Flashcards in Pathology Deck (311)
What is contained in the white pulp of the spleen?
Areas of lymphocytes aggregated in PALS around central arteries
Name some permanent sites of lymphocyte aggregation
Tonsils (palatine, lingual, pharyngeal)
Peyer's Patches in the ileum
What are the 5 classes of immunoglobulin?
IgG, IgM, IgA, IgD, IgE
What holds the heavy and light chains together in an immunoglobulin?
What are the 2 regions of an immunoglobulin?
Fab region: (fragment antigen-binding) variable region. Consists of 2 antigen binding sites, one at the end of each arm
Fc region: (fragment crystallisable) determines the biological activity, eg complement binding
Which antibody is the first to be produced in response to an antigen?
Which is produced during the secondary response?
IgM (primary response)
IgG-has a higher affinity for the antigen and more biological activities than IgM. Secreted by memory cells
Which is the main antigen in serum?
Where is IgA found?
Mucosal surfaces and in mucosal secretions
What are the functions of antibodies?
Neutralise by preventing pathogen attachment, invasion of host cells, replication, toxin production
Activate complement system
Opsonisation by Fc receptors and complement receptors
Cytotoxicity of antibody-coated cellular antigens by killer lymphocytes
What are the sites of action of IgG and IgM, IgA, IgE, and IgD?
IgG and IgM: function in lymphoid tissues, in the circulation and in tissues
IgA: works at mucosal surfaces which it almost coats, by preventing foreign antigens getting into tissues by preventing attachment to endothelial surfaces
IgE: found at v. low levels in circulation. Mostly attached to mast cells which have specific IgE receptors. When IgE meets its specific antigen, it causes mast cells to degranulate and release inflammatory molecules eg histamine
IgD: found in trace amounts. No known protective function
What percentage of T cells survive the thymic journey?
Removes most self-reactive T cells
What are high endothelial venules (HEV)?
Where are they located in the lymph node?
Post-capillary cells in secondary lymphoid tissues
Enable lymphocytes to leave the blood supply and enter lymph tissues eg lymph nodes
Located in the paracortex
Where is mucosa-associated lymphoid tissue located?
GI tract, respiratory tract, genito-urinary tract
Tonsils, Peyer's patches, appendix
1. Attachment of eg bacteria by non-specific receptors to phagocyte
2. Phagosome forms around the bacteria
3. Lysosome fusion and killing. Digestion.
4. Release of microbial products
What are the 3 complement cascades?
What is the central event in complement activation?
Cleavage of C3
How is the lectin pathway (of complement) initiated?
Starts with mannan-binding lectin (MBL) or ficolin binding to certain sugars on bacteria, viruses and fungi. This binding leads to the cleaving of C2 and C4 to activate C3.
MBL is a pattern recognition receptor; a protein produced by the liver
Explain the alternative pathway of complement
Surface components of certain bacteria and parasites are able to directly activate C3, resulting in C3b generation. This is then stabilised by factors B and D, and the activated C3b then acts as an enzyme, C3b convertase, which activates further C3 and converts it to C3b. This cycle is inhibited by factor H, however a number of foreign components including bacterial walls, helminths and endotoxins bind factor H and remove this inhibitor. As a result, C3 activation occurs, and membrane-bound C3b can cause C5-C9 activation, leading to cell lysis.
Name some initiators of the alternative pathway of complement activation
Many gram-negative bacteria
Lipopolysaccharides from gram-negative bacteria
Many gram-positive bacteria
Fungal cell walls
Some viruses and parasites
Complexed IgG and IgA
What are the biological effects of complement?
Cell lysis: C5-C9 MAC
Neutralisation of bacterial/viral attachment to host tissues, prevention of tissue invasion, presentation of pathogen replication, prevention of toxin release
Opsonisaton: antigens become coated with C3b, making them more likely to be taken up by phagocytes
Inflammatory response: C3a and C5 proteins increase vascular permeability at site of infection, activate neutrophils and cause mast cell degranulation, which releases vasoactive amines that induce smooth muscle contraction, leading to signs of inflammation eg redness, swelling, heat, pain
Clearance of immune complexes
However, can cause damage to host tissue eg if immune complexes are deposited
Why is it good that C3a and C5 cause increased vascular permeability?
Increased permeability causes increased fluid leakage from blood vessels and leakage of immunoglobulins and complement molecules. Increased migration of PMNs and macrophages and their microbicidal activity.
What are the control mechanisms for complement?
Lability (breaks down quickly)
All cells have surface protection by specific complement receptor molecules (Factor I and H cleave C3) (C3b receptor on RBCs)
C1 inhibitor binds C1r and so stops C2/4 binding
What are PAMPs?
Molecules on pathogens (mainly bacteria) recognised by receptors on cells of innate immune response (PPRs)
What are PPRs?
Where are they found?
Pattern recognition receptors
Primitive part of innate immune system
Found on phagocytes and mast cells
Identify and bind PAMPs
Where are T cells distributed?
What about B cells?
T cells: lymph node paracortex, spleen PALS
B cells: lymph node cortex, splenic follicles (germinal centres)
What are the 2 types of T lymphocyte?
What percentage of each make up the total number of T cells>
Th cells (T helper): CD4+, assist both antibody production and cytotoxic T cell effects. 65%
Tc cells (cytotoxic T cells): CD8+, kill infected host cells and tumours. 35%
What are the 2 types of T cell receptor?
TCRαβ and TCRγδ (less common)
What are the 2 classes of MHC gene?
MHC class I: presents Ag to Tc cells (enables killing of infected host cells). Expressed on most nucleated cells.
MHC class II: presents Ag to Th cells (assists Ab production and Tc activity). Expressed on macrophages, APCs, B cells, activated T cells.
Explain the 2 pathways for antigen processing
Endogenous: HOST CELLS process infective agents and express on cell surface with MHC class I. Targeted by Tc cells-host cell killed.
Exogenous: MACROPHAGES etc digest infective agent and produce peptides to present on surface MHC Class II, or to be picked up by other cells eg dendritic cells to present to Th cells to activate them.