Blood and Immune System Notes


Blood Components

  • Blood is spun to separate its components.

  • Plasma: 55% of blood volume, consists of water and dissolved substances.

  • Cellular components:

    • Red blood cells

    • White blood cells

    • Platelets

Cellular Components of Blood

  • Red Blood Cells:

    • Carry oxygen

  • White Blood Cells:

    • Fight infection

    • Types include neutrophils, lymphocytes, and monocytes.

  • Platelets:

    • Bits of membrane-enclosed cytoplasm that aid clotting

Immunology

  • Our immune system is our defense system

  • The immune system has TWO major functions:

    • Differentiates between what is you and what is not you (self versus non-self).

    • Seeks and destroys what is not you.

Useful Definitions

  • Pathology: the study of diseases and how they progress.

  • Pathogen: something that causes a disease, for example bacteria or virus.

  • Immune System: a system of defenses to stop invading pathogens

  • Immunogenic: something which induces an immune response in the body, this can be a humoral (antibody) and/or cell-mediated immune response.

  • Antigen: a molecule which induces an immune response via a lymphocyte. Pathogens have many antigens on their surface.

  • Antibody: a molecular component of the immune system that recognizes and binds (interacts with) antigens.

Overview of the Immune System

  • Innate Immunity (always deployed):

    • First line of defense: External innate defenses

      • Skin

      • Secretions

      • Mucous membranes

    • Second line of defense: Internal innate defenses

      • Phagocytic cells

      • Natural killer cells

      • Defensive proteins

      • Inflammatory response

  • Adaptive Immunity (activated by exposure to specific pathogens):

    • Third line of defense: Internal adaptive defenses

      • Lymphocytes (B cells and T cells)

      • Antibodies

  • The Lymphatic System: involved in internal innate immunity and adaptive immunity

External Innate Defenses

  • How do pathogens enter the body?

External Innate Defenses: Barrier Defenses

  • Easiest method to stop something: put a wall in its path!

  • Barrier defenses include:

    • Skin

    • Mucous and mucous membranes

    • Bodily secretions

  • All pathogens must get around innate barriers to get access to the body.

Internal Innate Defenses: Phagocytosis and Inflammation

  • Vasodilation and increased permeability of blood vessels

  • Blood cells leave blood vessels and enter injury site causing redness, heat and swelling

  • Phagocytosis of pathogen

  • Natural killer cell recognition and killing of virus-infected cells

  • "Cleanup and repair"

Inflammation

  • Tissue injury; release of chemical signals such as histamine

  • Dilation and increased leakiness of local blood vessels; migration of phagocytic cells to the area

  • Phagocytic cells engulf bacteria and cell debris; tissue heals

Phagocytosis

  • Performed by phagocytes, e.g., neutrophils, monocytes/macrophages

  • Engulf and Digest

Inflammation - What Happens First?

  • Tissue cells are damaged by the wound

  • Damaged cells release chemicals – histamine

  • Histamine makes the nearby blood vessels get leaky – fluid enters nearby tissues and causes swelling.

  • Fluid includes factors to assist with healing and clotting

  • Phagocytic cells are activated – recognize and engulf bacteria

Internal Adaptive Defenses

  • B-cells and T-cells

  • Adaptive immune response is generated in the lymphatic system, carried out all over the body.

  • B cells – develop and specialise in the bone marrow -make antibodies

  • T cells – develop in bone marrow and mature in the thymus

  • Both require activation to be functional –how are they activated?

Specificity

  • Activated by exposure to specific pathogens

  • Specific shapes of receptors detect specific pathogens

  • Born with a massive repertoire of B and T lymphocytes.

  • Each lymphocyte represents a different antigen

  • Specificity randomly produced by rearrangement of the genes coding for the B cell and T cell antigen receptors

Antigens and Antigen Receptors

  • Antigens have two important characteristics:

    1. Immunogenicity - the ability to provoke an immune response by stimulating the production of antibodies or T-cells

    2. Reactivity - the ability of the antigen to react specifically with the antibodies or cells it provoked.

  • Most antigens have several epitopes that are recognized by antibodies or T-cells

  • Antigen recognition activates lymphocytes to undergo “clonal expansion” that mediate adaptive immunity

Remembering Invaders

  • Memory B cells (and T cells) can live for decades in lymph nodes

  • Are activated if the body is exposed a second time to the same pathogen

  • This secondary response is much faster, stronger and lasts longer than the first

  • Provides the basis for infection induced immunity and vaccination

Adaptive Immune Response

  • What if the immediate response didn’t deal to all of the bacteria?

  • Even if the phagocytes did get them all….

  • Bacteria grow very fast, 20min doubling.

  • Spreads the bacterial infection

  • T cells recognize the antigen and then "help" B-cells.

  • B-cells will clone themselves and make antibodies as well as saving a copy of themselves for future infections (memory B cells).

  • And even if phagocytes did ingest some bacteria…

Using Antibodies to Understand the SARS-COV-2 Pandemic

  • Antibodies against SARS-CoV-2 are induced promptly after infection

  • Antibodies are important markers of previous infection and immunity

  • Nucleocapsid and Spike/RBD are the immunodominant antigens and most commonly used in serology

Application of Antibody Assays

  • Detecting historical infections

  • Estimating prevalence

  • Understanding persistence and protection

  • ELISA method

  • The RBD of the Spike protein binds to the ACE2 receptor to infect human cells

  • Neutralizing antibodies (Nabs) bind to the RBD and block the interaction. The virus cannot enter human cells

Serology

  • “We’re using serology where there’s a question about whether the infection is acute or [if] it is a historical infection,” - Director-General of Health Dr Ashley Bloomfield

Serology for an Individual vs a Population

  • An antibody test in an individual provides data on a single persons infection or vaccine history

  • A serosurvey is the collection and testing of blood from a defined population to estimate the prevalence of antibodies against an infectious pathogen as an indicator of exposure.

Seroprevalence in Dec 2020

  • NZBS collected 10,156 samples

  • 350 repeated samples

  • 9,806 samples run on screen

  • 18 seropositive samples

  • 6 PCR positive, 4 extensive overseas travel, 8 previously undiagnosed

  • A crude seroprevalence (n=8) is 0.082%

  • Applying statistics (correct for testing parameters), true prevalence is 0.103%

  • In range with Australian studies at a similar time (0.15-0.79%) and MUCH lower than settings where COVID-19 was not well controlled (>10%)

Understanding Persistence and Protection

  • Neutralising antibodies persist for up to 8 months post infection (December 2020)

  • Whitcombe et al., Clinical and Translational Immunology, 2021

Variants and Vaccinations

  • Vaccinations were effective against Delta

  • Needed a 3rd dose to protect against omicron

Hybrid Immunity

  • Eligible Booster if >30 years old or immune compromised and not had covid for 6+ months

Post-Pandemic Surges in Respiratory Infections

  • Discussion of various articles and reports on the post-pandemic surges in respiratory illnesses, attributing it to an "immunity gap."

Immunity Dynamics Study

  • Distinct epidemiological effects of the elimination strategy.

  • An extended 2-year period of low pathogen exposure led to:

    • Screened 330 eligible donors who regularly donated in Auckland over the timeframe (Mar2020-Mar2023)

    • 150 selected based on Auckland demographics (2018 census)

Study Results

  • Significant reduction in all antibodies (except SpeA and HKU1) between 2020-2023.

  • Percent reduction ranged from 10-16%.

  • SARS-CoV-2 exponential increase over the same time.

  • Suggests reduced pathogen circulation impacted immunity.

  • Reduced immunity likely contributed to post-pandemic infection surges.

  • Informs how these unintended consequences can be better managed in future pandemic responses

Lecture Summary

  • Innate immunity: defenses against general characteristics of invaders, first line of defense, response is general, but rapid Innate defenses include the skin, mucous and mucous membranes Innate processes include phagocytosis and inflammation

  • Adaptive immunity: defenses against specific antigens, has memory of prior antigen encounters, response is highly specific/ effective but slower; Antibodies: part of the adaptive immune response, highly specific molecules, can be measured to understand infection and vaccination