I Innate immunity (natural or native immunity) Instant Immediate Initial response Induces adaptive immunity Integrates with adaptive immunity
A
Adaptive immune system Acquired Await days = no immediate response Accurate = specific Autoregulation Autoimmunity
The Immune Response
Innate immunity is the first line of defense against infections. Innate immunity is specifically against microbes, while adaptive immunity is against any "foreign" substance (including cancer cells, autoantigens, etc.).
Innate immunity is the oldest mechanism of defense. Adaptive immunity (T and B lymphocytes) appeared in jawed vertebrates (sharks) and is superimposed on innate immunity to improve host defense. In a sense, adaptive immunity is an "add-on" to innate immunity.
The organs of the immune system are positioned throughout the body. They are called lymphoid organs because they are home to lymphocytes, small white blood cells that are the key players in the immune system.
Bone marrow, the soft tissue in the hollow center of bones, is the ultimate source of all blood cells, including white blood cells destined to become immune cells. The thymus is an organ that lies behind the breastbone; lymphocytes known as T lymphocytes, or just "T cells," mature in the thymus.
Lymphocytes can travel throughout the body using the blood vessels. The cells can also travel through a system of lymphatic vessels that closely parallels the body’s veins and arteries. Cells and fluids are exchanged between blood and lymphatic vessels, enabling the lymphatic system to monitor the body for invading microbes. The lymphatic vessels carry lymph, a clear fluid that bathes the body’s tissues.
Small, bean-shaped lymph nodes are laced along the lymphatic vessels, with clusters in the neck, armpits, abdomen, and groin. Each lymph node contains specialized compartments where immune cells congregate, and where they can encounter antigens.
Immune cells and foreign particles enter the lymph nodes via incoming lymphatic vessels or the lymph nodes' tiny blood vessels. All lymphocytes exit lymph nodes through outgoing lymphatic vessels. Once in the bloodstream, they are transported to tissues throughout the body. They patrol everywhere for foreign antigens, then gradually drift back into the lymphatic system, to begin the cycle all over again.
The spleen is a flattened organ at the upper left of the abdomen. Like the lymph nodes, the spleen contains specialized compartments where immune cells gather and work, and serves as a meeting ground where immune defenses confront antigens.
Behcet's disease is a rare, chronic, lifelong disorder that involves inflammation of blood vessels throughout the body. Symptoms of Behcet's disease include recurrent oral ulcers (resembling canker sores), recurrent genital ulcers, and eye inflammation. The disorder may also cause various types of skin lesions, arthritis, bowel inflammation, and meningitis (inflammation of the membranes of the brain and spinal cord).
A neutrophil travels along the capillary endothelial layer. Endothelial cells are triggered to express selectins on their surface for neutrophil integrin-mediated adherence. Transendothelial migration allows the neutrophil to traverse the blood endothelial layer. Squeezing into the extra-capillary space where migration towards a chemotactic gradient (chemotaxis) helps it to locate the pathogen. Subsequent phagocytosis ensues.
These are a focus of central fibrinoid necrosis surrounded by a palisade of epitheloid cells, occurring as a typical feature of sero-positive rheumatoid arthritis.
Subcutaneous nodules commonly occur on extensor surfaces subject to external pressure, for example, the upper forearm and elbow. Occasionally, they arise within the lungs or heart.
Nodules are rare in sero-negative rheumatoid arthritis.
A 77-year-old woman underwent surgical resection of a 1.5-cm papillary carcinoma of the right breast. Isosulfan blue dye (8 ml) was used intraoperatively to define the associated lymphatic drainage. Three sentinel nodes were excised from her axilla 5 minutes later, followed by the lumpectomy. By the time of wound closure, blue hives had developed on both upper arms and the chest as a result of an allergic reaction to the dye. Her cardiorespiratory system remained stable.
She was treated with intravenous phenylephrine (50 mg), had an uneventful recovery, and was discharged home 4 hours later. Blue hives occur in up to 1.5% of patients injected with this dye; the cause is probably a type I, IgE-mediated hypersensitivity to the dye.
A type of auto immune inflammatory myositis (recognized in females).It has 2 types according to age of presentation : 1- Juvenile dermatomyositis (JDM) : affects children and tends to be more severe 2- Adult dermatomyositis (ADM) : typically affects adults around the age of 50
It`s pathology described as cell mediated injury targeted at striated muscle with resultant atrophy, oedema, coagulation necrosis, fibrosis and calcification. -There is elevation of: * muscle enzymes (CK) * elevated muscle specific antibodies o anti RNA o anti Mi2
Dermatomyositis may be associated with interstitial lung disease : typically gives a patchy and subpleural consolidation with parenchymal bands. internal malignancy : can occur as part of a paraneoplastic syndrome (e.g lung cancer)
Radiographic features
Plain film
Plain radiographs show extensive sheet-like dystrophic calcifications in the soft tissues of the leg consistent with dermatomyositis.
* typically shows dystrophic calcification in muscles and soft tissues (calcinosis universalis) o sheet like although at least four patterns have described with childhood dermatomyositis 4. o classically seen affecting the thigh regions * chest radiograph may show diaphragmatic elevation * acroosteolysis
Fluoroscopy
Barium swallow
* may show disordered peristalsis involving the upper oesophagus : portion supplied by skeletal muscle
MRI
T2 : generally hyper intense signal throughout the affected muscles ; calcific areas may be low signal ; perimuscular oedema may additionally appear as high signal ; signal intensity may return to normal after treatment .
Angioedema: is the development of large welts below the surface of the skin, especially around the eyes and lips. The welts may also affect the hands, feet, and throat. The condition can be associated with allergies and histamine release.
#H1 antihistamines are effective for treating nasopharyngeal itching, sneezing, watery rhinorrhea, and ocular itching, tearing, erythema.
*Side effects associated with older H1 antihistamines include sedation, visual disturbance, urinary retention, and arrhythmias #Newer H1 antihistamines:( terfenadine (Seldane) astemizole (Hismanal))
*These agents exhibit less sedation associated with their reduced ability to cross the blood brain barrier. *However, there are very important drug-drug interactions associated with this category.
For example, macrolide antibiotics such as erythromycin, clarithromycin (Biaxin), ketoconazole-class broad-spectrum antifungal drugs, inhibit terfenadine (Seldane) or astemizole (Hismanal) metabolism.
Toxic levels of terfenadine (Seldane) or astemizole (Hismanal) may induce potentially fatal cardiac arrhythmias.
These new H1 antihistamines are contraindicated for concurrent use with macrolide antibiotics and ketoconazole-class and fungal drugs or in the presence of impaired hepatic function or inpatients predisposed to arrhythmias.
#Topical alpha-adrenergic agonists:
*Phenylephrine (Neo-Synephrine) or oxymetazoline (Afrin) reduce nasal congestion/obstruction.
Efficacy duration: limited due to rebound rhinitis and systemic effects which may include insomnia, irritability, and hypertension -- the latter which is seen more commonly with oral alpha adrenergic agonists.
#Oral alpha-adrenergic agonists may be useful in diminishing antihistamine-mediated sedation while improving antihistamine efficacy in relieving congestion. However, there is a concern that these agents due to their potentially hypertensive effects, may precipitate adverse cardiovascular effects, such as stroke. Recently, there has been an effort to remove such "pressor" agents from common over-the-counter cold medications.
#Cromolyn sodium: This agent is a liquid provided as a nasal metered-does spray. Cromolyn sodium (Intal) is not associated with side effects and typically is used prophylactically to reduce episodic allergen nasal mast cell activation. This agent may be used as part of a anti-asthma drug regimen.
#ntranasal glucocorticoids:
*Intranasal glucocorticoids are the most potent drugs available for management of established rhinitis (seasonal or perennial) and including vasomotor rhinitis
Topical-to-systemic activity greater for: flunisolide (AeroBid) or budesonide (Rhinocort), compared to beclomethasone (Banceril) or triamcinolone (Aristocort).
*Despite the different route of administration, intranasal-administered glucocorticoids exhibit the same efficacy but with reduced systemic side effects compared to same agent administered orally. *Side effects include local irritation, which is the most frequent side effect to Candida over-growth which is an unusual side effect *Topical high potency glucocorticoids exhibit superior efficacy compared antihistamines during pollen season.
#Immunotherapy (hyposensitization): This approach is based on repeated, subcutaneous injections of gradually increasing allergen (specific for the symptom complex) over a period of 3-5 years.
*Contraindications include significant cardiovascular disease and unstable angina *Cautious use applies to patients receiving beta adrenergic blockers (due to difficulty in managing possible anaphylactoid responses to treatment)
**Clinical Management Sequence:
1.Identification of allergens confirmed by allergens-specific IgE skin testing and/or serum assay. 2.Avoidance of offending allergen 3.Mild symptoms: prophylaxis with topical cromolyn sodium or single (bedtime) dose of chlorpheniramine (Chlor-Trimeton) or astemizole (Hismanal) or terfenadine (Seldane) (decision based on side effects and presence of other concurrent medications or disease. 4.Prominent symptoms: Topical beclomethasone (Banceril) or if needed budesonide (Rhinocort) or flunisolide (AeroBid) 5.Management failure: immunotherapy
A patient has secondary antibody deficiency due to B-cell suppression His primary pathology is likely to be
a) Waldenstrom macroglobulinemia b) X-linked agammaglobulinemia c) immunoglobulin A deficiency d) immunoglobulin M deficiency e) common variable immunodeficiency
The correct answer is A
Explanation Antibody immunodeficiency can be primary or secondary. Secondary antibody deficiency due to B-cell suppression can occur with multiple myeloma, Waldenstrom macroglobulinemia, or chronic lymphocytic leukemia. Secondary deficiencies leave patients susceptible to the same pathogens that can cause recurrent pneumonia in patients with primary antibody deficiencies Primary antibody deficiencies include X-linked agammaglobulinemia, common variable immunodeficiency, selective immunoglobulin A or immunoglobulin M deficiency, and hyperimmunoglobulin M immunodeficiency. These disorders are characterized by chronic or recurrent pyogenic infection, especially pneumonia, caused by encapsulated bacteria (eg, S pneumoniae, H influenzae, and S aureus) and P aeruginosa . Untreated or recurrent pneumonia may lead to bronchiectasis.
The main cell of the specific immune response is the small lymphocyte.
LIMPHOCYT RECIRCULATION
1) B and T lymphocytes constantly enter the blood stream from the peripheral lymphatic tissue via the lymphatics and the thoracic duct and circulate around the body. '
2) They reenter the lymphoid tissue at another site.
3) Lymphocytes form 20 - 40% of the circulating white blood cell Circulating lymphocytes are mainly T cells with a few B cells.
Immune response & elimination of antigen
1) Antigens can enter the body through the mucosa or skin.
2) Meeting the mucosa associated lymphoid tissue or the cutaneous lymphoid tissue.
3) The antigens are carried to the regional lymph nodes via lymphatics
4) If the antigen enters the blood stream it will be filtered by the spleen.
5) Lymphocyte recirculation ensures that B and T lymphocytes are constantly patrolling the body looking for antigen.
6) Antigen will meet the corresponding lymphocytes specific for the antigen →immune response (activation, proliferation and differentiation of lymphocytes)
7) The immune response takes place in the PERIPHERAL LYMPHOID TISSUE(rich in macrophages and dendritic cells).
* At the mucosal or skin surface immune response takes place in the MALT or cutaneous immune system.
* o The immune response to tissue antigens takes place in the lymph node.
* o The immune response to circulating antigens takes place in the spleen.
8) Antibodies from B cells or effector T cells go to the site of infection and eliminate the antigen.
9) The memory cells remain in the lymphoid tissue.
10) The second time the antigen enters there are a large number of antigen specific lymphocytes (memory cells) in the lymphoid organs so the secondary response is faster and greater than the primary response.
CYTOKINES
1) Cytokines are small soluble proteins that act as multipurpose chemical messengers,secreted by a cell, and act on itself or another cell to change the activity of that cell.
2) They play an important role in both non-specific and specific immunity.
3) cytokines Can be produced by a wide variety of cells such as endothelial cells etc.
4) Some cytokines act on the bone marrow to increase cell proliferation and differentiation.
* eg. colony stimulating factors include GM-CSF, G-CSF, M-CSF.
Feature of cytokines
1) ONE cytokine can ACT on many different cells.
* e.g. TNF acts on the liver to produce acute phase proteins and on the Neutrophils to activate it.
2) DIFFERENT cytokines can have the SAME action.
* e.g. TNF from macrophages and lymphotoxin from T cells have the same actions.
3) Cytokines can act on the same cell that produced it (AUTOCRINE ACTION), on nearby cells (PARACRINE ACTION) or on distant cells (ENDOCRINE ACTION).
Post exposure HIV prophylaxis is recommended if there is:-
* unprotected receptive anal intercourse
* unprotected receptive vaginal intercourse
* unprotected insertive vaginal intercourse
* unprotected insertive anal intercourse
* unprotected receptive fellatio with ejaculation
with a HIV positive person or if the person is a HIV risk group (gay or bisexual men, injection drug users or sex workers), and if the exposure is isolated and the patient is commited to safer sex in the future and the exposure occurred within 72 hours of presentation for care.
Exposure to persons known to be HIV infected
if medication regimen of source patient is unknown => prescribe Zivudine (AZT/ZDV) 300mg bid + Lamivudine (Epivir) 150mg bid + Indinavir (Crixivan) 800mh q8h or nelfinavir (Virasept) 1250mg bid or 750mg tid
Combivir 1 tablet bid may be substituted for zidovudine and lamivudine
if medication regimen of source patient is known => prescribe 2 NRTIs and 1 protease inhibitor that are different from the source patient's regimen
possible substitues for zidovudine and lamivudine:- stavudine (d4T/Zerit) 40mg bid for > 60kg and 30mg bid <> 60kg and 125mg for <>
Exposure to person or persons of unknown HIV status but who probably have high HIV risk factors :
significant exposures => treat as if an exposure to a known HIV-infected person with an unknown medication regimen, as above
exposures that might result in HIV infection => treat with zidovudine and lamivudine without a protease inhibitor
Exposure to person or persons of unknown HIV status but who probably have low HIV risk factors
significant exposures => treat with zidovudine and lamivudine. A protease inhibitor could be added if the patient requests it, if the provider believes that the exposure history is unclear, other exposures also occurred, or if other factors relating to exposure history or HIV status are compelling
exposures that might result in HIV infection => treat with zidovudine and lamivudine without a protease inhibitor
Additional caveats
* PEP should not be provided to patients whose exposure history has no known possibility for HIV transmission
* PEP should not be given to persons already infected with HIV
* providers may consider PEP for any patient who appears to be at risk after an HIV exposure but whose circumstances are not delineated in the above categories
Providers are reminded that PEP should only be prescribed as part of a comprehensive program to reduce future HIV risk-related behaviours. Multiple prescription requests for PEP should be strongly discouraged and must be averted through risk reduction counselling.
Definitions:
High HIV risk factors: trading sex for drugs or money, IV drug use, unprotected anal or vaginal intercourse with persons with HIV risk factors
Significant exposures include the following: anal or vaginal intercourse without a condom or with condom breakage; exposure to semen or blood onto mucosal or nonintact surfaces, and intravenous needle sharing
Examples of exposures that might result in HIV infection are as follows: cunnilingus, fellatio, semen or blood on healing skin wounds
I Innate immunity (natural or native immunity) Instant Immediate Initial response Induces adaptive immunity Integrates with adaptive immunity
A
Adaptive immune system Acquired Await days = no immediate response Accurate = specific Autoregulation Autoimmunity
The Immune Response
Innate immunity is the first line of defense against infections. Innate immunity is specifically against microbes, while adaptive immunity is against any "foreign" substance (including cancer cells, autoantigens, etc.).
Innate immunity is the oldest mechanism of defense. Adaptive immunity (T and B lymphocytes) appeared in jawed vertebrates (sharks) and is superimposed on innate immunity to improve host defense. In a sense, adaptive immunity is an "add-on" to innate immunity.
The organs of the immune system are positioned throughout the body. They are called lymphoid organs because they are home to lymphocytes, small white blood cells that are the key players in the immune system.
Bone marrow, the soft tissue in the hollow center of bones, is the ultimate source of all blood cells, including white blood cells destined to become immune cells. The thymus is an organ that lies behind the breastbone; lymphocytes known as T lymphocytes, or just "T cells," mature in the thymus.
Lymphocytes can travel throughout the body using the blood vessels. The cells can also travel through a system of lymphatic vessels that closely parallels the body’s veins and arteries. Cells and fluids are exchanged between blood and lymphatic vessels, enabling the lymphatic system to monitor the body for invading microbes. The lymphatic vessels carry lymph, a clear fluid that bathes the body’s tissues.
Small, bean-shaped lymph nodes are laced along the lymphatic vessels, with clusters in the neck, armpits, abdomen, and groin. Each lymph node contains specialized compartments where immune cells congregate, and where they can encounter antigens.
Immune cells and foreign particles enter the lymph nodes via incoming lymphatic vessels or the lymph nodes' tiny blood vessels. All lymphocytes exit lymph nodes through outgoing lymphatic vessels. Once in the bloodstream, they are transported to tissues throughout the body. They patrol everywhere for foreign antigens, then gradually drift back into the lymphatic system, to begin the cycle all over again.
The spleen is a flattened organ at the upper left of the abdomen. Like the lymph nodes, the spleen contains specialized compartments where immune cells gather and work, and serves as a meeting ground where immune defenses confront antigens.
Read More
Behcet's disease is a rare, chronic, lifelong disorder that involves inflammation of blood vessels throughout the body. Symptoms of Behcet's disease include recurrent oral ulcers (resembling canker sores), recurrent genital ulcers, and eye inflammation. The disorder may also cause various types of skin lesions, arthritis, bowel inflammation, and meningitis (inflammation of the membranes of the brain and spinal cord).
A neutrophil travels along the capillary endothelial layer. Endothelial cells are triggered to express selectins on their surface for neutrophil integrin-mediated adherence. Transendothelial migration allows the neutrophil to traverse the blood endothelial layer. Squeezing into the extra-capillary space where migration towards a chemotactic gradient (chemotaxis) helps it to locate the pathogen. Subsequent phagocytosis ensues.
These are a focus of central fibrinoid necrosis surrounded by a palisade of epitheloid cells, occurring as a typical feature of sero-positive rheumatoid arthritis.
Subcutaneous nodules commonly occur on extensor surfaces subject to external pressure, for example, the upper forearm and elbow. Occasionally, they arise within the lungs or heart.
Nodules are rare in sero-negative rheumatoid arthritis.
A 77-year-old woman underwent surgical resection of a 1.5-cm papillary carcinoma of the right breast. Isosulfan blue dye (8 ml) was used intraoperatively to define the associated lymphatic drainage. Three sentinel nodes were excised from her axilla 5 minutes later, followed by the lumpectomy. By the time of wound closure, blue hives had developed on both upper arms and the chest as a result of an allergic reaction to the dye. Her cardiorespiratory system remained stable.
She was treated with intravenous phenylephrine (50 mg), had an uneventful recovery, and was discharged home 4 hours later. Blue hives occur in up to 1.5% of patients injected with this dye; the cause is probably a type I, IgE-mediated hypersensitivity to the dye.
A type of auto immune inflammatory myositis (recognized in females).It has 2 types according to age of presentation : 1- Juvenile dermatomyositis (JDM) : affects children and tends to be more severe 2- Adult dermatomyositis (ADM) : typically affects adults around the age of 50
It`s pathology described as cell mediated injury targeted at striated muscle with resultant atrophy, oedema, coagulation necrosis, fibrosis and calcification. -There is elevation of: * muscle enzymes (CK) * elevated muscle specific antibodies o anti RNA o anti Mi2
Dermatomyositis may be associated with interstitial lung disease : typically gives a patchy and subpleural consolidation with parenchymal bands. internal malignancy : can occur as part of a paraneoplastic syndrome (e.g lung cancer)
Radiographic features
Plain film
Plain radiographs show extensive sheet-like dystrophic calcifications in the soft tissues of the leg consistent with dermatomyositis.
* typically shows dystrophic calcification in muscles and soft tissues (calcinosis universalis) o sheet like although at least four patterns have described with childhood dermatomyositis 4. o classically seen affecting the thigh regions * chest radiograph may show diaphragmatic elevation * acroosteolysis
Fluoroscopy
Barium swallow
* may show disordered peristalsis involving the upper oesophagus : portion supplied by skeletal muscle
MRI
T2 : generally hyper intense signal throughout the affected muscles ; calcific areas may be low signal ; perimuscular oedema may additionally appear as high signal ; signal intensity may return to normal after treatment .
Read More
Angioedema: is the development of large welts below the surface of the skin, especially around the eyes and lips. The welts may also affect the hands, feet, and throat. The condition can be associated with allergies and histamine release.
#H1 antihistamines are effective for treating nasopharyngeal itching, sneezing, watery rhinorrhea, and ocular itching, tearing, erythema.
*Side effects associated with older H1 antihistamines include sedation, visual disturbance, urinary retention, and arrhythmias #Newer H1 antihistamines:( terfenadine (Seldane) astemizole (Hismanal))
*These agents exhibit less sedation associated with their reduced ability to cross the blood brain barrier. *However, there are very important drug-drug interactions associated with this category.
For example, macrolide antibiotics such as erythromycin, clarithromycin (Biaxin), ketoconazole-class broad-spectrum antifungal drugs, inhibit terfenadine (Seldane) or astemizole (Hismanal) metabolism.
Toxic levels of terfenadine (Seldane) or astemizole (Hismanal) may induce potentially fatal cardiac arrhythmias.
These new H1 antihistamines are contraindicated for concurrent use with macrolide antibiotics and ketoconazole-class and fungal drugs or in the presence of impaired hepatic function or inpatients predisposed to arrhythmias.
#Topical alpha-adrenergic agonists:
*Phenylephrine (Neo-Synephrine) or oxymetazoline (Afrin) reduce nasal congestion/obstruction.
Efficacy duration: limited due to rebound rhinitis and systemic effects which may include insomnia, irritability, and hypertension -- the latter which is seen more commonly with oral alpha adrenergic agonists.
#Oral alpha-adrenergic agonists may be useful in diminishing antihistamine-mediated sedation while improving antihistamine efficacy in relieving congestion. However, there is a concern that these agents due to their potentially hypertensive effects, may precipitate adverse cardiovascular effects, such as stroke. Recently, there has been an effort to remove such "pressor" agents from common over-the-counter cold medications.
#Cromolyn sodium: This agent is a liquid provided as a nasal metered-does spray. Cromolyn sodium (Intal) is not associated with side effects and typically is used prophylactically to reduce episodic allergen nasal mast cell activation. This agent may be used as part of a anti-asthma drug regimen.
#ntranasal glucocorticoids:
*Intranasal glucocorticoids are the most potent drugs available for management of established rhinitis (seasonal or perennial) and including vasomotor rhinitis
Topical-to-systemic activity greater for: flunisolide (AeroBid) or budesonide (Rhinocort), compared to beclomethasone (Banceril) or triamcinolone (Aristocort).
*Despite the different route of administration, intranasal-administered glucocorticoids exhibit the same efficacy but with reduced systemic side effects compared to same agent administered orally. *Side effects include local irritation, which is the most frequent side effect to Candida over-growth which is an unusual side effect *Topical high potency glucocorticoids exhibit superior efficacy compared antihistamines during pollen season.
#Immunotherapy (hyposensitization): This approach is based on repeated, subcutaneous injections of gradually increasing allergen (specific for the symptom complex) over a period of 3-5 years.
*Contraindications include significant cardiovascular disease and unstable angina *Cautious use applies to patients receiving beta adrenergic blockers (due to difficulty in managing possible anaphylactoid responses to treatment)
**Clinical Management Sequence:
1.Identification of allergens confirmed by allergens-specific IgE skin testing and/or serum assay. 2.Avoidance of offending allergen 3.Mild symptoms: prophylaxis with topical cromolyn sodium or single (bedtime) dose of chlorpheniramine (Chlor-Trimeton) or astemizole (Hismanal) or terfenadine (Seldane) (decision based on side effects and presence of other concurrent medications or disease. 4.Prominent symptoms: Topical beclomethasone (Banceril) or if needed budesonide (Rhinocort) or flunisolide (AeroBid) 5.Management failure: immunotherapy
Read More
A patient has secondary antibody deficiency due to B-cell suppression His primary pathology is likely to be
a) Waldenstrom macroglobulinemia b) X-linked agammaglobulinemia c) immunoglobulin A deficiency d) immunoglobulin M deficiency e) common variable immunodeficiency
The correct answer is A
Explanation Antibody immunodeficiency can be primary or secondary. Secondary antibody deficiency due to B-cell suppression can occur with multiple myeloma, Waldenstrom macroglobulinemia, or chronic lymphocytic leukemia. Secondary deficiencies leave patients susceptible to the same pathogens that can cause recurrent pneumonia in patients with primary antibody deficiencies Primary antibody deficiencies include X-linked agammaglobulinemia, common variable immunodeficiency, selective immunoglobulin A or immunoglobulin M deficiency, and hyperimmunoglobulin M immunodeficiency. These disorders are characterized by chronic or recurrent pyogenic infection, especially pneumonia, caused by encapsulated bacteria (eg, S pneumoniae, H influenzae, and S aureus) and P aeruginosa . Untreated or recurrent pneumonia may lead to bronchiectasis.
The main cell of the specific immune response is the small lymphocyte.
LIMPHOCYT RECIRCULATION
1) B and T lymphocytes constantly enter the blood stream from the peripheral lymphatic tissue via the lymphatics and the thoracic duct and circulate around the body. '
2) They reenter the lymphoid tissue at another site.
3) Lymphocytes form 20 - 40% of the circulating white blood cell Circulating lymphocytes are mainly T cells with a few B cells.
Immune response & elimination of antigen
1) Antigens can enter the body through the mucosa or skin.
2) Meeting the mucosa associated lymphoid tissue or the cutaneous lymphoid tissue.
3) The antigens are carried to the regional lymph nodes via lymphatics
4) If the antigen enters the blood stream it will be filtered by the spleen.
5) Lymphocyte recirculation ensures that B and T lymphocytes are constantly patrolling the body looking for antigen.
6) Antigen will meet the corresponding lymphocytes specific for the antigen →immune response (activation, proliferation and differentiation of lymphocytes)
7) The immune response takes place in the PERIPHERAL LYMPHOID TISSUE(rich in macrophages and dendritic cells).
* At the mucosal or skin surface immune response takes place in the MALT or cutaneous immune system.
* o The immune response to tissue antigens takes place in the lymph node.
* o The immune response to circulating antigens takes place in the spleen.
8) Antibodies from B cells or effector T cells go to the site of infection and eliminate the antigen.
9) The memory cells remain in the lymphoid tissue.
10) The second time the antigen enters there are a large number of antigen specific lymphocytes (memory cells) in the lymphoid organs so the secondary response is faster and greater than the primary response.
CYTOKINES
1) Cytokines are small soluble proteins that act as multipurpose chemical messengers,secreted by a cell, and act on itself or another cell to change the activity of that cell.
2) They play an important role in both non-specific and specific immunity.
3) cytokines Can be produced by a wide variety of cells such as endothelial cells etc.
4) Some cytokines act on the bone marrow to increase cell proliferation and differentiation.
* eg. colony stimulating factors include GM-CSF, G-CSF, M-CSF.
Feature of cytokines
1) ONE cytokine can ACT on many different cells.
* e.g. TNF acts on the liver to produce acute phase proteins and on the Neutrophils to activate it.
2) DIFFERENT cytokines can have the SAME action.
* e.g. TNF from macrophages and lymphotoxin from T cells have the same actions.
3) Cytokines can act on the same cell that produced it (AUTOCRINE ACTION), on nearby cells (PARACRINE ACTION) or on distant cells (ENDOCRINE ACTION).
Post exposure HIV prophylaxis is recommended if there is:-
* unprotected receptive anal intercourse
* unprotected receptive vaginal intercourse
* unprotected insertive vaginal intercourse
* unprotected insertive anal intercourse
* unprotected receptive fellatio with ejaculation
with a HIV positive person or if the person is a HIV risk group (gay or bisexual men, injection drug users or sex workers), and if the exposure is isolated and the patient is commited to safer sex in the future and the exposure occurred within 72 hours of presentation for care.
Exposure to persons known to be HIV infected
if medication regimen of source patient is unknown => prescribe Zivudine (AZT/ZDV) 300mg bid + Lamivudine (Epivir) 150mg bid + Indinavir (Crixivan) 800mh q8h or nelfinavir (Virasept) 1250mg bid or 750mg tid
Combivir 1 tablet bid may be substituted for zidovudine and lamivudine
if medication regimen of source patient is known => prescribe 2 NRTIs and 1 protease inhibitor that are different from the source patient's regimen
possible substitues for zidovudine and lamivudine:- stavudine (d4T/Zerit) 40mg bid for > 60kg and 30mg bid <> 60kg and 125mg for <>
Exposure to person or persons of unknown HIV status but who probably have high HIV risk factors :
significant exposures => treat as if an exposure to a known HIV-infected person with an unknown medication regimen, as above
exposures that might result in HIV infection => treat with zidovudine and lamivudine without a protease inhibitor
Exposure to person or persons of unknown HIV status but who probably have low HIV risk factors
significant exposures => treat with zidovudine and lamivudine. A protease inhibitor could be added if the patient requests it, if the provider believes that the exposure history is unclear, other exposures also occurred, or if other factors relating to exposure history or HIV status are compelling
exposures that might result in HIV infection => treat with zidovudine and lamivudine without a protease inhibitor
Additional caveats
* PEP should not be provided to patients whose exposure history has no known possibility for HIV transmission
* PEP should not be given to persons already infected with HIV
* providers may consider PEP for any patient who appears to be at risk after an HIV exposure but whose circumstances are not delineated in the above categories
Providers are reminded that PEP should only be prescribed as part of a comprehensive program to reduce future HIV risk-related behaviours. Multiple prescription requests for PEP should be strongly discouraged and must be averted through risk reduction counselling.
Definitions:
High HIV risk factors: trading sex for drugs or money, IV drug use, unprotected anal or vaginal intercourse with persons with HIV risk factors
Significant exposures include the following: anal or vaginal intercourse without a condom or with condom breakage; exposure to semen or blood onto mucosal or nonintact surfaces, and intravenous needle sharing
Examples of exposures that might result in HIV infection are as follows: cunnilingus, fellatio, semen or blood on healing skin wounds
Read More
