Overview of the immune system in health& disease Flashcards
What are the primary organs of the immune system?
- Thymus
- Bone marrow
What are the secondary organs of the immune system?
- Spleen
- Lymph nodes
- Mucosal associated lymphoid tissue
Outline the mechanisms of defense used in natural immunity
- skin, mucous membranes
- Enzymes, complement,acute phase proteins
- Macrophages and neutrophils
- Natural killer( NK) cells
Outline the mechanisms of defense used in adaptive immunity
- Lymphocytes
- T cells: cytokines, killing
- B cells: antibodies
What can trigger inflammation?
- Infections: (bacterial, viral, parasitic) & microbial toxins
- Trauma
- Physical & chemical agents
- Tissue necrosis
- Foreign bodies ( splinters, dirt, sutures)
- Immune reactions ( aka hypersensitivity reactions)
What is the function of inflammation?
- To neutralize/destroy the harmful agent
- To alert the body to the threat of tissue injury
- To limit the extent of tissue injury
- To prepare the injuries for repair
Outline the symptoms of inflammation and the physiological responses associated with them
- ) Heat ( Calor): due to increased blood flow and elevated cellular metabolism
- ) Redness (Rubor): due to vasodilation & increased blood flow
- ) Swelling (Tumor): due to vasodilation; extravasation of fluid (permeability); cellular influx ( chemotaxis) & elevated cellular metabolism
- ) Pain (Dolor): release of soluble mediators; permeability; Chemotaxis & elevated cellular metabolism
Outline the phases of inflammation
- ) INITIATION: Induction of the acute inflammatory response
- ) AMPLIFICATION: Dependent on the extent of injury
- ) DESTRUCTION: Phagocytosis, enzymatic, non-enzymatic mechanisms
- ) TERMINATION: Resolution of inflammation, anti-inflammatory mediators
What are the molecular sensors of the innate immune response?
- Pattern recognition receptors ( PRRs)
What are the molecular sensors of the innate immune response able to detect?
- Conserved pathogen structures ( Pathogen Associated Molecular Patterns, PAMPs)
- Endogenous insults
- Exogenous danger signals ( Danger Associated Molecular Patterns, DAMPs)
What mediates the recognition in innate immunity?
Diverse recognition elements, 4 key families of pattern recognition receptors
- Toll like receptors (TLRs, transmembrane receptors)
- Rigl-like receptors (RLRs, cytoplasmic RNA helicase)
- NOD-like receptors (NLRs, cytoplasmic sensors)
- C-type lectin receptors (CLRs, transmembrane receptors)
What is the function of Interleukin 8 ( IL-8) ?
-Good chemotaxic agent for neutrophils, recruiting them to the site of inflammation
What is the function of Interleukin 12 (IL-12)?
-Drives the development of certain types of T cell e.g Th1
Which interleukins up-regulate vascular adhesion molecules?
TNF-alpha
IL-1
IL-6
Which interleukins increase vascular permeability?
TNF-alpha
IL-1
Which interleukins allow for vasodilation?
TNF-alpha
IL-1
IL-6
Which interleukins induce maturation of dendritic cells
TNF-alpha
IL-1
IL-6
What are the 5 inflammatory cascades
- ) Complement
- ) Coagulation
- ) Bradykinin
- ) Arachidonic acid
- ) Free radicals
What does the resolution phase of inflammation involve?
- Clearance of injurious stimuli
- Clearance of mediators and acute inflammatory cells
- Replacement of injured cells
- Normal function
Outline the characteristics of chronic inflammation
- Self perpetuating, may develop in the course of recurrent or progressive acute inflammation, or low grade irritants that fail to elicit a classical acute inflammatory response
- Chronic inflammatory cells: lymphocytes, macrophages
- Neo-vascularization
- No/less exudation
- Prominent fibrosis
Outline the characteristics of acute inflammation
- flush,flare& wheel
- acute inflammatory cells: Neutrophils
- vascular damage
- More exudation
- Little/no fibrosis
What is granulomatous inflammation?
- A distinctive pattern of the chronic inflammatory reaction
- A protective response to chronic infection or foreign material, preventing dissemination & restricting inflammation
Which diseases may present with granulomatous inflammation?
- TB
- Fungal infections
- Leprosy
- Schistosomiasis
- Foreign material
- Autoimmune diseases
- Rheumatoid arthiritis
- Crohn’s disease
- Sarcoidosis
What are the differences in the systemic manifestations found in acute & chronic inflammation
Acute: fever, often high
Chronic: Low grade fever, weight loss, anemia
What is the importance of IgA
-Important in the gut immune system and breast milk
Outline the pneumonic ‘DAMEG’
-helps to remember the immunoglobulin classes IgD IgA IgM IgE IgG
How can we classify the immunologic diseases for hypersensitivity?
Type I: Immediate hypersensitivity
- Immune mechanism= IgE antibody
- Mechanism of tissue injury= Mast cells & their mediators
- EG: allergic rhinitis, asthma, systemic anaphylaxis
Type II:
- Immune mechanism= IgM, IgG Abs to cell surface extracellular matrix Ag
- Mechanism of tissue injury: Opsonisation& phagocytosis of cell; complement & FcR- mediated recruitment & activation leukocytes
- EG: drug allergies, transfusion reaction, autoimmune haemolytic anaemia, Graves diseas, myasthenia gravis
Type III:
- Immune mechanism: immune complexes of circulating Ags & IgM or IgG Abs
- Mechanism of tissue injury: Complement & FcR-mediated recruitment & activation of leukocytes
- EG: serum sickness, SLE
Type IV:
- Immune mechanism:
1. ) CD4+ (Delayed- type hypersensitivity)
2. ) CD8+ CTLs ( T cell mediated cytolysis) - Mechanism of tissue injury:
1. ) Macrophage activation: cytokine mediated inflammation
2. ) Direct target cell lysis, cytokine-inflammation
What are the stages of anaphylaxis?
- ) Generalised itching; urticaria
- ) Swelling away from the sting;incontinence
- )Difficulty in breathing
- ) Fall in BP; loss of consciousness
Outline allergen crosslinkage of cell- bound IgE
- occurs on the surface of a mast cell
- Type I hypersensitivity; this signals degranulation
- The allergen cross links with IgE Fc receptors found on the surface of the mast cell
How can we diagnose type I hypersensitivity?
- ) Skin test:
- Done under clinical conditions
- Wheal( swelling) and flare (redness around the outside)
- Measure the size of the wheal& flare reaction- this tells you how allergic the patient is to that particular allergen - ) Immunoassay:
- You need enzyme or radio labelled anti-IgE + IgE antibody in test sample + allergen coated paper disc
- This is the radioallergosorbent test (RAST)
- a blood test using radioimmunoassay test to detect specific IgE antibodies, to determine the substances a subject is allergic to.
Outline the difference between a RAST test and a skin allergy test
-A skin allergy test determines allergy by the reaction of a person’s skin to different substances
