Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Immunology: Research + Clinic > HC7: Autoimmune disease and therapeutic antibodies > Flashcards

HC7: Autoimmune disease and therapeutic antibodies Flashcards

HC 7

1
Q

Autoimmune disease types

A
  • Organ specific or systemic
    > the disease is always throughout whole body, but could focus on organs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Autoimmune disease age

A

Mostly young age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Common features autoimmune diseases

A
  • Central and peripheral tolerance
  • Genetic predisposition and environmental factors like HLA type for strength of immune response
  • Autoantibodies, auto-reactive B/T-cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Acute rheumatism

A
  • Streptococcal infection: cell wall stimulates antibody response
  • With some earlier species: some antibodies cross-react with heart valve, causing rheumatic fever
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Rheumatioid arthritis (RA) symptoms

A
  • Common form rheuma
  • Young patients mostly, in 20s, mostly women
  • Pain and swelled hands
  • Inflammation in joints > cartilage (kraakbeen) of joints is destroyed
  • Knobs on hands
  • attacks in phases
  • synoviocytes inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Synoviocyte inflammation: synovitis

A

Mucosa of the joint > grows > inflammation > blood vessels enter tissue > inflammatory cells enter to destroy cartilage and bone
» in RA
> damage caused causes more inflammation: vicious cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Cytokines involved in chronic inflammatory arthritis (RA)

A
  • TNFa, IL-6, IFN-y, IL-1, OPGL, IL-17
    > immune cells induced
    > influence osteoblasts and osteoclasts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Chronic inflammation in joint leads to bone destruction evident as erosions. What happens when prolonged severe chronic arthritis?

A

Deformity and disability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Rheumatoid factors (RFs)

A

Agglutanation of RBCs by antibody against serum gamma-globulins (y-globulins) against IgG > IgM against self-antigen IgG Fc (auto-antibodies)
> these are called RFs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

RA: citrullination of proteins

A
  • Antibodies bind citrullinated proteins
  • Citrullination: breakdown process of cell, proteins are broken down, and in this process the PAD enzyme converts arginine in citrulline > citrullination (make protein more susceptible for proteolytic degradation).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Presence RA Abs

A

Present before expression of arthritis
> anti-CCP (anti citrullinated proteins) and IgM-RF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Trigger for RA

A

Can be smoking
> inflammation (chronic bronchitis)
> when right gene composition (specific HLA type (HLA-DR2) 2 gene: anti-CCP antibodies made
> RFs that bind immune complex of low affinity anti-CCP IgG made
> Take five IgGs at one time, RF is IgM, pentamer with high avidity
> activation complement
> damage induced
> more inflammation
> vicious cycle of damage and inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Phases RA

A
  • Pre-articular or lymphoid phase: autoimmunity: anti-CCP and RFs
  • Transition phase
  • Articular phase
    > articular localization: osteoporosis, functional decline, cardiovascular disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Ankylosing spondylarthritis and HLA

A

Most known HLA associated disease: HLA-B27
> 10% HLA-B27 prevalence
> pain in back
> 10% chance of diagnosing someone wrong when HLA typing.
> 87% relative risk
> known as Bechterew disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Becheterew disease and symptoms

A
  • Young men affected
  • Spinal joints
    > stiffen in back and SI joints affected (sacroiliac joints in hip)
  • inflammation in other joints as well
  • chronic inflammation > anemia > higher risk cardiovascular disease and fatigue
  • Create Bamboo Spine: vertebrae grow together
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Is HLA-type enough for Bechterew diagnosis

A

No more needed: 2 other SpA (ankylosing spondylarthritis)
> like family background
> uveitis: inflammation in eye: less common in HLA-B27

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What happens to HLA-B27 in Bechterew?

A

Wrong folding? Interaction with KIR (T-cells and NK-cells are KIR+)? Modulation microbiome and indirect modulation acquired immunity? Unknown yet.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Jicht disease

A
  • Men mostly
  • Alcohol consumption, renal problems
  • Red feet, very painful acute attacks
    (Bechterew and RA are more chronic: morning stiffness)
  • joints are destroyed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Jicht trophi

A

Large knobs with white paste inside
> uric acid crystals inside them: metabolic disease
> urate oxidase absent in humans: not metabolized
> neutrophils take the crystals up but die: dead neutrophils are white paste
> concentration uric acid to high > precipatation (neerslag) of uric acid crystals)
» derived from nucleic acids from nutrients and purine metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Jicht causes

A
  • Genetic predisposal for high uric acid > Jicht
  • Renal dysfunction > Jicht
  • Too much alcohol > Jicht
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Bechterew kind of disease

A

T-cell mediated autoimmune disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

RA kind of disease

A

Antibody mediated autoimmune disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Jicht kind of disease

A

Metabolic disease, causing inflammation of joints

24
Q

Multiple sclerosis (MS) character

A
  • Autoimmune disease of nervous system
  • Inflammation of retina is possible
  • Nervous paths destroyed in spinal cord and brain
  • In young women mostly, like RA
  • Autoreactive lymphocytes induce inflammatory reaction leading to demyelination and damage to axons
  • When attacks: damage, nervous deficit over time
25
Q

2 types of MS

A
  • Relapsing remitting RRMS (85%): peaks which pass threshold of being clinical and slow increase towards SPMS: secondary progressive MS. After reaching threshold in progressive trend, progressive increase in severity and constantly clinical
  • Primary progressive MS (PPMS) (15%): progressive MS towards clinical threshold with smaller and less prevalent attacks
26
Q

Risk factors MS

A
  • Genetic: HLA-DR2
  • Women
  • Smoking
  • Maybe EBV (Epstein-Barr Virus)
27
Q

Pathogenesis MS

A

Unknown trigger sets up inflammation in brain
> at sites inflammation, activates T-cells auto-reactive for brain antigens cross blood-brain barrier and enter brain, where they re-encounter antigens on microglial cells and secrete cytokines like GM-CSF and IFN-y > increase inflammation and more immune cells and complement > chronic autoimmune disease through positive feedback from inflammation

28
Q

Psoriasis

A

Class 1 (MHCI, CTLs) mediated disease > inflammation of skin, against skin associated antigens

29
Q

Hashimoto thyroiditis

A

Autoantibodies and autoreactive T-cells against thyroid antigens > hypothyroidism > underproduction thyroid hormones

30
Q

Systemic lupus erythematosus

A

Autoantibodies and autoreactive T-cells in kidneys, brain > autoreactivity against DNA and nucleosomes
» not organ specific
» young people affected
» can be very acute: systemic: spinal cord, kidneys etc, quick destruction

31
Q

Vasculitis

A

Precipitation of autoreactive cells in circulation, happens in severe cases of for example Lupus

32
Q

Therapy autoimmune disease

A
  • Steroids
  • Cytotoxic drugs
  • Cyclosporine etc (T-cell inhibition)
  • JAK-inhibitors
  • Biologicals
    > mAbs
33
Q

JAK-inhibitors

A
  • Target JAK-STAT pathway
    > inhibit inflammation
    > for RA for example
    > coupled to cytokines which are pro-inflammatory or cytokine receptors
34
Q

Biologicals: hybridoma technology

A
  • Fuse spleen cell with myeloma cell
    > monoclonal antibodies made
    > one antibody secreting cell clone that can replicate indefinitively
    » from one clone, for one antigen of interest
    » from polyclonal to monoclonal Ab therapy
    > Select for monoclonal population
35
Q

mAb treatment use in autoimmune disease

A

When selectively block something
> selective depletion of autoreactive lymphocytes for autoimmune disease
> biologicals that block TNFa, IL-1, IL-6 to alleviate autoimmune disease
> to block cell migration to sites of inflammation for MS (block blood brain barrier crossing)
> block co-stimulatory pathways to activate lymphocytes for RA

36
Q

mAb types

A

-omab: fully mouse: autoreactivity against it
-ximab: chimeric: change variable part of antibody: VH/VLs
-zumab: humanized: just CDRs are mouse, anti-idiotypic antibodies possible
-umab: fully human, not immunogenic

37
Q

TNF-inhibitors

A

Monoclonal antibodies used mostly
> Infliximab IFX: chimeric
> Adalimumab ADL: human
> Golimumab GLM: human, best binding affinity
> Etanercept ETN: TNF receptor with Ab Fc tail
> Certoluzimab CZP: small fragment of only Fab and no Fc tail

38
Q

Infliximab and Adalimumab are most used anti-TNF mAbs, why

A

Golimumab with strongest binding is very expensive

39
Q

Certoluzimab application

A

In pregnancy
> in third trimester, FcRn brings IgG from mother to child > you do not want anti-TNF in child
> no Fc tail, only Fab fragment
> cannot be bound by FcRn: not transferred

40
Q

Problem infliximab

A

Is chimeric
> anti-antibodies, anti-IFX
> if immune response stronger than the infliximab > only immune complexes made (anti-Abs on IFX) and no effect of treatments
> immune complexes can create attacks when IV is on

41
Q

Therapeutic antibodies for RA

A
  • Anti-TNF
  • Anti-IL-6
  • Anti-CD28: Abatacept (block co-stimulation T-cell)
  • Anti-CD20: Rituximab: for B-cell
    > when mAb treatment stopped: relapse
42
Q

Screening when anti-TNF

A

when tuberculosis latent in lungs and anti-TNF given, tuberculosis in whole body and destroys everything: so screening is important

43
Q

Rituximab

A

Anti-CD20 for example against RA
> removes naive B-cells and memory B-cells in circulation
> does not remove plasmablasts (PBs), plasma cells (PCs), long lived plasma cells and memory cells in tissue
> repeated infusions required
> Rituximab is cancer therapy for B-cell leukemia
> induce apoptosis B-cells

44
Q

Rituximab in RA combined with:

A

Methotrexate
> Rituximab + methotrexate given when anto-TNF treatment not possible or not wanted by patient

45
Q

Problem Rituximab and SARS-CoV-2

A

Vaccination did not work for Sars-CoV-2
> humoral immune response does not work (via B-cells), antibodies do not protect against Sars-CoV-2

46
Q

MS treatment mAbs

A
  • Natalizumab
  • Rituximab / Ocrelizumab (B-cell depletion)
47
Q

Natalizumab

A
  • Prevent lymphocytes from crossing blood-brain barrier
  • Severe demyelination disease caused by reactivation of Jacob-Creutzfeldt virus is risk: screening beforehand
  • Immunocompromised patients: progressive multifocal leukoencephalopathy
48
Q

Rituximab / Ocrelizumab for MS

A
  • When Natalizumab does not work
  • Ocrelizumab binds CD20 like Rituximab
    > B-cell depltion
    > Rituximab is chimeric and Ocrelizumab humanized
    > cells which kill Rituximab are also killed and Ocrelizumab is low immunogenic
    > gain control of disease
49
Q

Does Rituximab work against Ankylosing Spondylitis / spondylarthritis / Bechterew?

A

No

50
Q

Disadvantage Immune Checkpoint Inhibition in immune-oncology?

A

If too much response > autoimmunity > T-cells become overactive
» PD-1, PD-L1 and CTLA4 blocked
» inhibit immune checkpoint of tumor cell with anti-PD-L1 and anti-PD-1

51
Q

CAR T-cells against B-cells

A

Chimeric antigen receptor CART-19 against CD19 > B-cells
» whereas anti-CD20 (Rituximab) works against naive B-cell and memory B-cell in circulation, CAR T-cells with CART19 receptor work against pro- B-cells and plasmablasts as well. > broader target

52
Q

Rituximab for SLE (Lupus) (Systemic lupus erythematosus)

A

Low effect anti-CD20 > does not work against plasmablast
» however, CART19 cells against the B-cells work better
» with only one treatment, complete remission

53
Q

CAR T-cell challenges

A

Toxic effects: get very sick
Lymphodepletion
T-cell immunity
Fertility
Permanent organ damage
Costs

54
Q

Bispecific T-cell engager (BiTE) therapy for refractory arthritis

A

Anti-CD3 (T-cell) and anti-CD19 (B-cell) bispecific
> Blinatumomab

55
Q

Why does Rituximab not work against SLE, and why do CAR T-cells work?

A
  • Antibodies (Rituximab) are hydrophilic and stay in circulation
    > CAR T-cells can go to lymph nodes: deeper depletion
    > CAR T-cells work against pro-B cell and plasmablast
    > first chemo and then CAR T-cells to make space for it.
    > not chemo if Rituximab

Immunology: Research + Clinic (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions