Download Immune Response 101

Bio260 – North Seattle College
Immune Response
Colleen Sheridan
Got an extracellular microbe? - How to activate the humoral immune response.
The humoral immune response ends up activating B cells to make tons of antibodies that are very specific for a
certain microbe. This microbe will have had a part of its replication cycle outside of cells (extracellularly;
exogenously) and so could be extracellular bacteria or free viruses or other parasites. The antibodies have
numerous protective effects and play a significant role in inhibiting microbial growth and pathogenesis.
Here are the steps that need to happen in order for the immune response to make these very specific antibodies
against our microbe:
1. Microbe activates dendritic cell  2. Dendritic cell activates microbe-specific T helper cells  3. T helper
cell activates microbe-specific B cells  4. B cell makes lots of microbe-specific antibodies.
1. Microbe activates dendritic cell
a. Extracellular microbe invades.
b. Activation of innate immunity may include: complement, phagocytes, inflammation
c. Dendritic cell takes up microbe through phagocytosis, chews it up in the phagolysosome, and
displays some of the microbial protein antigens on MHC class II on the dendritic cell membrane.
d. PRRs (TLRs) on dendritic cell recognize microbial structure as DANGER! and signals
production of costimulatory molecules on its cell membrane.
e. Now dendritic cell membrane has microbial antigens displayed on MHC class II and
costimulatory molecule that says, “DANGER is here!” Time to go activate a T helper cell.
2. Dendritic cell activates microbe-specific T helper cells
a. Dendritic cell migrates to a draining lymph node where it can interact with T cells.
b. A specific TCR on a CD4 T cell recognizes a specific microbial antigen/MHC class II complex
on the dendritic cell. This is signal 1.
c. The CD4 T cell recognizes the costimulatory molecule that says, “DANGER is here!” This is
signal 2.
d. The CD4 T cell, having received both signal 1 and signal 2 from the dendritic cell, proliferates
and they become memory and effector CD4 T helper cells, able to secrete cytokines.
3. T helper cell activates microbe-specific B cells
a. Also in the lymph node, a specific BCR (basically, a membrane-bound antibody) on a B cell
recognizes a specific microbial antigen from our microbe. This is signal 1.
b. The B cell engulfs the antigen by endocytosis, chews it up, and, like our phagocytes, displays
some of the microbial protein antigens on MHC class II on the B cell membrane.
c. A microbe-specific effector CD4 T helper cell recognizes a specific microbial antigen/MHC
class II complex on the B cell and sends a cytokine signal to the B cell. This is signal 2.
d. The microbe-specific B cell, having received both signal 1 and signal 2, proliferates and they
become memory B cells and plasma cells, now able to secrete antibodies.
4. B cell makes lots of microbe-specific antibodies
a. The plasma cells are antibody-making machines, and start secreting tons of microbe-specific
antibody.
b. IgG antibodies are found in blood and tissue fluids. IgA antibodies are found in mucus on
mucous membranes. Other antibody types are also found in blood and tissue fluids.
c. The primary response takes about 10-14 days to make “a substantial amount” of antibody to be
effective. The secondary response is quicker because there are many T helper and B memory
cells around to make more specific antibody faster.
d. Antibodies 1) opsonize targets and make them tasty, 2) activate complement, 3) immobilize and
prevent bacteria from adhering, 4) cross-link bacteria making them easier to eat by phagocytes,
5) help NK cells kill infected cells (ADCC), and 6) neutralize viruses and toxins.
Got an intracellular microbe? - How to activate the cell-mediated immune response.
The cell-mediated immune response ends up activating microbe-specific CD8 cytotoxic T cells that go on to kill
microbe-infected cells. This microbe will have had a part of its replication cycle inside of cells (intracellularly;
endogenously) and so could be intracellular bacteria or viruses or other parasites. Killing infected cells disrupts
the ability of the microbe to replicate itself.
Here are the steps that need to happen in order for the immune response to make these very specific CD8
cytotoxic T cells against our microbe:
1. Microbe activates dendritic cell  2. Dendritic cell activates microbe-specific T helper cells through MHC
class II  3. T helper cell and dendritic cell activate microbe-specific T cytotoxic cells through MHC class I 
4. T cytotoxic cell kills microbe-infected cells.
1. Microbe activates dendritic cell
a. Intracellular microbe invades.
b. Activation of innate immunity may include: interferon response, inflammation, phagocytes (to
eat up dead cells)
c. Dendritic cell takes up microbe through phagocytosis, chews it up in the phagolysosome, and
displays some of the microbial protein antigens on MHC class II on the dendritic cell membrane.
d. Dendritic cell also has special mechanism that no other cell has! It can take antigen from
extracellular source and display them on MHC class I as well.
e. PRRs (TLRs, NLRs or RLRs) on dendritic cell recognize microbial structure as DANGER! and
signals production of costimulatory molecules on its cell membrane.
f. Now dendritic cell membrane has microbial antigens displayed on MHC class II, MHC class I,
and costimulatory molecule that says, “DANGER is here!” Time to go activate T cells.
2. Dendritic cell activates microbe-specific T helper cells through MHC class II
a. Dendritic cell migrates to a draining lymph node where it can interact with T cells.
b. A specific TCR on a CD4 T cell recognizes a specific microbial antigen/MHC class II complex
on the dendritic cell. This is signal 1.
c. The CD4 T cell recognizes the costimulatory molecule that says, “DANGER is here!” This is
signal 2.
d. The CD4 T cell, having received both signal 1 and signal 2 from the dendritic cell, proliferates
and they become memory and effector CD4 T helper cells, able to secrete cytokines.
3. T helper cell and dendritic cell activate microbe-specific T cytotoxic cells through MHC class I
a. Also in the lymph node, a specific TCR on a CD8 T cell recognizes a specific microbial
antigen/MHC class I complex on the dendritic cell. This is signal 1.
b. A microbe-specific effector CD4 T helper cell being activated by the same dendritic cell sends a
cytokine signal to that CD8 T cytotoxic cell. This is signal 2.
c. The microbe-specific CD8 T cytotoxic cell, having received both signal 1 and signal 2,
proliferates and they become memory and effector T cytotoxic cells, now able to kill-infected
cells.
4. T cytotoxic cell kills microbe-infected cells
a. The effector T cytotoxic cells travel to the site of infection and recognize infected cells by the
antigen/MHC class I complex that they are specific for.
b. This triggers the release of intracellular vesicles from the effector T cytotoxic cell that contain
cell-killing proteins and enzymes, resulting in the death of the infected cell.