Inflammation

Question 1

What is inflammation?

Answer 1

Initial response of the body to an insult

Question 2

What is an insult?

Answer 2

Infection (pathogen)
UV exposure
Cancer growth
Wound

Question 3

Where are immune cells produced?

Answer 3

Bone marrow - HSC - Myeloid progenitor (eosphinophils, monocytes (macrophages, dendritic cells), mast cells, neutrophils) and Lymphoid progenitor (B, T cells and NK Cells)

Question 4

How do dendritic cells take up pathogens?

Answer 4

Macropinocytosis
Phagocytosis
Endocytosis

Question 5

What is clonal deletion?

Answer 5

Removal of self antigens

Question 6

What are the methods of tolerance?

Answer 6

Deletion (Primary tolerance)
Anergy (signal 1 without signal 2) and Supression (Treg,Breg,DCreg) - Secondary tolerance
Ignorance (sequestration of Antigen)

Question 7

What are the signals required for DC activation of T Cells?

Answer 7

Signal 1 - MHC-TCR
Signal 2 - CD80/86-CD28
Signal 3 - Cytokines (INF-Y - Th1, IL-4,5,19 - Th2)

Question 8

Why do we need 3 signals for activation of T cells?

Answer 8

Ensure we do not get inappropriate activation of T cells - potent

Question 9

What is septic inflammation?

Answer 9

Infectious inflammation - inflammation in response to an infectious agent - generates PAMP and DAMP, recognised extraceullarly by TLRs - include LPS, flagellin and CpG oligonucleotides.

Question 10

What is aseptic inflammation?

Answer 10

Only generates DAMPs - NOD - Cathepsin G, heat shock protein

Question 11

What are hypo immune coniditions?

Answer 11

Chronic Infection

Cancer

Question 12

How does chronic infection work?

Answer 12

Persistence of pathogen in immunocompetent individual - leads to progressive disease and comorbidities (increased cancer risk, autoimmune disease risk, depression, pain etc.) Certain diseases such as EBV and CMV do not cause progressive diseases and are tolerated. Certain diseases such as malaria, HIV-1 evade host immune responses by exploiting regulatory processes

Question 13

How does cancer work?

Answer 13

Normally immune surveillance recognises neo antigens and destroys malignant cells

In cancer, cells evade immune system and cancer develops - often in tumour microenvironment (area around tumour)

Genetic/environmental factors

One suspected mechanism is cancer cells can disable NLCR5 which prevents MHC1 processing and prevents CD8 CTL response

Question 14

What are some examples of autoimmune diseases?

Answer 14

Graves disease - antibodies attack the TSH receptor on the thyroid - leads to hyperthyroidism - irregular heart beat, trembling, weight loss

MS - immune system attacks the myelin sheath surrounding the CNS - Th17 expresses adhesion molecules and can cross the BBB and attack myelin - coordination loss, weak muscles, pain

T1D - destruction of insulin being produced by beta cells - unknown cause - may be genetics or virus (enterovirus antibodies) or vaccines (HiB, smallpox)

Question 15

How does allergy work?

Answer 15

Immune response against harmless particles (allergens) such as dust, insect bites, food, pollen

Type 1 Hypersentivity reaction - IgE mediated - histamine - sm contraction in bronchial and vasodilation

Question 16

What are the different types of alloimmunity?

Answer 16

Hyper Acute - within minutes - main target for therapy - T cells attack graft and cause necrosis

Acute - few days - B and T cell response

Chronic - many years later - gradual narrowing of vessels in graft - ischaemia - graft death