HIS05 Introduction Of The Immune System Flashcards
Modern immunology
Study of cells and tissues that mediate immunity + genes and proteins underlying their functions (molecular immunology)
Organisation of immune system
Immune system (Lymphoid organs + Immune cells) —> Immunity (functional state of protection from infectious disease) —> Innate immunity (natural + non-specific) + Adaptive immunity (acquired + specific)
Adaptive immunity: could be enhanced by vaccination
Immune response: collective and coordinated responses to invasion of foreign substances
Immune cells
Lymphocytes
- T cell
- specifically recognise + respond to foreign antigens
- provide specificity for immune responses (consists of distinct subsets with different functions but very similar morphology) - B cell
- develop in bone marrow in mammals (bursa of Fabricius in birds) - NK cell
- recognise and kill **tumour cells + **virus-infected cells
- express neither B / T cell receptors
- up to 15% of lymphocytes
Accessory cells (not specific for different antigens but contribute to cognitive and activation phases of immune responses)
- APC
- Macrophage + Dendritic cells + ***B lymphocytes —> present antigen to B / T cells - Phagocytes
- Macrophage + ***Neutrophil
Lymphoid organs
Central / Primary lymphoid organs:
—> provide appropriate microenvironment for **development and **maturation of lymphocytes
1. Bone marrow
2. Thymus
Peripheral / Secondary lymphoid organs:
—> provide environment in which lymphocytes can ***interact with antigens and with accessory cells
1. Spleen
2. Lymph nodes
3. Mucosa-associated lymphoid tissue (MALT) (e.g. tonsils, adenoids, Peyer’s patch of ileum)
Cells involved in immune response
Innate immunity
- Neutrophil
- Macrophage (APC: Bridging between innate and adaptive immunity by activating T cell)
- Dendritic cell (APC: Bridging between innate and adaptive immunity by activating T cell)
Adaptive immunity
- B cells (secrete Ab)
- T cells (secrete **cytokine, kill **tumour cell, ***virus-infected cells)
Innate immunity
- Present at birth
- ***not enhanced by successive exposures to foreign substances
- do ***not discriminate among most foreign substances
- Defence barriers
- Cell
- **Phagocytes (Phagocytosis) —> Macrophage, Neutrophil
- **NK cells (Cytotoxicity) - Humoral: Soluble factors
- **Acute phase proteins
- **Complements
- ***Interferons
Phagocytes
Macrophage + Neutrophil
Functions: 1. ***Phagocytosis: Phagosome forming —> Lysosome fusion —> Damage and digestion —> Release of microbial products
Other functions of Macrophage:
2. **Cytokine production
3. **Antigen presentation
—> Mediate adaptive immune response
Phagocytosis in Erythrocyte clearance: Oxidative damage / Cellular senescence —> Loss of membrane constituents on RBC (CD47, Sialic acids) —> Activate phagocytes —> Clearance of RBC
Clinical implications:
1. Enhanced destruction of RBC (over-activation of phagocytes reflected by Splenomegaly) —> Anaemia
- Impaired clearance of dying cells (early apoptotic cells) in SLE
—> cells get secondary necrosis and release of danger signals
—> inflammation and accessibility of autoantigens
—> disturbed affinity maturation
—> autoimmune reaction - Macrophage activation syndrome
—> massive production of cytokines
—> severe inflammation
—> organs and tissues damage
Dendritic cells
- Lymphoid / Myeloid
- ***Most potent APC
- ***Enhance proliferation of T cells
- ***Activate B cell
- Clinical implications: autoimmunity, infection, transplantation (enhance immune tolerance), immunotherapy
Charles Janeway Jr.
Pattern recognition theory of innate immune cells:
Pathogen-associated molecular patterns (on pathogens) + Pattern recognition receptors (on innate WBC)
Pattern recognition by immune cells
Adaptive immunity: Antigen receptors (***B / T cell receptors)
Innate immunity:
Pattern recognition receptors (***Toll-like receptors, Scavengers receptors etc.)
—> recognise LPS on bacteria
Adaptive immunity
- acquired during life
- ***induced by exposure to foreign substances
- ***enhanced after successive exposure to the antigen
- Mediated by B and T cell
- Humoral immunity (can be transferred to unimmunised individuals by **cell-free portion of blood (substances in body fluid))
- B lymphocyte:
—> **Ab production —> specific elimination of antigens
—> Antigen recognition
—> B cell activation
—> Cross-talk with T cell - Cellular immunity (can be transferred to unimmunised individuals with **cells from immunised individual)
- T Lymphocyte:
—> **Cytokine secretion
—> ***Direct cytotoxicity
Helper T cell: secrete cytokines + interact with B cell and macrophages
Cytotoxic T cell: kill target cells infected by virus / other pathogens
Antigen
Foreign substance that induce immunity
Epitope - Antigenic determinant
- Discrete site on antigen recognised by both B and T cell
- can be ***multiple epitopes on single antigen
- ***Immunologically active region (on surface of pathogens) binding to B / T cell receptors (recognised by B / T cells)
—> important for vaccine design and treatment
3 Phases of adaptive immune responses
- Recognition
- Lymphocyte recognise and bind to antigens by Antigen receptor on B / T cells - Activation
—> Proliferation (clonal expansion) + **Differentiation
—> give rise to **Effector + ***Memory cells - Reaction
- Effector cells: eliminate antigens
- Memory cells: immunological memory
***Cardinal features of adaptive immune responses
(記: SDSDM)
- Specificity
- immune responses specific for distinct antigens
- by antigen receptors on B / T cell - Diversity
- lymphocyte can discriminate >=10^9 distinct antigens
- result of numerous different clones of lymphocytes generated in an individual - Self-regulation
- ALL normal immune responses wane with time after antigenic stimulation
- e.g. 4 phases of primary Ab response: Lag —> Log —> Plateau —> Decline (due to activation-induced cell death)
- abnormal destruction of lymphocytes (e.g. HIV —> AIDS)
- failure of lymphocyte apoptosis —> accumulation —> defective homeostasis
(e.g. Canale-Smith syndrome
—> Lymphadenopathy and Splenomegaly
—> Increased numbers of lymphocyte (5-20 fold)
—> Elevated levels of Igs (hyper-gammaglobulinemia)
—> Fas-gene mutation (fas +/-)) - Immunological Memory
- Memory B / T cells - Discrimination of Self from Non-self
- lymphocytes able to recognise and respond to foreign antigens but unresponsive to self antigens —> Tolerance
- transplantation immunology
- autoimmune diseases
- tolerance induction in foetus (immune system that is different from adults’ —> recognise foreign proteins but avoid rejection of mother’s cells)
Tolerance induction in foetus
Dendritic cells establish fetal tolerance to maternal antigens in vivo
Fetal dendritic cells activated by Maternal allogeneic antigens
—> suppress T-cell mediated rejection
Clinical significance:
- Pregnancy and Perinatal complications
—> Recurrent spontaneous miscarriage
—> Gestational diabetes
***Clonal selection theory of adaptive immunity
Explain **Lymphocyte specificity + **Antigen recognition
- An immunologically competent cell (B / T cell) expresses surface receptors for a single antigenic epitope (i.e. all receptors on one cell are identical)
- When host exposed to antigen, epitopes on antigen will bind to cells with appropriate receptors
- Specific binding of antigen to B / T cell induces proliferation of these lymphocytes —> “clones” of ***identical cells (having surface receptors with same specificity / binding site)
- B cell will mature into Plasma cell —> secrete Ab with same specificity as surface receptors on parent B cell
- Some cells generated during clonal expansion will become Memory cells with same antigen specificity
- Contact between B / T cell and antigen (for which they are specific) during embryonic development —> destruction / elimination of that clone
- Removal of antigen-specific clones —> antigen-specific non-responsiveness —> Tolerance
Summary (記: SSET):
1. **Specificity for BCR / TCR binding to Ag
2. Clonal **selection (specific B / T cell)
3. Clonal **expansion (proliferation and differentiation) —> Effector cells + Memory cells
4. Central **tolerance (deletion / suppression of autoreactive B / T cells in bone / thymus at early stage)
—> Immune tolerance: No immune response to antigens
How does immune system work
- ***Cooperation of innate and adaptive immunity
- Clinical significance: Immune dysfunction due to immune imbalance - ***Connection to Nervous system + Endocrine system
- Sepsis: complex exaggerated version of inflammatory arm of immune defences
- Immune cell-derived neurotransmitter regulates immunity
Adaptive immune features of NK cells
NK cells show memory functions during infections
***Stages of immune responses
Initial infection:
- Innate immunity (0-4 hours)
- recognition by **Pre-formed, **Non-specific Effectors - Early induced response (4-96 hours)
- ***recruitment of Effector cells
—> recognition, activation of Effector cells - Late adaptive response (>96 hours)
- transport of antigen to **Lymphoid organs
—> recognition by Naive B / T cells
—> clonal **expansion and ***differentiation to Effector cells
Re-infection:
- Protective immunity
- recognition by ***Pre-formed Ab and Effector T cells - Immunological memory
- recognition by **Memory B / T cells
—> rapid **expansion and ***differentiation to Effector cells
***Summary
Phagocyte:
- Macrophage
- Neutrophil
APC:
- Macrophage
- Dendritic cells
- B cell
Lymphocytes:
- B cell
- T cell
- NK cell
Innate:
- Neutrophil
- Macrophage (APC: Bridging between innate and adaptive immunity by activating T cell)
- Dendritic cell (APC: Bridging between innate and adaptive immunity by activating T cell)
- NK cell
Adaptive:
- B cells (secrete Ab)
- T cells (secrete **cytokine, kill **tumour cell, ***virus-infected cells)
Cellular immunity:
- Phagocytes
- NK cell
- T cell
Humoral immunity:
- Acute phase protein, Complement, Interferon
- B cell
