Download B Cells respond to antigens by differentiating into plasma cell

Immune Response to Infection
Infectious Agents
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Viruses
Bacteria
Parasites
Protozoa
Primary response:
• Natural Killer Cells:
– Non-antigen specific.
– These cells attack any foreign microbe in the
body and attempt to kill it.
• Macrophages:
– Respond to all invading microbes, ingest and kill.
– Presents antigens from the microbe cell wall on
the external cell wall of the microphage to
activate T cells.
Secondary response:
• B Cells respond to antigens by differentiating
into plasma cell.
• Plasma Cells:
– Secrete one specific antibody for a particular
antigen based on the cell line from the B cell.
• Helper T Cells:
– Secrete interleukin hormone to stimulate clonal
growth of activated T and B cells.
Tertiary response:
• Cytotoxic T Cells:
– Bind to body cells infected by the microbes and
secrete toxic substances killing cell and invader.
• Antibodies:
– Complex with antigen which aggregates microbes
together to deactivate the organisms.
Viral Infections
Overall Response to Viral Infections
Innate Immune Response
T cell activation
DCs can be directly infected by virus.
If DCs are not infected by virus, DCs can still internalize viral antigens from the suroundings
through phagocytosis, endocytosis and macropinocytosis.
The antigens can be presented in the context of both class II and class I MHC through cross-prim
Lysis of infected
cells
DCs are activated by recognition of
Viral PAMPs through TLRs.
DC
virus
Secondary lymphoid tissues
Ag-MHC I
CD8 T cell
CTL
Ag-MHC II
CD4 T cell
TH1
infection
Viral antigen Endocytosis
Pinocytosis
phagocytosis
IL12
IFN-
TH1 failitates CD8 T cell
activation by producing IL2
and activation of DCs
through CD40L-CD40
B cell activation
DC
Viral antigen
TH cells
B cell
Natural
antibody
Seoncdary lymphoid tissues
Antigen-antibody
complex
B1 cells
B cell activation
FDC
antibodies
Antibody Interaction with Viruses
• Neutralize
• Advantage antibodies to be at site of entry –
mucosal surface
• Secretory IgA in mucous secretions plays an
important role in host defense against viruses
by blocking viral attachment to mucosal
epithelial cells
Viral Response to Host Immune
Response
• HCV (Hepatitis C Virus) Evades Anti-viral Effect Of
IFNs By Inhibiting Action Of PKR
• HSV (Herpes Simplex Virus) Decreases Expression
Of MHC I, Avoids CTL Elimination
• CMV (Cytomegalovirus) Also Decreases
Expression Of MHC I
• HIV (Human Immunodeficiency virus) Decreases
MCH II Expression, No TH1 Support for CTL
• Influenza Virus, Keeps Changing Antigens
– Antigenic Drift
– Antigenic Shift
Bacterial Infections
Bacterial Infections
• Bacterial Infections Are Eliminated By Humoral Immunity
– Exception: intracellular bacteria Ex. TB
– DTH Is Important In Elimination Of Intracellular Bacteria
– Antibodies Eliminate Bacteria Or Bacterial Toxins
• Opsonization Of Bacteria
• Neutralization Of Toxins
– Exotoxins (Ex. Diptheria)
– Endotoxins (Ex. LPS)
• Lysis Of Bacteria Thru Complement Pathway
• Complement Activation Thru Mast Cell Activation Results In Localized
Inflammation
– Vasodilation and Extravasation (Neutrophil Accumulation)
• Bacteria Enter Host Thru
– Respiratory Tract, GI Tract, Genitourinary Tract, Skin
Bacteria Evade Host Defense Mechanisms
• Bacterial Infection Involves 4 Steps
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Attachment
Proliferation
Invasion Of Host Tissue
Toxin Induced Damage To Host Cells
• Attachment
– Some Bacteria Have Pili
– Some Bacteria Secrete Adhesion Molecules (Bordetella Pertussis)
– Immune System Response To Attachment Is IgA
• Prevents Attachment
• Some Bacterial Evade IgA Thru Proteases That Decrease ½ Life Of IgA
– Ex. Heamophilus Influenzae
• Some Bacteria Avoid Phagocytosis By Surrounding Themselves In A
Polysaccharide Capsule. Ex. Streptococcus Pneumoniae
Immune Response Against Pathogen Can Cause
Pathogenesis
• Overzealous Immune System Can Be Pathogenic
– Bacterial Septic Shock
• Predominant Cytokines Involved: IL-1 and TNF-
• Source: M
– Intracellular Bacteria Cause Granulomas
• Extensive Tissue Damage
• Ex. Tuberculosis
• Tuberculosis (Mycobacterium Tuberculosis)
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3 Million Fatalities Every Year Globally
M Ingest M.T But Cannot Digest It
Eventually Burst Releasing Bacilli
M And TH1 Cells Form Granulomatous Lesion,
Containment+Destruction Of Healthy Tissue
– INF- and IL-12 Are Crucial In Eliminating Pathogen
Immune Response to MTb
• CD4+ T cells are activated within 2–6 weeks after infection.
• Infiltration of large numbers of activated macrophages.
• Wall off the organism inside a granulomatous lesion called a
tubercle .
• A tubercle consists of a few small lymphocytes and a compact
collection of activated macrophages, which sometimes differentiate
into epithelioid cells or multinucleated giant cells.
• The massive activation of macrophages that occurs within tubercles
often results in the concentrated release of lytic enzymes. These
enzymes destroy nearby healthy cells, resulting in circular regions
of necrotic tissue, which eventually form a lesion with a caseous
(cheeselike) consistency
• As these caseous lesions heal, they become calcified and are readily
visible on x-rays, where they are called Ghon complexes.
Protozoan Diseases
• Protozoans are unicellular eukaryotic organisms:– Amoebiasis, Chagas’ disease, African sleeping sickness, malaria,
leishmaniasis, and toxoplasmosis.
• The type of immune response that develops to protozoan
infection and the effectiveness of the response depend in
part on the location of the parasite within the host.
• Many protozoans have life-cycle stages in which they are
free within the bloodstream - humoral antibody is most
effective.
• Many of these same pathogens are also capable of
intracellular growth- cell-mediated immune reactions are
effective in host defense.
Diseases Caused by Parasitic
Worms (Helminths)
• Unlike protozoans, which are unicellular and
often grow within human cells, helminths are
large,multicellular organisms that reside in
humans but do not ordinarily multiply there and
are not intracellular pathogens.
• Although helminths are more accessible to the
immune system than protozoans, most infected
individuals carry few of these parasites for this
reason, the immune system is not strongly
engaged and the level of immunity generated to
helminths is often very poor.
Schistosomiasis Mansoni
• More than 300 million people are infected with
Schistosoma, a trematode worm that causes a chronic
debilitating infection.
• Infection occurs through contact with free-swimming
infectious larvae, called cercariae.
• When cercariae contact human skin, they secrete digestive
enzymes that help them to bore into the skin,where they
shed their tails and are transformed into schistosomules.
• The schistosomules enter the capillaries and migrate to the
lungs, then to the liver, and finally to the primary site of
infection, which varies with the species. S. mansoni and S.
japonicum infect the intestinal mesenteric veins.
Immune Response against Viruses
Immune Response against Bacteria
Immune Response against
Parasites/Worms