Microb Seminar Group 3 (LATEST)

AUTOIMMUNITY & INTOLERANCE
(GROUP 3)
GROUP MEMBERS MATRICS NUMBER

AWG MOHD RAHIM BIN AWG AINI 1170640
HASIF AIMRAN BIN ABD JALIL 1181987
NORLIYANA ALIA BINTI KHEBIR 1181990
RAIHANA ALIYYA BINTI ZAHARI 1181991
UMMU SHAHIDAH BINTI ZAKARIYA 1181996
NURSYAZWANI BINTI TUAN MAHAZAN 1182004
LO 1:
Describe development of tolerance via central and
peripheral tolerance
CENTRAL T LYMPHOCYTE TOLERANCE
-If lymphocyte that has not completed its maturation counteract with self antigen ->
Displayed as a peptide bound to self MHC molecule -> Lymphocyte will receive signal that
trigger apoptosis
-Self-reactive cell dies before it can be functionally , this process called as Negative
Selection
-Some immature CD4+ T cells that recognize self antigens with high affinity do not die but
develop into regulatory T cells and enter peripheral tissue.
-Immature lymphocytes may interact strongly with an antigen if the antigen is present at
high concentrations in or high affinity.
-A protein called AIRE (autoimmune regulator) for the thymic expression of these
peripheral tissue antigens to eliminate the self reactive T cell or to develop regulatory T
cell.
PERIPHERAL T CELL TOLERANCE
- Induced when mature T cells recognize self antigens in
peripheral tissues, leading to functional inactivation(anergy) or
death or when self-reactive lymphocytes are suppressed by
regulatory T cells
1) Anergy
- Refer : Induction of functional
unresponsiveness of T cell when these cells
recognize self antigen.
- Mechanism :
1. Abnormal signalling by TCR complex due

to absence of costimulation – activation of
enzymes (ubiquitin ligases) that modify
signalling protein & target them for
intracellular destruction by protease.
2. Inhibitory signals from other receptors
- Cytotoxic T-lymphocycte-associated antigen

4 (CTLA-4 or CD152)
- Programmed cell death protein
(PD-1,CD279)
2) Immune suppression by
regulatory T cell
- Regulatory T cells develop in thymus and

peripheral lymph nodes or tissue.
- Most regulatory T cell are CD4 that

expressed IL-2 receptor (CD25)and
transcription factor (FoxP3)- required for
development and function of the cells
- They also need IL-2 from T helper cell to

develop into regulatory T cell.
- Mechanism :
• Some regulatory cells produce cytokines (e.g,

IL-10,TGF-B) – inhibit the activation of
lymphocytes, dendritic cell and macrophages
• Regulatory cell express CTLA-4,may block or

remove B7 molecules made by APC – APC
incapable providing costimulation via CD28
and activating T cells .
• Regulatory T cell, that has high expression of

IL-2 receptor, may bind and consume
essential T cell growth factor – reduce the
availability for responding T cell
3) Apoptosis
- Recognition of self antigens may trigger

apoptosis pathways, resulting in elimination of
self-reactive lymphocytes.
- Mechanism :
1. Production of pro-apoptotic protein in T cells
– causing mitochondrial protein to leak out –

activate caspase .
- In normal immune response – proapoptotic
protein is counteracted by antiapoptotic protein –
induced by costimulation and growth factors
2. Co-expression of death receptor In their

ligands – generate signals through death receptor-
activation caspases – apoptosis (Fas-fas ligand)
CENTRAL B CELL TOLERANCE
• When immature B lymphocytes

interact strongly with self antigens
(high avidity) in the bone marrow, the
B cell either change their receptor
specificity (receptor editing) or are
killed (deletion)
• If the developing B cell react with self
antigen with lower avidity, the cell
becomes anergic and exits the bone
marrow in this unresponsive state.
Peripheral B cell tolerance
LO2:
Explain the condition of common
cases in autoimmunity
Systemic Lupus Erythematosus (SLE)
is an autoimmune disease in which the

immune system attacks its own tissues,
causing widespread inflammation and
tissue damage in the affected organs.
SYTEMIC LUPUS ERYTHEMATOSUS (SLE)
Autoantibody against several nuclear component

(antinuclear antibody, ANAs) : nucleic acid, histones,
nuclear protein
Antigen-antibody complex (autoantibody+ DNA) will
form in circulation and deposited in kidney and vascular
tissue
Complex activate complement cascade and attract
granulocytes causing inflammatory reaction
(glomerulonephritis)
Deposited and trapped against basement membrane of
glomerulus causing damage to kidney
Also cause vasculitis by immune complex deposition
that result in rash on cheek
Symptoms :
• Reddish rash on the cheek
• Fever
• Joint pain
Rheumatoid Arthritis (RA)
is a chronic inflammatory disorder of autoimmune

origin that attacks the joints, producing
inflammatory response.
T-helper cell(CD4) may initiate
the autoimmune response
Bone resorption, TNF and IL-1

(macrophages) will secrete
proteases to destroy hyaline
cartilage.
Pannus formation.
LO 3:
Explain method or step to manage autoimmunity
Treatment of Autoimmune Diseases
Aim : to reduce the patient’s immune response or inflammatory response sufficiently to
eliminate the symptoms
Monoclonal antibodies
- Inhibitor of Th-1 and Th- Immunosuppression and
Anti-inflammatories
17 pathway (Brodalumab) - Corticosteroids
- Inhibitors of leukocyte Treatment
(Prednisone)
migration (Natalizumab) - NSAIDs
- B-cell inhibitors
- DNA synthesis inhibitors
(Rituzimab)
Antibody to TNF and soluble

T-regulatory cells
receptor for TNF
- Antibody to TNF (Infliximab)
- TNF receptor (Etanercept)
*Immunosuppressive therapy must be given cautiously because the risk of opportunistic infections
*Long term usage requires concurrent treatment with antimicrobials
T regulatory cell adoptive therapy
Aim: suppress activation, proliferation and cytokine production of CD4 T cell

and CD8 T cell and suppress B cells and dendritic cells
Mechanism of action:
1. Formation of tolerogenic APCs

2. Soaking up IL-2 leading to CD-8 exhaustion
and apoptosis
3. Suppression of antibodies secretion by B-
cell and cause cell apoptosis
Example: Graft-versus-host-disease (GVHD)

and autoimmune hepatitis
Combination of CD4,CD25 and CD127 resulted in highly

purified population of T reg cells
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AUTOIMMUNITY & INTOLERANCE

GROUP MEMBERS MATRICS NUMBER

1. Abnormal signalling by TCR complex due

2. Inhibitory signals from other receptors

- Cytotoxic T-lymphocycte-associated antigen

- Regulatory T cells develop in thymus and

- Most regulatory T cell are CD4 that

- They also need IL-2 from T helper cell to

• Some regulatory cells produce cytokines (e.g,

• Regulatory cell express CTLA-4,may block or

• Regulatory T cell, that has high expression of

- Recognition of self antigens may trigger

1. Production of pro-apoptotic protein in T cells

– causing mitochondrial protein to leak out –

2. Co-expression of death receptor In their

• When immature B lymphocytes

is an autoimmune disease in which the

Autoantibody against several nuclear component

is a chronic inflammatory disorder of autoimmune

Bone resorption, TNF and IL-1

Antibody to TNF and soluble

Aim: suppress activation, proliferation and cytokine production of CD4 T cell

1. Formation of tolerogenic APCs

Example: Graft-versus-host-disease (GVHD)

Combination of CD4,CD25 and CD127 resulted in highly

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