Immunopathology Flashcards
Is the immune system a multi network system.
Yes
what 2 components is the immune system split into
innate and adaptive
what are the 3 main components of the innate immune system
barrier and chemical mechanisms
PRR
Cellular.
what are the 3 main components of the adaptive immune system
humoral and cellular.
what are the major receptors and molecules involved in the innate immune system
(recognise non foreign species but the response is non specific)
Pattern recognition receptors (PRR). Antimicrobial peptides Cells Complement componenets Cytokines
what is the function of cytokines
mediate host defines system and direct and recruit adaptive immune responses.
what molecule of the innate immune system do anti rheumatic drugs work on
cytokines.
do pattern recognition receptors have diversity for different antigens
Yes- each immune cell group has the same antigen recognition receptor this is however specific to the spieces e.g. bacteria no to the organism
what are the 2 groups of pattern recognition receptors
- Cell surface (transmembrane) and intracellular receptors – TLRs, NLRs, RLR’s and CLR’s
- Fluid-phase soluble molecules.
what family do the fluid phase recognition PRR associated with
C type lectin family.
what is the function of fluid phase recognition molecules
recognition of microbial complex carbohydrates
Bind via carbohydrate recognition domains
role in neutralisation
role in recruitment of adaptive response.
what are the 3 pathways within the complement system
classical
MB-lectin
Alternative pathway.
what stimulates the classic pathway
antigen and antibody complex.
what stimulates the MB lectin pathway
MB lectin binds mannose on pathogens
whats stimulates the alternative pathways
pathogen surface.
what complex do the terminal complememnt components form
MAC
what does factor C3b do
binds to complement receptors on phagocytes
oppsinisation of pathogens
removal of immune complexes.
what do factors C3a and C5a do
peptide mediators of inflammation and phagocyte recruitment,
what are the 3 main cytokines of the innate immune system
IL1, IL6, TNF
what is the function of IL1 and what produces it and what does it act on
source- macrophages, endothelial and epithelial.
Target- hypothalamus
Function- increase coagulation, increase inflammation, increase acute phase proteins)
what is the function of IL6 and what produces it and what does it act on
source- macrophages, endothelia, T lymphocytes.
Target- hepatocytes and liver.
Function- increase acute phase proteins and increase B lymphocyte proliferation.
what is the function of TNF and what produces it and what does it act on
source- macrophages, T lymphocytes
Target- endothelia.
Function- increase coagulation and inflammation
Target hepatocytes- increased acute phase proteins, increase neutrophil activation.
Target- hypothalamus
Function- increased fever.
what is the function of a macrophage
phagocytose and kill bacteria, produce antimicrobial peptides and cytokines
what is the function of plasmacytoid dendritic cells.
produces IFN- antiviral and anti tumour.
what is the function of myeloid dendritic cells
interstitial DC’s produce IL2 and IL10 (found in lung heart intestines and kidney).
Langerhans DC’s produce IL12 are located skin, epithelia and thymic medulla.
where are dendritic cells found
T cell zones of lymphoid organs.
what is he function of natural killer cells.
kill host cells with low MHC and self peptide presentation
Express NK receptors that inhibit NK function in the presence of high expression of MHC
What is the function of NK T cells
lymphocytes with both T cell and NK surface makers that recognise lipid antigen of intracellular bacteria
what is the function of neutrophils
phagocytose and kill bacteria and produce antimicorbial peptides.
what is the function of eosinophils
kill invading parasites
what is the function of mast cells and basophilic
release TNF, IL6, IFN in response to bacterial PAMPs.
what is function of epithelial cells
produce anti microbial peptides and tissue specific epithelia, produced innate immunity e.g lung epithelia produces surfactant proteins that bind and promote clearance of invading microbes.
what are the primary lymphoid organs
bone marrow and thymus
what are the secondary lymphoid organs
immune response
spleen (white pulp)
lymph nodes and mucosal surfaces.
what is the mechanism of antigen presentation
Antigen internalised
broken down into peptides
Peptides associate with newly synthesised Class 2 molecules and are brought to the cell surface.
If the peptides are foreign they are recognised by helper T cells which are then activated.
Helper T cells produce cytokines needed by B cells, T cells , etc.
what is the function of MHC glycoproteins
present antigenic peptides to T cells.
what T cell do MHC 1 present to
T killer (cytotocxic cell)
what T cell do MHC 2 present to
T (helper cell)
what are the main antigen presenting cells
B cells
Dendritic cells
Macrophages
what is the main function of b cells
produce immunoglobulins
what is the function of t killer cells
kill.
what is the function of T helper cells
secrete growth factors (cytokines) which control immune response:
what is the function of suppressor T lymphocytes
damp down immune response
Binding of antibodies to antigens inactivates antigens by
Neutralisation
Agglutination
Precipitation of dissolved antigens
Activation of complement system.
mechanism by which cytotoxic T cells work
Cytotoxic T cells binds to infected cell
Perforin makes holes in infected cell’s membrane and enzyme enters.
Infected cell is destroyed.
define immunosupression
a natural or artificial process which turns off the immune response, partially or fully.
define immunodeficiency
the lack of an efficient immune system-susceptibility to infections
when is immunosupression commonly used
transplant rejection
autoimmune conditions
Lymphoproliferative diseases.
define hypersensitivity
Undesirable, damaging, discomfort-producing and sometimes fatal reactions produced by the normal immune system (directed against innocuous antigens) in a pre-sensitized (immune) host.
Type 1 hypersensitivity is also known as
Ig E mediated
Allergic
Anaphylaxis
what is the immunopathogenesis of Type 1
IgE Ab mediated mast cell and basophil degranulation- (Cross-linking of FceR by allergen)release of preformed and de novo synthesized inflammatory mediators
what common antigens cause IgE mediated disease
pollen, bee venom and animal dander.
what are the clinical features of type 1 reaction
fast onset- 15 mins 30 mins
weal and flare
can cause a second phase response.
what diseases are associated with type 1 hypersensitivity
Hay fever, allergic asthma
what cells produce IgE
plasma cells
On what cells are the high affinity IgE receptors found
Mast cells and basophils.
what is the function of histamines
Stimulation of irritant nerve receptors
Smooth muscle contraction
Increase in vascular permeability
what is the function of kallikrenin.
Activates bradykinin - similar actions to histamine
what 4 mediators are preformed in Type 1 hypersensitivity reaction and are involved in the early phase response
histamines, kallikrein and tryptase, and arachidonic acid mediators (prostglandins and leukotrienes)
what 3 substances are involved in the late phase response of type 1 hypersensitiviy
Basophils
Eosinophils
Granules- contain cytotoxic proteins.
what 2 substances are archadonic acid derived
leukotrienes and prostaglandins
what drives the main pathogenesis in allergy
cytokines
immunopathogenesis of type 2 hypersensitivity.
Antibody-mediated cytotoxic reactions
Binding of antibody to target antigen on cell membrane.
what does the formation of the antigen antibody complex result in
Activation of the complement cascade resulting in cell lysis
Aggregation of Fc portions of immunoglobulin/C3b with binding to FcRs/C3bR resulting in opsonisation, phagocytosis & destruction
Initiated by IgM or complement-binding IgG
what cells are typically affected by type 2 hypersensitivity
Haematopoietic cells.
Why is IgM more efficient in type 2 hypersensitivity reactions than IgG
IgM is pentavalent and IgG requires multiple binding sites
immunopathogenesis of hypersensitivity Type III.
IgG + Ag = AgAb complex
FcR in complex bind C1q
Complement activation leads to generation of activated complement fragments
C5a - attractant for neutrophils
C3b - Opsonin
Attempted phagocytosis of complexes - release of enzymes, oxygen radicals
Consequence is tissue damage
What cell mediates type 4 hypersensitivity
T cell mediated - CD4+ cells (MHC class II)
immunopathogenesis of hypersensitivity Type IV.
Initially perivascular infiltration of lymphocytes & monocytes.
Langerhan’s cells present neo-antigen to T cells
Ag-specific T cells release cytokines - recruitment of macrophages (non Ag-specific)
Activated macrophages cause tissue damage
Requires previous exposure to antigen.
give an example of the type IV hypersensitivity
Tuberculin skin reaction
define granulomas
Focal collections of inflammatory cells in tissues
what inflammatory cells are involved in a granuloma formation.
Macrophages
Epithelioid cells (phagocytic cells containing foreign material)
Giant cells
Lymphocytes
The T cells in granuloma formation are Th1 or Th2
Th1- secreter IL2 and IFN g.
Granulomatous diseases include
Mycobacterial • Tuberculosis • Atypical mycobacteria • Leprosy Unknow aetiology – Sarcoidosis – Wegener’s Granulomatosis – Crohn’s disease
which T cell is involved in type IV hypersensitivity
TH1
