Immunology

Question 1

Vaccination definition

Answer 1

inoculation of healthy individuals with weakened/attenuated strain or component of disease-causing agents which provides protection against disease

Question 2

Goal of pathogens

Answer 2

invade host and gain a foothold
multiply and persist
cause infection and disease
transmit to new hosts
IE WANTS TO MULTIPLY AND SPREAD

Question 3

function of immune system

Answer 3

pathogen recognition
pathogen clearance
resolution of inflammation
immunological memory

Question 4

first line of defence of immunity

Answer 4

anatomical and chemical barriers
eg. the normal microbiota, epithelial cells connected by tight junctions, tears, mucus and cilia, enzymes, stomach pH

Question 5

the basic schematic of the immune response

Answer 5

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

Question 6

Macrophages

Answer 6

function: phagocytosis and activation of bactericidal mechanisms, antigen presentation
induce inflammation by secreting cytokines and chemokines
scavengers which clear dead cells and cell debris

Question 7

phases of phagocytosis

Answer 7

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

Question 8

granulocytes

Answer 8

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

Question 9

Mast cells

Answer 9

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

Question 10

How do innate immune cells recognise pathogens

Answer 10

immune cells have pathogen recognition receptors (PRRs) which interact with patters that are often present on microbes called pathogen-associated molecular patterns (PAMPs)

Question 10

Dendritic cells

Answer 10

function: phagocytosis, antigen uptake, antigen presentation
activates t cells
patrols the extracellular space
crucial link between innate and adaptive immunity

Question 11

toll-like receptors (TLRs)

Answer 11

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

Question 12

Example of dendritic cell activation

Answer 12

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

Question 13

TLR in disease, and as treatment

Answer 13

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

Question 14

Lymphocyte overview

Answer 14

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

Question 15

Lymphocyte receptors

Answer 15

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

Question 16

epitopes and t cell receptor binding

Answer 16

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

Question 17

activation of t cells, and different types of effector t cells

Answer 17

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

Question 18

B Cell activation

Answer 18

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

Question 19

Antibody basics

Answer 19

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

Question 20

Antibody classes

Answer 20

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

Question 21

Antibody functions

Answer 21

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

Question 22

How the immune system can fail

Answer 22

the microbes evade the defences
immunodeficiency, aka you lack certain types of cells
induction to non-infections agents. aka allergy, autoimmunity, graft rejection

Question 23

Antigenic drift

Answer 23

a microbe alters its antigens so the antibodies no longer recognise it. eg influenza

Question 24

latent infections

Answer 24

if the cell can lie dormant in a non-replicating and non-protein producing state, the body cannot really target it. so it can wait until immunity wanes to return
HSV hides in the nerve cells attached to the lips

Question 25

Bridges-Good syndrome

Answer 25

aka chronic granulomatous disease
disorder in phagocytic cells, causing recurrent infections and excessive inflammation that forms granulomas

Question 26

Neutropenia

Answer 26

reduced neutrophils
primary: hereditary, secondary: chemotherapy
causes increased infections which affects skin and mucus membranes disproportionately

Question 27

AIDS

Answer 27

acquired immunodeficiency syndrome
caused by HIV
attacks t cells and macrophages
loss of control over infections and malignancies

Question 28

conventional immunosuppressive drugs

Answer 28

eg corticosteroids (inhibit inflammation), azathioprine (affect dna synthesis) , rapamycin (inhibits proliferation of effector T cells

Question 29

targeted immunosuppression

Answer 29

antibodies to specific proteins used in autoimmune disorders
anti-tnf alpha is often used in autoimmunity
neutralises local excesses of cytokines

Question 30

different types of mabs

Answer 30

-omab = fully mouse. mouse gets injected with tnf alpha proteins, and as they are foreign develops an immune response to them. but as this is foreign to humans we can get antibodies for the antibodies
-ximab = chimeric. mouse binding zone, with human constant zone
-zumab = humanised. mostly human with some murine sequences spliced in
-umab = fully human

Question 31

anti tnf antibodies approved for clinical use

Answer 31

infliximab - Crohn’s disease
adalimumab, certolizumab, golimumab - rheumatoid arthritis
inflix and ada are the most common in ireland. inflix is infusions, while ada is a pen you can inject yourself

Question 32

Infliximab

Answer 32

dose: infusion over 2 hours for adults. 5mg/kg week 0, 2,6, and every 8 weeks after. 10mg/kg if response lost
different people have different pharmacokinetics so people have different drug levels despite receiving the same dose. personalised therapy can help dose optimally as ifx levels can be monitored
when we tailor doses we have more efficient drug use and better patient outcomes
some patients lose response over time (secondary non-responders) due to the formation of antibodies to infliximab. the antibody-drug complexes are cleared rapidly and causes sub-therapeutic ifx concentrations

Question 33

Enzyme-linked immunosorbent assay

Answer 33

ELISA
direct binding assay for specific antigen antibody pairs
the antibody is tagged with a dye so it can be visually seen when it binds
absorbance is measured, and compared to an absorbance/concentration curve

Question 34

lateral flow tests

Answer 34

eg nucleocapsid antigen of covid 19 test, and human Chorionic Gonadotrophin (hCG) test (aka pregnacy test)
the machine contains the antibodies which will react if the antigen is present

Question 35

Immunohistochemistry

Answer 35

IHC
identifies proteins and microbes in cells or tissues.
the antibody you send in is attached to a florescent dye, so that the emitted light and the exciting light are of different frequencies

Question 36

cancer immunotherapy

Answer 36

tumour associated antigens - proteins and growth factors that cancerous cells over-express
Goals: discriminate between tumour and normal cells, specifically destroy malignant cells, integrate with conventional approaches
monoclonal antibodies - eg Herceptin anti HER2 (human epidermal growth factor) for breast cancer, or Rituximab anti CD20 for non-Hodgkin’s B cell lymphoma lymphoma
cellular immunotherapy: dendritic and t cells

Question 37

Immunotherapy - dendritic cells

Answer 37

mature dc display TAAs to t cells, which become cytotoxic attack TAA-expressing cells
eg. provenge. for advanced prostate cancer. attacks prostatic acid phosphatase. patient gives blood, the dcs are purified and given pap, so when they are given back to the patient, it activates t cells to attack the antigens