Lung Immunology

Get Started. It's Free
or sign up with your email address
Lung Immunology by Mind Map: Lung Immunology

1. Features of Lung Immunity

1.1. Structure and function

1.2. Innate defence mechanisms

1.3. Macrophages

1.4. Adaptive Responses

2. Lung disease

2.1. Infection

2.2. Allergy

2.3. COPD

2.4. Cancer

3. Immune Deficiencies and Lung Infection

3.1. IgG2- capsulated bacteria

3.2. IgG1/3, complement- Gram -ve bacteria

3.3. Lymphocyte- viral infection

3.4. HIV- pneumocystis

3.5. Defensins- cystic fibrosis

3.6. Chemotherapy, surgery and polar age- broad infection

4. Lung Structure and Function

4.1. Evolved as gas exchange apparatus

4.2. Upper airways conduct- 2 cm^2 cross section

4.2.1. Up to 23 bifurications- trachea to bronchi to bronchioles

4.3. Lower airways facilitate gas exchange- 75m^2 cross section

4.3.1. Respiratory bronchioles, 300m alveoli

4.4. Large mucosal surface

4.4.1. 9000L of air per 24hr resting

4.4.2. Filtration of entire cardiac output

4.5. Effectively sterile- efficiently protected

5. Respiratory epithelium

5.1. Pseudo-stratified columnar epithelium with goblet cells

5.2. Found in airway down to respiratory bronchioles

5.3. Protective- mucus traps particles and removes them by coordinated cilia action

5.4. Tight junctions (zonula occludens)

5.4.1. Variable impermeable barrier to fluid formed by claudin and occludin proteins joining cytoskeleton of adjacent cells

5.4.2. Prevents water loss and entry of infectious/allergenic agents

5.4.3. Increased permeability in asthmatic epithelial cells

6. Alveolar Epithelial Cells

6.1. Type I Pneumocyte

6.1.1. Extremely thin- 0.2 microns

6.1.2. Squamous, often below limit of detection

6.1.3. Minimal covering for capillaries

6.1.4. Supported by reticular connective tissue and a vasal layer

6.2. Type II Pneumocyte

6.2.1. Cuboidal cells, interspersed amongst Type I cells

6.2.2. Located at angular junction of alveolar walls

6.2.3. Characterised by redish, foamy or vacuolated cytoplasm

6.2.4. Secretory in nature- make surfacant and new type I and II cells

7. B-defensins and Surfactant protein

7.1. Defensins- small cationic detergent peptides

7.1.1. Highly conserved

7.1.2. Active against bacteria, fungi and viruses

7.1.3. Bind to membrane to form pores

7.1.4. Disrupt viral glycoproteins and envelope

7.1.5. High defensin levels associated with infection resistance in CF patiens

7.2. Surfactant proteins- SP A, SP D, C1q, Mannan binding lectin

7.2.1. Ca2+ dependent, collagenous, carbohydrate binding proteins

7.2.2. Bind and agglutinate pathogens

7.2.3. Promote phagocytosis

7.2.4. Fix complement

8. Inflammation during infection

8.1. Epithelial turnover and tight junctions

8.2. Cilial clearance

8.3. Mucus

8.4. Airway shape and longitudinal air flow

8.5. Coughs and sneezes clear diseases

8.6. Humoral branch includes lysozyme, lactoferrin, complement and defensins

8.7. Alveolar macrophages, mast cells

9. Lung Adaptive Immune Mechanisms

9.1. Lung is an immunoresponsive organ

9.1.1. Local IgA/E production in upper airways

9.1.2. Transuded serum IgG in lower airways

9.2. Local autonomous cell mediated immunity

9.2.1. Hylar lymph nodes at main bronchi

9.2.2. Inducible BALT

9.2.3. Parabronchial and parattracheal nodes

10. Effect of smoking

10.1. Weaker response to vaccination

10.2. Lower antibody titre

10.3. Adverse effect of smoking on Hep B vaccine

10.4. More risk of infection, lung tumours, and asthma

10.5. 4 fold increase in macrophage number but poor activation response

10.5.1. Poor APC function

10.5.2. Reduced phagocytic activity

10.5.3. Suppressed cytokine production

10.6. In lymphocytes

10.6.1. Decreased IgG, M, A and sA production but increased IgE production

10.6.2. Decreased functional antibody

10.6.3. Reduced NK function, decreased antigen and mitogen stimulation

10.7. In neutrophils

10.7.1. Increased neutrophil numbers

10.7.2. Reduced chemotaxis, phagocytosis and respiratory burst

10.7.3. Increased peroxidase and elastase activity

11. Asthma

11.1. Allergic Th2 mediated response

11.1.1. Can be induced by exercise, cold air, air pollution, infection, aspirin and obesity

11.2. Common alergens include dander, pollen and dust mites

11.3. Effector cells are IgE prime mast cells, eosinopils and basophils

11.4. Lower chance of Th1 cell mediated autoimmunity like diabetes or MS

11.5. Inflammatory disease of airway wall mediated by TH2 cytokines

11.5.1. IL-5 induces eosinophilia

11.5.2. IL-4 and IL-13 induce goblet cell metaplasia and bronchial hyperreactivity

12. APC in Asthma

12.1. DC

12.1.1. CD11c DC required for IL-3 production by Th2 cells

12.1.2. Plasmacytoid DC required for respiratory tolerance

12.2. Alveolar macrophages

12.2.1. Clear inhaled particles and pathogens

12.2.2. Prime Th1 response

12.2.3. Activated macrophages may be induced by respiratory synctitial virus or sendai virus and prime

12.2.4. Don't migrate to lymph nodes

13. Role of epithelial cells

13.1. TLR and NOD receptors induce cytokine production

13.2. IL-17E amplifies TH2 cytokine production and eosinophilia

13.3. IL-33 synergises with Stem cell factor and FCeR to activate granulocytes and enhance survival

13.4. TSLP activated DC and promotes Th2

13.5. IL-22 induces EC proliferation and production of antimicrobrial peptides

14. Immunological Therapies

14.1. Omalizumab

14.2. Anti CD4

14.3. Anti IL-5

14.4. Anti TNF

15. COPD

15.1. Chronic lung Injury

15.2. Marked by repeated episodes of inflammation

15.3. Continues tissue repair

15.3.1. Distorted matrix deposition

15.3.2. Mesenchymal cells proliferate

15.3.3. Lung architecture is altered

16. COPD Spectrum

16.1. Inhaled agents can cause alveolitis/ pneumonitis

16.2. Circulating agents can cause endothelial injury

17. COPD and fibrosis

17.1. In most cases no known initiating event is recognised, fibrosis is diagnosed

17.2. Th17 cells are activated and lead to

17.2.1. Defensin production by epithelial cells

17.2.2. Inflammatory cytokine production- IL-1 , IL-6, TNF

17.3. This leads to:

17.3.1. Neutropil and macrophage recruitment

17.3.2. Altered mucous production

17.3.3. Epithelial desquamation

17.3.4. Fibroblast proliferation

17.3.5. Collagen deposition