Immunology Flashcards
Desensitisation
- Only attempt when there are no other options
- High risk procedure (Informed consent)
- Only temporary tolerance, the hypersensitivity returns
- The exact mechanism is poorly understood
- IgE mediated reactions respond better
- Severe skin reactions such as Stevens Johnson and Toxic Epidermal Necrolysis are absolute contraindications
Desensitisation Procedure
The general process includes:
- Location – constant observation, resuscitation equipment available
- Premedication – usually an antihistamine and steroid dose
- Extremely slow infusion – start with 1/10,000 dose and work up by doubling the dose every 15 minutes
Antigen presentation
- Major site for interaction between antigen presenting cells and T Cells is lymph node
- They do this by chemotaxis.
- During the migration, DCs undergo a process of maturation and develop an increased ability to communicate with T cells.
- Enzymes within the cell digest the swallowed pathogen into smaller pieces containing epitopes, which are then presented to T cells using MHC.
Antigen-specific immune response that eradicates viruses
- Cytotoxic T cells destroy virally infected cells and tumor cells, and has been implicated in transplant rejection.
– Also known as CD8+ T cells
– Recognize their targets by binding to antigen associated with MHC Class I.
C3 Complement deficiency
C3 deficiency is associated with recurrent bacterial infections,
MAC, C5-C9 deficiency
Associated with infection by Neisseria species (especially the meningococcus)
Complement deficiencies
- Rare
- Predispose to bacterial infections
- Predispose to SLE (most common autoimmune disorder associated with complement deficiencies
C1 Deficiency
- Most commonly C1q
- 90% have SLE with clinical features
- commonly recurrent bacterial infections
- C1r and C1s - development of SLE particularly with renal complications (very rare
Highest risk of HIV transmission
Receptive anal intercourse
HIV entry to host cell
- Attachment by GP120 to CD4 antigen receptor
- Co-receptor CXCR4 (T cells), CCR5 (Macrophages)
- Post attachment viral envelope and host cell membrane fuses
- RNA released into cell
- Reverse transcriptase makes a DNA copy of the RNA genome then a second copy of the DNA is made. These then join covalently
5.
- R5 Strain: uses CCR5 for CD4 cell entry (less aggressive)
- X4 strain: uses CXCR4 for CD4 cell entry (more aggressive)
HIV R5 Strain
– most frequently transmitted
– less aggressive
– infects macrophages and T cells
– use CXCR5 for CD4 cell entry
HIV X4 strain
– infects only T cells and T cell lines
– more aggressive
– use CXCR4 for CD4 cell entry
HIV-2
– less virulent – lower viral load – lower rates of vertical transmission – slower progression – HIV-2 is less virulent. – Seen mainly in western central Africa and southern and western India.
HIV-1
is the most common type in western world
HIV-1
- Most common type in western world
- Painful mucocutaneous ulceration is one of the most distinctive manifestations of acute HIV infection. - - Shallow, sharply demarcated ulcers with white bases surrounded by a thin area of erythema may be found on the oral mucosa, anus, penis, or esophagus. These ulcerative lesions may reflect mucocutaneous disease associated with acute HIV infection or coincident sexually transmitted infections, such as herpes simplex virus, syphilis, or chancroid.
Hereditary angioedema
- Functional C1 inhibitor assay is 100% abnormal in hereditary angioedema.
- recurrent facial and lip swelling.These episodes are associated with abdominal pain, diarrhea and vomiting.No urticaria
- C3 and serum C1q are normal in HAE.
Mechanism of action of reverse transcriptase inhibitors (Nucleoside analogues)
Inhibit the following steps
- Reverse transcriptase makes a DNA copy of the RNA genome
- The original RNA strand is degreded
- A second copy of the DNA is made.
- These then join covalently
Mechanism of action of Protease inhibitors in HIV
Interfere with the cleavage of mRNA and Viral RNA made by protease
HIV Infection Process/Life Cycle
- Attachment by GP120 to CD4 antigen receptor
- Co-receptor CXCR4 (T cells), CCR5 (Macrophages)
- Post attachment viral envelope and host cell membrane fuses
- RNA released into cell
- Reverse transcriptase makes a DNA copy of the RNA genome then a second copy of the DNA is made. These then join covalently
- DNA enteres the nucleus and forms part of the host cell Chromosome with viral integrase (Pro viral DNA)
- RNA is synthesised from the proviral DNA yeilding mRNA and viral genome RNA
- Some of these protein are formed by clevange of this mRNA by protease
- GP41 and GP120 are inserted to the cell wall membrane and filled with viral RNA and budded off the cell
Tests for HIV exposure
- HIV DNA - best test
- HIV NNA Viral Load - some false possitives
- p24 antigen - 100% specific, but not sensitive (old)
- HIV antibodies - form months after exposure
Dx of AIDs
- Number of CD4+ lymphocytes
HIV disease progression
CD38 expression by CD8 cells is the strongest single predictive marker of disease progression at all stages of HIV
Aspirin exacerbated respirator disease (AERD)
- combination of:
o asthma
o chronic rhinosinusitis with nasal polyposis
o reactions to aspirin, NSAIDs – 30 min to 3h post ingestion and involve bronchospasm and nasal congestion
Mx With polyps management in order 1. oral steroids +/- Abs 2. Surgical debulking 3. Nasal steroid 4. Montelukast
For no nasal polyps management
- Oral steroids + Abs
- Nasal steroids
- Montelukast
Hypersensitivity Type 1
Specific IgE on mast cell ie: anaphylactic reaction to penicillin.
Hypersensitivity Type 2
IgG cytotoxic ie: hemolytic anemia
Hypersensitivity Type 3
Immune complex ie: serum sickness,GN
Hypersensitivity Type 4
- T cell mediated ie: contact dermatitis or drug related
secondary to activation of T cells, occurring 48 hours to weeks after the antigen exposure. If the drug is rechallenged, the reaction may occur within 24 hours - Reactions involving T cells have prominent skin findings because the skin is a repository for an enormous number of T cells
- Steve Johnson syndrome, TEN, DRESS (drug rash with eosinophilia and systemic symptoms), contact dermatitis, maculopapular rashes
Primary disorders of phagocytic function
- More susceptible to bacterial and fungal infections, but have a normal resistance to viral infections.
Chronic Granulomatous Disease
- Characterised by recurrent, life-threatening bacterial and fungal infections and granulomata formation
- Caused by defects in phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (phox).
- failure to produce reactive oxygen intermediates.
- Result in the inability of phagocytes (neutrophils, monocytes, and macrophages) to destroy microbial organisms once phagocytosed.
- The diagnosis is made by neutrophil function testing and mutation analysis.
- The most common organisms that infect pts with CGD are S.aureus and Aspergillus species
- Mx
- Early diagnosis of infections
- Antimicrobial and immunomodulatory prophylaxis
- Aggressive management of infectious complications.
Leukocyte adhesion deficiencies:
Results from an inability of neutrophils to leave the circulation in response to infection due to abnormal leukocyte integrins.
Hyperimmunoglobulin E syndrome:
Characterised by recurrent infections (principally bacterial), dermatitis and elevated IgE
Chediak-Higashi syndrome:
Rare disorder of severe congenital neutropenia that is characterised by recurrent pyogenic infections, partial oculocutaneous albinism, neuro abnormalities.
T Regulatory Cells (Previously Suppressor T Cells
- In
Carbamzapine allergy
HLA B1502
