Immunopathology Flashcards
Acquire immunity Hypersensitivity Auto-immunity Immuno-deficiency (89 cards)
1
Q
What involve in acquired immunity
A
. Specific antigen
. Lymphocytes T (virus) and B (bacteria)
. Memory
2
Q
Another name for acquired immunity
A
Adaptive immunity
3
Q
What’s the name for adaptive immune response to extracellular microbe (i.e. bacteria)? What regulated this process?
A
Humoral immunity
B lymphocytes
4
Q
What’s the name for adaptive immune response to intracellular microbe (i.e. virus)? what regulated this process?
A
Cell-mediated immunity
T lymphocytes
5
Q
What B cells produce? How do they cause destruction of microbes?
A
Antibody: IgM first then IgG, IgA, IgE in bone marrow
Phagocytosis by PMN and Mø
6
Q
What T cell produce? How do they cause destruction of microbes?
A
CD4 T helper cell: cytokines (Th1, Th2, Th17, Treg)
Cytokines activate and proliferate CD8 Tcells
CD8 T cytotoxic cell: apoptosis
7
Q
What are key features of antigens?
A
. bound to aB - immunogen
. high molecular weight (MW>10,000) proteins
. sometimes carbohydrate
8
Q
What is epitopes?
A
. Smaller fragments of antigens
. recognized by antigen combining site of aB or T cell R
. Comprised 8 AA (linear-T cell) or up to 20 AA (globular-B cell)
9
Q
Dendritic Cells prime T cells involve in
A
- Endocytosis
- Toll-like Receptor (TLR) Ligation
- Increase expression of MHC-1 co-stimulatory molecules
- antigen presentation
10
Q
Another name for MHC (major histocompatibility complex)
A
Human leukocyte antigen (HLA)
11
Q
Where does MHC-II/HLA present to?
A
CD4 T helper cells
12
Q
Where does MHC-I/HLA present to?
A
CD8 T cytotoxic cells
13
Q
What are the 3 main signals to activate T cell?
A
- MHC and peptide on DC present specific antigen : T cell R on T cell
- Co-stim signal CD80/CD86 of DC : CD28 of T cell
- CD40 on DC : CD40L on T cell
14
Q
Timeline of generating T cell response
A
4-5d : activate cytokines from Th1, Th2 and Th17
7-10d: activated T cytotoxic cell (with help of Th1)
1-2d : once memorized!
15
Q
What are the 2 main cytokines that stimulate Cytotoxic T cells?
A
IFN-a and TNF-a by Th1
16
Q
Primary role of Cytotoxic T cell?
A
Apoptosis
e.g. cancer tumour is a target of T cell killing
17
Q
What are main signals to activate B cell?
A
MHC-II / peptide / TCR
CD40 on DC : CD40L on activated Th cells
18
Q
How long does it take to activate B cell, to switch from IgM to IgG for the first time?
A
10 days
19
Q
How many heavy and light chains in each aB?
A
2 heavy
2 light
20
Q
Where in the aB determine the Ig isotypes?
A
Constant region of Heavy chain
21
Q
- What aB has the lowest affinity to antigen?
2. What aB has the highest quantity in serum?
A
- IgM
2. IgG
22
Q
What included in adaptive immunity? (important)
A
Humoral immunity (aB)
Cell-mediated immunity (T cell)
Tolerisation (autoimmunity)
Hypersensitivity (second-line exposure of allergen)
23
Q
What is the primary role of B cell?
A
produce immunoglobulin (aB)
24
Q
Can innate immunity involve T cell?
A
NO
only mast cell, Mø, NK cells and N˜
25
What is the main feature of hypersensitivity?
Only occurs on the SECOND (subsequent) exposures to antigen
26
Hypersensitivity rx are induced by allergens. List some examples of Allergen
```
. small soluble proteins or glycoproteins
. proteases
. dust mite faeces
. food (milk, nut,...)
. insect saliva
. drugs (penicillins, aspirin)
```
27
Main features of Type 1 hypersensitivity
. IMMEDIATE type
. IgE bound to mast cells (cross linking lead to degranulation)
. IL-4,5 from Th2 mediate IgE production
28
Predisposing factors to ATOPIC allergy (type 1 hypersensitivity)
. High affinity for IgE on mast cells and basophils
. Higher IgE levels (if >1µg)
. Genetic predisposition (Favor Th2- IL-4)
. Environmental pollutants can increase IgE (inhibit Th2 func and inhibit tolerance induction)
note: neonates may develop allergies if exposed to pollutants simultaneously (can train them)
29
In Type 1 Hyp, what lead to immediate response and what are those responses?
Degranulation of mast cells causes release of Histamine, proteases and chemotactic factor
- vasodilation
- vascular leakage (to tissues)
- Smooth m/s spasm
30
In Type 1 Hyp, skin rx to allergen peaks at __ mins, called __&__
In Type 1 Hyp, systemic manifestation is called __ shock
__ primes __ to migrate in response to chemotactic factors, called __ asthmatics
30 mins
wheal and flare (blister and red)
anaphylaxis
IL-5
Eosinophils
extrinsic
31
List some examples of local anaphylactic Type 1 Hyp
Allergic rhinitis - Hay fever
Asthma (smooth m/s)
Atopic eczema or urticaria
Food allergy (GIT)
32
Type 1 Hyp PATHOLOGICAL processes
. Smooth m/s contraction
. Vasodilation - fluid exudates
. Mucus secretion exceeded
. Eosinophil infiltration
33
Main features of Type 2 Hyp
. Cell-bound antigen coated with IgG
. Cells are opsonized by C3b
. Followed by phagocytosis destruction
. Complement cascade forms membrane attack complex (MAC)
34
Type 2 Hyp: Clinical examples
```
. Incompatible blood transfusions
. Hyperacute graft rejection
. Myasthenia gravis
. Graves disease
. Acute rheumatic Fever
. Drug hyp
```
35
Main features of Type 3 Hyp
. immune COMPLEX-MEDIATED
. IgG bound to SOLUBLE antigen
. Arthus rx skin test peaks at 3-8hrs with infiltration of polymorphs
. Complement activation generates anaphyatoxins and attract polymorphs
. 'Frustrated' phagocytosis due to C's mediated inflam
36
What can Ag:Ab complex (immune complex-mediated hyp) activate?
- Platelet aggregation
- Complement (anaphylatoxin and polymorphs)
- Mø
37
Something special about Type 3 Hyp
Have 3 phases
1. formation of immune complex
2. deposition of immune complex
3. immune complex mediated inflammation
38
In local vs. systemic rx of Type 3 Hyp
. Excess __ lead to precipitated immune complex. E.g. __
. Excess __ gives soluble immune complexes. E.g. __
aB
Pigeon Fanciers Disease
antigen
Serum sickness or deposition of immune complexes in kidney glomerulus
39
Main features of Type 4 Hyp
. DELAYED types
. T-cell mediated response (cytokines IFN-g, GM-CSF)
. Skin test - infiltration of mononuclear cells peaking at 24-48hrs (Th recruit Mø)
. Diagnostic for T cell immunodeficiency
40
Type 4 Hyp examples of reaction
AIDS
Contact dermatitis (e.g nickel)
TB
chronic granuloma
41
What's special about Type 4 Hyp in the skin?
Staining of CD4 T cell (granuloma)
42
Immediate vs. Delayed Hyp type
. ITH develop in _ mins while DTH develop in _ hrs
. Central appearance is _ for ITH & red induration for DTH
. Peripheral appearance is _ for both ITH & DTH
. __ cells (Ig_) involved in ITH & __ cells involved in DTH
30mins
24-48 hrs
blister
red
```
Mast cells (IgE)
Th cell
```
43
What is another term for autoimmunity?
Tolerisation
44
What is tolerisation
. prevents auto-reactivity in the thymus, but:
. auto-reactive cells destroyed by apoptosis
. low affinity auto-reactive T cells may 'escape' deletion in the thymus
note: auto-aB and auto-reactive t cells can be found WITHOUT accompanying disease
45
What does NON-self reactive clones of T cell do?
enter periphery for normal immune func
46
What are Regulatory T cells and what do they control?
Tregs: CD4, CD25, FoxP3+ cells
Control T cell proliferation by production of IL-10 + TGF-b
note: regulatory effect depends on cell-cell contact
47
Features of autoimmune disease (7)
. increase mononuclear cells infiltration [lymphocytes, Mø, and p/m cells]
. Loss of tolerance to self
. genetic predispositions HLA
. Classified by 4 Hyp types
. Female bias
. Patient often have multiple autoimmune disease (systemic, local)
. Environmental influences
48
4 SYSTEMIC autoimmune diseases
SLE (Systemic Lupus Erythematosus)
Sjögren's syndrome
Scleroderma
Rheumatoid arthritis
49
How does the immune system recognise self
. HLA present unique antigens (Genetic susceptibility)
. Molecular mimicry
. Following infection and tissue damage
50
SYSTEMIC autoimmune disease (1)
| SLE
. Caused by: lots of auto-aB forming immune complex
. Major auto-aB: at nuclear antigens (ANAs)
. Manifestations: nephritis, skin lesions, arthritis
. Disease remitting and relapsing
. common, esp. 20-30s yrs
51
In SLE, what are inherited susceptibility and environmental triggers
. inherited: MHC-II and complement
| . environment: UV radiation
52
Diagnosis of SLE
. Photosensitivity
. Rashes
. Arthritis (joint pain?)
. Disorder (renal, neurological,...)
note: SLE can affect skin, joints, kidney, etc.
53
SLE associate with what types of Hyp?
Type 2 and 3
54
SYSTEMIC autoimmune disease (2)
| Systemic sclerosis
. Also called scleroderma
. accumulation of fibrous tissue in skin others (=increase collagen production)
. CD4 T cell involved
. female bias (older women)
55
Possible mechanism for sclerosis
Cytokines (growth factors) and Ischemia to increase fibrosis/collagen)
56
```
SYSTEMIC autoimmune disease (3)
Rheumatoid arthritis (RA)
```
. Increased TNF cytokines activate B cell, Mø and endothelial cell
. Involve rheumatoid factor and fibroblast
. Pannus formation
treat: have aB bound therapy to clean up TNF cytokines
57
SYSTEMIC autoimmune disease (4)
| Sjögren syndrome
. Destruction of exocrine glands (lacrimal and salivary glands)
. Symptoms: dry eyes and mouth
. infiltration of CD4-T and B cells
. Female bias (older women)
. Have rheumatoid factor and 50% have ANAs
58
What is rheumatoid factor and ANAs?
Rheumatoid factor = aB bind and form immune complex with IgG. Involved in RA and Sjögren syndrome
ANAs = auto-aB directed at nuclear antigens
59
4 LOCAL autoimmune diseases
```
Multiple sclerosis (neuro)
Hashimoto's Thyroiditis (endocrin)
Type 1 diabetes (endocrin)
Crohn Disease (GIT)
```
60
LOCAL autoimmune disease (1)
| Multiple sclerosis
```
. Demyelinating disorder
. occur at any age
. female bias
. Caused by: CD4 T cells (specific for antigens from myelin sheath)
. Th1 cells activate Mø
. Relapsing - remitting disease
```
61
LOCAL autoimmune disease (2)
| Hashimoto's Thyroiditis
. HYPOthyroidism (destruction of thyroid)
. thyroid epithelial cells are destroyed by:
- CD8 (direct destruction)
- CD4 (toxic cytokines)
- auto-aB and ADCC
62
What appear in histological feature of Hashimoto's thyroiditis
. Thyroid parenchyma contains a dense lymphocytic infiltrate with germinal centre
63
LOCAL autoimmune disease (3)
| Type 1 diabetes
. B-islet cells of pancreas attacked by CD8 T cells (also CD4 T)
. pancreas no longer making insulin
. may associate with viral infection
. Have class2 alleles (HLA-DR3,4) in most of Caucasians
64
LOCAL autoimmune disease (4)
| Crohn's disease
. Lesions along GIT
. HLA-DR1 association
. NOD2 involvement (inflammasome)
. CD4 T cell activation and granulama formation (site of necrosis)
65
Gross pathology of Crohn's Disease
- mucosal ulcers and thickened intestinal wall
- perforation and ass. serositis
- creeping fats
66
Main types of Immunodeficiency
Primary and Secondary Immune Deficiencies
67
What are deficiencies in the INNATE response
Defective in:
- production of polymorphs
- response to chemotactic stimuli
- leucocyte adhesion (LFA-1 defect)
- lysosomes (pyogenic infections)
- no production of reactive O2 intermediates
68
What infections occur in deficiencies of complement, in innate response?
```
Pyogenic infections (immune complex disease)
Neisserial infections
```
69
Is deficiency in innate response the same with acquired immune response?
NO
70
What are indications of T lymphocyte immunodeficiency?
. reduce CD3+ T lymphocytes (genetic marker)
. variations of circulating CD4+ and CD8+ lymphocytes (AIDS)
. low response to polyclonal activators (Concanavalin A)
. decreased type Hyp
. changes of T cells area in the lymph node
71
What are indications of B lymphocyte immunodeficiency?
. reduced aB (Ig+ve)
. reduce opsonisation
. poor response to polyclonal activators (LPS in vitro)
. poor aB response to vaccination with inactivated vaccines
. increased susceptibility to pyrogenic infections
72
Examples of Primary immunodeficiency Disorder
```
T+B - Severe Combined Immunodeficiency Disorder (SCID)
T - DiGeorge Syndrome
T+B - Bare Lymphocyte Syndrome
B - X-linked agamma-globulinemia
B - Hyper IgM syndrome
```
73
Which primary immunodeficiency is classified as stem cell disorder
SCID
74
What are the 2 factors causing SCID?
ADA deficiency and cytokine signaling mutation
- ADA: enzyme in purine metab
- cytokine mutation: result in no growth factors for cell survival
75
What is sad for SCID patient?
highly susceptible to infection
| 'Bubble' boy
76
Which primary immunodeficiency disorder has FAILURE of B cell?
X-linked Agammaglobulinemia
| aka Brutons disease
77
Which primary immunodeficiency disorder has ELEVATED levels of B cell? specific Ig type involved?
Hyper IgM Syndrome
| - increase IgM and reduce IgG+A
78
What is the cause of Hyper IgM deficiency?
deficiency in:
- CD40L, CD40
- activation-induced cytidine deaminase (AID)
- Uracil DNA glycolase (UNG)
79
Which primary immunodeficiency disorders with little/no thymus gland?
DiGeorge Syndrome
| - so no development of T cell for cell-mediated response
80
Which primary immunodeficiency disorder has lack of MHC-II?
Bare Lymphocyte Syndrome
- so no activation of CD4
- also reduced IgG, IgA
81
What is one common thing in patient with primary immunodeficiency disorders?
very susceptible to infections
82
Secondary immunodeficiency can be seen in patients with:
```
. autoimmune disease
. neoplasms
. measles, chicken pox, mumps, severe trauma leprosy, Hodgkins disease
. malnutritions
. HIV-AIDS
. Cancer or infection
```
83
In Secondary immunodeficiency, patient with INFECTION (i.e. measles) have predominance of what?
. strong Th1 response but also require Th2 response
84
In Secondary immunodeficiency, patient with NEOPLASMS have predominance of what?
. one type of WBC (i.e. B cells in myeloma)
| . also absence of WBC due to chemotherapy
85
Does AIDS classified as primary or secondary immunodeficiency?
Secondary
86
What is AIDS
Acquired immune deficiency syndrome
. gp120 glycoprotein of RNA retrovirus infecting CD4 T cells
. Co-factor required
. associated with Type 4 Hyp
87
What are co-factor required for AIDS
members of chemokine receptor family
- Mø tropic HIV : CCR5
- lymphotropic HIV: CXCR4
88
In AIDS patient, where has higher CD4 for HIV-RNA retrovirus to bind to?
Th cells (compared to Mø and DC)
89
AIDS patient is susceptible to what?
Mycobacterium tuberculosis
