Basic Immunology

Question 1

What are the 2 main categories of the immune system?

Answer 1

Innate and adaptive

Question 2

Explain the differences in

• resonse time
• specificity, memory, response to repeat infection, cellular components and humeral components

Answer 2

Innate: Response hours, limited specificity, no memory, identical response to repeat infection, phagocytes/NKC, complement pathway

Adaptive: réponse days, diverse specificity, efficient memory, in repeat infection much more rapid and vigorous response, T cells/Bcells, antibodies

Question 3

What are the main types of phagocytes?

Answer 3

• Monocyte/macrophage lineage

- granulocytes (neutrophils, mast cells, basophils and eosinophils

Question 4

What is the most abundant type of leukocyte?

Answer 4

Neutrophils

Question 5

How are phagocytes routinely activate?

Answer 5

Attracted to chemokine and activate by cytokines that are secreted by antigen specific T cells

Question 6

How do NK cells detect tumour cells to virally infected cells?

Answer 6

CD16 receptor (FcyRIII) - attaches to specific antibodies bound to tumour cells/virally infected cells
KIRs (killer cell immunoglobulin like receptors) - interacts with MHC class 1 on target cells

Question 7

Describe the 3 ways in which the complement pathway can be activated (both adaptive & innate.

Answer 7

• Classic pathway (Antigen-antibody complex) adaptive immunity
• Alternative pathway (C3b bind to hydroxyl/amine group on surface of pathogen) Innate
• Lectin pathway (lectin binds to glycoproteins + carbohydrates on surface of pathogens)

Question 8

Briefly describe the complement pathway

Answer 8

The most abdundant complement C3 is activated by either of the 3 pathways, all coverage as C5-C9 interact to form a membrane attack complex which binds to the membrane of target cells → transmembrane channel salt & water can flow = lysis

Question 9

Where are B cells developed?

Answer 9

Bone marrow

Question 10

Briefly describe the activation of B cells

Answer 10

Antigens bind to antibodies on the surface of the naive B cells. They are internalised and complex with MHC class II and returned to the cell surface.

Antigen-specific T cells recognise these and secrete cytokines causing clonal B cell proliferation and differentiate into plasma cells which produce antibodies.

Question 11

What are the 5 main types of antibodies?

Answer 11

IgM, IgG, IgA, IgE, IgD

Question 12

What is the basic structure of antibodies?

Answer 12

2 identical light chain
2 Identical heave chains
Differ in size, charges carbohydrate content and amino acid sequence.
Antigen binding fragment (fab) region → antibodies antigen specificity
Fc region → effector function

Question 13

For IgM describe:

• % of serum immunglobin pool
• Shape
• Role in primary/secondary response?
• Can it cross the placenta?
• what is its effector function

Answer 13

• 5-10%
• pentamer
• 1st antibody in primary response
• Can not cross placenta, 1st antibody the newborn baby produces.
• potent activator of complement pathway due to 4 complement binding pathway

Question 14

For IgG

• % of serum immunglobin pool
• Role in primary/secondary response?
• Can it cross the placenta?
• what is its effector function

Answer 14

• 70-80%
• predominant in Secondary immune responses not primary
• Can cross into placenta
• Activate complement and bind to phagocytes

Question 15

For IgA

• % of serum immunglobin pool
• Where is it abundant?
• Role in primary/secondary response?
• Can it cross the placenta?
• what is its effector function

Answer 15

• 10-20%
• Salivia, tears, mucus, breast milk
• Important in secondary immune response
• No but secreted in breast milk important for fetes in first few months of life
• Induce phagocytosis, prevent attachment to mucosal cells

Question 16

For IgE

• High affinicty for which cells
• what is its effector function

Answer 16

• Mast cells and basophils

- Degranulation release of active mediators, allergic manifestations

Question 17

How does vaccination improve future secondary responses to infection.

Answer 17

As vaccination expose the immune system in an inocus antigen, this produces primary antibody response and leads to generation of long lived antigen specific memory B cells.

Subsequent expose to same pathogen leads to faster more intense secondary response.

Question 18

T cells recognise antigens through the T cell receptors, what 2 main types of TCRs have been categorised?

Answer 18

alpha/beta TCRs - 95% circulating T cells

gamma/delta TCRs - T cells in mucosal surfaces (small intestines, pregnant uterus)

Question 19

Explain the maturation of T cells

Answer 19

Generated in bone marrow
matured in thymus
- negative selection if regonise self antigens
- single positive for CD4 or CD8
mature cells leave thymus and travel to secondary lymphoid tissues

Question 20

Describe effector function dependant on CD4/8 group

Answer 20

T helper (Th) cell, CD4 + MHC class II
cytotoxic T (Tc) cell, CD8 + MHC class I

Question 21

CD4 positive T cells can be categorised into Th1 and Th2.

What cytokines do they release and what impact does that have on immunity?

Answer 21

Th1 produce IFN-y and IL-2 which activate macrophages and CD8 T cells → cell mediated immunity

Th2 produces IL-4 & IL-5 which activates B cells to produce antibodies → humeral immunity

Question 22

What are the main categories of cytokines?

Answer 22

Interferons 
Interleukins 
Chemokine
Growth factors 
Many overlaps between these groups

Question 23

Main roles of chemokines

Answer 23

form concentraction gradient along which circulating leucocytes can imgrate towards the stimulus

Question 24

What are the main groups of Class I MHC.

What is the length of the protein it can present to CD8 positive T cells.

Answer 24

HLA A/B/C/E/F

8-9 amino acids

Question 25

What are the main groups of Class II MHC. | What is the length of the protein it can present to CD4 positive T cells.

Answer 25

HLA-DR, HLA-DQ, HLA-DP 15-24 amino acids

Question 26

``` Describe the terms: Autograft Isograft Allograft Xenograft ```

Answer 26

Autograft: one part of body to another on same individual Isograft: transfered betwee genetically identical indvidual Allogrft genetically different, same species xenograft different species

Question 27

Describe graft vs host diease

Answer 27

The grat initiates a rejection response again recipient Immune competent T cells from graft recognise MHC or minor histocompatibility as forming and initateimmune response against the host.

Question 28

How to prevent graft vs host

Answer 28

careful match of HLA groups removal of all T cells from the graft effective immunosuppression

Question 29

Describe 3 main types of graft vs host

Answer 29

Hyeracute (mins to hours) natrually occurring antibodies Acute rejection (days to weeks) donor leukocytes migrate out of graft and initiate primary immune response - Type IV hypersensitivity Chronic months-years: occlusion of blood vessels, macrophage infiltration and smooth muscle proliferation

Question 30

Explain main features of type 1 hypersensitivity reaction and examples

Answer 30

- Allergen + IgE activate mast cells which release histamine - Once mast cells are sensitised on repeat exposures → explosive release of histamine/leukotriene e.g.: Allergic asthma, anaphylaxis

Question 31

Explain main features of type 2 hypersensitivity reaction and examples

Answer 31

IgM + IgG antibodies bind to antigens on cells or extracellular material. Generally cytotoxic tissue specific e.g Haemolytic anaemia (RBCs), good pastures (glomerula membrane) graves TSK receptor, myasthenia graves

Question 32

Explain main features of type 3 hypersensitivity reaction and examples

Answer 32

Failure to clear immune complexes, which travel in the blood and are deposited (kindey, joints) - where they activate the complement pathway, attract granulocytes ``` Examples Lupus RA viral hepatitis farmers lung/ pigeon fanciers lung post strep gloemrular neuritis ```

Question 33

Explain main features of type 4 hypersensitivity reaction and examples

Answer 33

Localised inflammatory reaction caused by T cells at site of antigen, develops over 24-72 hours. Foreign: Nickle Autoimmun: IBD, MS, T1DM, hasimatos GVHD

Question 34

What are the 2 immunological interfaces of pregnancy?

Answer 34

1. Extravillous cytotrophoblst which invades into decide - tissue/tissue 2. Surface if the chorionic villus (syncytotrphoblast) and maternal blood (gas + nutrient exchange - tissue/blood extended 2: syncytiotrophoblast in maternal circulation

Question 35

Which class of MHC does the extravillous cytotrophoblast express?

Answer 35

``` MHC class 1 ONLY HLA-C/E/G (not A/B) no MHC class II ```

Question 36

Which class of MHC does the syncytiotrophoblast express?

Answer 36

Neither MHC class 1 or 2

Question 37

What maternal immune cells are found at the interactive between invasive extravillous cytrotrophoblast

Answer 37

T cells, macrogphafes, dendritic cells No B cells Decidual NK cells (70%) - not cytotoxic, produces cytokines/chemokines/angigenic factors

Question 38

What is unique about HLA-G

Answer 38

Very little polymorphism (4 alleys) maternal & paternal likely to be identical and therefore unlike to induce an alloreactive maternal T response during pregnancy Does not induce immune response but instead implantation, trophoblast invasion and placentation

Question 39

What is the difference of the immune response between the fetal leukocytes that entre the maternal bloods vs extravillous cytotrophoblast/syncytiotrophoblast?

Answer 39

Fetal leucocytes express HLA-A HLA-B HLA-C can simulate antoboud mediated and cell mediated immunity

Question 40

Explain the process of haemolytic diease of the newborn

Answer 40

RHD- mother has RHD +ve baby. Fetal blood enters maternal circulation, mother produced Anti RhD antibodies + memory B cells post partum. No clinical significant until 2nd pregnancy with Rhesus +ve baby. IgG crosses placental barrier and damages fetal RBCS → fetal anaemia, impaired platelet function and dysfunction of liver and spleen

Question 41

How is the maturation of CD+ve into Th1 & Th2 changed in pregnancy?

Answer 41

Placenta produces Th2 promoting cytokines (IL4 &IL10) + progesterone which inhibitors Th1 response. Bais to T2 immunity (humoral rather than cellular. Product paternal DNA

Question 42

Affect of shift of T1 on - RA - Herpes/malria - Lupus

Answer 42

- RA is Th1 mediated - temoprary remission - Exacerbation of intracellular disease herpes & malaria - Worsening of LUPUS (Th2 mediated)

Question 43

What is the incidence of antiphopholipid syndrome in the obstetric population? What is the risk of fetal mortality?

Answer 43

2-5% 85-95% Consider antiphospholpid if high rates of miscarriage and blood clots