January 17 Notes

Immunology, January 17, 2008.

I. Immunity and phagocytes
a. Macrophages
http://www.macrophages.com/content/macrophages/images/tissues/ (Site has many links to view real pictures of various macrophages in different tissues of the body)
i. Resident macrophages
*live in tissues, not circulating in blood
1. Microglia-brain
2. Alveolar-lung
3. Kuppfer cells-liver, microbes of blood
4. Splenic macrophages- spleen; microbes of blood
*3 kinds in "marginal zone" where blood flow is heaviest
ii. Monocytes-
undifferentiated macrophages
b. Dendritic cells-"antigen presenting cells"
*Kill through phagocytosis, break down stuff, present broken down material on cellular surface
*Presented to B cells and T cells

i. In skin
1. Langerhans- found in epidermis
2. Dermal and interstitial dendritic cells
ii. In gut mucosa
interaction with specialized epithelial cells in intestine (M-cells)
iii. Circulating: Plasmacytoid dendritic cells
Dendritic cells circulating in blood
*Secretion of interferon (cytokine) upon encounter of viral motifs
II. Selection of lymphocytes
a. Self vs. nonself recognition- kill anything that is not self, leave self alone
*Inate immune system: responds to unique molecules of mibrobes LPS, LTA, Flagellin
b. Immunoglobulin production-family of proteins coded by set of related genesproduction: all immunoglobulin stick to epitopes on antigens based on chemical properties
i. B-cells
*Immunoglobulins stick to extracellular pathogen parts (ex: bacteria [not to be confused with viruses-intracellular) (home in bone marrow)
*Can be against proteins, carbohydrates, lipids (Gram(-)LPS: saccharide part)
1. Antibody
*B-cell immunoglobulins:
**Attached to B-cell
**Secreted by plasma cell(antibodies)
2. B-cell antigen receptor (surface immunoglobulin)

  • Two arms with antigen-binding variable regions

ii. T-cells: has only one arm
1. T-cell receptor
*attach to antigens belonging to intracellular pathogens (ex. viruses/intracellular bacteria)
Can only recognize proteins
Only recognize antigen presented by antigen presenting cells
c. Constant region
*amino acid sequence doesn’t change
d. Variable region

  • amino acid sequence is different among every ALL B-cells & among ALL T-cells (i.e. every lymphoid cell has it very own variable region)

*When matching antigen binds to immunoglobulin, owner of immunoglobulin clones self a lot: clonal expansion (figure 1-12)
*Vast majority of B-cells and T-cells make immunoglobulins that bind to self antigens/ kill self before enter blood stream
i. Generation of variable region diversity
**rearrangements, lots of mutation to DNA(reason every lymphoid cell has own variable region)
III. Major histocompatability complex (MHC) and antigen presentation
1. Presents non-self antigens to TCRs and B-cell immunoglobulins
2. In the thymus, bone marrow, immature B- and T-cells are presented self-antigens
a. If self antigens stick to their immunoglobulins, they die
a. MHC class I
1. Present on all cells
a. present antigens from intracellular pathogens to T- and B-cells.
2. MHCI w/ antigen interacts w/ CD8, cytotoxic T-cells
b. MHC class II
1. Only present on specific immune cells
a. Ex. macrophages, dendritic cells, B-cells
2. Present antigens from extracellular pathogens
c. Cluster differentiation (CD) cell markers
i. CD4+ T-cells
-MHC II interact with these
ii. CD8+ T-cells
-MHC I with antigen interact with these

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