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Flashcards in Immunology I Deck (34)
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1

Intracellular, Extracellular, Viral, Fungal, Parasitic, and Malignant Cells vs. Body

Intracellular fought by cell mediated immunity
Extracellular fought by antibodies
Viral infections always fought by cell mediated immunity
Fungal infections fought by antibodies (extracellular) and cell mediated immunity (intracellular)
Parasitic and malignant cells fought by cell mediated immunity

2

Innate Immunity: General Information

Natural, none-adaptive, Nonspecific
Phagocytes: Monocytes, macrophages, PMN neutrophils
Exterior defenses: Skin, Stomach acidity, Mucus, Cilia, Microflora

NK is only lymphocyte involved in innate immunity
Complement system: humoral because it is composed of proteins that are soluble (other molecules) and innate because it is always present and classical is purely innate, can be activated by bacteria themselves
Skin – very good at protecting against infections, in order for infection to occur, there must be a mechanism to penetrate such as mosquito bite
Mucus – can capture the bacteria and removed movement of cells/cilia
Microflora – give the opportunity to live in our body in exchange for removal of bacteria that enter the body
Flushing of urinary tract – urine is sterile and has antibacterial effects
Lysozyme in tears

3

Soluble Factors and Physiological Responses

Soluble Factors for Humoral Immunity (part of innate) that doesn't include Ab (part of adaptive): 
Lysozyme, Complement System, Antiproteinases, C-reactive protein, DNAse, RNases

Physiological responses:
Weakness of infectious agent: chemotactic substances, chemicals that are released and will be detected by WBCs and follow the concentration of the substance and the highest concentration is the site of release and then it will detect the bacteria and kill them
Formyl methionine: comes from prokaryotes/bacteria because we do not have the formyl group; this leads the WBCs to the bacteria
Mast cells & PMNs
Leukotrienes & Histamines

4

Mechanisms of Killing with O2

Toxic oxygen: oxygen radicals, hydrogen peroxide, and hypochlorous acid (HOCl)

These are found within the lysosome. When the bacteria is phagocytosed, the oxidases/toxic molecules come into contact with bacteria and destroy

5

Innate Immunity

Pathogen recognized by receptors encoded in the germline, therefore the receptors cannot change
Receptors have broad specificity
Recognize many related molecular structures:
Pathogen-associated molecular patterns (PAMPs)
PAMPs are polysaccharides & polynucleotides
Found in pathogens with few variations
Absent from host
Pattern recognition receptors (PRRs)
Immediate response
No memory of prior exposure

6

Adaptive Immunity

Pathogen recognized by receptors generated randomly, so have more flexibility; we have many Ab because there is a constant and variable part of the Ab; variable is composed of somatic recombination (not in germline) to give ability to produce many Ab with different specificities without costing the genome space

Receptors have very narrow specificity
Recognize a particular epitope (must be present or cannot recognize the antigen) derived from polypeptides and are pathogen specific
B-cell (BCR) and T-cell (TCR) receptors are antigen-specific; B cell receptor is partially associated with cell, but can be released and find the antigen somewhere else and attack; T cell receptor never leaves, so recognition is its only role
Slow response (3-5 days) since you need time for B- & T-cell clones to develop
Memory of prior exposure: Anamnesis
Only in vertebrates

Develop in response to foreign antigens like microorganisms, viruses, transplanted tissues and organs
Important components: B and T cells, and also
Antibodies (Abs) = Immunoglobulins (Ig):
IgA, IgG, IgM, IgE, IgD

7

Defensins

Protected by defensins:
Skin, GI tract lining, Genitourinary tracts lining, Lining of the nasal passages, Lungs lining

Peptides that are different because they are positively charged, which most proteins are negatively charged
These can bind to the membranes of the cells and destroy the membrane; in lining of intestine, genitourinary tract
Produced mainly by neutrophils

8

Monocyte vs. PMN receptors

Monocytes/Macrophages: Complement receptors (CR) 1-3 bind with different affinities to C3b, C3bi &C4b, FcR I (receptor for IgG 1 & 3), MHC class I (receptor for CD8), MHC class II (receptor for CD4)

PMN: CR 1-3 and MHC class I (receptor for CD8)

Some of the receptors that are on monocytes or neutrophils (PMNs) – part of the innate immunity
Bacteria tagged with C3b and CR I binds to it and the macrophages captures the bacterium and swallows it
FcRI: binds IgG 1 and 3: bacteria is labeled by the Ab and the FcRI receptor binds and phagocytosed by the macrophage
Major Histocompatibility Complex (MHC): HLA (human lymphocytes antigen) is the same as MHC; all nucleated cells have MHC I except RBCs, which is formed by cell mediated immunity like T cell CD8 (cytotoxic T cell)
MHCII is found in only some cells that act as antigen presenting cells (APC) to the T helper cells/ CD4; CD4 is a molecule that is used by the HIV virus and destroys the function to the T helper cell, which is essential for the function of the B cells, activation of macrophages and other cells, and CD8 cells; essentially HIV destroys the immune system through this one step

9

Antibody Mechanism

Abs specific binding sites bind Ags on microbe 1
No specific Ag. so no binding of microbe 2
Fc of the Ab binds FcR on phagocytes
Ag-Ab complex activates complement by the Ab’s Fc

10

Immunization

Active immunization: acquired in response to Ag (antigen) administration ex. MMR

Passive immunization: acquired through administration of already made Ab from immunized individual ex. physician that goes to endemic disease area

Adoptive transfer: transfer of immunity by transplanting immunocompetent cells and gaining new immune system
people who need new immune system bc their original is nonfunctional via bone marrow transplant
Dangerous bc of compatibility effect
Graft vs host – graft (bone marrow you receive) acts against host and can possibly kill

11

Humoral vs. Cell Mediated Immunity

Acquired humoral (soluble) immunity is based mainly on Abs made by B cells (mature B cells = plasma cells)
Other components of humoral immunity: complement & cytokines

Acquired cell-mediated immunity useT helper cells (TH) and Cytotoxic T cells (Tc)
Other components of cellular immunity (WBC): phagocytes, macrophages, neutrophil, natural killer cells (NK)
NK: only lymphocyte in innate immunity; differs from other lymphocytes because does not have specific antigen receptor

The differentiation between humoral and cell mediated is important because if we have a bacterial infection outside of our cells, this is responsded by humoral; if have bacterial or viral infections that are inside cells, then Ab cannot do anything against them so need cell mediated

12

Complement Functions

1 Lysis /MAC- intrinsic ability to lyse cell membranes of many bacterial species
2. Chemotaxis- complement products attract phagocytes to the site of the reaction
3. Opsonization- complement components coat the bacterial surface and allow phagocytes to recognize & engulf bacteria

Activation by:
Intrinsic ability to recognize microbial components
Recognition of Ab-Ag complex

13

MHC

MHC = HLA (human lymphocytes Ag)
Two classes: I & II
Important in presenting Ags to TH and TC cells
MHC I presents Ag peptides to TC/cytotoxic T cells (CD*8); in all cells of the body
MHC II presents Ag peptides to TH/ helper T cells (CD4)

14

Cytokines

Cytokines are produced by WBCs and can facilitate the communication between cells
They can activate and inhibit other cells
Small peptides synthesized by cells of the immune involvement
Regulators: activate cells and inhibit cell functions
Major means of communication among cells of the immune system (IS) and between IS and others cells
Examples: Interleukins (IL-2, IL-4) and Interferons

15

Clonal Selection Theory

Postulates:
1. T and B cells exist with almost unlimited specificities before any contact with foreign Ags
2. Ag-specific receptors recognize foreign Ags
BCR: Ab on B cell surface
TCR on T cell surface
3. Each B or T lymphocyte has a single specificity
It recognizes one epitope
4. Ag’s epitopes binding to B or T cells triggers their differentiation and proliferation
5. Exposure of T and B cells to self-Ags lead to negative selection: cells that recognize self-Ags are shut off/eliminated during maturation (aka cell death)

16

Harmful Effects of the Immune System

Hypersensitivity or allergic reactions
Autoimmune diseases
Immunodeficiencies
Graft rejection

17

Genetic Recombination & Immune Response Diversity

Antigenic specificities are numerous (10^6-10^7)
If 1 gene = 1 polypeptide which elicits 1 "response”, do we need >10^7 genes? No, somatic genetic recombination occurs “within“ a gene that encodes the Ig proteins
Ab is composed of 2 types of polypeptides: H-chain and L-chain and each chain has a variable domain
Recombination mechanism generates Ab & TCR specificity

18

Cells of the Immune System

Lymphoid Lineage: T helper cells (TH), Cytotoxic T cells (Tc or CTL), B cells, Natural Killer [NK; large granular lymphocytes (LGL)] (Contain granules with enzymes can kill tumor, virus-infected cells and bacteria)

Myeloid Lineage: 1. Polymorphonuclear granulocytes including neutrophil, basophil & Mast cells, Eosinophil; 2. Mononuclear phagocytes including dendritic cells & macrophages

Megakaryocytic “Lineage”: Platelets

19

Hematopoiesis

Hematopoiesis: process of blood cell maturation from stem cell to functional RBC and WBC; RBC and WBC are formed in the bone marrow

Stem cells
1. Totipotent- cell ability to differentiate and generate a new organ or organism
Examples: zygote

2. Pluripotent - cell ability to develop into limited different types of mature cells, depending on hormonal or external effects
Examples: myeloid cells and lymphoid cells; hemopoietic stem cell, which is a common ancestor of lymphoid and myeloid cells

20

Myeloid and Lymphoid Cells

Myeloid cells
erythrocyte, neutrophil, monocyte (which turns into a macrophage) eosinophil, basophil & mast cell, megakaryocyte (which turns into a platelet)

Lymphoid cells
Lymphocytes: T cell, B cell (which turns into a plasma cell), NK cell

Dendritic Cells- progenitor cell unknown

21

Polymorphonuclears (PMN)

Majority neutrophils from bone marrow at 7 million/minute, but short lived (2-3 days)
Conistitute 60-70% of WBCs
Called neutrophil because they take up eosin of H&E stain poorly
Multilobed nuclei
Granules- Lysosomes:
1. Azurophilic, Primary granules contain: hydrolases, peroxidases, lysozyme
2. Secondary granules granules contain: lactoferrin &
lysozyme

22

Neutrophils

Produce: reactive oxygen metabolites, hydrolytic enzymes, nitric oxide, antibiotic proteins like defensins,
seprocidins, cathelicidins, and bacterial permeability inducing protein
Chemotactic activity in response to: complement fragments (C5a- chemotactic substance), products of platelets & leukocytes, bacterial products, proteins produced during fibrinolysis

23

Functions of Neutrophils

Primary function is phagocytosis, which is enhanced by opsonization with complement (C3b) and Abs; digestion of phagocytosed elements is vital or develop granulomas
Secondary function is to promote inflammatory reactions, especially acute
No specificity for Ags
Diapedesis/Extravasation: PMNs leave the circulation by adhering to the endothelium & squeezing out of the blood vessel
Increased susceptibility to infections in case of polymorph extravasation deficient individuals and individuals with low numbers of PMNs

24

Example of Clonal Selection: B cells

Antigen independent: occurs independently of presence of antigen in body (uncommitted cells)
Antigen dependent: needs antigen present (committed cells)
Uncommitted: do not have specific receptor and become anything; these proliferate and produce cells that have a specific receptor; happens before exposure to antigen; if take our cells and look at them, we will find many types of B cells and only difference is the type of receptor that can recognize one antigen or another
Committed: recognize only a specific epitope, and does not recognize any other type of epitope; wait for antigen part of bacteria/infectious agent in order to proliferate and secrete Ab capable of binding to any foreign Ag

25

Basophils and Mast Cells

Infamous for reaction of hypersensitivity; commonly fight parasitic infections; Least prevalent leukocytes with a high affinity for Fc receptors for IgE
In the US, parasitic infections are not that relevant/very few cases per year; so other affects of these cells are allergic reactions
Difference: basophil (S shaped nucleus and round) is in circulation and mast cells are stationary in the tissues like mucosa (MMC) or connective tissues (CTMC); activated by IgE
Granules contain heparin, histamine, SRS-A, and ECF-A, prostaglandins, thromboxanes, leukotrienes
SRS-A (slow-reacting substance of anaphylaxis) to attract eosinophils to area of worm infestation or allergen localization
ECF-A (eosinophil chemotactic factor A)

26

Monocytes/Macrophages

Professional phagocytes
Monocytes enter circulation from bone marrow then migrate into various organs and tissues
Mature into macrophages, Kupffer cells (liver), Histiocytes (connective tissue), dendritic cells (lymph nodes, spleen), glial cells (brain), Langerhans cells (skin)
Reticuloendothelial system (RES) is a network formed mainly by the collection of monocytes and macrophages
Mononuclear phagocyte system

27

Differential WBC Count

Neutrophils are the majority and lymphocytes can change according to infection
If no infection, % of lymphocytes will be low and vice versa with an infection

28

Platelets

Anucleate and derived from megakaryocytes
Contain granules at the ultrastructural level
Their major functions are blood clotting and inflammation
Following injury to endothelial cells, platelets adhere to the surface of the damaged tissue, where they release substances that increase vascular permeability,activate complement, and attract leukocytes

29

Functions of Lymphocytes

LGL =large granulocyte
Summarizes the functions of lymphocytes
Central role of Th cells, produces cytokines that activates the Tc, macrophage, NK cells, and antigen presenting cell itself (APC) like B cells, which produce MHC II and this peptide will be recognized by Th cell receptor, so in addition to that CD4 is produced; if peptide isn’t present and MHC presented the T cell wont recognize it because it needs the peptide in addition to the MHC II
The NK cells and cytotoxic T cells cannot phagocytize, only produce molecules for release
HIV: Th with CD4; HIV binds to CD4 and introduce its DNA into the T cell and eliminate CD4 so T cells will not be activated; system deprived of T cells and immune system is destroyed; once the number of T cells goes under 400 they are infection prone and death will be soon

30

B and T Lymphocytes

B and T lymphocytes are made in bone marrow
T cells go from bone marrow to thymus to develop; thymus is an organ that starts working in the womb and shortly after birth, but by puberty the thymus almost disappears and the T cells are developed by an early age
B cells have two stages of development; fetus is in liver, but after birth the site of production is in the bone marrow
B and T cells have specific receptors that recognize the antigen and in general lymphocytes have many nuclei but little cytoplasm
NK (natural killer) cells do not express Ag receptor
Lymphocytes have high N:C (nucleus : cytoplasm) ratio
LGL (NK; Large granular lymphocytes) have lower N:C ratio
LGL = Large granular lymphocytes. Do not confuse LGL with granulocytes