5&6 - Immunopathology Flashcards
Immune system categories
Innate or adaptive
Innate system categories
Barrier and chemical mechanisms
PRR
Cellular - phagocytes NK cells
Adaptive system categories
Humoral
Cellular
Lymphoid precursor can turn into what
NK cell
Plasmacytoid dendritic cell
T cell (from thymus)
B cell (from bone marrow)
T cells can split into
CD8+ cytotoxic T cell
CD4+ T cell
What does PRR stand for?
Pattern recognition receptors
Examples of PRR
Toll-like receptors (TLR’s), NOD-like receptors, Rigl-like receptors, C-type lectins (CLR’s), scavenger receptors
Antimicrobial peptide examples
-defensins, cathelin, protegrin, granulysin, histatin, secretory leukoprotease inhibitor and probiotics
Cells of the innate immune system examples
Macrophages, dendritic cells, NK cells, NK-T cells, neutrophils, eosinophils, mast cells, basophils and epithelial cells
Complement components of the innate immune system
Classic and alternative complement pathways and proteins that bind complement components
Cytokines of the innate immune system
Autocrine, paracrine, endocrine cytokines that mediates host defense and inflammation, as well as recruit, direct and regulate adaptive immune responses
What are PRR?
Inclusive term for antigen recognition receptor in innate system
2 groups of receptors either cell surface (transmembrane) and intracellular receptors, fluid-phase soluble molecules
Fluid phase recognition molecules’ family
C-type lectin family
Things belonging to C-type lectin family
Collectins - mannan-binding lectin; surfactant protein A&D
Recognition of microbial complex carbohydrates
Bind via carbohydrate-recognition domains
Role in neutralisation of pathogen
Role in recruitment of adaptive response
Complement pathways
Classical - antigen - Ig complexes
MB-lectin - mannose-binding lectin binds mannose on pathogen surfaces
Alternative - pathogen surfaces
Cells of the innate immune system
Macrophages Plasmacytoid dendritic cells (DCs) Myeloid dendritic cells Natural killer cells (NK) NK-T cells Neutrophils Eosinophils Mast cells and basophils Epithelial cells
What are plasmacytoid dendritic cells? (DCs)
Produce large amounts of interferon (IFN) - antitumour and antiviral activity.
What are myeloid dendritic cells
Interstitial DCs are strong producers of IL-2 and IL-10 in T cell zones.
What do mast cells and basophils release? why?
Release TNF-, IL-6, IFN- in response to bacteria
V(D)J recombination how does it work?
D to J recombination. So these are spliced.
V combines with DJ recombination.
Mechanism of antigen presentation
- Antigens are internalised
- Broken down to peptides
- Peptides associated with newly synthesised class 2 molecules and brought to 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.
Histocompatibility antigens
- Glycoproteins found on mammalian cells make us unique
- First found on white cells (called human leucocyte antigens or HLA)
- 6 families coded for by gene in MHC
How many classes of histocompatibility?
Two
Class one HLA receptors
HLA-A, HLA-B, HLA-C
Class two HLA receptors
HLA-DP, HLA-DQ, HLA-DR
Function of class 1 and 2 MHC proteins
T cells only see antigen in association with MHC proteins.
Proteins are there to present antigenic peptides
MHC1 = cytotoxic (CD8)
MHC2 = helper T (CD4)
Ways inactivating antigens via antigens
Neutralisation (blocking viral binding sites)
Agglutination of microbes
Precipitation of dissolved antigens
Above 3 enhance phagocytosis
Activation of complement system (leads to cell lysis)
How do cytotoxic T cells work
- Bind to infected cell
- Perforin makes holes in infected cell’s membrane and enzymes enter
- Infected cell is destroyed
What do Th1 cells activate
CD8+
IgG antibody from B cells
Macrophage activation
What do Th2 cells activate
Eosinophil
Mast cell + basophil
B cells - IgM, G, A and E antibody
Types of hypersensitivity
I - IgE mediated reaction
II - Cytotoxic rxn
III - immune complex reaction
IV - cell mediated reaction
Type I hypersensitivity features
Anaphylactic
IgE mediated mast cell and basophil degranulation - released synthesised inflammatory mediators
Fast onset - 15-30 mins
Can have two phase response
Common antigens = pollen, bee venom, animal dander
Associated disease = hay fever, allergic asthma
What does degranulation mean?
Granules inside cells releasing their content to outside of cell e.g. release histamine, proteases, chemotactic factors
Why is there sometimes a late-phase rxn in type I hypersensitivity?
Synthesis of lipid mediators can turn into arachidonic acid which makes leukotrienes and prostalandins
What does histamine do
Stimulate irritant nerve receptors
Contract smooth muscle
Increase vascular permeability
What does the last phase response initiate?
Basophils and eosinophils
Basophils have similar properties to mast cells
Eosinophils contain cytotoxic proteins and attracted to sites of allergic inflammation by chemokines. They release the contents of their granules which = major source of tissue damage in allergic response.
Also initiates more T cells which make more cytokines
Type II rxn features
Antibody-mediated cytotoxic rxns
Binding of antibody to antigen results in:
- activation of the complement cascade resulting in cell lysis
- Aggregation of Fc portions of Ig/C3b binding to FcRs/C3bR resulting in opsonisation, phagocytosis and destruction
What is type II activated by?
Initiated by IgM or complement-binding IgG
IgM most efficient since pentavalent whereas IgG requires multiple binding
What cells are usually affected by type II rxn?
Haematopoietic cells
What is type II rxn related to?
Blood group incompatibility
Autoimmune haemolytic anaemias
Affecting neutrophils
Affecting platelets
Type III rxns are…
Immune complex rxns
What are the immune complex rxns involved in type III?
- IgG + Ag = AgAb complex
- FcR in complex bind C1q
- Complement activation leads to generations of activated complement fragments
- C5a = attractant for neutrophils; C3b - opsonin
- Attempted phagocytosis of complex - release of enzymes and O2 radicals
- Consequence is tissue damage
Other antibody-mediated immunopathology
Inactivation = direct (B12 deficiency), indirect and receptor blockade
Type IV rxn features
T cell mediated - CD4+ cells (MHC Class II)
Delayed type e.g. Tuberculin skin rxn
Infiltration of lymphocytes and monocytes
Langerhan’s cells present neo-antigen to T cells
Ag-specific T cells release cytokines
Activated macrophage cause tissue damage
Requires previous exposure to antigen
Granulomatous rxns
Granulomas - focal collections of inflammatory cells in tissues
T cells are Th1-type (secrete IL2 and IFNy)
Release of IL-12 by macrophages critical in initiation of response
Examples of granulomatous diseases
Infections: mycobacterial (TB, atypical mycobacteria, leprosy)
Unknown aetiology: sarcoidosis, Wegener’s granulomatosis, Crohn’s disease
