Innate immunology Flashcards
Immunity is split into two types of responses
Innate and Adaptative
Define immunology
the way in which your body defends itself from the outside
Specificity innate immunity
- Present from birth
- Relatively non-specific
- No memory
Specificity adaptive immunity
- Involves very specific recognition of precipitating agent (antigen)
- Powerful memory generated
Primary lymphoid tissues function
Produce cells involved in the immune response and educate adaptive immune cells not to recognise ‘self’
Secondary lymphoid tissues function
Designed to allow adaptive immune cells and antigens to get together to initiate the adaptive immune response
the innate and adaptive immune system is referred to a ‘smart’ system explain
its memory allows it to respond rapidly to a second encounter with a pathogen
dendritic cells are?
crucial cells for linking innate and adaptive response
Myeloid progenitor is respinsible for?
all/ most cells involved in immunity
Lymphoid progenitor define
the precursor for the cells involved in the adaptive immune response. Mainly B & T lymphocytes; there also some natural killer cells
innate immunity stems from?
tissue damage from trauma or infection causes complex series of cellular and chemical events which aim to unit spread, to eliminate pathogen/toxins to repair damage
4 types of defensive barries
anatomical
physiological
phagocytic
Inflammatory
How does skin act as a defensive barrier?
Mechanical barrier that stops the entry of microbes
List anatomical barriers
skin
mucosal surfaces
How does mucosal surfaces act as a defensive barrier?
Competition for attachment and nutrients
mucus entrapment
cilia propulsion
List physiological defensive barriers
Temperature
low pH
Chemical mediators
List examples of chemical mediators involved in defensive barriers
lysosomes, interferon, collectins, cytokines and complement proteins
Phagocytic defense barriers involves?
specialised white blood cells taking up and destroy pathogens
Endocytosis define
Uptake of extracellular material
Phagocytosis define
active uptake of particulate material through formulation of finger-like projections of cytoplasm ( & attempted) degradation of material
pinocytosis define
uptake of soluble material
How does an inflammatory response act as a defensive barrier?
release of many mediators, changes in vascular permeability, serum proteins with anti-bacterial activity
How do phagocytes destroy organism by intracellular mechansims? begin from site of infection
- At site of infection, specialised wbcs take up organisms/toxins
- Later on in immune responses/in blood other wbcs phagocytose
- Organism destroyed by intracellular mechanisms
How do phagocytes recognise pathogens?
by cell surface receptors that identify the agent as foreign
PAMPS
Pathogen Associated Molecular Patterns
PRR
Pattern Recognition Receptors
How do phagocytes recognise pathogens directly?
PRR bind to molecules,
PAMPs only found on microbes or modified host cells
How do phagocytes recognise pathogens indirectly?
Serum proteins (antibodies, complement, lectins) can coat or ‘opsonise’ particles which are then recognised by receptors on phagocytes
destructive enzymes work best at what pH? low or high
low pH
Digestion- attempted destruction of taken up material can happen how? 2 ways
oxygen independent
oxygen dependent
3 ways digestion can be oxygen independent
acidification
enzymes
defensins
acidification (how)
phagolysosome acidifies due to lactic acid and H+ produced
enzymes involved in disgestion (oxygen independent)
lysosomes, lipases, proteinases
digestion by defensins involves polypeptides. EXPLAIN
- electrostatically attracted to pathogens
- from pores in the surface
- most abundant protein in neutrophil granules
Digestion can be attempted by oxygen dependent pathway how?
respiratory bust through reactive oxygen or nitrogen intermediates (ROIs & RNIs) also known as free radicals
Mechanism for respiratory bust
involves cytoplasmic and membrane associated enzymes which oxidise molecules and leave them with unpaired electrons (very unstable)
ROIs & RNIs hvae potent anti-microbial properties that can be secreted by the phagocytes
free radicals have potent anti-microbial properties such as:
damage proteins, lipids, cell membranes, DNA
Summary of phagocytosis
- Bacterium becomes attached to membrane evaginations called pseudopodia
- Bacterium is ingested, forming phagosome
- Phagosome fuses with lysosome
- Lysosomal enzymes digest captured material
- Digestion products are released from cell
when bacteria is ingested it forms?
a phagosome
Membrane evanginations are called?
pseudopodia
rubor
redness
calor
heat
dolor
pain
tumor
swelling
Inflammation is one of the body’s early defence reaction to ?
infection/ damage
5 signs of inflammation
Rubor, Calor, Dolor, Tumor, Loss of function
Inflammation involves large number of chemicals and cells acting in concert to do what? and why?
to increase blood flow, permeability vasculature
why? to limit infection spread and tissue damage, promoting healing
permeability vasculature refers to?
allowing cells out of the blood into the tissue
permeability vasculature refers to?
allowing cells out of the blood into the tissue
During inflammation how are immune cells activated?
At site mediators are released from activated tissue wbcs:
- Stimulate release of granulocytes and monocytes, activate hypothalamus and liver- Acute Phase Protein Production (CRP,SAA,MBL)
- Increase expression of Adhesion molecules on endothelial cells lining blood vessels & on local wbcs
- other factors affect vascular tone and integrity of endothelial layer
Where are granulocytes and monocytes released from when stimulated during inflammation?
bone marrow
when hypothalamus is activated during inflammation, what does this lead to?
fever
when liver is activated during inflammation what is produced?
Acute Phase Protein production ( CRP, SAA, MBL), which bind to a number of “molecules” and oxidise
benefit of increasing expression of adhesion molecules during inflammation
allows cells to attach to endothelium
During inflammation other factors affect vascular tone and integrity of endothelial layer allowing?
attached cells to pass into tissues
List some inflammatory mediators
includes wide range of proteins, lipids and chemicals
-cytokines/chemokines
-enzymatic cascades
-complement components
-prostaglandins and leukotrienes
cytokines are categorised how?
Pro- inflammatory and anti-inflammatory
List of pro-inflammatory
IL-1,6, 12, TNF (tumour necrosis factor alpha) IFN (interferon gamma)
Fucntion of IL-12
Activates adaptive immune responses ( T cells)
IFN gamma function
acts later on contributing to chronic inflammation by recruiting macrophages to sites of damage/ infection
IL-1, IL-6 & TNF alpha are early alarm signals causing local & systemic activation of:
fever, vascular permeability, production of acute phase protein increased adhesion of molecule expression
what activates T cells in adaptive immunity?
IL- 12
what IL recruits macrophages to sites of damage/ infection?
IFN
List cytokines in anti-inflammatory response
IL-10
chemokines consist of 2 families ,name them
CC & CXC
Chemotaxis
ability of the cell to move up a chemokine gradient
on binding specific receptors on wbcs, what do chemokines do?
stimulate migration & activation of these cells towards the gradient of the chemokine
chemokines are defined by?
presence of 4 cysteine residues and sequence of amino acids involving the first two major families
fugitaxis
works other way of chemotaxis - high to low chemokine gradient
e.g. IL-8
fibrinolytic pathway
-Endothelial damage
- Activation of Hageman factor (factor XII)
- Activated fibrinolytic system
- Plasmin
- complement activation
Plasmin can lead to two different pathways:
fibrinolytic and clotting
Clotting pathway
- endothelial damage
- Activation Hageman factor
- Activated clotting cascade (thrombin)
- fibrinopeptides + fibrin clot
- Fibrin degradation
- Increases vascular permeability , neutrophil chemotaxis
what does the clotting pathway do?
increase vascular permeability and neutrophil chemotaxis
what does the fibrinolytic pathway do?
complement activation
what does the kinin pathway do?
increases vascular permeability
vasodilation
Pain
Smooth muscle contraction
steps for kinin pathway
- Endothelial damage
- Activation of Hageman factor
- prekallilkrein
- Kallikrein
- Kininogen converted to bradykinin
- increases vascular permeability, vasodilation, pain, smooth muscle contraction
kinin, clotting and fibrinolytic pathway all contribute to what type of response?
innate
define complement
group of serum and cell surface proteins
role of complement (3):
regulate inflammatory and immune responses
acts as opsonins to increase phagocytosis
lyse cells and microorganisms
complement components present in what form? in blood
inactive prescursors
Role of prostaglandins
Cause vascular dilation & enhance effect of histamine & bradykinin on vascular permeability
role of leukotrienes
promote wbc migration into tissues
NTKs (natural killer cells) share expression of what?
some T cell & some MC/ granulocyte surface markers
NKs also have receptor for antibody. This is helpful why?
can attcak antibody coated target cells such as tumuor cells - (process called ADCC)
ADCC (NKs)
antibody dependent cellular cytotoxicity
NKs are the same progenitors as T cells but?
branch off early with no T cell receptor (specific antigen recognition system)
Killing mechanism of NKs
- form pores in target cell membrane by secreted molecules e.g. perforin & granzymes
- also induce apoptosis
- kill a range of tumour targets & virally infected cells
