Immunology & Atopy Flashcards
What are the antigen presenting cells of the body? List 7
CD4 binding
- Monocyte
- Macrophage
- Dendritic cell
- Langerhan cell
- B cell
- Microglia (brain)
- Kupfer cells (liver)
Discuss the two immune systems in the body and their features
INNATE:
1. Fast
2. No memory
3. Recognition of pathogenic molecular patterns
4. E.g. TLR, mucosal immunity
ADAPTIVE:
1. Slow (days)
2. Able to learn
3. Strong response via antibodies
4. Memory against PAMP via antigen presenting cells binding with helper T-cells
5. E.g. vaccines
Discuss Cell-mediated Immunity
- Cell-mediated immunity does not depend on antibodies for its adaptive immune functions and is primarily driven by mature T cells, macrophages and the release of cytokines in response to an antigen.
- Strong PAMP (Pathogen Associated Molecular Pattern) response –> Th1 –> Cytokines –> Cytotoxic
Major Histocompatbility Complex (MCG) proteins:
1. Class I: present on all cells, binds to CD8
2. Class II: present on APCs and B-cells, bind to CD4
T-CELL SUBCLASSES
A. CYTOTOXIC
- Expresses CD8
- Recognizes antigen expressed with Class I MHC
B. HELPER (Th)
- Expresses CD4
- Recognizes foreign antigen and Class II MHCs
- Required IL-1 for activation
- 2 Subsets
1. Th1 - stimulates IgM, IgG and IgA and increases cell-mediated response, attacks intracellular pathogens (e.g. IFN-gamma, TNF-beta, IL-2)
2. Th2 - type 2 inflammation, more effective in stimulating IgE antibody secretion; humoral response: attacks extracellular pathgens; (e.g. IL-4, 5, 13)
C. DELAYED HYPERSENSITIVITY (TDH) Class II MHC activation
- Requires IL-2
- IL-2, 12 - proliferation of T/B cells, cytotoxic killing
- NK T-cells (does not need prior sensitization, kills intracellular pathogens/viruses)
Discuss Humoral Immunity
- Humoral immunity produces antigen-specific antibodies and is primarily driven by B cells.
- Weak PAMP response –> Th2 –> esoinophils/mast cells via IgE
- B-cells bear surface receptors (Fc) similar to Immunoglobulins
- Do not need joint recognition of self-markers (MHCs) and antigen like T-cells
- T cells help activate and amplify the humoral response
T-dependent activation:
- Antigen is bound, processed and expressed with surface MHC II
- T cell expresses GP39 which binds to B-cell CD40, which causes cell proliferation and plasma cell differentiation
T-independent activation:
- Inefficient
- Provides mainly IgM
- Antigens include carbohydrates from bacterial capsule and cell wall
https://www.youtube.com/watch?v=rp7T4IItbtM
Discuss Complement. 4 activities
Primary humoral mediator of antigen-antibody reactions
2 pathways of activation:
1. Classical - activated by IgG or IgM; C1 –> C4b, 2b
2. Alternative - activated by PAMPs; C3 –> C3b
4 Biological activities:
1. Chemotaxis (the directed migration of cells in response to concentration gradients of extracellular signal)
2. Opsonization (an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes)
3. Cell Activation by fusion of fragments to neutrophils and macrophages
4. Cell Lysis through the membrane attack complex (MAC) - (forms pores in the plasma membrane of pathogens or targeted cells, leading to osmolysis)
“COAL”
Regarding Cytokines, discuss:
1. What are they
2. Mechanisms of action
3. Types
CYTOKINES:
- Polypeptide signal proteins that modulate cell function
- Proliferation, differentiation, regeneration, wound healing
MECHANISMS OF ACTION:
1. Autocrine: secreted by cells which are modulated by it
2. Paracrine: secreted by cells which modulate neighbouring cell populations
3. Endocrine: secreted by one population of cells with distant effects
CATEGORIES:
1. Angiogenic growth factors (TGF, EGF, PDGF, FGF)
2. Bone morphogenetic protein
3. Interleukins
4. Interferons (INF)
5. TN
Regarding interferons, discuss:
1. What are they and what are their effects?
2. What are the types?
3. What are their side effects?
INTERFERONS:
- Immunomodulatory secretory proteins with a broad range of effects
FUNCTIONS:
1. Cytotoxicity
2. Cytostatic
3. Anti-viral
4. Anti-proliferative
5. Oncogenic inhibition
6. Stimulation of other cytokines and immune modulators (e.g. NK cells, macrophages)
TYPES:
1. Type I interferons
- IFN-alpha produced by leukocytes and IFN-beta produced by connective tissue cells
- In response to viral infection or exposure to ds-RNA
- Significant anti-viral effects - decrease viral replication, increase cell membrane proteins, decrease lymphocyte mitogenesis (increase mitosis in a cell)
- Delayed type hypersensitivity reactions
- Type 2 interferons
- IFN-gamma produced by T-lymphocytes in response to antigenic stimuli
- More potent immunomodulatory effect than Type I interferons
- Increase expression of cell membrane antigens (including MHCI/II and Fc receptors)
- Humoral response: B cell proliferation, production differentiation and proliferation of mast cells, eosinophils
SIDE EFFECTS:
1. Early constitutional: fatigue, headache, nausea, fever, chills
2. Delayed: Leukopenia, alopecia, neurotoxicity, polymyalgia, arthralgia, growth retardation
3. Rare: Spastic diplegia
Describe the allergic reaction at the cellular level
Early response (5 minutes post-exposure)
- Mediated by mast cells and basophils
- Allergen binds to IgE –> allergen-IgE complex binds to Fc on mast cell, cross linking of IgE triggers activation
- Activation causes degranulation of mast cells pre-formed mediators (histamine, heparin, tryptase, beta-glycosaminidase, eosinophil & neutrophil chemotactic factors)
- Synthesis of mediators from membrane bound phospholipids (PGs, LTs, PAF)
Late response (~4 hours post-exposure)
- Mediated by neutrophils and eosinophils
- Reaction is secondary to cytokines
Four cellular effects of histmine in atopy
Main mediator of early allergic reaction
1. Vasodilation
2. Increased capillary permeability
3. Bronchoconstriction
4. Tissue edema
What are the five proteins found in eosinophils?
- Charcot Leyden crystal
- Eosinophil cationic protein (ECP)
- Major basic protein (MBP)
- Eosinophil Peroxidase (EPO)
- Neurotoxin
“CEMEN”
