Lecture 41 Introduction to Immunology Flashcards
Two forms of immunity
Innate immunity and Adaptive immunity
Innate mechanisms
first line of defense, non-specific response
adaptive mechanisms
second line of defense, highly specific with memory
active immunity
antigens enter body and trigger both innate and adaptive immune system = long term protection
passive immunity
antibodies given to person for period = short term protection (no memory cells)
examples of passive immunity
antibodies passing from mother to foetus across placenta, breast milk
cells in immune system derived from
common pluripotent hematopoietic stem cells in bone marrow
two lineage from stem cells
myeloid and lymphoid
myeloid lineage generates
- polymorphonuclear leukocytes
- monocytes
- dendritic cells
- mast cells
lymphoid lineage
- B cells
- T cells
- NK cells
polymorphonuclear leukocytes
- neutrophil
- eosinophil
- basophil
polymorphonuclear leukocytes are also called
granulocytes = same thing
granulocytes are characterised by
multilobed nuclei, cytoplasmic granules
neutrophils
- principal phagocytic cell of innate immunity
- migrate to site of infection
- release oxygen free radicals
- release degranulate proteins
- release cytokines (TNF)
microbicidal
agent in killing microscopic organisms
eosinophils
- defender against multicellular parasites
- allergy and asthma
- ‘e’www for parasite = ‘e’osinophils
basophils
- inflammatory allergic reactions
- release potent vasodilator = histamine`
monocytes
- bean shaped nuclei
- mature into macrophages
- kill pathogens by phagocytosis
- free radical production
- inflammatory cytokines
myeloblast matures into
basophil, neutrophil, eosinophil, monocyte
monocyte matures into
macrophage
common myeloid progenitor generates
megakaryocyte, erthyrocyte, mast cell myeloblast
megakaryocyte matures into
platelets
common lymphoid progenitor
Natural killer cell, small lymphocyte
small lymphocyte generates
T lymphocyte and B lymphocyte
B lymphocyte turns into
plasma cells ( and memory cells)
macrophages
- innate and adaptive immunity
- phagocytose
- microbicidal mechanisms
- APC
- recruit neutrophils
dendritic cells
- phagocytose
- procecss and present antigens = APC
- stimulate T cells to initiate immune response
mast cell
- close association with allergy and inflammation
- release histamine
- phagocytose
Neutrophils have receptor that detects formylated peptides, why?
bacteria incorporate N-formyl methionine into first position of peptides = recognised by receptor
innate immune system = what receptors on cells detect foreign material
Toll-like receptors = TLR
what molecules are recognised as foreign by TLRs
lipopolysaccarides on bacteria, proteins in flagella, double stranded RNA
how do lysozymes work against bactera
break bond between N-acetylglucosamine and muramic acid
how does penicillin work
interferes with synthesis of peptidoglycan in cells walls
mechanism of resistance to penicillin
- mutation in penicillin binding proteins
- production of B-lactamase to detsory B-lactam ring
- resistance transferred by ‘transformation’ and plasmids during ‘conjuagtion’
B lymphocyte
produces antibodies, presents antigens, produces memory cells
T lymphocytes
- stimulates B cells
- kill virally infected and tumour cells
what is NK cell derived from as part of lymphoid lineage
large granular lymphocyte
NK cell
- release perforins
- release granzymes
- trigger apoptosis
- tumour immunosurveillance
primary lymphoid tissue = development and maturation of lymphocytes
bone marrow = B cells
thymus gland = T cells
secondary lymphoid tissue
lymph nodes, spleen
lymph nodes found where
jaw, neck, axilla (armpit), elbow, groin, behind knee
spleen located
lymphoid organ in abdomen
function of spleen
removes damaged/old RBCs, activates lymphocytes
structure of spleen
red pulp = erythrocytes removed
white pulp = lymphocytes stimulated
innate immune system components
- mechanical barriers
- physiological
- chemical mediators
mechanical barriers
skin, mucous membranes, cilia propel microbes out of body
physiological immune system barrier
stomach acid, fever response hear inhibits pathogen growth
chemical mediators innate system
lysozyme cleaves bacterial cell wall, interferon induces antiviral defenses in cells
phagocytic leukocytes
monocytes, macrophages, dendritic cells, neutrophils
two types of adaptive immune response
humoral and cell-mediated immunity
humoral immunity
B cells = produce antibodies
cell-mediated immunity
T cells
non infected tissue, cell behaviours
In blood = monocytes and neutrophils pass healthy tissue
In cells = macrophage digests dead cells, dendritic cells are dormant
wave 1 infected tissue = dendritic cells
exit infected cell, migrate to lymph nodes, signal to lymphocytes
wave 1 infected tissue = neutrophil action
from blood-stream enter infected cells
wave 2 infected tissue = monocytes
flood in from blood-stream = become inflammatory macrophages
wave 2 infected tissue = neutrophils
killed pathogen and themselves in the process = pusu
wave 2 infected tissue = macrophage
clear debris, some migrate to lymph nodes
infected tissue = resolution
inflammatory macrophages change properties to repair damage
what cells do macrophages phagocytose?
DYING cells = recognised as plasma membrane changes profile when a cell dies
OPSIONIZED cells =
surface coated with complement proteins or antibodies
opsionised cells and pathogens
immune response concept = cells/pathogens coated in opsonins to be recognised by macrophages
opsonin
any molecule that enhances phagocytosis by marking an antigen for an immune response
opsonin examples
antibodies = IgG and IgM
complement proteins = C3b and C4b
Fc receptor on macrophage
binds to antibodies coating cell/pathogen
ANA
antinuclear antibodies
CD4+ cell
T helper cell
CD8+ cell
Cytotoxic T cell
dendritic cell specialisation
specialised receptors on surface
professional APCs
macrophages, dendritic cells, B cells
what makes professional APCs
all have MHC II comlexes
immunogen
an antigen that causes an immune response
antibodies are called
immunoglobulins
different classes of anitbodies
IgA, IgD, IgE, IgG and IgM
how many total B cells in blood
around 3 million
how many B cells in blood specific to one specific antigen
about 30
when specific antibodies are produced in B cell
transported to surface on B cell = B cell receptors (BCRs)
when do B cells divide
when B cell binds to its cognate antigen = proloferation
after a week of division, now many identical B cells in blood
around 20,000
vdj recombination
B cells and T cells = randomly assemble different gene segments to generate unique antigens
vdj segments = building blocks for variable region of antibody
V = variable D = diversity J = joining
Fc region on anitbody
the constant region, encoded by C - gene
how many different variations of segments in coding for antigen binding site
46 variable, 23 diversity, 6 joining
how many c-gene variants exist
5
what are the c-gene segments
Alpha (IgA) Delta (IgD) Epsilon (IgE) Gamma (IgG) Mu (IgM)
=hence the classes of antibodies are characterised by the constant region, Fc
antibody diversity is because
rearrangement of immunoglobulin gene segments to create huge diversity in mature B cells
somatic hypermutation
.
function of antibodies = opsonization
bind to bacteria and viruses, Fab region of antibody binds to antigen and Fc tail region binds to Fc receptor on macrophage = phagocytosis
function of antibodies = pathway
classical pathway activated = lysis of bacteria, triggers complement activation
primary response of antibody
following exposure: slow rise in IgM, the slow rise in IgG
secondary response of antibody
following exposure: rapid, great rise in IgG, limited rise in IgM
T cells respond to
antigens presented via the MHC of another cell = antigens bound to cells, not found in blood
MHC
Major Histocompatability Complex
histocompatible meaning
two individuals are histocompatible if tissues can be transplanted between without rejection
MHC variance
not because of VDJ recombination or TCR, we inherit polymorphic genes from parents
antigens as complex with MHC molecules
APCs = peptides presented in association with MHC
importance of MHC association with antigens
allows immune cells to distinguish between normal antigens on surface of all cells, and foreign ones
endogenous vs exogenous meaning
endogenous = within or inside cell exogenous = outside
MHC class I present where
almost every cell in body
MHC class II present where
only on specialised APC immune cells = macrophages, dendritic cells, B cells
MHC class I present what antigens
endogenous antigens, synthesised in cytoplasm
MHC class II present what antigens
exogenous antigens, originate extracellularly from foreign bodies
production of MHC class I molecules
- samples of proteins made on ribosomes are chopped up into short peptides by the proteasome
- fragments transported to ER, where peptides of ~10 amino acids can bind to MHC class I proteins
- complex transported via golgi to cell surface
production of MHC class II molecules
- phagocytosis
- foreign peptide fragments are bound to MHC class II proteins in endosome]
- transported to cell surface
what cell recognises MHC class I
CD8+ = cytotoxic T cells
what cell recognises MHC class II
CD4+ = T helper cell
best way to kill virus
destroy cells that virus has infected before the cell releases new viral particles
best way to kill virus/yeasts
generate antibodies = agglutination of particles, mark them for ingestion or further attack by complement system
autoimmunity
misdirected adaptive immune response = type 1 diabetes, rheumatoid arthritis, Crohn’s disease, thyroiditis, multiple sclerosis
hypersensitivity reactions
over reaction of adaptive immune response = peanut allergy, asthma
immunodeficiencies
components of immune system are absent/defective = AIDS
