Clinical Immunology and implication Lecture.pptx

Immunology and related disease.

1. Clinical Immunology By, Dr. Md. Zahirul Huq MBBS, FCPS (Medicine) Assistant Professor (Medicine) Khulna Medical College Hospital, Khulna.

2. Clinical Immunology Table of Contents Introduction Classification Innate immunity Adaptive immunity Acute inflammation Acute Phase response Chronic inflammation Presenting problems in immune disorder Recurrent infection, Intermittent fever Anaphylaxis Immune deficienc y Warning sign of immune deficiency Investigation for immune deficiency Amyloidosis Autoimmunity, Atopy , Allergy Hypersensitivity Angioedema Transplant rejection,

3. The immune system consists of an intricately linked network of lymphoid organs, cells and proteins that are strategically placed to protect against infection . Immune defences are normally categorised into two types: A) Innate immune response, which provides immediate protection against an invading pathogen, and B) Adaptive or acquired immune response, which takes more time to develop but confers exquisite specificity and long-lasting protection. Introduction

4. Introduction (Contd.) Innate and adaptive immunity do not work in isolation, but rather in concert, largely driven by cytokines produced by the specific immune cell populations

5. Clinical Immunology Components of Innate immune system Physical barriers Phagocytes- Neutrophils , Monocytes , Macrophages. Dendritic cells Cytokines Integrins Complement Mast cells Basophils Natural Killer cells

6. Clinical Immunology Components of Adaptive immune system: Organs involved in Adaptive immune system: Thymus, Spleen, Lymph nodes, Mucosa- associated lymphoid tissue, Lymphatics Types: two types: Humoral immunity: Mediated by B-Cells which Produces antigen specific antibodies. Cellular Immunity: Mediated by T-Cells

7. Clinical Immunology Inflammatory Response: Acute inflammation Chronic inflammation A) Acute inflammation Acute phase response Septic Shock Resolution of inflammation

8. Clinical Immunology Acute phase response: It refers to the production of a variety of proteins by the liver in response to inflammatory stimuli. Acute phase proteins: C-reactive protein Serum amyloid -A Alpha-1 anti trypsin Alpha-1 antichymotrypsin Lactoferrin Ferritin Haptoglobin Immunoglobulin are not acute phase protein.

9. Clinical Immunology : Clinical features of acute inflammation i

10. Clinical Immunology : Laboratory features of acute inflammation C- Reactive Protein: 1.It is an acute phase reactant produced by liver. 2. It opsonises invading pathogens. 3. More sensitive early indicator of the acute phase response. 4. Direct biomarker of acute inflammation. 5. Useful in monitoring disease activity. Rise: within 06 hrs of the start of inflammation. Half life: 18 hrs.

11. Clinical Immunology : Laboratory features of acute inflammation ESR (Erythrocyte sedimentation rate): 1. Indirect measure of inflammation. 2. Determined by composition of plasma proteins and morphology of circulating erythrocytes. Plasma Viscosity: Affected by Fibrinogen, Immunoglobulins .

12. Clinical Immunology Presenting problems in Immune disorders: 1. Recurrent infections 2. Intermittent fever 3. Anaphylaxis

13. Clinical Immunology : Recurrent infections Aetiology Infections secondary to immune deficiency occur because of defects in the number or function of phagocytes, B cells, T cells or complement. Investigations Initial investigations should include full blood count and white cell differential,CRP , renal and liver function tests, urine dipstick, serum immunoglobulins with protein electrophoresis, and HIV testing. Additional microbiological tests, virology and imaging are required to identify the causal organism and localise the site of infection. If primary immune deficiency is suspected on the basis of initial investigations, more specialised tests should be considered,. Management If an immune deficiency is suspected but has not yet been formally characterised , patients should not receive live vaccines because of the risk of vaccine-induced disease. Further management depends on the underlying cause and details are provided later.

14. Clinical Immunology : Intermittent fever Intermittent fever: Intermittent fever has a wide differential diagnosis, including recurrent infection, malignancy and certain rheumatic disorders, such as Still's disease,Vasculitis and SLE but a familial fever syndrome is a potential cause.

15. Clinical Immunology: Anaphylaxis Anaphylaxis is a potentially life-threatening, systemic allergic reaction characterised by circulatory collapse, bronchospasm , laryngeal stridor , often associated with angioedema , and urticaria . The risk of death is increased in patients with pre-existing asthma, particularly if this is poorly controlled, and in situations where treatment with adrenaline (epinephrine) is delayed.

16. Clinical Immunology: Immune deficiency .

17. Clinical Immunology : Immune deficiency .

18. Clinical Immunology : Secondary immune deficiency .

19. Clinical Immunology : Amyloidosis Types: 1. Reactive amyloidosis 2. Light chain amyloidossis 3. Dialysis associated amyloidosis 4. Senile systemic amyloidosis 5. Hereditary systemic amyloidosis . Definition: Amyloidosis is the name given to a group of acquired and hereditary disorders characterised by the extracellular deposition of insoluble proteins.

20. Clinical Immunology: Amyloidosis Clinical features: The clinical presentation may be with nephrotic syndrome, cardiomyopathy or peripheral neuropathy. Amyloidosis should always be considered as a potential diagnosis in patients with these disorders when the cause is unclear. Investigations The diagnosis is established by biopsy, which may be of an affected organ, rectum or subcutaneous fat. The pathognomonic histological feature is apple-green birefringence of amyloid deposits when stained with Congo red dye and viewed under polarised light. Immunohistochemical staining can identify the type of amyloid fibril present. Quantitative scintigraphy with radiolabelled serum amyloid P is a valuable tool in determining the overall load and distribution of amyloid deposits.

21. Clinical Immunology : Amyloidosis Management The aims of treatment are to support the function of affected organs and,in acquired amyloidosis , to prevent further amyloid deposition through treatment of the primary cause. When the latter is possible, regression of existing amyloid deposits may occur.

22. Clinical Immunology: Autoimmunity Autoimmunity It can be defined as the presence of immune responses against self tissues. Atopy : It is the tendency to produce an exaggerated IgE immune response to otherwise harmless environmental substances. Allergy: can be defined as the clinical manifestation of this inappropriate IgE immune response. .

23. Clinical Immunology: Allergy .

24. Clinical Immunology: Hypersensitivity Type I hypersensitivity is relevant in allergy but is not associated with autoimmune disease. Type II hypersensitivity causes injury to a single tissue or organ and is mediated by specific autoantibodies . Type III hypersensitivity results from deposition of immune complexes,which initiates activation of the classical complement cascade, as well as recruitment and activation of phagocytes and CD4+ lymphocytes.Generalised deposition of immune complexes gives rise to systemic diseases such as SLE. Type IV hypersensitivity is mediated by activated T cells & macrophages,which together cause tissue damage .

25. Clinical Immunology .

26. Clinical Immunology: angioedema .

27. Clinical Immunology: Angioedema Angioedema is an episodic, localised , non-pitting swelling of submucous or subcutaneous tissues. Pathophysiology The causes of angioedema are summarised in Box 4.18. It may be a manifestation of allergy or non-allergic degranulation of mast cells in response to drugs and toxins. In these conditions the main cause is mast cell degranulation with release of histamine and other vasoactive mediators. In hereditary angioedema , the cause is C1 inhibitor deciency , which leads to increased local release of bradykinin . Angiotensin -converting enzyme (ACE) inhibitor-induced angioedema also occurs as the result of increased bradykinin levels due to inhibition of its breakdown. .

28. Clinical Immunology : Angioedema Clinical features Angioedema is characterised by soft-tissue swelling that most frequently affects the face (Fig. 4.15) but can also affect the extremities and genitalia. Involvement of the larynx or tongue may cause life-threatening respiratory tract obstruction, and oedema of the intestinal mucosa may cause abdominal pain and distension.

29. Clinical Immunology : Angioedema I nvestigations Differentiating the mechanism of angioedema is important in determining the most appropriate treatment. A clinical history of allergy or drugexposure can give clues to the underlying diagnosis. If no obvious trigger can be identified, measurement of complement C4 is useful in differentiating hereditary and acquired angioedema from other causes. If C4 levels are low, further investigations should be initiated to look for evidence of C1 inhibitor deficiency.

30. Clinical Immunology: Angioedema Management Management depends on the underlying cause. Angioedema associated with allergen exposure generally responds to antihistamines and glucocorticoids . Following acute management of angioedema secondary to drug therapy, drug withdrawal should prevent further attacks, although ACE inhibitor-induced angioedema can continue for a limited period post drug withdrawal. .

31. Clinical Immunology: Angioedema .

32. Clinical Immunology: Transplant rejection .

33. Clinical Immunology . THANKS