CASE 6 Flashcards
what are the effects of mast cells and basophils in the innate immune system?
vascular leak, bronchoconstriction, intestinal hyper mobility, inflammation
what is the effect of eosinophils in the innate immune response?
granules contain cytotxic cationic granule proteins (capable of producing tissue damage) and histamine
mast cells vs basophils
mast cells — present in relatively high numbers in skin and mucosa, can survive for months or years in situ
basophils — minority population, can only survive a few days in the blood
mast cell responses in the skin
increased blood flow and increased permeability — vasoconstriction, endothelial cell activation, cellular recruitment (neutrophils and eosinophils)
mast cells responses in airways
decreased diameter and increased mucus — coughing (expulsion), immobilisation of pathogen by mucus and cytoprotection
mast cell responses in GI tract
increased fluid secretion and increased peristalsis — expulsion of GIT contents (parasites), immobilisation of pathogen by mucus and cytoprotection
mast cell responses in blood vessels
increased blood flow and increased permeability — increased tissue fluid, lymph flow to lymph nodes, cells/protein in tissues
name 2 functions of eosinophils
- attack multicellular parasites
2. tissue remodelling
what antibody is mainly responsible for the initial immune response after a 1st vaccination?
IgM
what antibody is mainly responsible for the initial immune response after the 2nd vaccination?
IgG
name 5 actions of T lymphocytes in cell-mediated immunity
- kill virus-infected cells
- resistance against intracellular pathogens
- activate macrophages
- help antibody respones
- immunoregulatory function
T cells cannot see antigen in isolation. what do they need to see it with?
need to see antigen in the context of an antigen-presenting cell (eg. dendritic cell) and in the context of MHC
MHC class 1 vs class 2
CD8 lymphocytes (cytotoxic T cells and suppressor T cells) — MHC class 1 CD4 (T Helper cells) — MHC class 2
endogenous pathway vs exogenous pathway
endogenous pathway (intracellular antigens) — MHC class 1 on outside, viral or intracellular bacteria are fragmented then cross cell membrane by transporter protein. CD8 T cells
exogenous pathway (extracellular antigens) — MHC class 2, endocytosis. CD4 T Helper cells
what is CD3?
= part of T cell receptor complex
- all T cells express this
what is CD4+?
- T helper cells
- MHC Class 2 restricted
- helps activate Tc cells, activates macrophages (Th1) and helps antibody responses (Th2)
what is CD8+?
- Tc cells
- kill virus infected cells
by what mechanism do T and B cell antigen receptors form?
random recombination events and gene rearrangement
how do self-reactive antigen receptors arise and why do we limit the production of them?
= random selection of gene segments from a large gene pool generates >10^7 antigen specificities and therefore can generate self-reactive antigen receptors due to the wide range of possibilities.
— we limit the production of self reactive T and B cells to prevent the immune system from making tissue damaging reactions against self proteins
how many rounds of selection to T cells undergo to get rid of unwanted self-reactive T cells and what are the rounds?
2 rounds of selection =
- positive selection — for host MHC class 1 or 2. at this stage the cells are double positive. if T cell fails to recognise host MHC and self-peptide it is deleted — apoptosis
- negative selection — to remove self-reactive T cells. occurs when double positive T cells bind to bone marrow derived antigen presenting cells, macrophages and dendritic cells, expressing class 1 or 2 MHC with self peptides (low affinity cells escape)
what is a double positive T cell?
expresses both CD4 and CD8 molecules
what are the 2 populations of T reg cells?
- natural T regs = produced in thymus
2. inducible T regs = produced in periphery, usually mucosa
what do T reg cells do?
produce anti-inflammatory cytokines (inhibit proliferation of nearby cells), IL-10 + TGF-B (control/dampen down immune system responses — prevent allergy and autoimmunity)
what is an autoimmune disease?
a disease that develops when a specific immune response develops to self-antigen
what is allergy?
inappropriate or excessive immune responses to allergens
what is an allergen?
an antigen that triggers allergic respones
what are induction and elicitation?
- induction = 1st exposure — individual is ‘primed’
- elicitation = subsequent exposure to same allergen — sensitised individual shows clinical manifestations
describe the different types of hypersensitivity
- type 1 = immediate hypersensitivity
- type 2 = cytotoxic reactions
- type 3 = immune complex disorders
- type 4 = delayed hypersensitivity
describe type 1 hypersensitivity
= acute/immediate — occurs within minutes
- IgE mediated
- most allergic reactions (food allergy, asthma, rhinitis, atopic eczema)
how does anaphylactic shock come about after a large load of allergen?
large load of allergen —> increases vascular permeability and airway constriction —> can’t supply vital organs and fall in blood pressure —> anaphylactic shock
what is the sensitisation phase of type 1 hypersensitivity?
- the Fc part of IgE binds to mast cells/basophils, exposing its variable region
- mast cells/basophils are ready to work the next time the pollen appears
- when the antigen reappears, they will come into contact with sensitised (IgE-loaded) mast cells and stimulate it and cause an initial phase reaction and secondary reaction
how long does IgE loading take?
10-15 days
what is the initial phase reaction in type 1 hypersensitivity?
upon stimulation, the mast cells undergo degranulation, secreting preformed products (primary mediators)
what are the preformed products (primary mediators)
include histamine and proteases
what are the effects of proteases?
proteases do further tissue damage, causing the release of more inflammation mediators
what are the effects of histamine?
- vasoconstriction
- increased vascular permeability leading to partial oedema in the area
- spasmatogenic: histamine receptor are found on smooth muscle lining of the various tracts. histamine causes them to contract
- increases glandular secretions = luminal obstruction
- causes narrowing of the lumen of the tract
what is the secondary reaction of type 1 hypersensitivity?
upon stimulation, the mast cells secrete cytokines
what cytokines are secreted by the stimulated mast cells?
IL-3, IL-5 and leukotrienes