Immunopathology and Hypersensitivity Flashcards
What are the general principles of the immune response?
- Multilayer defense
- Pathogen recognition
- Effective inter-cellular communication
- Self-regulation
- Limitation of host damage
- Adaptive responses to changing pathogen
- Multiple mechanisms of pathogen clearance
What are the innate and adaptive branches of the immune system?
Innate= Cellular (phagocytes & natural killer), PRR, barrier and chemical mechanisms Adaptive= Cellular, humoral
What are pattern recognition receptors?
- Antigen recognition receptors of innate system
- Common recognition of PAMPs & DAMPs
- 2 groups: cell surface & intracellular receptors
Name the major components of the innate immune system
- Pattern recognition receptors
- Antimicrobial peptides
- Cells
- Complement components
- Cytokines
Describe fluid-phase recognition molecules
- C type Lectin family= Collectins (surfactant protein A&D)
- Recognition of microbial complex carbohydrates
- Bind via CRDs
- Neutralisation of pathogens
- recruitment of adaptive response
What is the source and target of TNF?
Source: macrophages & T-lymphocytes
Target: Hepatocytes, neutrophils, inc inflammation & activation
What is the source and target of IL6?
Source: macrophages, T-lymphocytes, endothelia
Target: inc B-lymphocyte proliferation
What cell types of the innate immune system are there?
- Macrophages
- Natural killer
- Eosinophil & neutrophil
- Plasmacytoid & myeloid dendritic
- Mast cells & basophils
What is the mechanism for antigen presentation?
- Antigens internalised
- Broken down to peptides
- Associated with newly synthesised class 2 molecule and brought to surface
- Foreign peptides recognised by T-helper which are activated
- Produce cytokines needed by B&T cells
What does HLA stand for? What is its other name? What is ir?
- Human leucocyte antigens
- Histocompatability antigens
- glycoproteins on cell surface making them unique
What are functions of Class 1&2 MHC proteins?
Class1: present peptides to cytotoxic T cells
Class2: present peptides to helper T cells
What is the function of
B-lymphocytes?
Potential to secrete antibodies: humoral immunity
What is the function of killer/cytotoxic T cells?
Kill- cellular immunity
What is the function of helper T cells?
- Secrete growth factors (cytokines) which control immune response
- Help B&T lymphocytes
- Target of HIV
What is the function of suppressor T lymphocytes?
Dampen down immune response
How can binding of antibodies to antigens inactivate the antigens?
-Neutralisation (blocks viral binding sites& coats bacteria)
-Agglutination of microbes (clumping together)
-Precipitation of dissolved antigens
ALL ENHANCE PHAGOCYTOSIS
Activation of complement system (leads to cell lysis)
How does cell lysis occur?
1) Cytotoxic T cell binds to infected cell
2) Perforin makes holes in infected cell’s membrane, enzymes enter
3) Infected cell destroyed
Define immunosuppression and immunodeficiency
IS= Natural/artificial process which turns off the immune response
ID: A result of IS and the lack of an efficient immune system, susceptibility to infections
When is immunosuppression seen?
- Inhibit transplant rejection
- Autoimmune diseases
- Lymphoproliferative diseases
Define hypersensitivity
Undesirable/damaging and sometimes fatal reactions produced by immune system in a pre-sensitized host.
What types of hypersensitivity are there?
I) IgE Mediated
II) Cytotoxic reaction
III) Immune complex reaction
IV) Cell mediated reaction (DTH)
Describe a form of type I hypersensitivity
- Anaphylactic (severe reaction)
- Mast cell & basophil degranulation
- Release of preformed & de novo inflammatory mediators (histamine) & lipid mediators (leukotrienes)
- Pollen, bee venom, animal dander, hayfever, allergic asthma
What are the clinical features of anaphylaxis?
- Fast onset
- Weal & flare
- Sometimes late 2nd phase
- contraction of s.muscle
- Dilatation of blood vessels
- Mucous glands
Describe immunoglobulin E
- Produced by plasma cells from class-switched B cells
- Under control of IL-4 & CD40L
- Extremely low serum levels
- High affinity receptor for IgE on mast cells & basophils
- Stable binding over long periods
What happens in the early phase response of a reaction?
- Mast cell FCER1 presents at high density
- cross-linking by allergen leads to activation of mast cells
- degranulation & release of preformed mediators
- synthesis of lipid mediators
Name some preformed mediators
- Histamine= s.muscle contraction, inc vascular permeability, stimulation of irritant nerve response
- Kallikrein= activates bradykinin
- Tryptase
What are lipid mediators?
- Arachidonic acid derivatives
- Phospholipase A2 broken down to arachidonic acid
- Finally forms leukotrienes
- And Prostaglandins
What happens in the late phase response of a reaction?
- Basophils= similar properties to mast cells but over longer time scale
- Eosinophils= Granules contain cytotoxic proteins, attracted to site of inflammation by chemokines, release contents of granules in tissue - major source of tissue damage in allergic response
- T cell= in both early&late response, cytokine production by activated T cells needed for ongoing response
- Cytokine-driven activity major source of pathogenesis in allergic reaction
Name some examples of allergic diseases
- Asthma
- Rhinitis
- Dermatitis
- Food allergy
Describe type II hypersensitivity
- Antibody mediated cytotoxic
- Binding of antibody to antigen causes activation of complement cascade=cell lysis
- Aggregation of Fc portions of immunoglobulin binding to FcRs = opsonisation/phagocytosis/destruction
What is type II hypersensitivity initiated by?
- initiated by IgM (sometimes IgG)
- IgM most efficient since pentavalent
- IgG requires multiple binding
What is effected in type II hypersensitivity?
- Haematopoietic cells
- Neutrophils
- Platelets
- Blood group incompatbility
- Autoimmune haemolytic anaemias
Describe type III hypersensitivity
- IgG + Ag= AgAb complex
- Complement activation leads to generation of activated complement fragments
- C5a= attractant for neutrophils
- C3b= opsonin
- Attempted phagocytosis of complexes leads to release of enzymes& O2 radicals
- Results in tissue damage
Name some diseases from type III hypersensitivity, their route into the body and the site of immune complex deposition
-Vasculitis-Blood vessel walls
Nephritis- Renal glomeruli
Arthritis-joint space
ALL INTRAVENOUS ROUTE
Subcutaneous route- arthus reaction- perivascular area
Inhaled route- Farmer’s lung- alveolar/capillary interface
Give some examples of other antibody-mediated immunopathology
- Inactivation= DIRECT: Intrinsic factor in B12 deficiency
- Inactivation= INDIRECT: binding to hormone results in clearance of AgAb complex
- Receptor blockade= Myasthenia Gravis
Describe type IV hypersensitivity
- T cell mediated (CD4+/MHC class II)
- Delayed (tuberculin skin reaction)
- Age-specific T cell release cytokines- recruitment of macrophages
- Activated macrophages cause tissue damage
- Requires previous exposure to antigen
- Hapten(allergen) presented to skin causes reaction in langerhan cells
Give examples of other cell-mediated immunopathology
- Tcell mediated cytotoxicity
- CD8+/MHC class I
- Contact dermatitis (combination of DTH& cytotoxic reaction)
- Nickel/poison ivy can act as hapten with epidermal proteins
What are granulomatous reactions?
- Focal collections of inflammatory cells in tissue (macrophages, epithelioid cells, giant cells & lymphocytes)
- Th1- type T cells secrete IL2& IFNy
- _IL-12 release by macrophages critical in initial response
Name some granulomatous diseases
- Infections: mycobacterial= TB, atypical mycobacteria, Leprosy
- unknown = Sarcoidosis, Wegener’s Granulomatosis, Crohn’s
