IMI9: hypersensitivity, allergy and autoimmunity

Question 1

what are parasites?

Answer 1

eukaryotic pathogens that live in or on another organism called host at the expense of that host

Question 2

what are protozoa?

Answer 2

first animals and relates to unicellular eukaryotic microorganisms of astonishing diversity that can be facultative or obligate intracellular or extracellular pathogens

Question 3

give an example of a parasite.

Answer 3

malaria

Question 4

what are the 5 stages done by a malaria to invade?

Answer 4

1. infection
2. liver stage
3. blood stage
4. gametocyte production
5. transmission

Question 5

what are helminths?

Answer 5

multicellular eukaryotic parasites

Question 6

what are the 3 stages of a helminths life?

Answer 6

egg
larva
adult stage worm

Question 7

how do helminths invade?

Answer 7

invade their human host through skin penetration, ingestion of contaminated food or via insect vectors

Question 8

do helminths proliferate in host?

Answer 8

no they more typically release eggs to allow them to. infect new hosts

Question 9

can helminths be phagocytosed?

Answer 9

no they re too big to be phagocytosed

Question 10

what are the primary immune defences against helminths?

Answer 10

granulocytes

physically disturbing the infected area so that the parasite can be ejected from the body

Question 11

what are the 4 types of granulocytes?

Answer 11

mast cells
neutrophils
basophils
eosinophils

Question 12

what type of immunoglobulin is secreted against helminths and bigger multicellular antigenic stimuli?

Answer 12

IgE

Question 13

how are granulocytes activated?

Answer 13

granulocytes have IgE-specific Fc receptors 9FcepsilonR) on their surface
IgE that are bound to helminths bind to FcepsilonR and activate granulocytes and release granules

Question 14

what happens during the degranulation of mast cells?

Answer 14

releases toxins to kill the parasites

triggers tissue level responses that have evolved to purge the parasite from the body

Question 15

what are granulomas?

Answer 15

made up of a cluster of tightly packed macrophages. the macrophages are packed so tightly that the cell membranes fuse to create enormous multinucleate cells that can be surrounded by a cage of ECM proteins which is a process called fibrosis

Question 16

when do granulomas form?

Answer 16

form if prolonged inflammatory reaction fails

Question 17

what happens if these granulomas are not degraded or removed afterwards?

Answer 17

macrophages will continue to release inflammatory signals which means that the inflammation will be ongoing which can lead to immunopathology

Question 18

what is atopy?

Answer 18

the launching of an IgE response against inappropriate targets

Question 19

what are the 3 major atopic diseases?

Answer 19

allergy
eczema
asthma

Question 20

what is the hygiene hypothesis?

Answer 20

higher level of atopic disease where people grow up in more sterile environment
so if our immune system is not exposed to pathogens that stimulate IgE responses, then our immune system will be more highly sensitised to react to something else

Question 21

what is hypersensitivity?

Answer 21

exaggerated immune response to a foreign substance which will lead to images to a host’s own cells

Question 22

what are the 4 types of hypersensitivity? and what do they consist of?

Answer 22

type I hypersensitivity–> over-reaction of the IgE response that is normal during helminths infections and inesct bites
type II hypersensitivity –> antibody-mediated complement activation on cells
type III hypersensitivity –> mediated by antibody complexes activated cellular inflammatory responses
type IV hypersensisitivy –> driver by innapropriate helper T cell activation of cellular responses

Question 23

why are these reactions called hypersensitivity reactions?

Answer 23

because if these processes are directed at the wrong target, they can give rise to immunopathology (=disease caused by the immune response)

Question 24

what are autoimmune disease?

Answer 24

when adaptive immune system produces and uses antigen receptors that are specific for molecules present in our bodies

Question 25

what cells are the core of autoimmunity?

Answer 25

T and B cells

Question 26

are T and B cells self-reactive? if yes what does it mean for them to be self reactive?

Answer 26

yes
self-reactive B cells will have antigen receptor that binds to the native state of a self-protein which will result in the release of auto-antibodies
self-reactive CD8 T cells will have a TCR that recognises a self-peptide presented on MHC class I which will enable them to kill cells making that antigen
self reactive CD4 T cells have a TCR that can bind to self-peptides presented on MHC class II which will lead to 2 major consequences:
- potential to wrongly: induce an inflammatory state in response to normal tissue homeostasis process
- support the survival of self-reactive B cells in the germinal centre

Question 27

what are the 3 main places where tolerance is established or maintained?

Answer 27

central tolerance
peripheral tolerance to antigens
specificity for foreign antigens during Ig affinity maturation

Question 28

what are the mechanisms that can give rise to the breaches in tolerance that lead to autoimmunity?

Answer 28

molecular mimicry
epitope spreading 
immune deregulation
epitope modification
idiotype cross-reactivity
T cell bypass

Question 29

what do self reactive adaptive immune molecules do?

Answer 29

trigger a reaction causing damage through either complement-mediated cell killing or chronic inflammation triggered by immune complex or T cell activation

Question 30

what are the 3 types of clinical treatment of autoimmune disease?

Answer 30

steroids
immunosuppressants
biologics