Immunology Theme 4 Flashcards

Question 1

Q

what are the Aims of tissue and organ transplantation, what can be the issue with this

Answer

A

• Transplants must be physiologically viable
• The process should not harm the recipient
• The transplant should not be rejected by the recipient’s immune system
- Must mitigate for successful transplantation

But: immunosuppression to prevent rejection is not selective
- Susceptible to infections/cancers

Question 2

Q

outline the hypersensitivity mediated by 1st phase of rejection - hyperacute rejection

Answer

A

Type II hypersensitivity caused by preexisting antibodies binding to the graft

Question 3

Q

outline what occurs in the 1st phase of rejection - hyperacute rejection

Answer

A

Pre-existing antibodies (IgG) to non-self antigens bind vascular endothelium of transplant and activate complement causing endothelial damage and haemorrhage of graft.
Activation of clotting cascade causes vascular blockage.
Anti-HLA antibodies may arise as the result of pregnancy, multiple blood transfusions and previous transplants
Rejection circumvented by antigen cross matching and serological testing

Question 4

Q

specifically, what is hyperacute rejection caused by

Answer

A

ABO or HLA Class I antigen mismatch

Preexisting antibodies (IgG) to ‘non-self’ antigens bind vascular endothelium of transplant and activate complement causing endothelial damage and haemorrhage of graft. Activation of clotting cascade causes vascular blockage.

graft becomes engorged and purple due to hemorrhage

Question 5

Q

why might Anti-HLA antibodies may arise

Answer

A

as the result of pregnancy, multiple blood transfusions and previous transplants

Question 6

Q

Outline Alloreactions in transplant rejection and graft-versus-host reaction

Answer

A

Type 4 hyposensitivity reactions – T cell mediated (delayed)

• Graft vs host – transplant anything to do with blood, with T cells in it from the donor, which cause a reaction with the host tissue. Common form of morbidity/mortality in transplants due to leukaemia. The T cells attack the recipient’s tissues and there is a potentially fatal graft vs host reaction

(occurs when a kidney is transplanted or heamotopeitc cells)

Question 7

Q

what is an Alloreaction:

Answer

A

immune response by one individual to the alloantigens of another caused by alloreactive T-cells

Question 8

Q

what is an alloantigen

Answer

A

antigens that vary between the individuals of the same species e.g. HLA because this is the most polymorphic gene area (differs most) in the make up. These are recognised by the recipient in transplantations.

Question 9

Q

outline Preparation for transplantation

Answer

A

MHC is the overview term for HLA and other things lol so can use interchange
Limit ischaemia (inadequate blood supply) which leads to tissue damage and inflammation within the organ
Cadaveric vs live donation
Limit HLA I and II mismatch

Question 10

Q

how do CD8 and CD4 cells respond if there is a mistmatch. what form of hypersensitivity is this

Answer

A

Alloreactive CD8+ T-cells respond to HLA class I differences
Alloreactive CD4+ T-cells respond to HLA class II differences

Organ attacked and destroyed leading to acute rejection - a form of type IV hypersensitivity

Question 11

Q

what is the Gross appearance of an acutely rejected kidney

Answer

A

• May be rejected by Type IV reaction
• Red areas of haemorrhage
• Grey areas of necrosis
• Overall swollen appearance
• Immunosuppressive drug cover before AND after surgery
- This increases likelihood of infections so individuals must be kept in hospital

Question 12

Q

how may Acute progress to chronic rejection and what hypersensitivites are involved

Answer

A

Hyperacute - antibodies (type II)
Acute - T- CELLS mediated T-cell mediated (type IV)
Chronic rejection - Involves type III rejection

Question 13

Q

outline Chronic rejection of a kidney transplant, what hypersensitivites are involved

Answer

A

Type III hypersensitivity reaction - deposition of immune complexes

Immune complexes between Alloantibodies and HLA molecules (form within vessels of organ). this recruits inflammatory cells then t cell immunity. immune effectors enter wall of artery due to the damage and cause more damage
Fibrosis - key feature of chronic rejection

fibrosis: body attempted to repair – however this is not regeneration  compromised function  failure and rejection.

Question 14

Q

what can Chronic rejection also caused by

Answer

A

ischaemic reperfusion injury, viral infection (Due to immunosuppressant drugs) and relapse of original disorder (e.g. leukemia where you don’t get rid of the original disease  failure of bone marrow)

Question 15

Q

outline the importance of Polymorphism in the human major histocompatibility complex (MHC) in relation to transplantation

Answer

A

Ch 6 - HLA present which codes for MHC

Very unlikely that HLA genes will be identical between individuals
When considering transplantation, we look for individuals with a degree of similarity rather than with identical genes.

HLA matching improves the survival of transplanted kidneys

Question 16

Q

outline how there is Differential sensitivity of organ transplant procedures to HLA matching

Answer

A

Simple (corneal) transplant - doesn’t require much of a HLA match (more less HLA neutral) unlike bone marrow
The eye is immune privaleged site like the CNS – don’t get immunocompetent cell therefore the corneas are available for anyone
Liver is tolerant to HLA mismatch
Bone marrow – full of WBC expressing a lot of HLA (class II) designed to undergo immune responses so matching is a requirement
Chemotherapy to kill cancer cells and kill recipient bone marrow (to prevent host vs graft reaction) – bone marrow replenished by graft bone marrow

Question 17

Q

outline Conventional immunosuppressive drugs in clinical use

Answer

A

corticosteroids- mimic natural hormones (may be given in severe acute inflammation e.g. to footballers)

Cyclosporin A
- Side effects headaches, gingival overgrowth , diarrhoea, nausea and vomiting, kidney dysfunction, tremor, hirsutism (excessive growth of hair in women in a male-like pattern)

Question 18

Q

outlinee Examples of Immunological diagnosis and therapy

Answer

A

ELISA
Immunofluorescence direct and indirect
FACS
Monoclonal antibodies
Cytokines
N.B. vaccination/immunosuppression

Question 19

Q

outline The unique specificity of antibodies is the basis for detection of specific proteins in the lab

Answer

A

Antibodies will recognise specific proteins
Binds specific molecules to detect them
Fc- crystalline fragment – binds to receptors in cells
constant regions differs between classes
variable regions- very diverse

Question 20

Q

outline the Production of specific antibodies

Answer

A

Conventional immunisation- mixed specificity and limited quantity

Monoclonal antibodies- - limitless supply of antibodies of a single specificity (homogenous) with very good quality.

Recombinant antibodies- limitless and single specificty but DNA technology used to make better

humanise antibodies
Manipulate IgG genes,
make mice immunoglobulin into human immunoglobulin

Question 21

Q

outline the Production of monoclonal antibodies for use in clinical assays and therapeutically

Answer

A

immunise mouse with antigen and extract cells from it (from spleen)

fuse with cancer cell (myeloma) - tumour of b cells NOT same and myeloid
this means they become immortal can live for lots of generations and maintain their properties (hybridoma cells – cells which ultimately produce the monoclonal antibodies)

grow in drug containing medium where myeloma die and b-cells die - important antibody cells survive

select for antigen specific hybridoma

clone the selected hybridoma cells

Question 22

Q

How are immunodeficiencies diagnosed?

Answer

A

Measure levels of IgG, IgM, IgA and IgE – used in diagnosis and therapy

Lymphocyte count

Flow cytometry to characterise deficiency

If you suspect someone has immunodeficiency, then count their Ig levels, and WBC levels)

Question 23

Q

what does flow cephalometry allow for

Answer

A

uses monoclonal antibodies to identify/numeral WBC specific cell types in a mixed population.

FC allows you to enumerate the number of cells that are expressing a specific protein on its surface

The 1% of cells claiming to express IgM and TCR are likely to be false positives as there are no cells which express both.

Question 24

Q

outline the Diagnosis of X-linked agammaglobulinaemia using flow cytometry

what is expressed on all T-cells

Answer

A

Patient with XLA has very little CD19 – marker for B cells
Cells in the box on the lower left express neither CD3 or CD19 – neutrophils, monocytes or eosinophils

CD3 expressed on all T-cells
CD4 Is just on helper tcells
CD8 is just on cytotoix

Question 25

Q

what are the 2 ways autoimmune diseases analysed/diagnosed?

Answer

A

Physiological dysfunction-
e.g. deficiency in endocrine or musculature issues (autoimmune diseases often treat in endocronine clinic as hormone replacement needed)
E.g. ptosis (eyelids droop over eyes) in myasthenia gravis (treated by neostigmine)
E.g. hyperthyroidism in Graves’ disease (autoantibodies to TSH receptor producing too much thyroid hormone  tachycardia/sweaty palms/jumpy)

Autoantibody detection - use ELISA (below)

Question 26

Q

what does ELISA (enzyme linked immunosorbent assay) detect

Answer

A

Detect serum autoantibodies and antigens

* Use a spectrophotometer

Question 27

Q

what does Immunofluorescence detect for and what we looking for in the case of an autoimmune disease

Answer

A

Can look at tissue sections

uses Fluorescently labelled antibodies

In the case of autoimmune disease, you are looking for antibodies attached to the tissues (not ones that are free in the blood).

Question 28

Q

outline how Indirect immunofluorescence can be used for biopsy material in good pastures sydrome

Answer

A

autoantibody detection-

immune complexes deposited in the glomeruli causing inflammation and damage

Question 29

Q

How are allergies diagnosed- what are the controls

Answer

A

• Intradermal skin test – place suspect antigen into skin

Saline – negative control (for injections)
Histamine – positive control - shows what result we would expect in an allergic reaction.

There to mimic the hypersensitivity reaction (mast cells secrete when degranulate)

Put suspected antigen in (positive/negative result)
Looking for wheal (swelling) and flare (red area)

Question 30

Q

what are some agents used to manipualte the immune response

Answer

A

hormones
antibodies
adjuvants
cytokine- cytokine signalling pathway inhibitors e.g. Tofacitinib for rheumatoid arthritis

Question 31

Q

what are therapeutic monoclonal antibodies

Answer

A

• Anything with -mab at the end

Question 32

Q

how can the follwing be treated with monoclonal antibodies :

rheumatoid arthiritis
chronic asthma
lymphoma

Answer

A

RA- anti-TNFa can dampen down joint inflammation

asthma- Anti igE- removes igE required for mass cells degranulation

lymphoma- antiCD20 can get rid of b-cells

Question 33

Q

what are the Anti-inflammatory effects of anti-TNFα in rheumatoid arthritis

Answer

A

RA is systemic – it affects joint and all body too!- activation of liver proteins – this antibody supresses inflammation caused by this

Question 34

Q

what is C reactive protein is an indication of

Answer

A

protein produce in the liver, used as an indicator of peripheral cytokines (mediating inflammtion)

Question 35

Q

what is the action of Action of Omalizumab (therapeutic and experimental)

Answer

A

Therapeutic anti-IgE
• Anti-IgE prevents mast cell from acquiring cell-surface IgE (cant bind to its receptor)
• So when they encountered the environmental antigen that trigger asthma Mast cell cannot be activated as all the IgE is mopped up.

Experimental anti-IgE:
•Anti-IgE cross-links IgE bound to receptor and activates mast-cell deregulation
•Inflammatory response

Question 36

Q

what is the difference between benign and malignant cancers

Answer

A

Benign – contained within a particular area (doesn’t cause harm but can depend on location e.g. benign tumour in CNS may spread and cause harm or in the brain)

Malignant- Proliferation and invasion of tissues are key features of malignant cancer - change in morphology

Question 37

Q

what are the characteristics of caner

Answer

A

• Very similar immunologically to healthy tissue
- Self cells hidden from the immune system
• Grows/progresses slowly - compare this to infectious pathogens
- Less recognition by the immune system
• Survival rates are increasing  may be a manageable chronic disease

Question 38

Q

How do we know the immune response can recognise and reject tumours?

Answer

A

• Immunodeficient animals have increased incidence of cancer
• Immunosuppressive therapy and infections increase cancer incidence
• Cancer incidence increases with age due to immunosenescence/dysregulation
-Zinc important micronutrient
• MHC differences influence tumour survival

Question 39

Q

outline 2 ways cancer cells can become transformed which allows the immune system to recognise them- why is this important

Answer

A

Peptide antigens presented by MHC class I on normal cells , but the cell undergoes a mutation and becomes cancerous

Tumour specific antigen- new antigen (body not seen before) due to the mutation- therapeutic targets
Tumour associated antigen- reactivation of embryonic genes not normally expressed in the differentiated cell.
Overexpression (quantitative change) of normal self protein by a tumour cell changes density of self-peptide presentation, allowing recognition by T-cells

Need to be able to recognise cancerous antigens to evoke an immune response

Question 40

Q

outline how HPV, HeptB and - Epstein- Barr virus can be associated with cancer

Answer

A

HPV - certain strains can cause warts (benign) and rare cases can transform cells causing cancers of urogenital tract.
HeptB- chronic infection can transform liver cells - hepatic carcinoma
Epstein- Barr virus- chronic infection leading to lymphomas (cancer of mature lymphocytes not like leukemia immature WBC).

Question 41

Q

outline how Viruses can cause cancer

Answer

A

They set up chronic infections- induce hyperplasia (over growth of tissues)

Virally encoded proteins can interfere with normal mechanisms for controlling division (first step to transformation)- cell proliferation can lead to cancer

Question 42

Q

outline which bacterial infection can cause stomach ulcers and stomach cancer

Answer

A

. Helicobacter pylori

Question 43

Q

outline the Aetiology and progression of HPV-associated cervical cancer

Answer

A

As you go from left to right, you get an increasing event of transmalignant carcinoma. Disruption of the normal architecture, and micro-anatomy. Cells get larger, shape changes, prominent nuclei and starting drilling into the tissues below.

16&18 HPV strains associated with cancers - vaccination offered with these strains (70% of cervical cancer caused by these strains)

Question 44

Q

outline the Mechanism of the association between HPV and cervical cancer

Answer

A

Human papilloma virus (HPV) infect epithelial cells
It inhibits tumour suppressor mechanisms (p53) which protects genome as it delays the cell cycle allowing for repair mechanisms- Mutations not repaired – transformation can occur
Cells proliferate beyond normal regulatory mechanisms

Question 45

Q

why has there been an improvement in HPV cervical cancer

Answer

A

Vaccination, screening and surgery

Question 46

Q

why may the vaccine for HPV not prevent cervical cancer incidence

Answer

A

• Due to latency period of 5-15 years

Question 47

Q

how can hept b and hept c infection be passed on

Answer

A

• Blood, blood contaminated instruments, mother to child

Question 48

Q

what do hept b and hept c viruses cause

Answer

A

liver cirrhosis (scarring, fibrosis and loss of function) and hepatocellular carcinoma

Both infections have long incubation period (may be clinically silent)

Question 49

Q

what is the mechanism of hept c

Answer

A

inhibits activation of dendritic cells (knock on effect: lack of specific T-cells and impaired viral clearance)

HCV mutates rapidly

• HBV and HCV promote Treg cell activity

Question 50

Q

how can Monoclonal antibodies be used to target specific antigens in cancers

Answer

A

Target cancer molecules: killing of B-cells in lymphoma (Rituximab)
Target host immune system to boost performance: checkpoint inhibitor drugs (e.g. ipilmumab)
identify size and location of tumour (conjugated to radioactive isotope)

Question 51

Q

what are the types of bone marrow transplants-

Answer

A

allogenic- HLA matched from donor (non-self)

autologous (self)

Question 52

Q

outline whether allogenic or autologous BMPTs ones may cause graft versus host reaction (GVHR) and which ones give graft versus leukaemia (GVL) effect - are these effects good?

Answer

A

allogenic (non self)

may get GVHR and you can die lol :)
BUT also get beneficial GVL- donor cells attack leukaemia cells too

autologous (self)

don’t get GVHD :)
also don’t get GVL :(
higher relapse rate :(

Question 53

Q

what do New BMT regimens involving therapeutic use of donor T-cells promote

Answer

A

Promote GVL effect
Give donor T-cell primed to attack the cancer
Replace stem cells (reconstruction of haemopoiesis) but also giving T cells to kill any of the cancerous cells which cause the problem

Question 54

Q

outline An example of adoptive T-cell therapy

Answer

A

Adoptive t- cell therapy KILLS leukaemia cells – adding to cells to benefit patient

Chimeric antigen receptors – modified t-cell receptors to target tumour cells and kill them - confer antitumor specificity to a patient’s lymphocytes

Question 55

Q

outline Importance of the mouth in terms of immune responses

Answer

A

• Proximal region of the both the alimentary and respiratory tracts
• Principle point of entry of pathogens (along with the nose) -70% enter by this route
• Common anatomical features with other mucosal surfaces (which are…list)
- Mouth part of mucosal immune system
• They are all lined by glandular epithelia bathed in secretions e.g. saliva
• But the mouth has a unique anatomy…. Teeth!

Question 56

Q

what are Elements of the immune response in the mouth

Answer

A

salivary glands

salivary IgA-adaptive immune response to streptococci
Lactoferrin- binds iron which is a co-factor for many bacteria
Mucin - highly glycosylated protein, coaggregates bacteria- can also allow Anchorage of antibodies and protective coat where there is lack of keratin in the oral epithelium

Epithelial cells

make AMPs and TLRs
exfoliate, shedding of top layer is defence as bacteria will be removed and swallowed

GCF
- antibodies
- complement
- cellular elements- neutrophils and AMPs
(plaque fluid is not a defence)

Question 57

Q

what is the Importance of saliva in the oral immune response

Answer

A

• The mouth is well-served by salivary glands
– Major (parotid; submandibular; sublingual)
– Minor (many and widely distributed)
• Note flow characteristics: bacteria must attach or multiply in fluid phase
• Saliva has many components dedicated to host defences
• Note these often act in complexes (heterotypic association)
• They also must act in different phases of the mouth: soluble phase; mucosal surface; tooth surface; plaque biofilm

Question 58

Q

outline the salivary host defences

Answer

A

AMPs distrust bacterial membranes 
Adhesive protei- agglutination
Lactoferrin- binds iron
Cyastin- protease inhibitor
Lysozyme

Question 59

Q

how is the gingival crevicular fluid an Interface with the systemic immune defences

Answer

A

Junction between teeth and gingiva particularly susceptible to infection from plaque biofilm- junctional epithelial is very thin and has hight turn over

GCF a serum exudate originating in the gingival crevice

Carries locally produced elements of innate and adaptive immunity

Question 60

Q

how is the Oral mucosa a host defence

Answer

A

Barrier function of keratinocytes (the major cell of the epithelium of the masticatory mucosa)
Desquamation of the oral epithelium- shedding which removes bacteria stuck to this surface
Epithelial cell products e.g. anti-microbial peptides
Mucous layer

Question 61

Q

what are the Phase 1: Natural host defence- what do they all mediate

Answer

A

Inactivation, clearance, prevention of attachment and prevention of invasion

Saliva and its components
Integrity of oral mucosa
Acquired enamel pellicle- layer of proteins from saliva, prevents bacterial attachment
Commensal bacteria -competition for nutrients and niches (dysbiosis may occur)
Vascularity- lots blood vessels (host defence)

Question 62

Q

what are the Phase 2: Innate immunity in the tissue-inflammatory responses- what do they all do

Answer

A

Containment, prevention of spread and clearance

Strong innate= strong adaptive
Elements of the GCF and the gingival tissues
Macrophages-phagocytosis and signalling
Neutrophils-phagocytosis (lots of blood vessels allow this)
Complement-opsonisation and killing
In health plaque confined to gingival margin
If plaque accumulates and moves into the crevice inflammatory responses ensue

Question 63

Q

what is the role of Neutrophils in the gingiva- what cytokine are they recruited by

Answer

A

Neutrophils pass through the gingiva in response to commensal bacteria (via IL-8). This is the physiological inflammation similar to that observed in the gut.
IL-8 and therefore neutrophil emigration is substantially up-regulated in response to pathogenic microflora e.g. in periodontitis
Individual with neutrophil defects have an Increased susceptibility to periodontitis (Neutropenia- more oral infections)

Question 64

Q

Compare and contrast the immune responses of the oral cavity (junctional and sulcular epithelium- JSE) with intestine

Answer

A

in the intestine there is a high microbial burden and bacteria are in suspension. in JSE microbial burden variable and bacteria in biofilm

INT- thick mucus
JSE- no mucin (its in oral mucosa but not crevice)

INT has (S)-IgA (main mucosal antibody)
SJE- has IgG instead (main circulatory antibody)

INT- epithelium has tight junction so difficult to get inflammation
JE- highly pours

INT- inflammation stable
JSE- damaging inflammation

Answer 65

A

Phase 1: Natural host defences in the oral cavity
- Inactivation, clearance, prevention of attachment and prevention of invasion

Phase 2: Innate immunity in the tissue-inflammatory responses
- Containment, prevention of spread and clearance

Phase 3: Adaptive immunity - Enhancement of innate immunity and provision of specific long-lasting immunity

Answer 66

A

• Adaptive immune response – very important!
• Secreted by salivary gland (along with S-IgM)
- Prevents initiation of plaque
• Inhibition of adherence & penetration; neutralisation of viruses and virulence factors;
• Form complexes with mucins -very effective in bacterial clearance
- Mucins allow antibodies to stick to epithelium and then to be swallowed
• IgA1 subclass against proteins, IgA2 against polysaccharides

Answer 67

A

Mucosal immune system is linked
Antigens and bacteria infect mouth from mother
Swallow and they go into peyers patches and antigen transported across the M cells in the gut . antigens presented on dendrtic cells in peyers patch
Activate t cells, which will help B cells
B cells move to all mucosal sites
Develop into plasma cells which secrete IgA
IgA comes from plasma cells (derived from gut) in salivary glands

Answer 68

A

• IgA is a DIMERr- joined together by a J chain which allows it to be secreted

Answer 69

A

MAMPS/ PAMPS- signal innate immunity

PRR recognise signalling via TLR

signals macrophages, dendritic cells, epithelial cells, fibrobaslts which signal cytokines, chemokine, AMPs and prostanoids (this is a cycle)

secondary phase: broadcast

Answer 70

A

LPS 
lipotechoic acid
proteases
DNA 
short chain fatty acids

Answer 71

A

IL-1b similar to TNF (if we inhibit TNF we inhibit inflammation e.g. in rheumatoid arthritis)
IL1 activates neutrophils, macropahes, capillary endothelial cells and the adaptive immune response (dendritic cells- antigen presentation) - all this is good

its bad if chronic

Answer 72

A

response is bad when chronic e.g. persistence of plaque-

chronic activation of IL1 (high in PD) which activated other cells:

such as osteoclasts (bone loss) ,
fibroblasts release MMPs which remove tissue and protein(mainly collagen) – PDL is made of lots of collagen so this is problem
neutrophils stimulation

Answer 73

A

inhibit MMPs which destroy collagen

Answer 74

A

Measles virus infects leukocytes causing immune suppression (to infections you are immune too)
The long-term effects of measles infection (increased morbidity and mortality) are well established
Measles now known to reduce immune memory against many pathogens e.g. influenza, herpesviruses etc.
Disrupts pathogen recognition
Measles induces immune amnesia, an effect not found in MMR vaccinated children- lost previous experience in terms of vaccination
Measles makes you more vulnerable to other infections

Answer 75

A

ELISA
Immunofluorescence direct and indirect
FACS
Monoclonal antibodies
Cytokines
N.B. vaccination/immunosuppression

Answer 76

A

Antibodies will recognise specific proteins
Binds specific molecules to detect them
Fc- crystalline fragment – binds to receptors in cells
constant regions differs between classes
variable regions- very diverse

Answer 77

A