L5&6- Immunopathology Flashcards
general overview of Innate immune system
Innate:
-Barrier and chemical mechanisms
- PRR (Pattern recognition receptor) - proteins expressed by cells to identify two classes of molecular patterns: 1) pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and 2) damage-associated (DAMPs), which are associated with cell components that are released during cell damage or death.
- Phagocytes, natural killer cells
General overview of adaptive immune system
Humoral
Cellular
Pattern recognition receptors
Antigen recognition receptor in innate system
Common theme is recognition of Pathogen-associated Molecular Patterns (PAMPs) but also Danger Associated Molecular Patterns (DAMP’s)
2 groups
- Cell surface (transmembrane) and intracellular receptors – TLRs, NLRs, RLR’s and CLR’s
- Fluid-phase soluble molecules
FLUID-PHASE RECOGNITION MOLECULES
C-TYPE LECTIN FAMILY
- COLLECTINS
- Mannan-binding Lectin
- Surfactant Protein A & D
Role in neutralisation of pathogen
Role in recruitment of adaptive response
Steps of Classical Pathway
Antigen+Antibody Complex –> c1, c4, c2 —> C3 convertase
From C3 convertase can go 3 ways:
1) c3a, c5a –> peptide mediators of inflammation, phagocyte recruitment
2) c3b –> binds to complement receptor on phagocyte —>opsonisation of pathogens —> removal of immune complexes
3) c3b —> c5b, c6, c7 ,c8 ,c9 —> Membrane attack complex, lysis of certain pathogens and cell
What is opsonization
An immune process where particles such as bacteria are targeted for destruction by an immune cell known as a phagocyte .
The process of opsonization is a means of identifying the invading particle to the phagocyte
Function of macrophages
Phagocytose and kill bacteria; produce antimicrobial peptides; bind (LPS); produce inflammatory cytokines
Function of Plasmacytoid dendritic cells (DCs)
Produce large amounts of interferon- (IFN-) which has antitumor and antiviral activity, and are found in T cell zones of lymphoid organs; they circulate in blood.
Function of Myeloid dendritic cells
Interstitial DCs are strong producers of IL-12 and IL-10
Langerhans DCs are strong producers of IL-12
function of Natural killer (NK)
Kill foreign and host cells that have low levels of MHC+ self peptides. Express NK receptors that inhibit NK function in the presence of high expression of self-MHC
Function of NK-T cells
Lymphocytes with both T cell and NK surface markers that recognize lipid antigens of intracellular bacteria such as M. tuberculosis by CD1 molecules and kill host cells infected with intracellular bacteria.
Function of Neutrophils
Phagocytose and kill bacteria, produce antimicrobial peptides
Function of Mast cells and basophils
Release TNF-, IL-6, IFN- in response to a variety of bacterial PAMPs
Function of Epithelial cells
Produce anti-microbial peptides; tissue specific epithelia produce mediator of local innate immunity, e.g. lung epithelial cells produce surfactant proteins (proteins within the collectin family) that bind and promote clearance of lung invading microbes
ADAPTIVE IMMUNE RESPONSE
Evolution in response to changing pathogen structures
In response to infection this lymphocyte undergoes CLONAL expansion
High degree of specificity
VDJ recombination enables multiple immunoglobulin structures
Mechanism of antigen presentation
Antigens are internalised
Broken down to peptides
Peptides associate with newly synthesised Class 2 molecules and are brought to the cell surface.
If the peptides are foreign they are recognised by helper T cells which are then activated.
Helper T cells produce cytokines needed by B cells, T cells , etc.
FUNCTIONS OF CLASS 1 MHC
The function of these proteins is to present antigenic peptides to T cells- T cells only see antigen in association with MHC Proteins.
MHC class 1 proteins present peptides to cytotoxic T cells
FUNCTIONS OF CLASS 2 MHC
The function of these proteins is to present antigenic peptides to T cells- T cells only see antigen in association with MHC Proteins.
MHC Class 2 proteins present peptides to helper T cells
Lymphocytes-function: B lymphocytes
develop potential to secrete antibodies: humoral immunity
Lymphocytes-function: T lymphocytes
Killer or cytotoxic T lymphocytes are able to kill. Cellular immunity
Helper T lymphocytes secrete growth factors (cytokines) which control immune response: Help B lymphocytes and T lymphocytes (Helper T cells are target of HIV)
Suppressor T lymphocytes may damp down immune response
Binding of antibodies to antigens inactivates the antigens by…?
Neutralization (blocks binding sites, coats bacteria)
Agglutination of microbes
—> Phagocytosis
Activation of complement —> cell lysis
What happens when cytotoxic t cell binds to foreign antigen?
Recognises non self antigen –> binds to infected cell –> Releases Perforin (hole forming) enzyme that can promote apoptosis –> infected cell destroyed
IL2
T cell growth factor (and IL 15)
Do we need to know the different cytokines for adaptive and innate immunity?
I don’t know? :s
