EMS lectures 4,5,6,7 Flashcards
What cells are of lymphoid lineage
natural T killer cell, small lymphocytes, T cell, B cell and plasma cells
What cells are of myeloid lineage
megakaryocyte, RBC, mast cells, myeloblasts, thrombocytes, basophils, neutrophils, eosinophils, monocytes, macrophages
What are the 5 major components of the innate immune system
Pattern recognition receptors antimicrobial peptides cells complement components cytokines
what are Pattern recognition receptors
antigen recognition receptor
- specific
- 2 groups
- cell surface (transmembrane and intercellular receptors - TLR, NLR, RLR, CLR)
- Fluid phase soluble molecules = c-type lectin family (collectins)
Role in neutralisation of pathogen and recruitment of adaptive response
Role of cell in innate immune system
Macrophage
Phagocytose and kill bacteria
produce inflammatory cytokines
Role of cell in innate immune system
Natural Killer cells
kill foreign and host cells that have low levels of MHC+ self peptides
Role of cell in innate immune system
NK T cells
recognize lipid antigens of intracellular bacteria by CD1 and kill infected host cells
Role of cell in innate immune system
Neutrophils
phagocytose and kill bacteria, produce antimicrobial peptides
Role of cell in innate immune system
eosinophils
kill invading parasites
Role of cell in innate immune system
mast cells and basophils
release TNF, IL6, IFN
Role of cell in innate immune system
Epithelia cells
produce antimicrobial peptides,
What is the adaptive immune response
evolution in response to changing pathogen structures
- unique antigen receptor on each lymphocyte
- clonal expansion of lymphocyte
What are the primary lymphoid organs and what is their function
bone marrow and thymus
lymphocyte development and selection
what are the secondary lymphoid organs and what is their function
spleen
lymph nodes
mucosal surfaces
immune responses
What is the mechanism of antigen presentation
1) Antigen internalised and broken into peptides
2) peptides associated with class 2 molecules
3) presented on cell surge
4) peptides recognised as foreign by T helper Cells
5) activated T helper cells secrete cytokines for T and B cells
What is the Histocompatibility antigen
- what are the classes of histocompatibility antigen
- gycoprotiens expressed on mammalian cells that make us unique found on white cells
- Human Leucocyte antigen (HLA)
- coded for by MHC
- Class 1 - HLA-A,B,C
- Class 2 - HLA-DP,DQ,DR
What is the function of class 1 and class 2 MHC cells
T cells only see antigents associated with MHC proteins
Class 1 MHC presents peptides to cytotoxic T cells
Class 2 MHC presents peptides
to helper T cells
function of B cells
secrete antibodies (humeral immunity)
function of killer T lymphocytes
kill cells - cellular immunity
function of helper T lymphocytes
secrete cytokines, stimulate B and T lymphocytes
function of suppressor T lymphocytes
dampen down immune response
Inactivation of antigens by the binding of antibodies can occur how?
neutralisation - coating and blocking binding sites
agglutination of microbes
precipitation of dissolved antigens
(enhances phagocytosis)
activation of complement system - causes cell lysis
define immunosuppression
natural or artificial process turns off immune response
define immunodeficiency
lack of efficient immune system
caused by immune suppression
define hypersenstivity
undesirable reaction to an innocuous antigen in a pre senstized host with a normal immune system
what are the types of hypersensitivity?
1) igE mediated reaction
2) cytotoxic reaction
3) immune complex reaction
4) cell mediated reaction
features of type 1 hypersensitivty reaction
IgE mediated
realease of preformed mediator - histamine
synthesis of lipid mediator - leukotriene
- FAST onset, weal and flare
- common allergens - hay, pollen, bee stings
- assoicated disease- hay fever, allergic asthma
Explain Immunoglobulin E
IgE
Produces by plasma cells from class switched B cell
production controlled by IL4 and CD40L - CD40 reaction
- low serum levels
High affinity for IgE receptor (FCeRI)on mast cells and basophils
What does the preformed mediator do?
Histamine
stimulate irritant nerve receptors and smooth muscle contractions
increase vascular permiabiltiy
What does the preformed mediator do?
kallikrein
activate Bradykinin
similar to histamine
What does the preformed mediator do?
Tryptase
unknown
when are preformed mediators released in the type one sensitivity reaction?
in the early phase
during the degranulation of mast cells
What is the role of the eosinophils and basophils in the late phase type 1 reaction?
Basophils - degranulate and release preformed mediators
Eosinophils - release contents of Granules (cytotoxic proteins)
- major source of tissue damage
- attracted to sites of allergic inflammation by chemokines
T cells - continue reaction with production of cytokines
explain type 2 hypersensitivity reaction
cytotoxic
IgM (or IgG) initiated
activated compliment cascade –> lysis
aggregation of Ig –> phagocytosis
usually affects haemopoietic cells
Associated diseases
ABO incompatibility
Autoimmune anaemias
Platelet disorders
Explain type 3 hypersensitivity
Immune complex formed
FcR binds to C1q
Compliment activation generates activated complement fragments
C5a - attract neutrophils
C3b - opsonin
attempted phagocytosis of complexes = release of enzymes and free radicals
TISSUE DAMAGE = RESULT
EXPLAIN type 4 hypersensitivty
T cell mediated - CD4, MHC2 delayed reaction Langerhans cells present NEOANTIGENS to T cells T cells release cytokines Macrophages recruited Macrophages cause tissue damage
Explain T cell cytotoxicity
CD8 MHC1 - contact demerits
Antigen presented by APC
Explain Granulomatous reaction
Collection on inflammatory cells in tissues
release of cytokines by T cells cause initial response
Caused by
TB, leprosy, sarcoidosis, crohn’s
Primary Causes of chronic inflammation
endogenous material
- necrotic adipose tissue
- uric acid crystals
exogenous material
- implanted prosthesis
- sutures
- asbestos fibres
Autoimmune
- SLE
- rheumatoid arthritis
Primary Granulomatous
- Sarocoidosis
- Crohns
Infections
- TB
- Leprosy
- some viral infections
How does acute inflammation progress to chronic
give an example
Most commonly supprative acute inflammation
- forms abscess
- walls thicken
- granulation and scaring
- recurrent inflammation leads to chronic
e.g. cholecystitis - call bladder inflammation from stones
What are the morphological features of chronic inflammation
infiltration by mononuclear cells (macrophage, lymphocytes, plasma cells)
- tissue distruction
- healing by fibrosis
Role of the macrophage in chronic inflammation
Increase inflammation - stimulating immune system
- release cytokines which recruits monocytes
- proliferate and immobilise in damaged tissue
- debride damaged tissue with proteases inducing angiogenesis and granulation
what is leukocyte extravasion
the recruitment of monocytes through the endothelium of the blood vessels into the damaged area of tissues
What is granulation tissue
new connective tissue and blood vessels that form on surface of wound during healing
- fibroblasts deposit collagen
- aim to repair by replacement of injured tissues with fibrous tissues
stimulated by macrophage debridement of damaged cells
What is fibrosis
formation of excess fibrous connective tissue during repair
fibroma - if from 1 cell line
macrophage induced
What is granulomatous inflammation
aggregation of macrophages, lymphocytes and histiocytic giant cells (aka langhans type giant cells)
often with caseous necrotic centre (= caseous epitheliod granuloma)
what are histiocytic giant cells
formed when macrophages are unable to digest material
- multinucleated >100
What are granulomatous diseases
Bacterial - TB, Leprosy Parasitic - schistosomiasis Fungal - Cryptococcus Synthetic material - silicosis Unknown - sarcoidosis, crohn's
What is chronic inflammation response to MI?
Myocardial fibrosis
how is inflammation involved in atheroma formation
macrophages adhere to epithelium and recruit other cells
How does inflammation in MS present?
plasma cells and t lymphocytes are found in white matter because macrophages have broken down myelin
