune system
- if we have 10^11 lymphocytes which can respond to 10^10 antigens, it means we only have a few cells for each antigen
- so we need to make sure these cells see a pathogen quickly, and really get going fast - or else you die
We have T and B cells that recognize
harmful non-self
but not many
(adaptive immunity)
What happens when a B cell becomes activated?
Clonal expansion
T cell help
Memory
Make protective antibodies
Clonal expansion (T cells) controlled by
IL-2
Mediate immunity
Memory
Vaccination - the triumph of
immunological memory
• Edward Jenner (1749-1823)
• noticed that milkmaids who caught cowpox did not get smallpox
• scraped fluid from a cowpox blister into the skin of 8yrold James Phipps who got a bit sick and recovered
• Phipps was then immune to cowpox and smal pox
After vaccination we respond
make more lymphocytes for the vaccine-memory cells
are also “primed”
Modern immunology is all about
communication
• cells have to know where they are and what is around them
Cells have thousands of different receptors to
sense the environment
• other cells
• hormones (chemical messengers)
• extracellular matrix
Receptors transmit signals from
the cell surface
to the nucleus to change gene expression and function
Inverse relation between the
incidence of prototypical infectious diseases and incidence of immune disorders from 1950-2000
Complex inflammatory diseases of the modern world
overactivity of the immune system • Crohm's • psoriasis • rheumatoid arthritis • ulcerative colitis
asthma allergies autoimmune diseases eg • type 1 diabetes • multiple sclerosis • SLE
