20. Definitions
• Immunity = protection against infections
• Immune system = collection of cells and molecules
that defend us against microbes
• Immune deficiencies → infections
• Immune excesses → autoimmune diseases
21. Innate (Natural) Immunity
• Always present (innate); doesn’t change over time
• First line of defense when bugs come
• Major components:
• Epithelial barriers (skin, GI, respiratory)
• NK cells
• Complement
22. Adaptive (Acquired) Immunity
• Second line of defense
• More specific (adaptive) and powerful than innate
• Major components:
• Lymphocytes
• Lymphocyte products
• Two types of adaptive immunity:
• Humoral immunity (mediated by antibodies)
• Cellular immunity (mediated by T cells)
28. Lymphocytes
• Present in lymphoid organs and in blood
• Groups
• T-lymphocytes (grow up in thymus)
• B-lymphocytes (grow up in bone marrow)
• Each one has receptors for a specific antigen
• Recognize millions of different antigens!
• Diversity generated by:
• rearrangement of antigen receptor genes
• different joining of the gene segments
• Gene rearrangement studies
32. T-Lymphocytes
• Live in blood, bone marrow, lymphoid tissues
• Two basic functions:
• kill stuff
• help other cells do their jobs
• T-cell receptor (TCR) complex recognizes antigens
• binds antigen
• sends signals to the T cell
• Antigens must be:
• displayed by other cells…
• …AND bound to an MHC receptor
38. MHC
• Collection of genes on chromosome 6
• Three regions: class I, class II, class III
• Highly polymorphic!
• Gene products:
• class I molecules
• class II molecules
• class III molecules (and other stuff)
Major histocompatibility (MHC) complex
39. class I MHC moleculeclass II MHC molecule
class II MHC genes class I MHC genesclass III MHC genes
40. MHC
• Encoded by three loci: HLA-A, HLA-B, HLA-C
• Display antigens from within the cell
(e.g., viral antigens) to CD8+ T cells.
• Present on all nucleated cells! (Good idea.)
Class I MHC molecules
41. MHC
• Encoded by three loci: HLA-DP, HLA-DQ, HLA-DR
• Display extracellular antigens (e.g., bacterial
antigens the cell has eaten) to CD4+ T cells
• Present mainly on antigen presenting cells, like
macrophages! (Makes sense.)
Class II MHC molecules
42.
43.
44. B-Lymphocytes
• Live in blood, bone marrow, lymphoid tissues
• Basic function: make antibodies (immunoglobulins)
• B-cell receptor complex recognizes antigens
• binds antigen
• sends signals to T cells
• Antigens can be free and circulating (don’t have to
be bound to MHCs or displayed by other cells to be
recognized!)
47. Natural Killer Cells
• Belong to innate immunity arm
• No highly variable receptors like T and B cells
• Main job: recognize and kill damaged or infected cells
• Antigens can be free and circulating (don’t have to be
bound to MHCs or displayed by other cells to be
recognized!)
51. Antigen-presenting cells
• Main job: catch antigens and display them to lymphocytes
• Dendritic cells
• Have fine cytoplasmic projections
• Present all over body: skin, lymph nodes, organs
• Capture bug antigens, display to B and T cells
• Other APCs
• Macrophages eat bugs and present antigens to
T cells, which tell macrophages to kill bugs
• B cells present antigens to helper T cells, which tell
B cells to make antibodies
60. Effector cells
• These guys carry out the ultimate immune
system task: eliminate infection
• Types of effector cells
• NK cells
• Plasma cells
• T cells (both CD4+ and CD8+)
• Macrophages
• Other leukocytes (e.g., neutrophils)
64. The Innate Immune Response
• Main bug barriers: skin, mucosa
• If bugs make it through epithelium, they
encounter innate immune system
• What happens in the innate immune system?
• Phagocytes eat bugs, kill them
• Cytokines are released
• Complement is activated
• The adaptive immune system is activated
67. Capturing and displaying antigens
• Dendritic cells in epithelium capture bug antigens,
transport them to lymph nodes
• APCs in lymph nodes eat antigens, display them
(using their MHC receptors) to T cells
• B cells in lymph nodes also recognize antigens
• Antigens and molecules produced during innate
immune response trigger proliferation and
differentiation of B and T cells
71. Cell-mediated immunity
• Naïve T cells are activated by antigen and
costimulators in lymph nodes…
• …then they proliferate and differentiate into
effector cells that go find the antigen.
• CD4+ T cells help macrophages eat bugs
• CD8+ T cells kill infected cells directly
• All these steps are dependent upon cytokines
How does the process work?
72. Cell-mediated immunity
• Polypeptides that do lots of different things:
• help leukocytes grow and differentiate
• activate T cells, B cells and macrophages
• help leukocytes communicate
• recruit neutrophils
• Made by lymphocytes and macrophages
• Examples: TNF, the interleukins, interferon γ
What are cytokines?
73. Cell-mediated immunity
• CD4+ T cells differentiate into two kinds of effector cells:
• TH1 cells (activate macrophages, cause B cells to secrete Ab)
• TH2 cells (activate eosinophils, cause B cells to secrete IgE)
• These guys go to the site of infection, and with the
help of macrophages and cytokines, do their thing.
• CD8+ T cells differentiate into cytotoxic T cells
• These guys kill cells that have microbes in their cytoplasm.
• They are like little assassins.
What kinds of effector T cells are there?
77. • B cells get activated by exposure to antigens
(sometimes with the help of CD4+ T cells)
• B cells differentiate into plasma cells (that make
antibodies)
• The antibodies do nasty things to bugs
How does the process work?
Humoral immunity
78. • Y-shaped glycoprotein
• 2 light chains (κ or λ)
• 2 heavy chains (α, γ, δ, ε, or μ)
• Constant regions of heavy chain form the Fc fragment
• binds to APCs
• defines isotype (immunoglobulin class: IgA, IgE, etc.)
• Variable regions of both chains form the Fab fragments
• binds to antigen
• defines idiotype
What is an antibody again?
Humoral immunity
79.
80.
81. • Bind to – and “neutralize” – bugs, so they can’t
infect cells.
• Coat (“opsonize”) bugs, making them yummy to
macrophages and neutrophils (which have
receptors for the Fc portion of IgG! How
handy!).
• Activate complement.
What do antibodies do?
Humoral immunity
82. What is complement?
Just give me the bottom line.
Humoral immunity
• It’s a bunch of proteins that poke holes in cells.
83. Okay, give me a little more information.
Humoral immunity
• Consists of about 20 plasma proteins (C1, C2, etc.)
• Can be activated in a few different ways
• by antigen-antibody complexes
• by bacterial LPS
• by bugs that have mannan on their surfaces
• Activation proceeds in a cascade fashion
• End results:
• cell lysis
• chemotaxis
• opsonization
87. Immunologic memory
• Most effector lymphocytes die after killing the bug.
• A few memory cells live on for years.
• expanded pool of antigen-specific lymphocytes
• respond faster, better than naïve cells
• vaccines depend on these guys
92. Innate immunity
1. Dendritic cell eats bugs
• Displays antigen to naïve T cells (which MHC?)
• T cells mature (put on costumes, and get
ready to do their jobs)
93. Innate immunity
1. Dendritic cell eats bugs
• Displays antigen to naïve T cells (which MHC?)
• T cells mature (put on costumes, and get
ready to do their jobs)
2. Neutrophil eats bugs; kills with toxic chemicals
94. Innate immunity
1. Dendritic cell eats bugs
• Displays antigen to naïve T cells (which MHC?)
• T cells mature (put on costumes, and get
ready to do their jobs)
2. Neutrophil eats bugs; kills with toxic chemicals
3. NK cell kills bugs
98. Adaptive immunity: Cell-mediated
1. Helper T cell does stuff
• Tells macrophage to eat bugs
• Tells B cell to make antibodies
2. Cytotoxic T cell does stuff
99. Adaptive immunity: Cell-mediated
1. Helper T cell does stuff
• Tells macrophage to eat bugs
• Tells B cell to make antibodies
2. Cytotoxic T cell does stuff
• Finds and kills infected cell (how?)
100. Adaptive immunity: Humoral
1. B cell makes antibodies, which coat bugs
• “Neutralizes” bugs
• Opsonizes bugs (yummy for who?)
