The immune system responds to different microbes through innate and adaptive immunity. Innate immunity uses mechanisms like phagocytosis, inflammation, and complement activation to respond quickly. Adaptive immunity produces antibodies and T cells for long-lasting protection. Extracellular bacteria are targeted by antibodies, phagocytes, and the complement system. Intracellular bacteria are responded to by NK cells, phagocytes, and CD8 T cells that activate macrophages. Viruses induce type I interferons and are targeted by antibodies and cytotoxic T lymphocytes that kill infected cells. Microbes have evolved ways to evade these immune responses like altering antigens, inhibiting antigen presentation, or infecting immune cells.

1. Basic Immunology II
Immunity to infections

2. General Features of Immune Responses to Microbes
1. Defense against microbes is mediated by the effector mechanisms of innate and
adaptive immunity.
2. The immune system responds in specialized and distinct ways to different types
of microbes to most effectively combat these infectious agents.
3. Survival and pathogenicity of microbes in a host are critically influenced by the
ability of the microbes to evade or resist the effector mechanisms of immunity.
4. Many microbes establish latent, or persistent, infections in which the immune
response controls but does not eliminate the microbe and the microbe survives
without propagating the infection.
5. Tissue injury and disease may be caused by the host response.

3. Immunity to Extracellular Bacteria
Extracellular bacteria are capable of replicating outside host cells.
They cause disease by two principal mechanisms:
They induce inflammation, which results in tissue destruction at the
site of infection.
Many of these bacteria produce toxins:
- Endotoxins
- Exotoxins
The immune responses against extracellular bacteria are aimed at
eliminating the bacteria and neutralizing the effects of their toxins.

4. Immunity to Extracellular Bacteria
• ..

5. Innate Immunity to Extracellular Bacteria
Principal mechanisms of innate immunity to extracellular bacteria are complement
activation, phagocytosis and the inflammatory response.
1.Complement activation :
Through PG and LPS by alternative pathway or by mannose binding lectin pathway. Results
in:
• Opsonization and enhanced phagocytosis
• Lysis of susceptible bacteria (e.g. Neisseria) by MAC
2.Activation of phagocytes and inflammation
— By mannose, scavenger receptors
— By Fc and complement receptors for opsonized bacteria
— By Dendritic cells .
— By TLRs during encounter with microbes.
Activated phagocytes secrete cytokines, which induce leukocyte infiltration into sites of
infection (inflammation).

6. Innate Immunity to Extracellular Bacteria

7. Adaptive Immunity To Extracellular Bacteria
Humoral immunity is the principal protective immune response against extracellular bacteria & it
functions-
• To block infection,
• Eliminate the microbes,
• Neutralize toxins.
Adaptive immune responses to EC microbes consists of :
1.Antibody production
The effector mechanisms used by antibodies to combat against polysaccharide-rich encapsulated
bacterial infections include:
Neutralization-mediated by high affinity IgG & IgA isotypes.
Opsonization and phagocytosis-mediated by some subclasses of IgG
Activation of complement by the classical pathway-mediated by IgM and subclasses of IgG.
2.Activation of CD4+ helper T cells
Produce cytokines that stimulate antibody production, induce local inflammation and enhance the
microbicidal activities of macrophages and neutrophils.

8. Adaptive Immune System to Extracellular Bacteria
..

9. What are the adaptive immune responses to extracellular
bacteria?

10. Immune Evasion by Extracellular Bacteria
The virulence of extracellular bacteria has been linked to a
number of mechanisms that resist innate immunity,
including:
Antiphagocytic mechanisms and
Inhibition of complement or inactivation of complement
products.

11. Immunity to intracellular Bacteria
Intracellular bacteria survive and even replicate within phagocytes. These
microbes are able to find a niche where they are inaccessible to circulating
antibodies.

12. Innate Immunity to Intracellular Bacteria
Mainly mediated by phagocytes and natural
killer (NK) cells.
Phagocytes like neutrophils and
macrophages ingest and attempt to destroy
pathogenic microbes.
Intracellular bacteria activate NK cells
by-
• Inducing expression of NK cell-activating
ligands on infected cells.
• Stimulating dendritic cell and
macrophage production of IL-12.
The NK cells produce IFN-γ, which activate
macrophages and promotes killing of the
phagocytosed bacteria. Thus, NK cells
provide an early defense against these
microbes, before the development of
adaptive immunity. (Write in Bengali)

13. Adaptive Immunity to Intracellular Bacteria
• The major protective immune response against
intracellular bacteria is T cell–mediated recruitment and
activation of phagocytes (cell-mediated immunity).
• Phagocytosed bacteria stimulate CD8+ T cell responses
if bacterial antigens are transported from phagosomes
into the cytosol or if the bacteria escape from
phagosomes and enter the cytoplasm of infected cells.
• In the cytosol, the microbes are no longer susceptible to
phagocytosis and for eradication of the infection, the
infected cells have to be killed by CTLs.
• Thus, the effectors of cell-mediated immunity, namely,
CD4+ T cells that activate macrophages and
CTLs(cytotoxic T lymphocytes), function cooperatively
in defense against intracellular bacteria.
• IFN-γ also stimulates the production of antibody
isotypes (e.g., IgG2a in mice) that activate complement
and opsonize bacteria for phagocytosis. This process
aids the effector functions of macrophages.

14. Innate and Adaptive Immunity to Intracellular Bacteria
• .

15. Immune Evasion by Intracellular Bacteria
Several intracellular
pathogens manage to evade the
host immune monitoring and
cause disease by replicating
inside the host cells.
These pathogens have evolved
diverse immune escape
strategies and overcome
immune responses by residing
and multiplying inside host
immune cells, primarily
macrophages.

16. Immune Evasion by Intracellular Bacteria

17. Innate Immunity to Viruses
The innate immune system is essential for the initial detection of invading viruses and
subsequent activation of adaptive immunity.
• The principal mechanisms of innate
immunity against viruses are inhibition of
infection by type I interferons and NK cell–
mediated killing of infected cells.
• Type I IFNs inhibit viral replication in both
infected and uninfected cells by inducing an
"antiviral state".
• NK cells kill other cells infected with a
variety of viruses and are an important
mechanism of immunity against viruses
early in the course of infection, before
adaptive immune responses have developed.

18. Adaptive Immunity to Viruses
Adaptive immunity against viral infections is
mediated by-
1. Antibodies, which block virus binding and
entry into host cells.
2. CTLs, which eliminate the infection by
killing infected cells.
Antibodies are effective against viruses only
during the extracellular stage of the lives of
these microbes. However, antiviral antibodies
bind to viral envelope or capsid antigens and
function mainly as neutralizing antibodies to
prevent virus attachment and entry into host
cells.
Elimination of viruses that reside within cells is
mediated by CTLs, which kill the infected cells.
The principal physiological function of CTLs
is surveillance against viral infection. Most
virus-specific CTLs are CD8+ T cells that
recognize cytosolic, viral peptides presented by
class I MHC molecules.

19. Immune Evasion by Viruses
Viruses have evolved numerous mechanisms for
evading host immunity.
1. Viruses can alter their antigens and are thus
no longer targets of immune responses.
2. Some viruses inhibit class I MHC-associated
presentation of cytosolic protein antigens.
3. Some viruses produce molecules that inhibit
the immune response.
4. Some chronic viral infections are associated
with failure of CTL responses, which allows
viral persistence.
5. Viruses may infect and either kill or
inactivate immunocompetent cells.