Immunology Flashcards
Vaccination definition
inoculation of healthy individuals with weakened/attenuated strain or component of disease-causing agents which provides protection against disease
Goal of pathogens
invade host and gain a foothold
multiply and persist
cause infection and disease
transmit to new hosts
IE WANTS TO MULTIPLY AND SPREAD
function of immune system
pathogen recognition
pathogen clearance
resolution of inflammation
immunological memory
first line of defence of immunity
anatomical and chemical barriers
eg. the normal microbiota, epithelial cells connected by tight junctions, tears, mucus and cilia, enzymes, stomach pH
the basic schematic of the immune response
the pathogen releases something that causes inflammation, such as lipopolysaccharides in gram negative cell walls
sensor cells of the innate immune system pick up the inflammation such as macrophages
they release mediators such as cytokines
then the target response begins, such as the production of antiviral proteins
Macrophages
function: phagocytosis and activation of bactericidal mechanisms, antigen presentation
induce inflammation by secreting cytokines and chemokines
scavengers which clear dead cells and cell debris
phases of phagocytosis
microbe or other particle is absorb into a the cell by the pseudopods encircling it
the phagosome is formed with its own plasma membrane
which combines with a lysosome full of digestive enzymes to form a phagolysosome
these enzymes break down the microbe
which leaves behind a residual body full of indigestible material
which is ejected from the cell
granulocytes
Neutrophils:
function: phagocytosis and activation of bactericidal mechanisms
most numerous of the granulocytes
Eosinophils:
function: release toxic proteins from granules that kill parasites
Basophils: kill parasites with granule proteins. allergy
Mast cells
found in: skin, intestines, airway mucosa
function: release granules containing histamine and proteases, protecting internal surfaces from pathogens including parasites
allergy is caused by too much histamine being released at the wrong time
How do innate immune cells recognise pathogens
immune cells have pathogen recognition receptors (PRRs) which interact with patters that are often present on microbes called pathogen-associated molecular patterns (PAMPs)
Dendritic cells
function: phagocytosis, antigen uptake, antigen presentation
activates t cells
patrols the extracellular space
crucial link between innate and adaptive immunity
toll-like receptors (TLRs)
span the cellular membrane that are expressed on innate immune cells that recognise structurally conserved PAMPs
when a PAMP (eg lps) is recognised by TLR4 as foreign, it activates a signalling cascade that eventually causes the release of pro-inflammatory cytokines
TLR2 forms heterodimers with TLR1 and TLR6 which recognises lipoproteins, cell wall beta-glycans and others
TLR3 ds RNA
TLR4 LPS
TLR5 flagella
TLR7 and TLR8 ss RNA
TLR9 DNA with unmethylated CpG
Example of dendritic cell activation
DOUBLE CHECK WITH VIDEO WHEN TIME
dendritic cell finds a PAMP
Cd14, a lps binding protein, binds to lps, and then interact with TLR4 which activates
TLR in disease, and as treatment
TLR are what cause septic shock when the body is flooded with lps, and single nucleotide polymorphisms for the code of a TLR can cause differences in disease susceptibility
as TLRs cause inflammation, inhibition can be used to treat inflammation
agonists are used in vaccines
OPN305 is a TLR2 antagonist which is used to treat heat ischemia, delayed graft function, rheumatoid arthritis
Lymphocyte overview
they have highly variable antigen receptors on their surface which bind to antigens
each lymphocyte matures bearing a unique variant of antigen receptor
they mature in the bone marrow (b cells) or the thymus (t cells)
they will find either the pathogen or a dendritic cell containing the antigens in the lymph nodes, spleen, or mucosal lymphoid tissues, eg in the GIT or nasal tract
until they interact with their antigen they are naïve cells, which are inactive. when they activate B cells become Plasma cells which produce antibodies, and T cells become Effector T cells
Lymphocyte receptors
coded for by the immunoglobulin gene (which is what antibodies are called whtn attached to the cell)
b cell receptors have two heavy chains, and two light chains. y shaped with two variable regions (aka antigen binding sites). when the b cell becomes a plasma cell it releases its
T cell receptors have one light and one heavy chain, and are just one strand. they will not detach from the t cell
epitopes and t cell receptor binding
epitope is the site where an antibody attaches to the antigen
the more different epitopes the body can locate on an antigen the greater the immune response
for t cells the epitope is often buried within the antigen, so first it must be broken down into peptide fragments. the peptide binds to a major histocompatibility molecule (MHC) which presents it to to a TCR
activation of t cells, and different types of effector t cells
t cells require both an antigen and a co-stimulatory signal
to cause it to proliferate and differentiate into its effective state
CD8 cells are cytotoxic and kill virus infected cells
CD4 cells are helper cells that interact with b cells. and there are regulatory cells that supress t cell responses
B Cell activation
requires 2 signals, one from the antigen bound to the antibody, the other from a helper t cell which recognises the antigenic peptides presented by the b cell
then starts to proliferate to aqquire effector functions
Antibody basics
found in the plasma of blood
has two regions. the fragment antigen binding dictates which antigen it will bind to (the arms of the y). FC region (leg of the Y) dictates what happens after the antibody binds
Antibody classes
MADGE
IgA: found in tears, saliva. protects against pathogens
IgD: part of the b cell receptor. activates basophils and mast cells
IgE: protects against parasitic worms. responsible for allergic reactions
IgG: the most common type. secreted by plasma cells. protects against viral and bacterial infections
IgM: responsible for the early stages of immunity. may be secreted into blood or on the surface of B cells
Antibody functions
neutralisation: antibodies bind to the toxins that would activate receptors. then get phagocytosed
Opsonisation: binds to the whole microbe in the extracellular space, and then gets phagocytosed
compliment activation: bind to the bacteria, and then activate the compliment cascade. which lyses the bacterium and then gets phagOCYTOSED
How the immune system can fail
the microbes evade the defences
immunodeficiency, aka you lack certain types of cells
induction to non-infections agents. aka allergy, autoimmunity, graft rejection
Antigenic drift
a microbe alters its antigens so the antibodies no longer recognise it. eg influenza
