Immune System Overview

Question 1

What causes athlete’s foot

Answer 1

Trichophytom rubrum (fungi)

Question 2

What is the innate immune system

Answer 2

0-96 hours, broad recognition, no memory, macrophages, NK cells and neutrophils

Question 3

What is the adaptive immuen system

Answer 3

slower, 4-7 days, specific recognition. Memory/recall response. T cells and B cells

Question 4

What are the roles of the cell in the innate immune system

Answer 4

Phagocytosis - bactericidal killing e.g. respiratory burst
Nitric oxide production and T cell activation
Pathogen recognition - T cell activation

Question 5

What do CD4 T cells do

Answer 5

produce cytokines to activate macrophages and B cells and to regulate immune response

Question 6

What do CD8 T cell do

Answer 6

recognise and kill infected cells in a specific manner. Produce cytokines

Question 7

What are the 5 inflammatory cascades

Answer 7

complement, coagulation, bradykinin, arachidonic acid, free radicals

Question 8

What does thrombin do

Answer 8

activates coagulation - increases vascular permeability and neutrophil taxis

Question 9

What does pain activate

Answer 9

Bradykinin pathway - increases vascular permeability, vasodilation, pain, smooth muscle contraction.

Question 10

What does arachidonic acid pathway activate

Answer 10

Arachidonic acid pathway from tissue damage. Aspirin and other NSAIDs can block this pathway.

Question 11

What happens in respiratory burst

Answer 11

free radicals. Neutrophils and macrophages which phagocytose and kill microorganisms in vacuoles. Produces high reactive oxygen species.

Question 12

What is the role of DCs

Answer 12

DCs is a phagocyte but it’s main duty is to pick up foreign antigen and go to a lymph node to activate T cells. Without cytokines, DCs cannot be activated.

Question 13

What is a mast cell

Answer 13

contain vasoactive protein called histamine. Causes vasodilation and increases permeability in blood vessels. Has inflammatory mediators (preformed in granules), can be released immediately. Low oxygen tension, direct tissue damage. C3a and C5a receptors. Mediated by IgE. Limited range of TLRs.

Question 14

How does innate immune system recognise foreign antigens

Answer 14

antigen via PAMPs and PRR. Ingests and destroys foreign antigens (phagocytosis). Instructs other cells - cytokines. Initiates and co-ordinates adaptive immune response.

Question 15

What is IgE important for

Answer 15

Protection of mucosal surfaces

Question 16

What is T4 hypersensitivity

Answer 16

: T cell mediated. CD4 (delayed type hypersensitivity) and CD8 + CTL (T cell mediated cytolysis). Macrophage activation: cytokine- mediated inflammation. Direct target cell lysis, cytokines inflammation. Contact dermatitis, graft rejection, rheumatoid arthritis, DM, asthma

Question 17

What is T3 hypersensitivity

Answer 17

immune complex. Immune complexes of circulating Ags and IgM or IgG Abs. Complement and FcR mediated recruitment and activation of leukocytes. Serum sickness, SLE

Question 18

What occurs in anaphylaxis

Answer 18

1 - generalised itching, urticarial
2 - Swelling away from the sting, incontinence
3 - Difficulty in breathing
4 - Fall in blood pressure, loss of consciousness

Question 19

What is DerP1

Answer 19

protein that gets inhaled from house dust mite. Causes mast cells in lungs degranulation. Causes allergic asthma.

Question 20

Describe T cells formation

Answer 20

cells start as stem cells in bone marrow. Migrate to thymus. Thymus is situated above the heart and between the lungs. Unlike PRRs, T cells are encoded of multiple genes and multiple gene segments. Cutting and splicing of these gene segments causes the generation of specificity and diversity.

Question 21

How is T cell specificity generated

Answer 21

When developing T cell is in the thymus, the beta chain of the T cell receptor is the first to be cut and spliced. 52 variable regions. Multiple joining regions and multiple constant regions.

1. D to J rearrangement
2. V to DJ rearrangement
3. Transcription
4. mRNA splicing

Question 22

What is Goodpasturesg

Answer 22

autoabs to type IV collagen (found in basement membranes and connective tissue) - type II hypersensitivity reaction)
All patients get glomerulonephritis. Only 40% get lung haemorrhage. None get ear problems.
Glomeruli filter plasma where antibodies are have access to BM. Cochlear BM not accessible to autoabs (e.g. of Ag sequestration - immunological ignorance)
In lung, BM separates alveolar epithelium from capillary endothelium so 40% lung disease caused by damage due to smoking

Question 23

What happens in central tolerance

Answer 23

deleting editing in thymus and bone marrow

Question 24

What happens in antigen segreation

Answer 24

physical barrier to self-antigen access to lymphoid system in peripheral organs

Question 25

What happens in peripheral anergy

Answer 25

cellular inactivation by weak signalling without c-stimulus in secondary lymphoid tissue

Question 26

What happens in cytokine deviation

Answer 26

differentiation of Th2 cells, limiting inflammatory cytokine secretion in secondary lymphoid tissue and sites of inflammation

Question 27

What happens in clonal exhausation

Answer 27

poptosis post activation in secondary lymphoid tissue and sites of inflammation

Question 28

What gene makes px prone to RA

Answer 28

HLA-DR4

Question 29

What type of hypersensitivity is RA

Answer 29

Type II, III, and IV hypersensitivity. Abs and immune complexes and immune cells all cause damage of the joints. Release of sequestered antigen -> APC with cross-reacting Ag (molecular mimicry) -> Inappropriate MHC expression on non-APCs

Question 30

How does rabies cause autoimmunity

Answer 30

Rabies virus glycoprotein has an AA sequence similar to insulin. Immune response directed at rabies virus could potentially react with self-insulin receptor.

Question 31

How does measles virus cause autoimmunity

Answer 31

Measles virus P3 protein has similar AA sequences to myelin basic protein. Immune response has potential to react with CNS mediating MS.

Question 32

How do T cell become activated

Answer 32

1 is presentation of MHC peptide antigen to T cell receptor. 2 is co-stimulation. Absence of co-stimulation will lead T cell to apoptosis.

Question 33

Describe T cell differentiation

Answer 33

There are subsets of CD4 T cells : Th1, Th2 and TH17. These subsets produce different cytokines upon encounter with antigen and activate different cell types. APC presents antigen through MHC to undifferentiated Th0 cell under influence of IL-12. This drives differentiate to Th1.

Question 34

What does IL-4 do

Answer 34

IL-4 drives the development of the cell to Th2 phenotype.

Question 35

What are Tregs

Answer 35

Natural Tregs are straight from thymus. Inducible Tregs from the periphery. Generated in thymus and periphery: Thymus derived CD4 and CD25 Treg: nTreg Peripherally generated CD4 and CD25 Treg: iTreg

Question 36

What are the actions of Tregs

Answer 36

``` Inhibitory cytokines (anti-inflammatory e.g. IL-10 or TGFbeta) Cytolysis: Treg actively kill effector T cells by apoptosis Targeting DCs: inhibition of DC maturation and function. ```