Year 1 foundation B Flashcards
Physical immune system
Nature- constitutive
Cellular mediators- epithelial cells e.g. resp/GI/ skin epithelium
Extracellular mediators- Mucous and antimicrobial factors
Example:
Skin has thick layer of dead cells in the epidermis, acts as a barrier and shedding removes microbes
Mucous membranes produce mucus that traps microbes
Defecation and vomiting expel microbes
Innate immune system
Nature- constitutive, rapid, non specific, no memory, does not improve overtime
Cellular mediators- Neutrophils, basophils, eosinophils, Dendritic cells, macrophages, NK cells
Extracellular mediators- cytokines, acute phase proteins, complement proteins.
Mechanism of immune response
Detection- via PRR’s of sentinel cells binding to PAMP’s or DAMP’s
Release of cytokines/chemokines- increasing vascular permeability, recruiting immune cells, activating complement
Mechanism of killing pathogens
Complement cascade- MAC complex, C3a+C5a activates mast cells
Phagocytosis, Netosis, degranulation allow presenting to adaptive immune system
Cell mediator types (Innate)
Granulocyte- kills via degranulation releasing inflammatory cytokines and molecules e.g. chemokines
Sentinels/ Phagocytes/ APC’s- detects, engulfs and presents the antigens of the pathogens to other immune cells and to activate the adaptive immune response. Tissue resident
Lymphocytes- Tissue or from blood, kills infected tumour cells, produce cytokines
Innate immune cells
Macrophage- Central round nucleus (horseshoe when a monocyte), phagocytose and present antigens
Dendritic-large branch like projections, similar to macrophage
Natural killer- single lobed, kills tumor and virus infected cells
by releasing perforin
Mast cells- fried egg nucleus, release heparin and histamines causing vasodilation and inflammation
Neutrophils- multi-lobed+granules, most abundant and first responder. Phagocytose, degranulate, NETosis
Basophil- two lobed+purple stained granules, during allergies and against parasites
Eosinophil-two lobed+orange stained granules, same as basophils but moreso against parasites
TLR’s
TLR’s are a subdivision of a type of PRR’s. These are receptors on top of sentinel cells detecting PAMPs and DAMPs
TL-2: Gram positive bacteria
TL-4: Gram negative bacteria
TL-3/7/9: Viral nucleic acid
Complement cascade
Lectin- MBL binds to mannose on pathogens surface
Classical- IgG binds to antigens on the pathogens surface
Alternative- Complement proteins Factors B, D, P directly interact with the pathogen
All of the 3 pathways produce C3 convertase- this cleaves C3 into C3a + C3b-> cleaves C5a +C5b
C3a and C5a bind to mast cells to release histamines. This increases vascular permeability and attracts phagocytes
C5b+C6+C7+C8+ polyC9- form a cylinder inserting onto the pathogens membrane allowing its content to leak out causing it to die
Phagocytosis, degranulation, Netosis
Occurs once the pathogen been detected via PAMPs and DAMPS
Phagocytosis 🡪 Ingestion of pathogens followed by presenting the antigens on their cell surface. This is the link to the adaptive immune response.
Degranulation 🡪 Release granules which will kill the pathogen (usually by creating holes in their cell membrane so they leak out)
NETosis 🡪 Neutrophil Extracellular Traps.
Neutrophils can release their chromatin in a web of fibers to trap the pathogen and kill it
Adaptive immune system
Nature- requires priming, responds slowly, highly specific, memory response present, improves with repeated exposure
Cellular mediators- B cells (plasma cells once able to produce antibodies), T cells (CD4+ and CD8+)
Extracellular mediators- Antibodies/ immunoglobulins
Mechanism of immune response
Humoral immune response- primary immune cells are B cells
Selection on T cells
Mechanism of killing pathogens
Antibody action- opsonisation, agglutination
T cell MHC complexes- endogenous and exogenous antigen processing
Adaptive immune cells
B cell- mature in bone marrow and reside in blood stream+lymph nodes. Primary cell type of humoral differentiation into antibody producing plasma cells
CD4+ (helper) T cell- mature in thymus and reside in lymph nodes. Exogenous processing + MHC class II to present antigens to B cells.
CD8+ (killer) T cell- mature in thymus and reside in lymph nodes. Endogenous processing + MHC class I to kill pathogen.
Immunoglobulin function
All 5 antibody classes aim to neutralize pathogens and pathogen products before they cause too much damage, and before WBCs digest them whilst they’re still harmful. They can also activate other parts of the immune system.
Activating the complement pathway
Opsonization 🡪 help WBCs phagocytose pathogens
Neutralization 🡪 bind to toxic pathogenic products
Agglutination 🡪 grouping together lots of pathogens to make it easier for WBCs to find the pathogens and kill them all at once
Immunoglobulin structure
Variable region- antigen binding region (Fab)
Constant region-Fc
Hinge region- flexibility (disulfide bonds)
Two identical light chains
Two identical heavy chains
Glycosylated
Immunoglobulin types
IgM- pentameric, predominant in primary antibody response. Agglutination
IgG- 75%, predominant in secondary antibody response. Opsonosation
IgA- predominant in mucous/ secretion e.g. breast milk, mucous (Resp and GI). Neutralisation
IgE- important in defense against parasites and allergic reactions by binding to mast cells.
IgD- B cell receptor. Antigens bind to IgD to activate B cell
Humoral immune response- B cell activation
Mature B-Cells are produced in the bone marrow, and then circulate in the blood and lymph.
The B-Cell will become activated when the antigen binds to its B-Cell Receptor (IgD antibody). This forms a complex.
The complex is internalized by the cell and broken down into fragments – one part of the pathogen fragment is combined with an MHC Class II Molecule to form a new complex. This is inserted onto the B-Cell surface
A CD4+ Helper T-Cell will bind and recognize this complex on the B-Cell. The CD4+ Cell will release IL-2 to activate that B-Cell, and make it proliferate into plasma cells
The plasma cells will make and secrete antibodies which can bind the antigen which was in the complex.
Memory B Cells are also produced by the activation
MHC molecules
MHC Molecules are proteins on cell surfaces that present antigens to T-Cells
MHC Class I
Found on the surface of every nucleated cell
Present antigens to CD8+ T-Cells
Alleles: A, B, C
MHC Class II
Found only on the surface of APCs/ B cells
Present antigens to CD4+ T-Cells
Alleles: DPB, DQB, DRB
Genes are on Chromosome 6 called the HLA.
Polygenetic- multiple genes to code
Polymorphic- each gene has multiple alleles
These characteristics provide resistance against rapidly mutating pathogens
Humoral immune response- T cell activation
Occurs during early life:
Positive Selection 🡪 Immature T-Cells that bind well with MHC Class I molecules will become CD8+ Cells. Immature T-Cells that bind well with MHC Class II molecules will become CD4+ Cells.
Negative Selection 🡪 Immature T-Cells that bind well with any other self material will undergo apoptosis. This is called central tolerance and will prevent immune reactions against your own body tissue. This process goes wrong in autoimmune diseases.
