Immunological Pathology Flashcards
1
Q
Allergic disease - definition
A
Innocuous antigens - not harmful
In sensitized host - mast cells primed with IgE
2
Q
Antibody mediated hypersensitivity reactions?
A
Type 1 - 3
3
Q
Cell mediated hypersensitivity reactions?
A
Type 4
4
Q
Type 1 hypesensitivity also known as?
A
Anaphylatic
5
Q
Type 2 known as?
A
Cytotoxic
6
Q
Immune complex hyper sensitivity reaction?
A
Type 3
7
Q
Type 4 hypersensitivty is also known as?
A
delayed type
8
Q
Antibodies involved in the hypersensitivity reactions: Type 1 Type 2 Type 3 Type 4
A
1 = Ige
2 and 3 = IgG and IgM
4 = NONE
9
Q
Diseases that cause each type of hypersensitivity reaction
A
Type 1 - allergic asthma - hay fever
Type 2 - autoimmune, penicillin allergy
Type 3 - lupus and vascilitis
Type 4 - RA, MS and IBD
10
Q
Signs of each hypersensitivity reaction?
A
Type 1 - weal and flare
Type 2 - lysis and necrosis
Type 3 - Erythema and odema
Type 4 - oedema
11
Q
Immune cells involved in each type of hypersensitivity?
A
Type 1 - eosinophils and basophils
Type 2 - compliment + natural killers
Type 3 - complement + neutrophils
Type 4 - lymphocytes and monocytes
12
Q
Components of the immune response that normal combat parasites? (4) Antibodies Inflammatory Lymphocytes Interleukins
A
IgE antibodies
Inflammation = eosinophils, mast cells basophils
Lymphocytes = T cells CD4+ type 2
Interleukin = 4, 5, 13
13
Q
Hygiene theory (3) Body creating Th2 > Th1
A
More siblings = less allergies
More parasitic infections = less allergies (geographic)
More infection ‘experience’ = body is able to dampen down immune response –> no ‘over the top’ reaction
14
Q
Genetic predisposition to allergies?
A
Polymorphisms in IL 4, 5, and 13 and receptors to IgG
15
Q
Th2 cells release which cytokines?
- Type one reaction
A
IL 4 and 5
16
Q
Affect of IL (in sensitization)
4
5
A
4 = class switching from IgM to IgE 5 = degranulation of eosinophils
17
Q
What do cytokines stimulate the release of in the ‘Late phase’ of type 1 sensitivity reaction
A
Leukotrines and prostaglandins
18
Q
Affects of an allergic reaction? Eyes nose mouth airways Skin GI
A
eyes = conjunctivitis nose = rhinitis mouth = oral allergy syndrome - tingling airways = asthma - bronchospasm, constrictions and mucosal hyperplasia skin = dermatitis GI = food allergies - V&D
19
Q
Atopic triad?
A
Asthma
Atopic dermatitis (eczema)
Rhinitis
20
Q
Diagnosis what kind of hypersensitivity?
A
TIME AFTER exposure to the allergen
21
Q
Test of allergies? (6)
Gold standard?
A
Blood test - IgE specific
Skin Prick - response > 3mm
Intradermal
Oral challenge - GOLD STANDARD for food allergy
Basophil Activation test - culture basophils
Component resolved diagnosis - test specific parts of proteins against IgEs
22
Q
Treatments for allergies (in order of increasing severity) (4)
+ Specific immunotherapy (sublingual and subcutaneous) = just for bee stings, animal hair and hay fever
A
Avoidance
Antihistamines
Steroids
Adrenaline
23
Q
Food allergies most common in children (80% grow out of)
A
milk and eggs
24
Q
Food allergies that you don’t grow out of
A
Soya beans and peanuts
25
Signs of food allergies (no seen in food intolerance)
| NOTE: V&D seen in both
Bronchospasm
Oral symptoms
Rhinitis
Urticaria - bumpy rash that itches
26
Autoimmunity is what type of immune response?
Adaptive
27
Roll of
T cells
B cells
In autoimmiune disease?
T cells = recognize self antigens
| B cells and plasma cells = make Auoantibodies
28
When does inflammatory response start in autoimmune diseases?
After the action of lymphocytes and autoantibodies
29
Genetic component of autoimmune disease?
MHC Class II polymorphism = predispose
30
Environmental components (environmental triggers) of autoimmune disease? (3)
Reason it present later in life
Trigger a genetic factor
Infection (eg. Rheumatoid disease)
Trauma
Smoking - replaces AA in the bodies proteins so they are recognized as non self
31
Immunoregulation (physiological) component of autoimmune disease
Autoimmunity attacks cancer cells that present with self antigens = protective
32
Process of developing tolerence
Lymphocytes produces to be nondescriminant
Exposed to self antigens
Either destroyed or mature depending on response
33
during the development of tolerance:
Negatively selected?
Positively selected mean?
Negatively selected = cell response to the self antigens and is destroyed
Positively selected = cell doesn't respond to self antigens and matures to a T/B Cell
34
Regulatory T cells - results in developing tolerance?
| Action in immune response?
Has slight reaction to self antigen - is kept
| Regulate an immune response
35
where is central tolerance developed in
B cells
T cells
B cells = bone marrow
| T cells = Thymus
36
Regulatory T cells are coded for by which gene
FOXP3
37
Causes of autoimmune disease (6)
Genetics - MHC class II
F>M
Age - advanced
Sequestered self antibodies - lymphocytes that aren't exposed to pathogens very often (Eg. in eye)
Environmental trigger
Continuation of inflammation - uncontrolled immune response
38
2 classifications of autoimmune disease
Organ specific
| Systemic
39
Organ specific autoimmune diseases
Hashimoto thyroiditis - hypothryoid
Graves disease - hyper thyroid
Myasthenia Gravis - neuromuscular junction
Pernicious anaemia - low B12
40
Action of autoantibodies in
| Hashimoto thyroiditis
Cause inflammation
41
Action of autoantibodies in Grave's disease
Mimic TSH and stimulates the thryoid gland
42
Action of autoantibodies in Myasthenia Gravis
Mimics ATcH and blocks receptors at neruomuscular jnct = can't move facial muscles
43
Action of autoanitbodies in Pernicious aneamia
Bind to intrinsic factor so B12 can't be taken up
44
Systemic autoimmune conditions (2)
Systemic Lupus erythematous (SLE or Lupus)
| Connective tissue disorders eg. Scleroderma
45
Disease process of lupus? (2 processes)
UV light --> damages skin --> releases nucleic contents --> stimulates sequestered antinucleaic self antibodies = rash
Antibodies + antigen immune complex accumulate in the blood vessels = type 3 hypersensitivity and kidney damage
46
Autoinflammatory disorders?
Eg. Polygenic crohn's
Cause?
Rare disease with an overactive innate immune response
No source of infection
Due to polymorphism in Compliment and cytokines
47
Serum compliment (C4 and C5) is a measure for?
Flare ups of Lupus
48
Elevated ferritin in the blood signifies?
an inflammatory response
49
ANA? what does it stand for? What does it diagnose?
Antinucelar antibodies
Diagnoses Lupus
NOTE: is an immunofluorescence assay that shows there are antinuclear antibodies present NOT their specific targets
50
Muliplex? what is it for?
Identifying the type of aninucleaic antibodies in lupus
NOTE: uses Synthetic Extractable nucleaic Antigens (ENA) incubated with the patient serum
51
Rheumatoid factor in the blood - what is it? what does it diagnose?
Antibody Vs Fc protein on IgG antibodies
Non specific for Rheumatoid arthritis and also vascilitis
52
Serum Anti - CCP - what is it? What does it diagnose? what is it used for?
Immunoassay for antibody against CCP
Specific for Rheumatoid arthritis
Prognostic measure
53
Anti- neutrophillic cytoplasmic antibodies (ANCA) - diagnoses what? 2 types of staining
Vascilitis
| Cytoplasmic or perinuclear = type of antibodies involved
54
Organ specific autoimmune testing method for liver disease?
Tissue block - using rodent tissue and ELISA (enzyme linked immuno assay)
55
Organ specific test for Primary biliary sclerosis?
Anti-mitochondrial antibodies assay
56
Organ specific test for Autoimmune hepatitis?
Anti-smooth muscle antibodies assay
57
Immunodeficiency definition?
The immune system is not effective enough to clear a pathogen
58
What is
Primary
Secondary
Immunodeficiency?
Primary - inherted/ genetic cause = RARE
| Secondary - due to external cause = more common
59
Causes of Secondary immunodeficiency (5)
```
Break down of physical barriers - CF, Burns, Age = thin skin
Drugs
Protein loss eg. Burns
Malignancy - lymphomas and myeloma
Infection - HIV and TB
```
60
Drugs that cause secondary immunodeficiency (6)
Steroids
Disease modifying Anti-Rheumatic drugs (DMARD)
Anticonvulsants
Myelinsupressants - Chemo
Rituximab
Antibiotics = kills of commensal gut flora
61
MyD88 and IRAK4 - in the innate immune response
intracellular signal proteins that cause cytokines to be produced
62
IRAK4 deficiency (genetic) results in
```
Recurrent infections (staph and strep)
NO raised CRP
```
63
Chronic Granulomatous disease - what is? what does it result in?
Lack of NAPDH complex in the phagolysomes
| Phagocytosis can't occur --> granulomas of macrophages not able to perform an immune response
64
Common sites of Granulomas
| Common bugs in granulomas
Lung, liver, skin and gut
| Staph, Kelbsiella and aspergillus
65
Test for Chronic Granulomatous disease
Blood serum + Nitroblue Tetrazolium chloride --> goes dark blue
66
C4 and C5 compliment deficiency results in?
SLE, infection and myositis (muscle inflammation)
67
C5-C9 (in MAC) compliment deficiency results in?
recurrent meningitis - N. meningitis
68
X - linked agammaglobinaemia? Adaptive immune system genetic mutation
What is it? - what Igs are lost?
Results in?
Lack of maturation of Bcells = no IgA or IgG
| Recurrent infections
69
Treatment of X linked agammaglobinaemia?
Subtaneous IgG injections
70
CVID - what does it stand for? what is it? eg.
Common variable immunodeficiency
Other B cell abnormalities
Eg. IgA deficiency
71
X-linker hyper IgM syndrome
What doesn't happen?
What are the effects?
Class switching can't occur
| Loss of antibody secretion + recurrent sinopulmonary infections
72
SCID - what does it stand for?
Severe combined immunodeficiency
73
SCID what is it? (3)
Loss/ reduced B and T cells
Loss/defected t cells molecules
Loss/ defected MHC II proteins
74
SCID effect?
VERY RARE and severe
Frequent opportunistic infections
'Bubble babies' - only survive with haemopoietin stem cell transplant
75
Action of Rituximab? = Secondary immundeficiency
Targets CD20 on Bcells --> kills them
76
Action of HIV? = secondary immunodeficiency
Kills CD4+ T helpers
77
Role of immunotheraputics?
Manipulate immune response to achieve desired immune response
78
Actions of immunotheraputics? (5)
Suppress
Stimulate
Guide in a certain way
Induce tolerance
79
Biologic drugs
Genetically engineered proteins made from human genes
| Target the immune system
80
3 classes of biologic drugs?
Mimic proteins - replace, increase amount or more potent
Monoclonal antibodies
Fusion proteins
81
Immunopoteniation mean?
To stimulate the immune system
82
Examples of immunopoteniation therapy? (2)
Vaccinations - Live (attenuated) and inactivated (suspensions)
Replacement therapy
83
Examples of Replacement Therapies (4)
HNIG - human normal immunogloblin (injection supplement Ig against specific pathogen)
G-CSF and GM-CSF = injected into bone marrow to create neurophils
IL-2 = T cell activation
Interferons - Hep C, B and MS
84
Immunosupression? when used?
Reducing the immune response
| Autoimmune disease, Transplants
85
Effects of Cortico steroids (immunosupressors)
On Innate system (3)
On Adaptive system (3)
Innate = decrease:
- neutrophil migration
- Cytokine production
- Arachidonic acid production for phagocytosis
Adaptive = decreases:
- Lymphocytes levels - lymphopenia
- T cells proliferation
- Ig Production
86
Side effects of Corticosteroids? (7)
```
Diabetes
Hypolipideamia
Reduced protein synthesis
Reduced wound healing
psychiatric issues
Cataracts
osteoporosis
```
87
Uses of Corticosteroids? (4)
Autoimmune disease = CTD, Vasculitis, RA
Inflammatory disorders = Crohns, polymyalgia Rheumatic
Lymphoma
Allograft rejections
88
What results in reversible immunosurpession by target transcriptional factors that activate T cells
Calcinerurin in inhibitors and Tacrolimus
89
Examples of mTOR (prevent t cell proliferation)
Sirolimus and Rapamycin
90
Cytotoxic immunosupressors: antimetabolites - what do they do?
Examples?
Prevent DNA replication
Methrotroxate (folate)
cyclophosphamide (DNA cross linking)
91
Uses of antimetobilte immunosupressive drugs?
| Side effects?
```
Methrotroxate = RA
Cyclophosphamide = IBD
```
Also SLE and vascilitis
Attack other fast dividing cells - bone marrow, GI
92
Types of DMARDs (5)
Usually monoclonal antibodies
```
Anti-cytokines (TNF, IL6 and IL1)
Anti-B therapies - Rituximab
Anti T cell activation
Anti-adhesion
Complement inhibitors
```
93
Adoptive immunotherapy - include?
| Used for?
Bone marrow and stem cell transplants
Lymphomas and Leukaemias
94
Immunomodulatory therapy - used to treat?
| What types?
Allergies
Steroids
Allergen specific immunotherapy
Monoclonal antibodies against immunogloblins
95
Allergen specific immunotherapy - what is it/ how does it work?
switching from Th2 - Th1 T cells = more regulatory cells and tolerance
Sublingual and subcutaneous
NOTE: side effects = anaphylaxis
96
Examples of Monoclonal antibodies against Immunoglobins - What Ig and what for?
Omalizumab - IgE. Vs. Asthma and chronic hives
| Mepolizumab - IL-5 prevents eosinophil activation
97
Opportunistic infections - what are they?
Are infections causes by pathogens with low pathogenicity
98
Why are babies considered immunocompromised?
Under developed immune system
99
Pathogens that commonly infect burns (2)
Psuedomonas and Group A strep
100
Neutropenia? what causes this?
Low Neutrophils
| Cancer treatments
101
Results of Neutropenia? (5)
```
Prolong infection
Lethal psuedomona infections
Ulcerations in mouth and bowel
Systemic Candida and aspillergillus
Recurrent skin infections - coagulase negative staph
```
102
Treatments for Neutropenic patients (3)
Prophylatic penicillin (in case of psuedomonas)
Gentamicin
Broad spectrum carbapenem
103
T cell deficiency are either?
Acquired
Congenital
Gestational - last trimester
104
Opportunistic infections in T cell deficient patients? (4)
Intracellular bacterial infections - listeria monocytogenes and TB
Viruses in transplant patients HSV, CMV, VZV
Candida
Cryptococcal Menengitis in HIV
105
Treatment of infections in T cell deficient patients?
Same AnitB's used in healthy patients
| Prophylactic acyclovir and ganciclovir in transplant patients
106
Opportunistic infections in hypogammaglobinaemias (low antibodies - genetic)?
```
Encapsulated bacteria (S. Pneumonia)
Parasites - Giardia Lamblia
```
107
Opportunistic infections in Compliment deficiencies?
Neisseria Meningitis
| Recurrent S. Pneumonia
108
Splenotomy patients - opportunistic infections?
Strep Pneumoniae
Haemophillus influenza type A and B
N. meningitis
Malaria
109
Treatments for splenotomy patients?
Vaccinate against HIB and malaria
| Prophylaxis penicillin
110
```
Organ transplant patients - infections when:
incision made?
From organ
Early immunosupression
Later immunosupression
```
```
Incision = s. Aureus
Organ = toxoplasmosis and CMV
Early = CMV and aspergillus
Late = zoster virus and listeria
```
111
MHC - major histocompatability complex - purpose?
On the cell service of all body cells to express self and non self antigens for inspection by T cells receptors
112
MHC are coded for on which chromosome and by which group of genes?
6p21.3
| HLA - human leukocyte antigen
113
Class I gene regions code for which HLAs? + what type of MHC?
```
HLA - A, B and C antigens
MHC class I proteins - on all body cells
```
114
Class II gene region codes for which HLAs and what MHC type?
HLA - DR, DQ and DP
| MHC Class II dedritic cells --> APC
115
Inheritance of MHCs?
Mendelian
Co -dominant
1 set of A, B, C, DR, DQ and DP from farther, one from mother - ALL are expressed
116
Chance of being a:
Mismatch
Half match
Full match
with sibling MHC and thus organ donations?
Mismatch = 1/4
Half match = 1/2
Full match = 1/4
117
Polymorphisms for each HLA allow?
capacity for individual to mount an immunological response against a antigen challenge
118
Test the donors MHC to determine mismatch (mm). what does 0mm mean?
6mm mean?
All 6 alleles of the HLAs are the same
| All 6 of the alleles of the HLAs are different
119
Immune response during transplant
Direct?
Indirect?
Direct? = interaction with the donors immune system eg. Donors dendrites present to recipients T cells
Indirect = the normal immune response to a endothelial damage due to surgical stress
120
Reaction frequency (%) ?
Compare the recipients antibody screen to the Donors database of antigens - to see the likely hood of a mismatch (a reaction)
121
Cross match test? - what is it? what does it test?
Donor lymphocytes + recipients serum --> immunofluescent assay
Shows whether there would be a hyperacute reaction (eg. to blood group)
