Immunity Flashcards
the immune system
- combats infective agents
- recognises and rejects foreign cells and tissues
- specific and non-specific
non-specific immune system (innate)
- first and second lines of defense
- primary defences
- skin
- mast cells + basophils
- histamine
- phagocytes
- complement proteins
- cytokines
- tears and mucus
primary defences
- present from birth
- quick-acting
- effective against a wide range of pathogens and foreign substances
- always same response
skin
- first natural barrier to infection
mast cells and basophils
- large mobile cells
- release histamine
histamine
causes inflammation response
phagocytes
large white blood cells which engulf foreign substances
complement proteins - general
blood proteins contributing to breakdown and removal of pathogens
cytokines
small protein molecules
tears and mucus
contain lysozymes
histamines
- dilate arterioles
- cause diapedesis
- increase tissue fluid formation
- sensory neurones become more sensitive
- activates complement proteins in plasma
complement proteins - specific
- attract phagocytes to site of reaction
- act as opsonins
- bind to, and form pores in, the surface of foreign cells
monocytes
- loads!
- migrate into tissues
- mature into macrophages
- can renew lysosomes
phagocytosis
1) phagocyte attracted to pathogen (due to chemical products of pathogen)
2) phagocyte CSM receptors attach to antigens on pathogen surface
3) pathogen engulfed to form phagosome
4) lysosomes move towards and fuse with phagosomes
5) lysozyme enzymes hydrolyse pathogen molecules
6) soluble products absorbed into cytoplasm or expelled from cell
specific immune response (adaptive)
- blood and lymph cells and proteins that attack, disarm, destroy and remove foreign substances
- responds slowly
- only effective against specific pathogens
- activated by antigens
B cells
- mature in bone marrow
- migrate to lymph nodes
T cells
- mature in thymus gland
- migrate to lymph nodes
immunological memory
immune response is sped up on repeated infection with the same pathogen
antigens
- molecules recognised as non-self, that trigger a lymphocyte immune response
- complex of proteins or glycoproteins (each cell has several)
- also occur in non-cellular substances
example of a non-cellular substances containing antigens
venom
diapedesis
cells in capillary walls draw away from each other
what does increased tissue fluid formation result in?
leucocytes, fluid, and antibodies increase in tissue
what are the two sections of the specific (adaptive) immune response?
- humoural
- cell-mediated
what are non-self antigens?
antigens from foreign organisms or substances to which the body has not yet become adapted
lymphocytes
- small leucocytes with little cytoplasm and spherical nuclei
- originate from stem cells in the bone marrow
- circulate in the lymph once mature
- only activated by specific antigens
lymphatic system
- nodes, spleen, adenoids, tonsils + bloodstream
- contains lymph
humoural response
uses soluble antibodies in the blood and lymph
antibody
- a unique globular protein that reacts with a specific membrane-bound antigen
- binding only occurs with complementary shape
- produced by small lymphocytes
In the humoural response, several types of reaction occur…
… depending on the ability of the antibody to bind to the antigen
which small lymphocytes produce antibodies?
B cells
B cells
- already exist in millions
- countless types, each of which produce a specific antibody
- mature in the bone marrow
- have immunocompetence, and self detection
- produce memory cells
when a B cell meets an antigen
- it divides mitotically (clonal selection)
- after several generations, the cells differentiate into plasma cells
plasma cells
- all formed from one type of B cell
- all secrete the same antibody
- lots of RER, Golgi and mitochondria
primary response
- the response of the immune system to an antigen it meets for the first time
- slow; takes days or weeks to recruit enough plasma cells to control infection
secondary response
- involves memory cells
- rapid man
antibody structure
- protein
- 4 polypeptide chains (quaternary structure)
- 2 light chains
- 2 heavy chains (long)
- disulphide bridges join light and heavy chains
- constant region (same AAs)
- variable region
- hinge region
variable region
- variety of AAs
- antigen binding site
- causes antibody specificity
How do antibodies trigger pathogen destruction?
1) agglutination
2) opsonisation
3) neutralisation
agglutination
- binding of antibodies causes pathogens to clump together
- helps prevent spread
- makes engulfing easier
opsonisation
- acts as an opsonin
opsonin
a chemical which makes the pathogen more easily recognised by phagocytes
neutralisation
- antibodies neutralise the effects of bacterial toxins by binding to them
How do antibodies tackle viruses?
bind to them, stopping them from attaching to the host
immunoglobins
- glycoprotein receptors on B cell membranes
- B cells contain multiple copies of immunoglobin genes
- genes recombine randomly during maturation, producing new unique genes for immunoglobin specificity
cell-mediated response
- occurs when pathogen is inside cell (mostly viral)
- when cells have become antigen presenting
- produces cells specific to invading pathogen
How are antigen presenting cells (APCs) produced?
- during infection, pathogen is digested
- antigens are bound to MHC (locus of DNA)
T-helper cells
- have particular receptor proteins on cell surface membrane, specific to antigen
- on meeting, cell divides mitotically
- some cells remain in blood and lymph as memory cells, others activate immune cells
Which immune cells to T-helper cells activate?
- B cells
- phagocytes
- Tc (cytotoxic T) cells
- macrophages
- Ts (suppressor T) cells
T-killer cells
- have complementary antigen-receptors
- attack cells that have been antigenically altered or larger pathogens
- produce perforin
describe a large pathogen
e.g. a unicellular parasite
perforin
punches holes in CSM
T-suppressor cells
- suppress immune responses where appropriate
- interact in antigen-specific manner with Th or B cells
macrophages
- large phagocytotoxic white blood cells which destroy pathogens
- derived from monocytes
- have indented nuclei
immune communication
necessary because humoural and cell-mediated response work in conjunction
cytokines
- activators or inhibitors of cell signalling pathways
- growth, differentiation and behaviour of cells
- e.g. interferons
interferon-alpha
- regulates growth genes
- used in medicine: boosts immune system and reduces tumour growth
monoclonal antibodies - basic
a single type of antibody produced by a B cell in response to a specific antigen that can be isolated and cloned
monoclonal antibodies - specific
- cloned B cell stimulated with an antigen epitope, fused with immortal malignant antibody-producing myeloma cell; hybridoma cell
- can multiply specifically and infinitely
general principles of monoclonal antibody use:
- attach to fluorescent dyes/radioactive labels
- also agglutinate antigens
- shows presence and extent of infection
pregnancy testing - how they work:
- monoclonal antibodies correspond to coloured particles (blue latex)
- hcG binds to particles
- hcG-antibody-colour complex moves along strip
- captured (immobilised) by another antibody to form a line
pregnancy testing - in general:
- done at home
- non-invasive
- reallllly early indicator
how is a pregnancy test a really early indicator?
placenta produces human chorionic gonadotrophin (found in mother’s urine) when fertilised egg binds to uterine wall
HSV1 testing
(3-G11) reacts with glycoprotein C complex
HSV2 testing
- 6-A6
- 6-E12
- 6-HII
herpes testing allows
serotyping - classification based on surface antigens
HIV testing - ELISA
- HIV p24 antigens manufactured and attached to petri dish
- wash with blood sample
- wash unattached antibodies away
- wash with marker antibody (specific to all human antibodies)
describe the marker antibody in the ELISA test
- black circle
- enzyme + substrate
separation of monoclonal antibodies
- antibodies immobilised on resin beads
- mixture poured over beads
- only target molecules attach
- beads washed with substance that releases the molecule
ELISA
enzyme-linked immunoabsorbant assay
ADEPT acronym
antibody direct enzyme prodrug therapy
ADEPT
- enzyme is attached to monoclonal antibody
- activates a drug (cytotoxic)
- attaches to target cancer cells
- large amount of inactive drug injected
- prodrug remains inactive around healthy cells
treating cancer with ADEPT
- suicidal protein caused by contact inhibition allows specificity to cancer cells
- stops blood vessel formation around tumours
- tag with cytotoxic drug
suicidal protein
blocks mitotic signals
Limitations of monoclonal antibodies
- ethics: humans cannot be immunised against antigens
- fused human lymphocyte-mouse myeloma cells are very unstable (recognised as foreign and eliminated)
- no suitable human myeloma cells to replace mouse
- antigenic variability -> mutation
ethical issues with monoclonal antibodies
- mice used to produce antibodies and tumour cells involves spleen removal and emulsification
- deaths associated with MS treatment
- trial for TGN1412 - 6 patients had multiple organ failure (they survived)
Why did the patients on the TGN1412 trial have multiple organ failure?
T cells produced chemicals overstimulating the immune response and attacked body tissue
advantages of monoclonal antibodies
- can target any molecule (including human ones)
- don’t kill adjacent cells
- produced in vast quantities, quickly
uses of monoclonal antibodies
- cancer treatment
- prevention of transplant rejection
- auto-immune treatment
- viral treatment
vaccinations
- artificial active immunity
active immunity
- delay between infection and full immune response
- vulnerable to toxins
attenuation
- weakening of pathogens
- culturing anaerobically away from temperature optimum
toxoids
- inactivated toxins
- no deleterious side-effects
herd immunity
- vaccinations administered to a large number of people at the same time
- results in general immunity
- reduces risk of encountering an infectious agent
why might vaccines be ineffective?
- inherited defective immune system
- defences weakened by infections/malnutrition
antigenic drift
small changes in pathogen antigens
antigenic shift
large changes in pathogen antigens
artificial passive immunity
ready-made antibodies against a toxin
natural passive immunity
- occurs when a fetus is still in the uterus
- maternal antibodies cross the placenta into fetal blood
- temporary; antibodies broken down by spleen and liver
- no immunological memory
what does natural passive immunity not give any immunological memory
because the baby did not make the antibodies itself
