OVERVIEW OF IMMUNOLOGY March 18, 2008 10:00-11:00

1. OVERVIEW OF IMMUNOLOGY March 18, 2008 10:00-11:00

2. CASE 1: THE IMMUNE SYSTEM AT WORK HPI: DL is a healthy woman of unknown age who appeared for a routine medical exam. This year she was able to obtain a flu shot and thus avoided the usual midwinter illness break. She smiles brightly and reports the successful completion of dental procedures to restore damage done by an errant golf ball. She attributes her unusually sunny disposition to a combination of that and excitement about her work. PE: T 36.2 C; HR 68, BP 110/70 Her physical exam was unremarkable except for what appeared to be a recently healed wound on her left hand. Upon query, she laughingly recounted injuring herself with pruning shears while getting her garden ready for Spring planting. The wound became mildly infected. There were never signs of systemic infection, and it healed without intervention although she thinks she might have put Neosporin on it at some point.

3. OBJECTIVES • What cells recognize foreign invaders and what types of receptors • do they use? • How do immune cells communicate with each other to ensure • that an appropriate response is made? • Where and how do immune cells develop? • What are innate and adaptive immunity and what roles do they • play in protection against different types of pathogen?

4. CASE 2: ALLERGY AND ASTHMA HPI: JK is an 8 year old girl presenting to the ER with shortness of breath, diffuse urticaria, angiodema, and hypotension. She was snacking on cashews. Within minutes, she felt a lump in her throat and became hoarse. Simultaneously, she developed facial swelling and an intensely pruritic rash. She became nauseous and vomited with crampy abdominal pain. En route to the hospital she experienced chest tightness, wheezing, and difficulty breathing. She is not on any medication and has no known drug allergies. She also has no personal history of atopy, but there is a family history of asthma. PE: T 37.7 C, HR 124, BP 82/53 JK appears ill and is in moderate respiratory distress. Significant findings are facial and periorbital non-pitting edema, perioral cuanosis, and stridorous breath sounds. Her lungs have diffuse wheezing. Her abdomen is soft, mildy distended, with diffuse periumbilical tenderness. She has dffusely distributed large, irregularly shaped pruritic, erythematous wheals on her trunk and extremeties.

5. Objectives • 1. What are the different types of hypersensitivity? • What other conditions are caused by hypersensitivity? • How does understanding the mechanisms of • hypersensitivity aide in identification and treatment of • conditions caused by hypersensitivity?

6. CASE 3: AUTOIMMUNE AND INFLAMMATORY DISEASE HPI: TN is a 25 year old African-American female. She presents with a fever, butterfly facial rash, oral lesions and joint pain. Four weeks ago, she started to experience fatigue and malaise. She developed a persistent low grade fever and painful oral ulcers. She started to notice discomfort in her wrists and knees. The discomfort worsened over the past week. She went to bed for a few days. When she decided to go outside for “some sun”, she developed a rash over her nose and cheeks. She also notes sharp chest pain upon inspiration. Prior to this, she was healthy and taking no medication. Two of her aunts have “some sort of skin disease”. PE: T 38.5 C, HR 86, BP 135/85 On exam, TN is ill appearing but not in acute distress. Significant findings are an erythrematous, raised rash over her nose and cheeks. She has multiple ulcerated lesions on her labia an gingiva and cervical lymphadenopathy. She has bilaterally symmetric diminished lung movement with diffuse crackles and a palpable spleen tip. She has grossly normal appearing wrists and knees with tenderness. There are no neurologic defects.

7. OBJECTIVES • What are antibodies (immunoglobulins) and what is their • role in immunity? • How does the immune system distinguish between self and • non-self? • What diseases are caused by the inability to correctly • distinguish between self and non-self?

8. CASE 5: IMMUNODEFICIENCY HPI:CE is a 1 year old boy who presents with 1 day of fever, cough and dyspnea. The mother recorded a fever of 102.3 F and notes increased irritability, rhinorrhea, frequent ear pulling, diarrhea and vomiting. The cough began yesterday and has progressed to rapid breathing. This is his sixth respiratory tract infection in the last 5 months, which includes one episode of bronchitis, three episodes of otitis media, and one episode of pneumonia requiring hospitalization. PE: T 39.4 C, BP 97/52, HR 135 On exam, he is in mild respiratory distress. His weight is 10% less than his previously recorded weight which was in the fifth percentile. His exam is significant for erythematous and purulent tympanic membranes, thick green sputum in the nasopharynx, chest retractions, diffuse ronchi, and diminished capillary refill. His chest X-ray showed diffuse infiltrates.

9. OBJECTIVES • What are the common forms of primary immunodeficiency? • How do deficiencies in specific components of the immune • lead to a clinical scenario?

10. CASE 4: TISSUE TRANSPLANTATION HPI: JM is a 45 year old diabetic man who had a kidney transplant 2 weeks ago. He now presents with shortness of breath, severe hypertension, rapid weight gain, and oliguria (decreased urine production). He has gained 10 pounds over the last 2 days and his blood pressure has increased from 130/85 to the 190s/100s. He has had a progressive decline in urine output to 500 ml/day. He reports increased shortness of breath with a new onset of orthopnea. The patient is taking cyclophosphamide for immunosuppression. PE: T 38 C, HR 85, BP 190/105 On exam he is in mild respiratory distress. His exam is significant for diffusely increased skin turgor, bibasilar crackles to midchest, a cardiac flow murmer, a distended abdomen with left lower quadrant tenderness to palpation, and significant lower extremity pitting edema.

11. OBJECTIVES • What is cell mediated immunity and how does it protect • against pathogens? • How do T cells recognize and eliminate foreign cells? • What is the MHC and how is it involved in immune responses? • What is tolerance and how does it develop?

12. Where there is no understanding, there will be no knowledge; where there is no knowledge, there will be no understanding Pirket avot

14. THE BIG PICTURE

15. Figure 1-2 THE PRIMARY GOAL OF THE IMMUNE SYSTEM: DEFENSE AGAINST PATHOGENS Pathogen---any organism with the potential to cause disease

16. Figure 1-7 PATHOGENS ARE ELIMINATED BY A TWO TIERED IMMUNE SYSTEM

17. Figure 8-5 part 1 of 2 STAGE 1: The pathogen breeches physical barriers (Active physical barriers..innate immunity)

18. Figure 1-14 STAGE 2: INITIATION OF THE IMMUNE RESPONSE (Innate Immunity) Macrophages recognize PAMPs on pathogen Pathogen is phagocytized

19. STAGE 3: LOCALIZED INFECTION Innate Immunity Macrophages release cytokines leading to localized inflammation Pathogen can be eliminated at this stage….but

20. Figure 8-5 part 2 of 2 STAGE 4: THE INFECTION SPREADS Pathogen spreads to lymphoid activating the adaptive immune system

21. Figure 1-18 STAGE 5: INITIATION OF THE ADAPTIVE IMMUNE SYSTEM IN LYMPHOID TISSUE

22. THE ADAPTIVE IMMUNE RESPONSE Figure 1-8 Antigen specific cells (T and B) are selected, expand, and mature Slow---But better next time