Immunology basics Flashcards
GRAFT VS HOST DISEASE
Cell signalling
Complement C4a and C5a are anaphylatoxins. They promote inflammation, stimulate smooth muscle contraction, increase vascular permeability and encourage mast cell degranulation to release further inflammatory mediators.
C5a is also chemotactic for monocytes and neutrophils, and stimulates leukocyte adherence to blood vessel walls at the site of infection, phagocytosis, and bactericidal activities.
IL-1 and IL-2 are produced by macrophages and polymorphs and have a target effect on T/B/NK cells. Interleukins are generally produced by macrophages, neutrophils, Th1 and Th2 cells. Their target effect is generally on T/B/NK cells to proliferate, differentiate and class switch.
TNF alpha is produced by macrophages, mast cells, NK cells and act on macrophages and tumour cells. The main effect of TNF alpha is to direct the macrophages to produce cytokines and also causes cell death. TNF beta is produced by Th1 cells and acts on phagocytes and tumour cells. It causes phagocytosis, NO production and cell death.
B Cell function & disorders
Binds to specific antigens
Can present antigens to T-cells via MHC
Once T cell activated, signals B cell to mature to plasma cell
Produce antibodies (B cell receptor in secreted form)
- IgG
- IgA
- IgM
- IgE
- IgD
Circulate in serum
Mark specific pathogens for destruction
T cell function & disorders
Antigen specific
All T-cells CD3+ (part of TCR) plus:
- *CD4+ = T Helper cells**
- Antigen recognition
- Cytokine signaling to co-ordinate macrophages, NK cells, B cells
- Can only recognize antigen via MHC molecule
- *CD8+ = Cytotoxic T cells**
- Kill cells with antigen on MHC1
- Similar mechanism to NK cell
Complement pathway- outline process/functions
Plasma proteins produced in liver, help destroy pathogens
‘complement’ the antibodies – signaling, cell destruction via formation of membrane attack complex (MAC), also act as chemotaxins to attract other cells
Mainly destroys gram –ve bacteria
-
Classical
- C1-9
- Inactive until subunits cleaved (when bound to ABs)
- Cascade of events -> C3b protein (opsonin), flags pathogen & makes it easier to destroy
- C5-8 & 9 form MAC - forms hole in bacterial cell membrane -
Alternative
- Involves C3b alone (slow rate opsonisation)
- Factor B & D -
Lectin binding
- Linked to classical
- Mannose binding lectin protein triggers cascade
Interleukins
Innate vs adaptive immunity
Innate immunity
- Non-specific
- ‘Feverishly fast’ minutes – hours, causes fevers
- No memory
- Includes physical barriers (skin, gut lining, cilia), chemical barriers (gastric pH)
Adaptive immunity
- Highly specific for each pathogen
- Uses antigen recognition
- Immunologic memory – priming, clonal expansion & deletion
Innate immunity- Outline cell types involved in innate immunity
Granulocytes/PMNs
Phagocytosis, histamine/pro-inflammatory molecule release
Neutrophils
- Phagocytic
- *Eosinophils**
- Stain pink with eosin dye
- Phagocytic- kill parasites
- Degranulation releases histamine
- Live in bronchiole epithelial lining (atopic asthma)
- *Basophils**
- Stain blue with hematoxylin
- NON-phagocytic
- Initiate allergic responses (inflammatory/histamine granules)
- *Mast cells**
- NON-phagocytic
- Release histamine
_Antigen presenting cells_ Present antigens (via MHC), release cytokines, phagocytose
- *Monocytes**
- Circulate in blood only
- Can enter tissue and change to macrophage
- *Macrophages**
- In tissue only
- *Dendritic**
- Lymph, blood, tissue
- Immature – consume protein in ICF
- Mature- after phagocytosis
- Antigen presentation to T-cells
Lymphoid lineage
- *Natural killer cells (lymphoid)**
- Large/granular
- Target infected cells (virus) & tumor cells
- Granules contain molecules that break cell lining (bind to phospholipid/create pores)
- Cell then undergoes apoptosis
Innate immunity- outline process of pathogen recognition/removal
Pathogen recognition
Occurs via PAMPs (pathogen associated molecular patterns)
Bacterial wall components (LTA/LPS, peptidoglycan)
Fungal wall components (mannan, flagella proteins)
Viral RNA/DNA
Immune cell recognizes via PRR (pattern recognition receptor)
Phagocytic PRRs – bind to PAMP for phagocytosis
Signaling PRRs - when high levels of pathogen, cytokine release (TNFa, IL1B, IL-6)
- TLRs (all leucocytes, epi & endothelial)
- Activate NF-kB to release cytokines
- Vasodilate, attract leucocytes, fever
- In cell, release interferon which stops viral replication
Cell destruction
Via oxidative burst (98%)
Production of nitric oxide/ROS (via NADPH oxidase/superoxide dismutase)•Destruction of whole cell & pathogens in it
**Via phagolysosome (2%)** Specific granules (release proteases/hydrolases)•Azurophilic granules•
