Prevalent immune diseases Flashcards
1
Q
When does innate immunity occur (1) and what does it involve (4)
A
- 0-12 hours
involves:
- Epithelial barriers
- Phagocytes
- Complement
- NK cells
2
Q
When does adaptive immunity occur (1) and what does it involve (2)
A
- Days 1-5
Involves:
- B lymphocytes → Antibodies
- T lymphocytes → Effector T cells
3
Q
What is inflammation (3)
A
- A complex, coordinated response to damage or pathogen
- Orchestration of cell movement activation and death
- via direct cell: cell contact and soluble mediators
4
Q
What is acute inflammation
A
Self-resolving
5
Q
What is chronic inflammation (2)
A
- Ongoing inflammation
- Linked to disease
6
Q
What are the signs of inflammation (5)
A
- Rubor - redness
- Dolor - pain
- Calor - heat
- tumour - swelling
- Due to Increased blood flow and vascular permeability
7
Q
What are the inflammation stages (5)
A
- initiation
- augmentation
- effection
- resolution
- apoptosis/phagocytosis/wound healing
8
Q
What factors affect inflammation (4)
A
- Food
- Environment
- Microbiota
- Exercise
9
Q
What diseases affect inflammation (5)
A
- Cancer
- COPD
- Obesity
- Cardiovascular disease
- Asthma
10
Q
What is autoimmunity (2)
A
- Immune response to own cells and tissues
- Failure of normal self-tolerance mechanisms
11
Q
What is tolerance (4)
A
- Random process for generation of antigen recognition - B & T cells
- We make self-reactive cells which must be removed or made non-functional
- Central or peripheral
- The immune response needs confirmation of ‘danger’ to mount a response - multiple signals
12
Q
What happens if the signals confirming danger are absent (3)
A
- Anergy - non-responsive
- Deletion/apoptosis - cells die
- Suppression - T-regs secrete inhibitory cytokines
13
Q
What happens during central tolerance (3)
A
- Lymphoid precursor → Immature lymphocytes
- Recognition of self-antigen
- Apoptosis/Change in receptors (receptor editing; B cells)/Development of regulatory T lymphocytes (CD4+ T cells only)
14
Q
What happens during peripheral tolerance (3)
A
- Mature lymphocytes
- Recognition of self-antigen
- Anergy/Apoptosis (deletion)/suppression
15
Q
Where does central tolerance take place (3)
A
- Generative lymphoid organs
- Thymus
- Bone marrow
16
Q
Where does peripheral tolerance take place
A
Peripheral tissues
17
Q
What are the autoimmune disease mechanisms (2)
A
- Genetic susceptibility
- Environmental exposure (Hygiene hypothesis/microbiota)
18
Q
What is the genetic susceptibility autoimmune disease mechanism (4)
A
- Certain HLA variants linked to autoimmunity
- Gender bias for some
- Mutations in the autoimmune regulator
- Self-antigens not presented in thymus
19
Q
What is the environmental exposure autoimmune disease mechanism (4)
A
- Inflammation – Sterile damage
- Infection
- Innate immune activation
- Alter how self-antigen are presented to the immune system (Pro-inflammatory cytokines/Molecular mimicry)
20
Q
What is chimerism & mosaicism (6)
A
- More than one DNA profile
- e.g. Fused zygotes
- e.g. absorbed twin
- A mother may possess the stem cells of her children
- Ongoing research
- DNA profiling Accuracy!!!!
21
Q
What happens when a mother possesses the stem cells of her children (4)
A
- stem cells reside unnoticed in the body
- If damage occurs stem cells proliferate
- stem cells replace damaged tissue
- then manifest disease
22
Q
What is microbiota (3)
A
- Mixed microbes that inhabit the GIT
- Bacteria, viruses, fungi, parasites
- Bacteria have been main area of research
23
Q
What is dysbiosis (2)
A
- Perturbation of microbial balance in the GIT
- Linked to diseases
24
Q
What issues can arise from the microbiota (7)
A
- Pain
- Autism
- Multiple sclerosis
- Cardiovascular risk
- Anxiety
- Depression
- Obesity
25
What is cancer (7)
1. Knudson’s Two hit theory
2. Genetic disease
3. Retinoblastoma gene
4. Oncogenes/tumour suppressor genes.
5. Immune dysregulation
6. Immune surveillance
7. Immunosuppression
26
How are cancers immunogenic (5)
1. T-cells, natural killer cells and macrophages surround tumours (e.g. Thymomas, testicular seminomas, malignant melanomas, medullary breast carcinomas)
2. Infiltrate is independent of infection and necrosis (Tumour-derived cytokines/chemokines)
3. Lymphocyte hyperplasia at draining lymph nodes
4. Pro-inflammatory cytokine effects (MHC II, ICAM-1 increased expression)
5. Spontaneous regression
27
What is tumour immune evasion (3)
1. Immune Editing – Select within Heterogeneous Tumour cells
2. Immunosuppression – PD-1/PD-L1, T cell phenotype programming
3. Tumour Infiltrating cells – Adaptive, Innate immune cells (Neutrophils, Macrophage (M1 and M2))
28
What are autoimmune haematological disorders (11)
1. Immune thrombocytopenia
2. Autoimmune Haemolytic anaemia
3. Autoimmune Neutropenia
4. Paroxymal nocturnal haemoglobinuria
5. Aplastic Anaemia & pure red cell aplasia
6. Acquired Haemophilia
7. Heparin Induced thrombocytopenia
8. Thrombotic thrombocytopenia and haemalyticuraemic syndrome.
9. Autoantibodies to self antigen
10. Alloantibodies – Pregnancy, transfusion or transplantation trigger
11. Direct complement activation
29
What are the mechanisms of destruction (4)
1. Autoantibody opsonisation and splenic removal (Phagocytosis) – Most common
2. Complement-mediated lysis via Autoantibody – Less common
3. Direct Complement action – Rare
4. Soluble immune complexes binding
30
What is soluble immune complexes binding done via (3)
1. CR1(C3b) receptor
2. Fc receptors
3. Phagocytosis
31
Which immune cells are involved in immune surveillance against cancer?
Natural killer (NK) cells
32
The major histocompatibility complex (MHC) is essential for:
Recognition of self and non-self antigens
33
Which cytokine is most associated with pro-inflammatory responses?
TNF-alpha
34
Hypersensitivity reactions are classified into how many types?
4
35
What is an example of a Type I hypersensitivity reaction?
Anaphylaxis
36
Tumor cells can evade the immune system by:
Expressing immune checkpoint inhibitors like PD-L1
37
The “Two-Hit Hypothesis” in cancer development refers to:
Two mutations needed for tumor formation
38
Which immune cells infiltrate tumors to attempt to control their growth?
T cells and NK cells
39
What is an example of an immunosuppressive therapy?
Corticosteroids
40
PD-1 and PD-L1 inhibitors are used in cancer therapy to:
Enhance T cell-mediated tumor destruction
41
