Immunology Flashcards

1
Q

Two parts of Immune System

A
  • Innate Immune System
    • Initial response to a pathogen
    • Includes:
      • Barriers to infection
      • Phagocytes
      • Mediated by non-antigen specific mechanisms
      • Rapid
  • Adaptive Immune System
    • Induced specific response to a pathogen
    • Includes:
      • B and T cells
      • Antibody- and cell- mediated
      • Response is antigen specific
      • Life-long immunity
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2
Q

Barriers to Infections

A
  • Physical barriers
    • Epithelium tight junctions
    • Skin. Waterproof and sealed off.
    • Mucous membranes (mucus limits access to tissue, distributes antiviral/antibacterial proteins)
    • ciliated epithelium (helps move inhaled particulates back out of the body)
    • GI system movement (peristalsis)
    • Urine flow
  • Chemical barriers
    • Sweat (provides an acidic pH helps ward off some bacteria)
    • Sweat, saliva, and vaginal secretions all have antimicrobial peptides (defensins) and enzymes that can kill microbes
    • Surfactant is produced in lungs and is a lipoprotein that binds to pathogens, opsonizing them, so that they are easier to be phagocytized by immune cells
    • Gastric juices provide for such low pH that most bacteria/virus/parasites cannot survive
    • Bile - quite basic and also act as detergents that can disrupt membranes of many bacteria
    • Vaginal secretions - low pH
  • Microflora
    • Commensal bacteria and fungi in body (especially skin and gut) help fight off pathogens.
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3
Q

Summary of 1st line defenses

A
  • Physically stop pathogen from reaching target sites (Physical Barrier)
  • Anti-microbial activity of bodily secretions (Chemical Barrier)
  • Microbiome - microflora preventing pathogens from growing and accessing desired niches (Microbial Barrier)
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4
Q

What happens when a pathogen gets through 1st line of defenses?

(Innate Immune System)

A
  • Macrophages (Phagocytes)
    • They not only phagocytize but also can present antigens to immune system. They can also release cytokines and chemokines, which trigger an immune response (e.g., vasodilation and increased vascular permeability to allow more immune cells to enter)
  • Leukocytes - white blood cells are also called in
    • Lymphocytes, monocytes (macrophage precursors), neutrophils, eosinophils, basophils
  • Neutrophils - kill bacteria by phagocytosis/degranulation/NETosis
    • Reside in blood
    • Recruited to site of infection by cytokine/chemokines
    • Kill bacteria mainly by 3 mechanims:
      1. Phagocytosis of bacteria
      2. Degranulation - Release anti-microbial compound
      3. Release of NETs (neutrophilic extracellular traps = DNA). NETs are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind pathogens. Vital and suicidal NETosis (either neutrophil survives or dies in the process)
  • Dendritic cells
    • Reside within tissue
    • Professional antigen presenting cells
    • Link b/w innate and adaptive immune system
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5
Q

Adaptive Immune Response

A
  • Creates millions of different B and T cells for specific antibody-mediated (humoral) and cell-mediated immunity
  • Antibody-Mediated Immunity (AMI)
    • Involved B lymphocytes, plasma cells and antibodies
    • Humoral immunity
      • Name derives from antibodies found in body fluids (humors - old medical term)
  • Cell-Mediated Immunity (CMI)
    • Involves:
      • T lymphocytes
      • Antigen-presenting cells (APCs): present antigen
      • MHC (major histocompatibility complex) molecules
    • Also referred to as cellular immunity
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6
Q

Antibody-mediated (humoral) immunity

A
  • Directed against extracellular microorganisms (i.e., in blood or tissue)
  • B-lymphocytes (B cells)
    • Differentiate into plasma cells which produce antibodies
    • Function as antigen-presenting cells (APCs)
    • B cells originate from stem cells in bone marrow (B cells - Bone marrow)
    • They also mature in bone marrow and then migrate to secondary lymphoid tissue (e.g., lymph nodes, spleen)
    • Exposed to antigens in secondary lymphoid tissue
    • Following exposure to antigen, they differentiate into plasma cells (short-lived) and memory cells (long-lived)
    • Plasma cells produce antibodies
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7
Q

Antibody Structure

&

2 classes of antibodies we care about

A
  • Basic antibody structure has 4 polypeptide chains
    • 2 identical light chains
    • 2 identical heavy chains
  • Regions of heavy and light chains
    • Variable region
    • Constant region
  • 5 different classes – we will focus on only two: IgM and IgG
    • Different classes differ in the constant region of the antibody
    • IgM
      • 1st immune response
      • activate complement proteins
    • IgG
      • 2nd response, major antibody circulating in plasma
      • promote phagocytosis by macrophages
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8
Q

Structures of Different Class of Antibodies

A
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9
Q

Primary Antibody Response

A
  • Primary Response
    • Following exposure to a new antigen, there is a slow rise in IgM followed by a slow rise in IgG
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10
Q

Secondary Antibody Response

A
  • Secondary Response
    • Following exposure to previously encountered antigen, there is a rapid rise in IgG and slow or no rise in IgM
      • Memory response
  • So the presence of IgM antibodies with or without IgG antibodies indirectly indications a new infection, whereas IgG antibodies without IgM indication a past infection.
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11
Q

Function of Antibodies

A
  • Neutralize extracellular toxins or viruses (Neutralization). Cannot find/infect its host cell
  • Coating of extracellular bacteria allowing for rapid detection (called ‘opsonization’) by phagocytes and phagocytosis
    • Opsonize = making visible
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12
Q

Other ways humans use Antibodies

A
  • Measure concentration of antigen specific antibody in a patient to determine if have had an immune response to it
  • Isolate plasma cell and fuse with myeloma cell to make hybridoma (hybrid b/w a plasma and a malignant myeloma cell)
    • Make an endless supply of monoclonal antibody for therapy
    • Use antibodies in diagnostic testing
      • Rapid tests
      • ELISAs/EIA
      • Western Blots
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13
Q

The Lympathic System

A
  • Lymph
    • Fluid and cells in lymphatic vessels
  • Lymphatic vessels
    • Collect and return interstitial fluid to blood
    • Transport immune cells throughout body
  • Lymph nodes
    • Kidney shaped organs at intervals along lymphatic vessels
    • Collect lymph
  • Lymph can only flow in one direction
  • Not a circulatory system meaning the components of the lymph are derived from blood.
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14
Q

Lymphocytes and Lymphoid Tissues

A
  • Lymphocytes refers to a type of immune cell involved in adaptive immunity, either B cell or T cell
    • Lymphocytes circulate between blood, lymph, and secondary lymph nodes
    • Pathogens from infected tissue sites are picked up by lymphatic vessels and arrive at closes lymph node (draining lymph node)
    • Architecture and size of nodes change in response to activation of lymphocytes
  • Lymphoid tissues and organs
    • Primary lymph organs
      • Important for the development and maturation of lymphocytes
      • Bone marrow (B cells) and thymus gland (T cells)
    • Secondary lymph organs
      • Where mature lymphocytes meet pathogens
      • e.g., lymph nodes, spleen
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15
Q

T lymphocytes and cell-mediated immunity

A
  • T lymphocytes originate from stem cells in bone marrow
  • Maturation takes place in thymus gland followed by migration to secondary lymphoid tissue
  • Respond to antigens on the surface of cells
  • Also known as T cells
  • Functional types of T cells
    • Helper (CD4 T cells)
      • Th1 and Th2
    • Cytotoxic (CD8 T cells)
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16
Q

CD4 T Cells

A
  • Helper T cells help activate B cells that release antibodies and macrophages, both of which destroy extracellular pathogens. In addition, helper T cells help activate cytotoxic T cells that kill cells infected with viruses and other intracellular microorganisms. Therefore, helper T cells are very important to almost all adaptive immune responses, including responses against both extracellular and intracellular pathogens.
17
Q

CD8 T Cells

A
  • Cytotoxic T cell recognizes complex of viral peptide with MHC class 1 and kills infected cell
18
Q

Antigen Presentation

A
  • Antigen presenting cells (APCs)
    • Present antigens to T cells
    • Ingest and process antigens then display fragments (short peptides) on their surface in association with molecules of major histocompatibility complex (MHC)
    • Ex: B cells, dendritic cells, macrophages
  • Major histocompatibility (MHC) molecules
    • MHC class I molecules
      • Expressed on surface of (almost) every cell
      • Present antigens to CD8 T cells
    • MHC class II molecules
      • Expressed on surface of APCs
      • Present antigens to CD4 T cells
19
Q

Clonal Selection

A
  • Circulating T cells have different specificities based on the T-cell receptor (TCR) expressed on their surface
  • Clonal selection refers to the process by which the immune system selects the correct T cell clone which expresses the TCR able to recognize the peptide being presented.
20
Q

Clonal Expansion

A
  • T cells with the correct TCR will bind to antigen being presented and differentiate into:
    • Effector T cells (short-lived)
    • Memory T cells (long-lived)
  • Eventually, all the short-lived T cells die, but the long-lived memory T cells persist to confer long-lasting immunity
21
Q

Roles of Effector T Cells in Immune Response

A
  • CD8 cytotoxic T cells
    • Enter bloodstream and travel to infection site
    • Kill cells infected with viruses and other intracellular microorganisms
  • CD4 Th1 helper T cells
    • Enter blood stream and travel to infection site
    • Help activate macrophages
  • CD4 Th2 helper T cells
    • Work within secondary lymphoid tissues
    • Help activate B cells
22
Q

Vaccines - Overview

A
  • Aim:
    • To produce the same immune protection which usually follows natural infection but without causing disease
    • To generate long-lasting immunity
  • This immunologic memory allows:
    • Rapid recognition and response to infection
    • Prevents or modifies effects of disease
23
Q

Types of Vaccines

A
  • Active Component
    • Live attenuated vaccines
    • Inactivated vaccines
    • Inactivated toxins / Toxoids
    • Subunit / Recombinant vaccines
    • Viral vector vaccines: A viral vector serves as a vehicle to introduce a part of the pathogen into the host
    • mRNA vaccines: mRNA encoding for part of the pathogen is introduced into the host
24
Q

Live Attenuated Vaccines

A
  • Pathogens weakened under laboratory conditions
  • Produces long-lasting immune response after 1-2 doses
  • Can cause mild form of the diseases
  • Cannot be given to immuno-compromised individuals
  • Ex:
    • Viral
      • MMR (Measles / Mumps / Rubella) vaccine
      • Chickenpox vaccine
      • Polio vaccine
    • Bacterial
      • BCG vaccine
25
Q

Inactivated Vaccines

A
  • Pathogen is inactivated by chemical process or heat
  • Can not cause the disease they are designed to protect against
  • Multiple doses usually required
  • Ex:
    • Viral
      • Influenza vaccine
      • Polio vaccine
    • Bacterial
      • Cholera vaccine
26
Q

Inactivated Toxins/Toxoid Vaccines

A
  • Toxin is inactivated by chemical process or heat
  • Cannot cause the disease they are designed to protect against
  • Multiple doses usually required
  • Ex: Tetanus
27
Q

Subunit / Recombinant Vaccines

A
  • Uses a part of the pathogen
  • Cannot cause the disease they are designed to protect against
  • Multiple doses usually required
  • Ex: Hep B vaccine
28
Q

Viral Vector Vaccines

A
  • A viral vector serves as a vehicle to introduce a part of the DNA into the host (could be same genetic information as with an mRNA vaccine)
  • Can not cause the disease they are designed to protect against
  • Pre-existing immunity against viral vector can be problem
29
Q

mRNA Vaccines

A
  • mRNA encoding for part of the pathogen is introduced into the host, host produces antigen!
  • Once a new pathogen is identified, quick turn-around from sequence identification to vaccine generation•
  • New technology - manufacturing process is complicated (needs to be very clean to avoid side effects)
  • Some require storage at low temps