#1 Overview & Basics 01.07 Flashcards
1. diff bw basic features of innate and acquired responses 2. diff bw types of immune cells and lymph tissues 3. learn concept of acquired immunity 4. learn terminology
types of innate immunity defence
- structural and chemical barriers
- cells from myeloid progenitor cells
- presenting antigens
how does innate immune response work?
control infection until acquired immune responses have been developed
how do innate cells work?
help to initiate acquired immunity by processing and presenting antigen to lymphocytes
give examples of structural and chemical barriers
structural: skin
chemical: enzymes
what general features of pathogens do innate cells recognise?
PAMPS (pathogen-associated molecular patterns)
give examples of PAMPS
- structures with repeating subunits
- peptidoglycans
- LPS (lipopolysaccharide)
what are PAMPS recognised by?
PRRs (pattern recognition receptors)
mechanism innate cells use to modulate their response
recognise signals from the acquired response
examples of innate cells
macrophages
dendritic cells
NK cells (natural killer cells)
neutrophils
examples of acquired immune response signals
lymphokines
antibodies
cells that modulate acquired immune response
lymphocytes
what do acquired immunity cells recognise?
antigen recognition
characteristics of antigens that immunity cells recognise
epitope
what is an epitope? what is another name for epitope?
sequences/groupings of amino acids
aka antigenic determinant
function of lymphokines
- “help” other lymphocytes
- regulate activities of innate cells
what do lymphocytes produce when encountering specific epitope?
lymphokines/cytokines
protein factors
tissues of immune system
bone marrow
lymph tissue
why is bone marrow important?
site where all elements of blood are derived from one type of progenitor cells
the one type, the holy grail progenitor cell
pluripotent hematopoietic stem cell
progenitor cells that derive from the PHSC
- myeloid progenitor
2. common lymphoid progenitor
describe the progenitor cell family tree
pluripotent hematopoietic stem cells –> myeloid progenitor + common lymphoid progenitor –> cells of the immune system
myeloid progenitor gives rise to what cells?
granulocytes/PMNs (polymorphonuclear cells)
macrophages
dendritic cells
mast cells
common lymphoid progenitor progenitor gives rise to what cells?
T cells
B cells aka lymphocytes
NK cells (natural killer cells)
4 types of granulocytes/PMNs
neutrophils
eosinophils
basophils
cells that make up much of the non-adaptive/innate immune system
granulocytes/PMNs
neutrophil function
phagocytic cells that help activate bacterial mechanisms
eosinophil function
kill antibody-coated parasites
basiphil function
unknown, but probs similar to eosinophils
list all the cells of the innate immune system
myeloid progenitor cells - granulocytes/PMNs = neutrophils = eosinophils = basophils - macrophages - dendritic cells - mast cells NK cells (natural killer cells)
macrophage function
- scavenger cells
- have receptors for common infectious agents
- take up antigen at sites of infection/inflammation
- process antigen by cutting into peptides
- present antigens (esp to naive T cells) in secondary lymphoid tissues
monocytes
the circulating, immature precursors of macrophages
dendritic cell function
- potent simulators of T cells
- take up antigen at sites of infection/inflammation
- process antigen by cutting into peptides
- present antigens (esp to naive T cells) in secondary lymphoid tissues
mast cell function
- degranulate to release histamine and other agents released in Type I hypersensitivity reactions
- bear IgE receptors
what cells have important roles in acquired immune response
all cells derived from myeloid progenitor cells EXCEPT FOR GRANULOCYTES/PMNs
what 2 cells help initiate the development of adaptive/acquired immune response?
- macrophages
2. dendritic cells
what cells give rise to the cells of the innate immune system?
myeloid progenitor cells
what cells give rise to the cells of the acquired immune system?
common lymphoid progenitor cells
these cells are the primary components of the adaptive/acquired immune system
lymphocytes
lymphocyte function
recognize foreign antigens
how to lymphocytes recognize foreign antigens?
express receptor molecules on surface
list the cells of the adaptive/acquired immune system
common lymphoid progenitor
- T cells
- B cells
(i.e., the lymphocytes)
why are NK cells different from other cells that derive from common lymphoid progenitor cells?
DO NOT express antigen-specific cell surface receptors :: they are unable to recognise specific antigens
where do all cells of the immune system originate?
bone marrow
cells of the immune system circulate in
circulatory system
lymphatic system
lymphocytes are generated from what cells?
common lymphoid progenitor cells
after being “born” in the bone marrow, where do lymphocytes go? what do they do here?
lymphoid organs
mature
define lymphoid organ
organized tissues where lymphocytes interact with non-lymph/antigen presenting cells
types of lymph organs
central/primary lymphoid organs
peripheral/secondary lymphoid organs
define central lymph organ
tissue where lymphocytes develop and mature
define peripheral lymph organ
tissue where adaptive immune responses are initiated; traps antigens, facilitates presentation of antigens to lymphocytes
what lymph cells both originate and mature in bone marrow?
B cells
where were B cells discovered?
in the Bursa of Fabricus (of birds)
where do T cells mature?
in thymus
two major functions of spleen
collect antigens from blood
dispose of dead RBC
most of the spleen is composed of
red pulp
where are RBC disposed of?
the red pulp of the spleen
what forms white pulp of the spleen?
lymphocytes
two parts of white pulp
periarteriolar lymphoid sheath (PALS)
B cell corona
periarteriolar lymphoid sheath (PALS) contains primarily
T cells
B lymphocytes are concentrated in
follicles of lymph nodes
what is occurring in germinal centers?
B cells are undergoing intense proliferation
note: this is a part of lymph node follicles
examples of gut-associated lymph tissues (GALT)
tonsils
adenoids
appendix
Payer’s patches
what do GALTs do?
catch antigen from epithelial surfaces of GI tract
most important, highly organized of the GALT tissues
Peyer’s patches
M cells
part of Peyer’s patches
collect antigens along intestinal mucosa
three types of cells on Peyer’s patches
M cells
B cells
T cells
lymphoid tissues that protect respiratory epithelium
bronchial-associated lymphoid tissue (BALT)
mucosa-associated lymphoid tissue (MALT)
name the peripheral lymphoid organs/tissues
spleen lymph nodes GALTs BALTs MALTs
two factors of inflammatory response
- uptake of antigen by phagocytes
- increase in lymph flow
where does lymph flow in an inflammatory response? why?
- toward the draining lymphoid tissue
- facilitates antigen transport to secondary lymph organs
each antigen-specific receptor expressed on an individual lymphocyte is ___
identical
describe self tolerance
immune system removes MOST lymphocytes that have receptors that bind to “self” antigens :: preventing host tissues
describe clonal selection
lymphocyte is stimulated by its receptor binding to antigen –> activated –> proliferates to give many more cells with identical antigen-receptor sensitivity
what is the central principle to adaptive immunity?
clonal selection
describe somatic recombination
entirely random process where the immunoglobulin gene segments that code for lymphocyte receptors are recombined into a complete coding region
describe B lymphocytes (B cells)
produce and secrete antigen-specific antibody molecules
which lymphocyte type is associated with humoral/antibody-mediated immunity?
B-cells
B-cell receptors (BCRs) have how many antigen binding sites?
two
BCRs can bind to what types of particles?
proteins (native or denatured)
carbs
nucleic acids
small chemical compounds
describe T lymphocytes (T cells)
lymphocytes that recognize peptide fragments of protein antigens presented of MHC molecules
name 2 differences between B and T cells
- number of antigen-binding sites on receptor (B: 2, T: 1)
2. B cells secrete their receptors, T cells do not
T-cell receptors (TCRs) have how many antigen binding sites?
one
what is the first signal of B cell activation?
B cell cognate antigen
what is the second signal of B cell activation?
T helper cell supplied cytokine signal
what is the first signal of T cell activation?
T cell cognate peptide antigen
what is the second signal of T cell activation?
co-stimulation signal from the antigen presenting cell
describe the B cell activation process
B cell binds to antigen –> endocytoses antigen –> breaks into pieces –> presents to antigen-specific T helper cell –> T helper provides cytokine signal to B cell
what does the T helper supplied cytokine signal do?
activates B cell
what do T cells specifically recognize on antigens?
peptide fragments
name the professional antigen presenting cells
dendritic cells
macrophages
B cells
antigen processing results in what?
peptide fragments
describe antigen presentation
professional antigen presenting cells present peptide fragments on their surface to T cells
what is part of the “presented” complex?
peptide fragment MHC class I or II molecule
do MHC molecules bind loosely or tightly?
loose
can a T cell receptor bind to presented peptide fragments that lack MHC buddy?
hell no
what happens when B cells are activated?
proliferate
differentiate
produce large quantities of antigen-specific antibodies
name different functions of antibodies
neutralization
opsonization
complement activation
two things that antibodies play an important role in
- activation of NK cells for antibody dependent cell mediated cytotoxicity (ADCC)
- activity of mast cell
describe antibody neutralization
neutralize some pathogen-derived toxins, some pathogens directly
describe antibody opsonization
coats antigens or pathogens :: facilitating uptake of antigen by phagocytes or NK cells
describe complement activation
when bound to specific antigen or pathogen, act as receptor for complement system
two kinds of T cells
- CD8+ T cells
- CD4+ T cells
CD8 T cells recognize antigens presented on
MHC class I molecules
CD4 T cells recognize antigens presented on
MCH class II molecules
describe activation of CD8+ and CD4+ T cells
- recognition of cognate peptide/MHC I or II complex
- stimulation by profesh antigen presenting cell
when a CD8+ or CD4+ T cell is activated it becomes an
armed effector CD8+ or CD4+T cell
purpose of armed effector CD8+ T cell
kill cells with cognate peptide/MHC I complex on surface
what types of cells in the body express MHC class I molecules?
trick question!
all cells
purpose of armed effector CD4+ T cell
secrete cytokines that modulate activity of other immune cells
armed effector CD4+ T cells are also called
T helper cells
armed effector CD8+ T cell are also called
cytotoxic T lymphoctes (CTLs)
killer T cells
armed effector CD4+ T cells can differentiate into what two types of cells
- T helper 1 CD4+ cells (TH1 CD4+)
- T helper 2 CD4+ cells (TH2 CD4+)
primary purpose of T helper 1 CD4+ cells (TH1 CD4+)
supply cytokine signals to macrophages
primary purpose of T helper 2 CD4+ cells (TH2 CD4+)
promote Ab-mediated immune response
4 types of pathogens
- bacteria
- viruses
- fungi
- parasites (protozoa and worms)
innate immunity is also called
non-adaptive immunity
acquired immunity is also called
adaptive immunity
4 characteristics of innate immunity
- rapid response (hours)
- fixed
- limited number of specificities
- constant during response
4 characteristics of acquired immunity
- slow response (days to weeks)
- variable
- numerous highly selective specificities
- improve during response
a hematopoetic stem cell can give rise to what 3 types of cells
- common lymphoid progenitor
- common myeloid progenitor
- common erythroid megakaryocyte progenitor
common lymphoid progenitor cells give rise to what cells?
B cell
NK/T cell precursor –> T cell and NK cell
common myeloid progenitor cells give rise to
common granulocyte precursor --> neutrophil, esinophil, basophil (aka granulocytes) unknown precursor (monocyte, mast cell)
common erythroid megakaryocyte cells give rise to
megakaryocyte –> platelets
erythroblast –> erythrocyte
what is the function of the precursor cell megakaryocyte? what is its size?
- platelet/thrombocyte formation, wound repair
- 10-15x RBC
what is the common name for thrombocyte?
platelet
what is the function of the cell of the blood, an erythrocyte?
clearance of immune complexes from the circulation
oxygen transport
innate cells do not express what on their surface? what do they express instead?
- highly specific receptors
- pathogen-associated molecular pattern receptors (PAMPS)
cells of the acquired immune system produce [high/low] specificity receptors. what do they recognize on a pathogen?
- highly specific
- specific structures
name the cells of the innate immune system
neutrophil eosinophil basophil mast cell NK cells
what is the most numerous immune cell in the body? what is the least abundant immune cell?
- neutrophils
- basophils
function of neutrophils
phyagocytosis and killing of microorganisms
describe a neutrophil: function, life span, amount in body, bacteria ID method
- highly phagocytotic
- engulf and kill microbes
- short-lived
- most numerous cell in the body
- receptors that bind to common components of bacteria
how do neutrophils identify and bind bacteria? give examples
receptors that bind common components of bacteria
Ex: mannose receptors, glycan receptors, LPS receptors)
function of an eosinophil
killing of IgE antibody-coated parasites through release of granule contents
how how do eosinophils identify and bind bacteria?
have receptors that bind IgE antibody molecules
what contents of eosinophils distinguish them?
granules that contain inflammatory mediators and toxic compounds
function of a basophil
control immune response to parasites
basophils function a lot like what cells?
eosinophils
what cell type is poorly characterized?
basophils
function of mast cell
expulsion of parasites from body through release of granules containing histamine and other active agents
what is the primary role of mast cells?
expel parasite pathogens from body
how do mast cells identify and bind pathogens?
high affinity IgE receptors on surface
how do mast cells get their special receptors?
IgE receptors are highjacked IgE molecules from circulation
what do the granules in mast cells contain?
histamine and other inflammatory mediators
name the professional antigen presenting cells (APCs)
dendritic cells
macrophages
do NK cells have antigen specific receptors?
no
what cell plays a role in both innate and acquired immunity?
NK cells
name the cells of the acquired immune system
B cells
T cells
plasma cells
NK cells
what are the two lymphocytes
B cells and T cells
what is the role of B cells
to produce antigen specific proteins aka antibodies
what is the role of T cells
to produce signals that direct the action of other cells or are specific effectors of cell-killing
what are plasma cells
fully differentiated B cells
what is the role of plasma cells
to work as antibody factories
B cells can differentiate into what 2 types of cells
plasma cells
memory cells
what are the central or primary lmphoid organs
thymus
bone marrow
what are the secondary lymphoid tissues
spleen
lymph node
GALT
what special cell does the GALT have? what does it do?
M cell (microfold cells) sample antigen from intestinal lumen
4 components of the Clonal (Selection) Hypothesis
- each lymphocyte bears a single type of receptor with a unique specificity
- if the lymphocyte is capable of binding a foreign invader with high affinity it leads to lymphocyte activation
- the differentiated effector cells will have the identical specificity as those receptors as its’ parent
- those bearing receptors for self molecules are deleted :: absent from repertoire
what is the importance of Somatic Recombination?
allows generation of many different types of Tcell receptor specificities and antibodies
what do T cell receptor and B cell receptors have in common?
variable regions, constant regions, trans-membrane regions, antigen binding site
what are the two “arms” of acquired immune response?
- extracellular infection –> Ab mediated immune response
2. intracellular infections –> T cell mediated
what is best to clear an extracellular infection?
Ab mediated immune response
what is best to clear an intracellular infection?
T cell mediated immune response
what is an antigen/determinant? **
any ligand that binds to a B or T cell receptor
most antigens are composed of ___ **
protein
TCRs bind only to… **
short peptide/protein segments
MHC I are found where?
on almost all host cells
MHC II are found where?
APCs
what do MHC molecules do?
bind to peptides and present them to T cells
differences between MHC I and II
I only has 1 transmembrane domain, whist II has 2
MHC I deal with what kinds of infections?
INTRAcellular
Ex: virus
MHC II deal with what kinds of infections?
EXTRAcellular
Ex: bacteria
what signals activate B cells?
T helper cells :: use MHC II
what signals activate T cells?
naive T helper/CD4 –> MHC II
naive CTT/CD8 –> MHC I
in macrophage mediated initiation of inflammation, secreted cytokines cause what results?
vasodilation
increased vascular permeability
:: fluid, protein, and inflamm cells leave blood enter tissue
name the two types of antibody mediated clearance
- neutralization
2. opsonization
word association: neutralization
IgA
IgG
bacterial toxins
word association: opsonization
extracellular bacteria
complement
C3b
CR1
name two types of opsonization
Ab meditated opsonization
complement assisted opsonization
how do CTT/CD8 kill and fight infection?
recognize with MHC I
what cell activated infected macrophages to kill internalized material? with what signals?
Th1
CD40 and IFN-gamma
