L2 - A Kelly - Immunity to infection Flashcards
are commensals useful bacteria?
yep
Opportunistic pathogens rarely cause disease unless …
host defence is compromised.
5 points about the immune system
- Constantly evolving
- Protects us from infection and cancer
- Network of cells products and tissues
- Removes debris
- Over 10% of human genes are involved in defence
innate infection reacts….
imediately
describe the barriers, cells and soluble components of the innate and adaptive immune systems
acute inflammation is ……
a stereotypic response to tissue injury (which can be sterile)
purpose of acute inflammation?
- to eliminate the initial cause of cell injury,
- remove damaged (necrotic) tissue resulting from the insult or the subsequent immune response
- and to initiate repair of the damage tissue.
Picture for you
what are the activators of inflammation?
- foreign / native soluble released factors
- tissue damage
inflammation involves:
(2)
Recruitment of leucocytes to site of injury, and the release of inflammatory exudate
4 characteristics of inflammation
- Calour (heat)- from increased blood flow
- Dolor (pain)- stimulation of nerve ending
- Rubor (redness)- increased circulation/vasodilation
- Tumor (swelling)- increased fluid in the tissues
describe the physcial epithelial barriers of the immune system
- Tight junctions between
o squamous epithelial cells (skin)
o mucosal glandular epithelia (GI & resp tract) - Cilia
- Keratin
describe teh secretions of the epithelial barriers in the immune system
- Mucous over glandular surfaces
- Stomach acid (low pH)
- Antimicrobial peptides (defensins, cathelicidins) damage microbe membranes.
- Enzymes in tears and saliva (lysozyme) or stomach (pepsin)
can you remember the cell lines of teh immune cells?
the hematopoietic stem cells differentiates into
- common lymphoid precursor
- common myeloid precursor
which cells come from the common lymphoid precursor?
plasma cells
effector T cells
NK cells
which cells come fform the common myeloid precursor
- Macrophages
- Dendritic cells
- Neutrophils
- eosinophils
- basophils
- mast cells
- platelets
- erythrocytes
where to leukocytes come from?
generate in bone marrow by haematopoiesis
Monocytes mature into ____ in the _____
macrophages in the tissues
Mast cells resident in …..
connective and mucousal tissues
Describe neutrophils
- Most abundant of all WBC
- Follow chemotaxins C5a and fMLF
- Phagocytose
- Very short lived
- Degranulate antibacterial proteins into ECF
- can extrude their DNA forming neutrophil extracellular traps (NETs) to trap microbes (PUS).
describe macrophages:
- phagocytose, and remove cellular debris
- 2 types
o M1: secrete cytokines and pro- inflammatory mediators that stimulate the acute inflammatory response.
o M2 / alternatively activated: associated with tissue repair and parasite killing and expulsion. - Release cytokines to induce inflammation / repair
describe Mast cells
- contain preformed mediators of inflammation such as histamine.
- function is to rapidly induce inflammation.
- Degranulate within seconds
- A wide range of factors can induce degranulation including allergens (IgE), danger signals (PAMPs, DAMPs) and complement components (C3a, C5a), and substance P (neurogenic inflammation).
what are sentinal cells
both mast and macrophages, when theyre beneath epithelial surfaces – sensing tissue damage
describe eosinophils and basophils
non-phagocytic granulocytes providing defence against helminths worms and other parasites
describe dendritic cells
- Bridge adaptive and innate immune system
- Recognise pathogens, drain to lymph nodes to start adaptive response.
Describe NK cells
- Important in viral infections
- circulate in the blood in a partially activated state ready to respond immediately
- kill infected cells and maintain or even increase the state of inflammation in infected tissue
- recognise infected host cells by:
- loss of self receptor expression on surface
- expression of stress surface markers indicating cell is in stress
- this is a balance between activating and inhibiting substances
- in healthy cells – inhibitory substances dominate
NK cells recognise infection and damage to cells using receptors that signal:
a. loss of molecules that normal cells express (missing-self)
b. expression of self molecules that are induced in stressed cells (induced-self)
NK cells activation and inhibition balance:
MHC class I molecules present …..
MHC class I molecules present peptide fragments, derived from cytosolic pathogens (eg viruses) to T cells, signalling that the virus infected cell should be killed
describe how NK cells kill viral infected cells
infected cell produces cytokines (type I INFs)
induce resistance in surrounding cells
increase expression of ligands recognised by NK receptors
activate NK cells to kill
Macrophages produce CXCL8 and IL-12 to recruit NK cells and cause their proliferation
Activated NK cells produce cytokines (IFNγ) which activate macrophages and upregulate their killing capacity
3 NK effector functions:
- Degranulate perforin – holes in membrane
- Bind Fc portion of antibodies – and kill cells attached with perforin.
- Activated Fc receptor is strong – can activate the NK cell alone
- Cytokines CXCL8 & IL-12 recruit and activate NK cells, which produce IFNγ which activates macrophages – increasing killing capacity, and initiates adaptive immune repsonse
what are Innate Lymphoid Cells (ILCs)
function to amplify signals produced during innate recognition. The ILCs help orchestrate the early innate response.
how any types of ICLs are there?
3
describe ILC1s
- ILC1s protect against viruses and intracellular pathogens, they help activate M1 macrophage responses and may assist TH1 polarisation (similar to TH1 T cells see later).
describe ILC2s
- ILC2s assist mucosal and barrier immunity against parasite and helminths infection, they indirectly help TH2 and M2 macrophage polarisation (similar to TH2 T cells see later).
describe ILC3s
- ILC3s protect against extracellular bacteria and fungi (similar to TH17 T cells see later).
Picutre
describe cytokines
- Small protein messengers
- Bind to receptors on target cells
- Low conc, shoert lived
o Autocrine – same cell that secreted
o Paracrine – nearby cells
o Endocrine-like – distant cells
4 characteristics that cytokines show
- Redundancy, several different cytokines may have the same function
- Pleiotropism, a single cytokine may have a variety of different effects
- Antagonism, one cytokine blocks the action of another
- Synergy, multiple cytokines work together to achieve an effect that is
- greater than the additive effect of each alone
- work through Jak/STAT signalling pathway
Subgroups of cytokines?
- Interleukins
- interferons
- TNF family members
describe histamine
Generated from histidine
Stored in granules in mast cells
Causes immediate capillary vasodilation.
whats special about IL-8
IL-8 now renamed CXCL8 is a member of a subgroup of cytokines called chemokines. These are involved in controlling cell movement (chemotaxis).
do some cytoines have systemic effects?
yep
which cytokine shave systemic effects?
IL-6
C-reactive protein
describe IL-6
- IL-6 stimulates hepatocytes to release acute phase proteins.
describe C reactive protein
- C-reactive protein (opsonin and complement activation) and Fibrinogen (fibrin clot formation)
decribe how fibrinogen can help limit bacterial growth
Fibrinogen is converted into insoluble fibrin strands. This can entrap bacteria limiting growth and dissemination and support the recruitment and activation of host cells facilitating elimination of infecting microbes.
PROSTAGLANDINS AND LEUKOTRIENES =are….
PROSTAGLANDINS AND LEUKOTRIENES = potent inflammatory mediators
describe teh production of certain arachodonic acid metabolites
Describe the clotting system
- Tissue damage
- activates thrombin
- converts fibrinogen to insoluble fibrin & fibrinopeptides.
- Fibrin forms a clot to limit spread of infection.
- Fibrinopeptides induce vascular permeability and neutrophil chemotaxis.
- Thrombin cleaves both C3 and C5 -> C3a & C5a.
describe teh Kinin system
- Tissue damage
- results in the generation of Bradykinin which increases vascular permeability, vasodilation, pain, smooth-muscle contraction.
- The pathway activates complement components C3 and C5.
describe teh fibrinolytic system
- tissue damage
- results in generation of Plasmin, a protease which degrades fibrin into products that recruit neutrophils (chemotactic).
- Plasmin activates complement C3.
describe teh complementn system
- Complement cascades is activated by numerous mechanisms.
- Results in opsonisation, membrane attack complex formation and generation anaphylatoxins (C3a, C4a and C5a)
Fat
Mamba
