MBB 150 03/23/2021

OVERVIEW OF THE IMMUNE RESPONSE

Why study immunology?

- To understand how our body fights against disease
- To look for solutions / cure / even prevention
- To understand vaccines / disease protection etc  improving or inducing immunity
- For self-preservation
- To restore homeostasis when immune system is perturbed

Pathogen
- Disease-causing organism
- Any organism that can perturb homeostasis in the body

Infection
- State wherein a pathogen enters and is able to multiply inside the body
- One indicator for infection is its focus (where the pathogen multiplies)
- Types of pathogens include:
o Viruses (obligate intracellular)
o Intracellular bacteria, protozoa and parasites (single-celled)
 Toxoplasma is a parasite from cats; is a problem for pregnant women (often
leads to miscarriage; this is why pregnant women can’t eat raw meat) and
immunocompromised
o Extracellular bacteria, parasites, fungi
 Clostridium tetani secretes toxins that targets the nerve cells (lock jaw, stops
breathing)
 Pneumonia
o Parasitic worms (extracellular)
 Ascaris, Schistosoma (burrows through skin, multiplies usually in the liver)

How do infections start?

- Entry of pathogen
o It broke some barriers / entry points
o Usually in this stage, nagpaparami ung pathogen, and we don’t feel anything yet
o But the [innate] immune system is already doing smth to control the replication / to try
and get rid of pathogen
o Minsan di kaya ng early innate immune system. Therefore, the adaptive immune system
is alerted and starts to kick in. They kick in during the inductive phase.
o After inductive phase, the adaptive immune system has learned how to combat the
pathogen correctly, then the effector phase kicks in.
o In effector phase, innate and adaptive immune system work together to control and
combat the pathogen, eventually getting completely eliminated.
o Adaptive immune system takes cover and enters memory phase. It stores cells for future
similar attacks.

(diagram)
Local infection, epithelium penetration (by the local innate immune system)
- May phagocytes (macrophages, dendritic cells) that engulf pathogens
- Ma resident cells din dun na nagrerelease ng proteins to kill pathogen
- Wound healing and inflammation (signaling factors, clotting factors)
o We should let the wound bleed muna to flush out the pathogen, then wash it with soap
and water to kill the pathogen.
o By doing these, we aid the innate immune system to prevent the infection.

Local infection of tissues

- Some proteins are there already pero they have to be processed for them to perform their fxn
(they don’t get processed until you encounter an infection)
o Activation of complement proteins, NK cells, phagocytes migrate to lymph nodes where
they encounter B and T cell, alerting the adaptive immune response (few hours after
local infection of tissues)
o Dendritic cells take up pathogens or antigens, process them, and migrate to lymph
nodes.
o Cytokines and chemokines are produced that promote production and migration of
more immune cells to site of infection
o NK cells will come into the site to kill infected cells (when infection is due to a virus)

Lymphatic spread
- Pag di pa contained dun sa local, initiation na ng adaptive response
o Dendritic cells arrive in lymph nodes
o Antigens are presented to naïve B cells and T cells, activating them
o B cells produce antibodies; helper T cells secrete cytokines for immune cell survival,
prolif, and diff; cytotoxic T cells become licensed to kill viral-infected cells (move from
the lymph nodes to the site of infection)
o This happens a few days after the infection (doesn’t peak until 3-5 days after)

Adaptive responses
- B cells mature into plasma cells
- Antibodies secreted into blood stream
- Cytotoxic T cells
- Cytokines promote appropriate cellular and antibody responses
- Innate immune response still occurs

Each phase does not occur in isolation.

Immunological memory
- Antibodies usually live for 6-8 months then disappear (die).
o They can cause problems if they stay there forever (they aggregate and can trigger
autoimmune response).
- Activated B and T cells enter a low metab state.
- But they live for long periods of time in lymph nodes and other tissues in this inactive state.
 - These cells get reactivated once the same antigen enters the body, resulting in “immunological
memory”  quicker, more intense response, these cells quickly perform their pre-programmed
effector function.
o This is why you only get measles etc. once in your lifetime.
Question: Dengue
- Has four variants
- Antibody-dependent cellular cytotoxicity
o If you get infected with a different variant than before, the antibodies for previous
variant cannot kill it, and then recruits cytotoxic T cells to kill infected cells, which
usually causes hemorrhagic fever.
o This is why the second infection of dengue is the deadliest one.
- Advice is you only administer the dengue vaccine to those na may record na before of dengue
o This became a problem with Dengvaxia vaccine
- The third and fourth infections are not that problematic.
o The body has learned how to control its immune response

Question: Fever
- Fever is part of the systemic innate immune response.

(table of phases of immune response)

Pag nilagnat kayo, and if it lasts for 3 days, magpa-blood test na kayo.
- At this point, dapat nagkick-in na ung adaptive immune response, and pababa na ung pathogen
count. Therefore, pababa na din dapat ung fever mo
- If it lasts for more than 3 days, then smth in your immune response is going wrong. Need na ng
external help (antibiotics)

Relation between stress and immune response

- Fight / flight response has an effect (it heightens) on immune response
o This is why goods pag stressed / iyak iyak ung bata pag nagvvaccine.
- The problem is chronic stress, and this lowers your immune response, making you
immunocompromised.

(summary of phases)