Biology 1202B Study Guide - Final Guide: Endometrium, Myelin, Gastrulation

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13 Apr 2012
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Lecture 24: Immunology (Chapter 44)
Disease has plagued all organisms for billions of years
The word ‘vaccination’ comes from ‘vacca’ (cow), used cowpox to defend against smallpox
What causes disease?
o Pathogens
o Viruses
o Bacteria
o Fungi
o Protozoa
o Parasites
o Protein
The immune system: made up of innate and adaptive immunity
3 lines of defence against invasion
o Physical barrier: prevent entry of pathogen
Mucus membranes have environments that are hostile to pathogens (stomach,
reproductive tract, epithelium tissues)
o Innate immune system (2nd line of defence): generalized internal chemical, physical and
cellular reactions against pathogens that have survived the physical barrier
o Adaptive (or acquired) immune system: most complex line of defence, reaction is
specific to a foreign substance
Most organisms recognize unique pathogen-associated molecular patterns (PAMPs) found on
microbial organisms, using host molecules called pattern recognition receptors (PRRs) once
specific PRRs are activated by PAMP, various components of innate or acquired immune
responses are activated
Innate Immunity
Innate immunity: immediate, nonspecific response targets invading pathogens and has no
memory of prior exposure to that specific pathogen invertebrates only have innate
o Inflammation: creates an internal condition that inhibits or kills many pathogens
o Specialized cells: engulf or kill pathogens or infected body cells (macrophages,
neutrophils, complement proteins)
Bacterial induction of inflammation:
o A break in the skin introduces bacteria, which reproduces
o Activated macrophages engulf the pathogens and secrete cytokines and chemokines
o Activated mast cells release histamine which dilate local blood vessels and increase their
permeability. Cytokines also make the blood vessel wall sticky, causing neutrophils to
attach
o Chemokines (from the macrophage) attract neutrophils, which pass between cells of the
blood vessel wall and migrate to the infection site
o Neutrophils engulf the pathogens and destroy them
Signs of inflammation: heat, redness, swelling (due to dilation of blood vessels), pus (dead
neutrophils), pain (migration of macrophages and neutrophils)
In addition to inflammation, there is another nonspecific defence mechanism, the complement
system interacting soluble plasma proteins that circulate in the blood and are normally
inactive. They are activated when they recognize molecules on the surface of pathogens
o They create a pore, and the bacteria can’t maintain osmotic balance, so the cell swells
and lyses
The innate immunity system is often unable to distinguish between viral pathogen and host
cells, so some go undetected. Strategies to identify viruses:
o RNA Interference (RNAi): interferes with the cell’s ability to transcribe and translate
genes, triggered by dsRNA
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Most viruses have dsRNA, so RNAi inhibits it, eliminating impact of the virus
o Interferon: viral dsRNA may cause the infected host cell to produce two cytokines (alpha
interferon and beta interferon) interferon binds to cell surface receptors, triggering
changes to gene expression pattern in the cell
They can affect ribonucleases, which degrade cellular RNA, thus protein
synthesis, so replication of the viral genome will stop
o Apoptosis: programmed cell death, pathogens may trigger abnormal cell activity that
activates apoptotic responses
o Natural killer (NK) cells: a type of lymphocyte, circulate in the blood and kill target host
cells activated by recognition of cell surface receptors or by interferons secreted by
virus infected cells
NK cells are not phagocytes
They secrete granules containing perforin, which creates pores in the cell’s
membrane, so cell swells and ruptures, and proteases, which degrade proteins,
and activate enzymes that degrade DNA and trigger apoptosis
Lecture 25: Immunology (Chapter 44)
Hematopoietic stem cells: form all the blood cells
Bone marrow is a source of stem cells
Adaptive Immunity
Specifically recognize foreign molecules and clears them from the body since the reaction is
specific, it may take several days to become effective
Antigen: any foreign substance that can elicit an adaptive immune response (generates
antibodies) most are macromolecules
Antigens are recognized by two types of lymphocytes
o B lymphocytes (B cells): differentiate from stem cells in the bone marrow. Released into
the blood and carried to capillary beds in the lymphatic systems
o T lymphocytes (T cells): produced by the division of stem cells in the bone marrow.
Released into the blood and carried to the thymus, where they differentiate
We know that lymphocytes recognize antigens because leukocytes (WBCs) in mice were killed
by irradiation, and mice couldn’t develop an adaptive immune response. Injecting lymphocytes
from normal mice into these irradiated mice restored the adaptive immune response
Two types of adaptive immune responses:
o Antibody mediated immunity (AMI, humoral immunity)
o Cell-mediated immunity (CMI)
Antibody-mediated immunity (AMI, humoral): a protein produced by the body in adaptive
immunity to destroy the antigen
o Lymphocyte recognizes and binds to antigen, activated lymphocyte clears antigen from
the body
o Activated lymphocytes differentiate into memory cells that circulate in the blood, ready
to initiate a rapid immune response (immunological memory)
o Each B and T cell have receptors (BCRs and TCRs), which bind to a portion of the antigen
called the epitope
BCRs: 2 identical light chains, 2 identical heavy chains
TCRs: alpha and beta chain chains are held together by disulphide bonds and
form a ‘Y’ shape
o 2 general phases:
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T Cell activation: dendritic cell engulfs and degrades a pathogen, becoming an
antigen presenting cell (APC) APC secretes interleukins which activate
secretion of cytokines, clonal cells differentiate into helper T cells
B cell activation and antibody production: B cell displays the antigen on the cell
surface, TCR on a helper T cell binds to the antigen interleukins from the T
cells stimulate the B cell to produce a clone of cells, clonal cells differentiate into
plasma cells, memory B cells
BCR and TCR antibody diversity: These proteins are encoded by different genes, diversity,
portions of the DNA segments are randomly chosen and joined together, ‘genetic
rearrangement’
o Each antibody type has the same AA sequence in the constant region of the heavy
chain/ light chain, but the variable regions differ in the heavy and light chains
o The variable regions of the chains from the specific antigen binding site
In humans, there are 5 classes of antibodies (classes are determined by the constant regions)
o
Lecture 26: Applications of Immunology (Chapter 44)
Allergies: allergens are antigens that elicit hypersensitivity or allergic reaction
o Allergens induce a B cell to secrete an overabundance of IgE antibodies, which bind to
receptors on mast cells (which produces histamine)
o Histamine produces a severe inflammation, usually in tissue directly exposed to the
allergen
Asthma: sever response to allergens causes constriction of airways, inflammation, build-up of
mucus treat with anti-histamines which block histamine receptors
Autoimmune reactions: occurs with a faulty immune system, ‘self’ cells are recognized as ‘non-
self’ and so are destroyed
o Type I diabetes: eliminate insulin producing pancreatic beta cells, so person can’t make
insulin
o Multiple sclerosis: eliminate myelin sheaths that insulate surfaces of neurons, leads to
muscle weakness and impaired coordination
How is antibody diversity (between 1- 100 million specificities) achieved with a limited number
of genes (35 000 that encode for proteins)
o The heavy chain is formed by one gene, IGH (immunoglobulin heavy)
o The light chain is formed by two genes, IGK (immunoglobulin kappa) and IGL
(immunoglobulin lambda)
o In the formation of the antibody, the heavy chain may be bound to a kappa or a lambda
light chain, so now there are 2 different combinations of antibodies, each with different
functions
o In addition, ordered yet random transcription will result in 8 different mat/pat allele
combinations of antibodies, each with potentially different functions
o VDJ: variable/diversity/joining segment recombination, the number of different ways is
multiplication of all three
Genetic rearrangement or somatic recombination
o Within B cells: 46 chromosomes per cell, alteration to somatic cells causes mosaicism
o DNA recombination: crossing over, deletions, causes DNA template to be smaller
Lecture 29: Animal Reproduction (Chapter 38)
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