Innate Immunity Flashcards
(22 cards)
First line of defence (barriers)
- skin
- mucous secretions
- normal microflora
Second line of defence (effector mechanisms)
- innate immune cells
- inflammation
- complement
- antimicrobial substances
Cellular mechanisms of innate immunity
- Elimination of microorganisms by phagocytosis
- Orchestration of the immune response by cytokine secretion
- Antigen presentation (activation of adaptive immune
response) - Tissue remodelling
Humoral mechanisms of innate immunity
- Neutralisation of toxic action
- Precipitation into insoluble form
- Opsonisation (make more accessible to phagocytes)
- Direct killing
Inflammation
- Heat
- Redness
- Swelling
- Pain
- Loss of function
Process of inflammation
- bacteria trigger macrophages to release cytokines and chemokines
- vasodilation and increased vascular permeability case redness, heat and swelling
- inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain
Systemic Acute Response - Cytokines
Brain (hypothalamus)
- prostaglandins
- fever, fatigue, sleep
Adrenal cortex
- corticosteroids
- anti-inflammatory effect
Liver
- Acute phase proteins
- facilitation of pathogen neautralisation
Bone Marrow
- colony stimulating factor
- myelopoiesis
Outcomes of acute inflammation
Resolution:
- clearance of injurious stimuli
- clearance of mediators and acute inflammatory cells
- replacement of injured cells
- normal function
Fibrosis:
- loss of function
Chronic inflammation:
- angiogenesis
- mononuclear cell infiltrate
- fibrosis (scar)
Pattern Recognition Theory - 1989
- All microbes have conserved molecular
patterns, referred to as PAMPs
(Pathogen-Associated Molecular Patterns) not
present in the host
(e.g., dsRNA, LPS, peptidoglycan) - Host cells have receptors called PRRs
(Pattern-Recognition Receptors) for recognition of
PAMPs
Complement System
- composed of more than 30 different plasma proteins, which are produced
mainly by the liver - many of the complement proteins are proteases that successively cleave
and activate one another
Complement activation results in:
* opsonisation of microorganisms to promote facilitation of
phagocytosis
* direct cytotoxic activity
* inflammatory response
Proteins and peptides with anti-microbial activity
- found in various secretory fluids, milk, saliva, tears, nasal secretions, granules
of phagocytic cells - Lyzozyme:
muramidase or N-acetylmuramide glycanhydrolase, hydrolyses petidoglycan
(specific for Gram+bacteria) - Lactoferrin:
is a multifunctional protein of the transferrin family, primary role is to sequester
free iron, and in doing so remove essential substrate required for bacterial
growth.
binds to lipopolysaccharide of bacterial walls, and the oxidized iron part of the
lactoferrin oxidizes bacteria via formation of peroxides. This affects the
membrane permeability and results in the cell lysis - Lipocalin-2 (NGAL):
sequesters bacterial siderophores for iron, active only against Gram- negative
bacteria
Lectins
Proteins which bind to carbohydrates.
Lectins are highly specific for sugar groups
present in other molecules, so can cause
agglutination of particular cells or precipitation of
glycol-conjugates and polysaccharides.
Have numerous biological functions and are
particularly important in pattern recognition and
pathogen elimination in the innate immunity
(such as mannose binding lectin)
Acute Phase Proteins
- C-reactive protein – binds to microbial carbohydrates - opsonisation
- Serum amyloid A – chemotactic to neutrophils and monocytes
- Mannose Binding Lectin - complement activation
- Ficolin - compliment activation
Macrophages
- Resident in almost all tissues
(constant surveillance) - Providing first line of defence
(phagocytosis) - Orchestration of inflammatory
responses (via cytokine and
chemokine secretion) - Antigen presentation
Dendritic cells
- have long finger-like processes, like the
dendrites of nerve cells - take up particulate matter by
phagocytosis and also continually ingest
large amounts of the extracellular fluid
and its contents by macropinocytosis - main role in the immune system is to
activate T lymphocytes by displaying
antigens derived from the pathogen on
their surface - a crucial link between the innate immune
response and the adaptive immune
response
Mast cells
- Have large granules with active
mediators (histamine) in their
cytoplasm that are released when
the mast cell is activated. Involved in
development of allergic reactions. - Are found in most tissues of the
body, particularly in locations that
are in close contact with the external
environment, such as skin, airways,
and intestines. They are, therefore,
ideally placed to participate in the
early recognition of pathogens
Neutrophils
- Circulate in the blood
- Upon inflammatory signal rapidly recruited to
the site of inflammation –the first wave - Short life span (24-48 hr)
- Main function is to eliminate pathogen
through phagocytosis and secretion of
granular content (pro-inflammatory mediators,
proteolytic enzymes, reactive oxygen species)
Eosinophils
- Stain red with acidic dyes
- Have granules containing a
variety of enzymes and toxic
proteins, which are released
when the cells are activated. - Defend against protozoan and
helminth parasites - Contribute to allergic
inflammatory reactions (e.g.
asthma)
Basophils
Stain bluish-black with basic dyes
Non-phagocytic
Release vasoactive mediators
e.g., histamine, prostaglandins,
serotonin, and leukotrienes from
granules
Play important role in development
of allergies and hypersensitivities
Monocytes
- Circulate in the blood
- Spleen serve as reservoir
- Upon inflammatory signal rapidly recruited to the
site of infection - Contribute to pathogen elimination by
phagocytosis - Contribute to inflammatory response
- Differentiate into macrophages in the tissue
Natural Killer cells
- Cytotoxic lymphocytes
- Play a major role in the rejection of tumors and cells
infected by viruses. - NK cells were first noticed for their ability to kill tumour cells
without any priming or prior activation (in contrast to
cytotoxic T cells, which need priming by antigen presenting
cells). They are named for this ‘natural’ killing. - NK cells kill by releasing small cytoplasmic granules of
proteins (perforin and granzyme) that cause the target cell to
dye from apoptosis - Additionally, NK cells secrete cytokines such as IFNγ and
TNFα, which act on other immune cells like Macrophage
and Dendritic cells to enhance the immune response.
Major Histocompatibility Complex (MHC)
Function: to bind to antigen inside the cell and
bring it to the cell surface to present to the T
cells
MHCI molecules found on almost all types of
nucleated cells
-Required to present
endogenous/intracellular antigens (self and
pathogenic) to recognize malignant cells
and virus-infected cells
MHCII molecules found only on antigen
presenting cells
-Required to present
exogenous/extracellularly derived antigen to
recognize infected cells
