lecture 32 Flashcards
how did we fight covid
body produces antibodies - counters viruses
why did people get infected with omicron if they already have covid antibodies
omicron = variant
mutations change aa sequence of areas that covid antibody binds to = diff now
so antibodies wont work
define antigen
any molecule - usually a protein that elicits an immune response
define antibody
iggs
proteins - present in blood and other body fluids
bind to antigens and marks them for destruction by phagocytic cells
tags as antigen to be removed
define autoimmune disease
immune reaction against its own antigens (proteins)
immune system must be able to distinguish between self and non self
what is adaptive immune response
antigen specific immune response
humoral and cellular immunity
define humoral immunity
production and secretion of antibodies by specialized lymphocytes - white cells = called b cells
define cellular immunity
Specialized lymphocytes called t cells produce t cell receptors that recognize and bind antigens found only on the surface of bodies own cells
eliminates cells that express foreign antigens
describe hematopoietic tree
Hematopoietic stem cell in bone marrow = makes all cells - differentiates and matures
what cells are adaptive vs innate immunity
adaptive immunity = antigen specific defence = t cell, b cell, nk cell
innate immunity = non specific defense but quick response = neutrophil, basophil, eosinophil, macrophage
describe development of humoral - b cell - and cellular - t cell - immunity
Lymphocytes = from stem cells
b cells mature in bone marrow
t cells mature in thymus
they recognize foreign antigen then differentiate and mature (b cells to plasma cells and t cells = attack)
autoreactive b and t cells are eliminated during development
what can each B and T cell recognize
a unique non self antigen that can elicit immune response
Diversity in antibody and t cell receptor - do not know what we will be exposed to
describe clonal selection of b cells
large pool b lymphocytes - each is specific for ONE antigen
antigen binds then b cell divides
describe clonal expansion of selected b cell
clone of b cell = specific for same antigen
Proliferation of lymphocytes = primary immune response
then plasma cell and secrets antigens
describe secondary response
by memory b cells that have been activated
if second expose = antigen binds memory cells
rapidly gives rise to secondary immune response = faster
what happens for t cells - clonal selection and secondary response
similar processes as b cell for t cell and t cell receptor
why do vaccines work
secondary immune response
describe vaccines- active agent
antigen of vaccine = makes primary immune response
intact but inactivated - non infective pathogen
Attenuated - reduced infectivity forms of pathogen
purified components of pathogen that have been found to be highly immunogenic
generates memory cells so body is ready when second infection happens
describe conventional methods vs next gen vaccines
conventional methods - culturing virus = takes long time
next gen vaccines = such as rna vaccines use host cells to produce antigen = much faster, put rna in body = antigen not produced outside body
what are immunoglobulins - explains
proteins that protect us
2 identical light chains
2 identical heavy chains
y shaped
heavy chains have additional diversity region
light chains have variable, joining and constant region, aa sequences here recognize specific antigens
describe light chains
2 types = kappa and lamda - 2 locus
encoded on diff chromosomes
Segments = v, j and c
kappa/kappa or lamda/lamda - not mix
describe heavy chains
five types - depends on aa sequence of constant region - alpha, delta, gamma, epsilon or mu
Segments = v, d, j and c
each type of light chain can potentially combine with each time of heavy chain
how many protein coding genes does human genome have
20 000 - 25 000
how many antibodies can humans produce
10^11 antibodies with diff specificities
name 3 ways that generate antibody diversity
somatic recombination
junctional diversity
somatic hypermutation
what do b cells produce - antibodies
Unique light and heavy chain combos that can recognize a specific antigen
describe somatic recombination of kappa light chain
between v and j segments
one v and one j = spliced together - intron removed and everything downstream of v and upstream of j segment
produces dna found in mature b cell
does not happen in germ line dna but b cell dna
how are v and j segements spliced together
rag1 rag2 and dna repair enzymes introduce ds dna breaks and join random v and j segements = occurs at level of dna
then transcription initiated by joining - 5’ to v segment
wont ever go back
what happens to pre-mrna - splicing
spliced to produce unique combo of v-j-c light chain
mature mrna only contains one v, j and c segment = translated to functional light chain = ligated
T or F = the immunoglobulin generated in a given b cell will NEVER be the same
FALLLLSEEE
will always be the same
what do heavy chains have
locus has multiple D - diversity gene segments in addition to v, j and c segments
describe math of antibody diversity
kappa = V - 30 and J - 5 = 150
lamda = V - 35 and J - 7 = 245
heavy chain = V - 100 and D - 23 and J - 5 and constant region - 5* = 100x23x5 = 11500
kappa x heavy = 1.7 mil
lamda x heavy = 2.8 mil
total = 4.5 mil
- while v d and j segments contribute to antibody specificity, constant regions of heavy chains dont
describe junctional diversity
imprecise junction
few nts are lost or gained
can cause frameshift = produced nonfunctional gene if 3 codons eliminated
also indels
describe somatic hypermutation
iggs subject to high mutation rate
deamination of cytosine –> becomes uracil
uracil is replaced by the dna repair mechanisms by another base = causes point mutation
changes aa sequence that recognizes antigen
what are t cell receptors composed of
alpha and beta chains that have variable regions
= membrane bound proteins expressed at surface
describe alpha chain - t cell receptors
44-46 v gene segments
50 j gene segments
single c segment
describe beta chain - t cell receptors
Similar to alpha chain but contains d gene segments
describe t cell receptor diversity- how
somatic recombination
junctional diversity
BUT NO HYPERMUTATION
