Immune System in Disease Flashcards
What are the 4 types of hypersensitivity?
type 1: immediate - allerg
type 2: antibody mediated
type 3: immune complex
type 4: delayed type
What is type 1 immediate hypersensitivity mediated by?
IgE, mast cells, lipid mediators
What is type 4 delayed type hypersensitivity mediated by?
CD4 T cell mediated
What response do allergens induce?
Th2 reponse
low dose, mucosal location
What are 3 properties of allergens?
- very stable
- high solubility in bodily fluids
- introduced in low doses
What are 4 allergic reactions?
- systemic anaphylaxis
- allergy rhinitis
- asthma
- food allergiesW
What are the 2 phases of type 1 immediate?
- sensitisation
- response (local or systemic)
What are the 3 steps in sensitisation?
- allergen cleaves occluding in tight junctions, entering mucosa
- DC primes T cell in lymph node
- plasma cell travels back to mucosa and produces IgE specific Ab
What is the response step?
allergen-specific IgE binds to mast cell, triggering degranulation
What are 3 results of mast cell activation?
- secretion of preformed mediators
- synthesis and secretion of lipid mediators
- synthesis and section of cytokines
What are 2 physiological effects of mast cell degranulation in the GI tract?
- increased fluid secretion and peristalsis
- diarrhoea, vomiting
What are 2 physiological effects of mast cell degranulation in the airways?
decreased diameter, more mucus
wheezing, coughing, phlegm
What are 2 physiological effects of mast cell degranulation in the blood vesesls?
more blood flow and perm
more fluid to tissues, lymph flow and effector response
What happens during the immediate phase?
wheal and flare
blood vessels dilate, leak plasma
more swelling around site of challenge (wheal)
blood vessels further dilate (flare)
What happens in the late phase?
involve cell infiltrates and sustained edema and/or smooth muscle contraction
What are the 2 outcome of type 2 hypersensitivity?
- injury dur to activation of effector mechanisms
- abnormal physiological response (graves, MG)
What causes type 3 hypersensitivity?
occurs if complexes are excessively produced and inefficiently cleared
What are 4 results of immune complex mediated damage?
- immune complexes deposit on basement membranes and blood vessel walls
- vasculitis
- glomerulonephritis
- arthritis
what elicits type 4 hypersensitivity?
- microbial infection
- intradermal injection of protein antigens
- contact with chemicals
What are the two phases of type 4 hypersensitivity?
- sensitisation
2 response
explain sensitisation in type 4
allergen penetrates skin and is taken up by local antigen
DC primes T cell in LN
explain response in type 4
re-exposure to antigen: Th1 recognises antigen and releases cytokines
recruitment and activation of phagocytes
What is the Mantoux test?
inject PPD to detect presence of Mtb-specific CD4 T cells
Why does gluten cause celiac?
gluten is a mix of glutamine and proline rich proteins
tTg converts glutamine into glutamic acid
gliding bind w high affinity to HLA-DQ2/8 resulting in T cell activation
Why are autoreactive cells not always activated?
- antigen not available
- absence of signal 2
- aitoreactive B cells don’t have auto reactive CD4+ T cells
Response to type 2/3
B cell production of auto antibodies
CD4 and CD8 T cells
DTH responses (TH1 activation of macrophages, cytokine production, pro-inflammatory mediator disease
CTL killing of stromal cells
provision of B cell help
macrophages
nitric oxide, proteases, oxidative radicals
Summary of normal pituitary
pituitary gland releases TSH which acts on thyroid to release thyroid hormones
thyroid hormones act on pituitary gland to shut down production of TSH, suppressing thyroid hormone synthesis
What happens in graves?
autoantibodies bind to TSH receptor on thyroid cels
stimulates receptor so enhanced production of thyroid hormones
What is lupus?
unknown trigger
many auto antigens
B cell hyperactivity
presence of anti-DNA autoantibodies and immune complex deposition in kidney
What are 2 examples of t cell mediated autoimmunity?
- insulin dependent diabetes mellitus (IDDM)
- MS
IDDM
organ spec., T cell med (CD4/CD8)
destruction of pancreatic beta cells which produce insulin
infiltration of lymphocytes, weak autoantibody response, T cell reactivity to islet proteins
loss of insulin secretion, resultant insulin dependence
MS
polygenic degenerative disorder of CNS which results in paralysis episodes while forming, and then chronic paralysis in late stages
What T cells for MS
CD4 T cells specific for myelin antigens promote an inflammatory response and degrade myelin sheath
Th1 nd Th17 responses = bad
Th2 responses = remission
2 categories of immunodeficiency?
- primary immunodeficiency disorders (inherited)
- gene mutations = immune system failure
- X-linked, autosomal recessive - secondly immunodeficiency disorders (acquired)
- infection, cancer, chemo, organ transplant
- suppression of immune responses
Treatment of immunodeficiencies
- antibiotics
- IVIG
- enzyme replacement
- bone marrow transplant
XLA
mutation in gene for Btk
Btw needed for signal transduction via pre-BCR
failure to make complete BCR leads to pre-B cell apoptosis
hyper IgM (x-linked)
x-linked hyper IgM syndrome is caused by mutations in CD40L = Defective CD40 signalling
